Retrospective evaluation of factors associated with the risk of seropositivity to Ehrlichia risticii in horses in New York State. A retrospective study was designed to determine the distribution of equine monocytic ehrlichiosis among the equine population in New York state, and to identify factors associated with risk of disease. Serum samples submitted to the diagnostic laboratory of the university during the period from January 1985 through December 1986 were examined for antibodies to Ehrlichia risticii, using the indirect fluorescent antibody technique. Factors evaluated included geographic origin and date of submission of the sample, and age, breed, and sex of the horse. Logistic regression analysis was used to identify which factors were significantly associated with the risk of seropositivity to E risticii, while simultaneously controlling for other factors. Of the 2,579 tested samples, 1,950 (76%) had positive results. Factors significantly associated with risk of seropositivity to E risticii were: breed of the horse (Thoroughbreds were 3 times more likely to have been exposed to E risticii, compared with non-Standardbred, non-Thoroughbred breeds); sex (female horses were 2.7 times more likely to have been exposed, compared with male horses); age of the horse (the risk of being exposed to E risticii increased with age, peaked at around 12 years, and decreased thereafter); and month of submission (horses tested during November and December had the highest odds of being seropositive [odds ratio = 2.1], and horses tested during March through April were least likely to be seropositive [odds ratio = 0.5], compared with horses tested during January and February).


Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles. The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of protein source in liquid formula diets on food intake, physiologic values, and growth of equine neonates. The effects of 2 liquid formula diets differing in protein source were evaluated in orphan foals. The response of 7 foals fed a diet containing casein as the protein source, and 6 foals fed a diet containing a combination of whey and casein, was compared with the response in a reference group of 8 mare-raised foals. Orphaned foals were fed 150 kcal/kg of body weight/d, divided into 6 equal feedings of 25 kcal/kg. Formula intake was comparable among the experimental groups, and foals fed the liquid formula diet grew as well as mare-raised foals. There was no difference among groups in mean daily body weight gain, wither height, heart girth, body temperature, pulse, respiration rate, capillary refill time, or skin tenting. Insulin and blood glucose concentrations increased in both groups of foals fed formula diets, returning to prefeeding values within 4 hours. Differences among groups were found for serum alkaline phosphatase, alanine transaminase, cholesterol, creatinine, and glucose values; all other serum chemical values were comparable among groups. Plasma amino acid determinations revealed that arginine and ornithine were significantly lower in foals in both experimental groups than in reference foals, suggesting that arginine may have been the limiting amino acid in these diets. Diarrhea developed in foals in all treatment groups, but in most cases was self-limiting. These results suggest that the protein source of liquid formula diets may be less important in foals than in infants.


Malabsorption of vitamin A in preruminating calves infected with Cryptosporidium parvum. Serum retinol, retinyl palmitate, and total vitamin A concentrations, and jejunoileal morphology were examined in neonatal calves infected with Cryptosporidium parvum. Group-1 calves served as noninfected controls and, after an adjustment period, were given 50 ml of saline solution i.v. every 12 hours for 6 days. Group-2 calves were inoculated with 10(7) C parvum oocysts and, after the onset of diarrhea, were given 50 ml of saline solution i.v. every 12 hours for 6 days. Group-3 calves were inoculated with 10(7) C parvum oocysts and, after the onset of diarrhea, were treated with difluoromethylornithine (DFMO, 200 mg/kg of body weight i.v., q 12 h) for 6 days. Group-4 calves were naturally infected with C parvum. Jejunoileal biopsy specimens were excised from calves of groups 1-3 at 3 and again at 15 to 16 days of age. During the course of diarrhea and 3 days after saline or DFMO administration, water-miscible retinyl palmitate was administered orally (2,750 micrograms/kg) to each calf in each group. Cryptosporidium parvum infection was associated with significant (P < or = 0.05) reduction in postadministration serum retinol, retinyl palmitate, and total vitamin A concentrations in calves of groups 2, 3, and 4. Cryptosporidium parvum infection caused significant (P < or = 0.05) reduction in villus height. Decreased villus height, villus blunting and fusion, and attenuation of the intestinal mucosa were associated with reduced absorption of vitamin A, as indicated by lower peak postadministration retinyl palmitate concentration in C parvum-infected calves. Intravenous administration of DFMO to group-3 calves did not improve retinol absorption.(ABSTRACT TRUNCATED AT 250 WORDS)


Bronchoscopy of the horse.

Bronchoscopy of the horse. The endobronchial anatomy of 12 lung specimens from horses and 12 healthy, standing, sedated horses was evaluated, using a 200-cm-long, 9.5-mm-diameter videoendoscope. On the basis of these findings, the nomenclature system of Amis and McKiernan was modified for identification of airways of horses during bronchoscopy. Lobar bronchi are identified on the basis of the side of the bronchial tree on which they were found and the order in which they originated from the primary bronchus. Thus, RB1, RB2, and RB3 referred to right cranial lobar bronchus, respectively. On the left side, the designation of LB1 and LB2 refer to the left cranial lobar bronchus and the left caudal lobar bronchus, respectively. Segmental bronchi are identified by consecutive numbers in the order of origination from the lobar bronchus. The direction of the segmental bronchus was denoted by the capital letter D (dorsal), V (ventral), L (lateral), M (medial), R (rostral), and C (caudal). Subsegmental bronchi were identified in the order of origination from the segmental bronchi, using lower case letters (eg, RB2, 1V, a or RB2, 1V, aV). For subsequent branching of the subsegmental bronchi, the branches were numbered consecutively by their order of origination (eg, RB2, 1V, aV, 1D).


Gastric emptying of nondigestible radiopaque markers after circumcostal gastropexy in clinically normal dogs and dogs with gastric dilatation-volvulus. Using radiopaque particles mixed with food, gastric emptying was assessed in healthy dogs not subjected to surgery, in healthy dogs 9 to 35 days after circumcostal gastropexy, and, in dogs 1 to 54 months after surgical treatment and recovery from gastric dilatation-volvulus (GDV). Circumcostal gastropexy surgery did not alter the 90% gastric emptying time for radiopaque particles in healthy dogs. However, 90% gastric emptying time was significantly (P less than 0.05) increased after circumcostal gastropexy in dogs with GDV, compared with healthy dogs after the same surgical procedure and recovery period. These results imply that dogs with GDV have delayed gastric emptying of solid particles. Whether delayed gastric emptying of markers detected in affected dogs after surgical treatment and recovery was the result or the cause of GDV was not determined. Results indicate that circumcostal gastropexy could be recommended as a prophylactic procedure for GDV in large breeds with deep thorax, because delayed gastric emptying of markers secondary to the surgical procedure is unlikely.


Immunotoxicity of ochratoxin A to growing gilts. Ochratoxin A (OA) was incorporated in the diets of growing gilts (mean body weight, 20.1 kg) at a concentration of 2.5 mg of OA/kg of feed and was fed continuously for 35 days. Humoral and cell-mediated immunologic measurements were evaluated to determine the effects of OA on immune function in swine. Cutaneous basophil hypersensitivity to phytohemagglutinin (PHA), delayed hypersensitivity to tuberculin, PHA-induced lymphocyte blastogenesis, interleukin-2 production, total and isotype immunoglobulin concentrations, antibody response to chicken RBC, and macrophage activation were used to evaluate immune function. Gilts treated with OA had reduced cutaneous basophil hypersensitivity response to PHA, reduced delayed hypersensitivity to tuberculin, decreased stimulation index for lymphoblastogenesis, decreased interleukin-2 production when lymphocytes were stimulated with concanavalin A, and decreased number and phagocytic activity of macrophages. Differences were not observed for total and isotype immunoglobulin concentrations, or humoral hemagglutination (chicken RBC) titer. These data indicate that OA may suppress cell-mediated immune response in growing swine.


The effect of hyperinflation on rib cage-abdominal motion. Abnormalities of rib cage-abdominal motion are common in patients with chronic obstructive pulmonary disease (COPD), but the basis of the abnormal motion has not been completely determined. Although airway obstruction has been shown to be a major factor in causing abnormal chest wall motion, the effect of hyperinflation (which has numerous adverse effects on respiratory muscle function) has not been systematically examined. We induced graded levels of hyperinflation in six healthy volunteers using continuous positive airway pressure (CPAP) levels of 10, 20, and 30 cm H2O. Chest wall motion was measured by a calibrated inductive plethysmograph. Rib cage-abdominal asynchrony and paradox were quantitated by the Konno-Mead method of analysis. CPAP levels of 10, 20, and 20 cm H2O produced increases in end-expiratory lung volume of 0.98 +/- 0.14 (SE), 1.90 +/- 0.31, and 2.42 +/- 0.37 L, respectively (p < 0.0001). This corresponded to an increase in the ratio of functional residual capacity to predicted total lung capacity from 0.38 +/- 0.08 at baseline to 0.74 +/- 0.14 at 30 cm H2O CPAP-comparable to that seen in patients with COPD. Hyperinflation induced an increase in inspiratory abdominal paradox, 1.0 +/- 0.7% at baseline versus 3.6 +/- 1.7% at 30 cm H2O (p < 0.05), but this is unlikely to be clinically significant. A significant increase in asynchrony or rib cage paradox did not develop with hyperinflation. In conclusion, the primary factor contributing to abnormal chest wall motion in patients with COPD is likely to be increased airway resistance, and hyperinflation makes only a minor contribution.


Effect of chronic renal failure on skeletal and diaphragmatic muscle contraction. The changes in muscle mechanical properties caused by the myopathy of chronic uremia was examined in the soleus and the diaphragm muscles of rats in which chronic uremia was produced by subtotal nephrectomy. Using an in vitro muscle preparation in two groups of rats (moderately and severely uremic), we determined that uremia had a significant detrimental effect on both muscles with respect to the force-frequency relationships. In the diaphragm it decreased by 15% in the moderate group and by 43% in the severe group. In the soleus it decreased by 20% in both groups. Twitch characteristics behaved differently in the soleus and the diaphragm muscles in that 1/2 RT and TPT increased significantly (p < 0.05) in the soleus (severely uremic group) but not in the diaphragm. Fatigability was increased in both muscles in the moderately uremic rats and in the diaphragm in the severely uremic rats; however, the fatigability of the soleus in the severely uremic group was not different from that in the control group. Our findings suggest that the myopathic changes occurring in chronic uremia affects the function of the soleus and the diaphragm in different ways. Other findings in the severely uremic group indicate that additional factors such as marked electrolyte imbalances may also affect the excitation-contraction coupling in different ways.


Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea. As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.


Size and mechanical properties of the pharynx in healthy men and women. Obstructive sleep apnea (OSA) has a marked male predominance. To determine whether there are differences in the mechanical properties of the pharynx of men and women that may contribute to the gender difference in disease incidence, we measured pharyngeal cross-sectional area during quiet breathing in 77 normal men and 98 normal women using the acoustic pulse technique. Standard pulmonary function tests were also performed. Pharyngeal mechanics were studied in 23 men and 34 women by measuring the change in pharyngeal area during a slow vital capacity maneuver. Gender was found to be the most important independent factor contributing to pharyngeal size. The men had a significantly larger pharynx than the women (3.63 +/- 0.10 versus 3.20 +/- 0.09 cm2, mean +/- SEM; p < 0.01). Pharyngeal mechanics were also different between men and women. The men had a larger change in pharyngeal area with changing lung volume than the women (0.60 +/- 0.14 versus 0.12 +/- 0.12 cm2, mean +/- SEM; p < 0.02). This difference persisted even after normalizing the data for pharyngeal size. We found that there are gender-related differences in the size and mechanical properties of the pharynx and speculate that the larger pharynx of men may be more than offset by greater changes in pharyngeal size with changing lung volume, contributing to the greater incidence of OSA in men.


Theophylline does not increase ventilatory responses to hypercapnia or hypoxia. Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness.


Effects of repetitive airway obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs. We examined the effects of multiple repetitive airway obstruction (RAO) on arterial oxygen saturation (SaO2) and pulmonary and systemic arterial pressure in eight anesthetized spontaneously breathing dogs. SaO2 was monitored at the tongue with a pulse oximeter. RAO created by an electrical valve that was attached to a tracheal cannula was alternated with seven consecutive spontaneous breaths until the nadir SaO2 (nSaO2) became constant or decreased to less than 35%. Tracheal occlusion durations of 15, 30, 45 and 60 s were chosen arbitrarily. In each animal nSaO2 decreased with every trial number in an exponential fashion, and the rate of nSaO2 fall was greater for the longer occlusion duration. In each animal the increases in pulmonary arterial pressure (PAP) and systemic arterial pressure (SAP) were inversely related to the nSaO2 values, and the relationship between nSaO2 and PAP or SAP was identical for all occlusion durations. Moreover, when the animals breathed pure oxygen and SaO2 did not decrease, there were no significant increases in the PAP and SAP at similar levels of pleural pressure (Ppl). In another six dogs, the effects of RAO on PAP and SAP were compared with those of intermittent hypoxic exposure without apnea, which was achieved by the inhalation of hypoxic gas (4 to 6% O2, 5% CO2 in N2) instead of RAO, to examine the effects of interruption of ventilation. The relationships between nSaO2 and both pressures did not differ significantly from those during RAO.(ABSTRACT TRUNCATED AT 250 WORDS)


Tracheal gas insufflation during pressure-control ventilation. Effect of catheter position, diameter, and flow rate. In the setting of acute lung injury, ventilatory strategies that adjust minute ventilation (VE) to achieve eucapnia often lead to alveolar rupture or damage. Tracheal gas insufflation (TGI) reduces the VE requirements of conventional mechanical ventilation by decreasing the effective dead-space fraction (VD/VT) of each breath. We studied the effect of catheter flow rate (Vcath) and position as well as catheter tip diameter and configuration on CO2 elimination during TGI-augmented pressure-controlled ventilation (PCV) in normal dogs. We studied three catheter positions (1, 5, and 10 cm above the carina) at Vcath of 2, 5, and 10 L/min (n = 6). When the catheter tip was positioned 1 cm above the carina, PaCO2 decreased significantly from a baseline (PCV alone) of 67 +/- 10 mm Hg to 52 +/- 11, 43 +/- 9, and 32 +/- 7 mm Hg (p < 0.05) at Vcath of 2, 5, and 10 L/min, respectively. For the same Vcath values, positioning the catheter tip 10 cm above the carina increased PaCO2 to 54 +/- 15, 46 +/- 12, and 40 +/- 11 mm Hg. Advancing the catheter tip 2 cm below the carina did not improve PaCO2 significantly (n = 3). At a catheter position of 1 cm above the carina and a Vcath of 10 L/min, changing the luminal inner diameter (1.5 versus 3.0 mm) or tip configuration (open tip versus occluded tip with two side holes) of the catheter did not change PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS)


HIV-1 envelope protein (gp120) inhibits the activity of human bronchoalveolar macrophages against Cryptococcus neoformans. Cryptococcus neoformans infections are a major cause of morbidity and mortality for HIV-infected persons. Containment of the initial respiratory inoculation to the lung appears defective in patients with AIDS despite the low burden of HIV in bronchoalveolar macrophages. We have studied the fungistatic activity of human bronchoalveolar macrophages (BAM) cultured with an encapsulated strain of C. neoformans in the presence of pooled human serum. We observed 51.6% fungistasis after 24 h of culture. Fungistasis was diminished if the pooled human serum was heat-inactivated but was not affected by anticryptococcal capsular IgG. HIV envelope protein (gp120) has been shown to interfere with lymphocyte activation in vitro. We studied the effects of gp120 on BAM function and found that fungistatic activity was inhibited 25% (p < 0.001). Although binding of yeasts was not affected, gp120 inhibited the internalization of bound yeasts by 46% (p = 0.025). These experiments indicate that gp120 decreases the internalization and fungistasis of C. neoformans by human BAM, and they suggest a mechanism to explain how a small number of HIV-1-infected cells in the lung could impair the containment of C. neoformans.


Two-year incidence of tuberculosis in cohorts of HIV-infected and uninfected urban Rwandan women. To determine the prevalence of Mycobacterium tuberculosis infection and the incidence of tuberculosis in HIV-infected and uninfected urban Rwandan women, 460 HIV-positive and 998 HIV-negative childbearing women were recruited from pediatric and prenatal care clinics and were enrolled in a prospective study in 1988 and followed for 2 yr. Tuberculin testing was administered 12 to 18 months after enrollment. Fifty-three percent of HIV-negative women had positive tuberculin tests (induration > or = 10 mm), with higher rates among older women and among women who had received BCG vaccine. Only 21% of HIV-positive women had positive tuberculin tests, with no relationship to BCG vaccine. Follow-up was available for 93% of subjects. Tuberculosis was diagnosed in 20 HIV-positive women and in two HIV-negative women. Features associated with an increased risk of tuberculosis among HIV-positive women included: age > or = 30, body mass index in the lowest quartile, low income, erythrocyte sedimentation rate > 75, positive tuberculin test, and chronic cough, chronic fever, and weight loss. Among Rwandan women who are infected with HIV, approximately half of those who are infected with M. tuberculosis do not have positive tuberculin tests. The rate ratio for development of tuberculosis among HIV-positive women was 22 (95% CI, 5 to 92). New algorithms are needed to improve the early detection of tuberculosis among HIV-positive patients in Africa.


The combined effect of rifampin and pyrazinamide within the human macrophage. A recent study in the murine model suggested that a combination of rifampin and pyrazinamide used as preventive therapy might shorten the duration of treatment time. Clinical trials using this combination have been initiated, but significant results will not be available for many years. The ex vivo human macrophage model has been instructive in expanding our knowledge of the activity of chemotherapeutic agents against intracellular virulent tubercle bacilli. Prior studies have shown rifampin to have a bactericidal effect in this model while even at clinically unachievable levels, pyrazinamide had only a bacteriostatic impact. This study finds an enhanced bacteriostatic effect when low, nonbactericidal levels of rifampin are combined with clinically achievable levels of pyrazinamide but not with higher bactericidal levels of rifampin. Adding pyrazinamide 2 days after the introduction of rifampin clearly enhanced the combined killing effect. However, reversing the order and adding rifampin 2 days after the introduction of pyrazinamide produced a result weaker than introducing the agents simultaneously. Our findings do not support the use of these agents as a potentially effective preventive therapy combination, but they suggest that the timing of the administration of these chemotherapeutic agents could be an important factor in their effectiveness.


Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels. Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of smoke inhalation on lung function and airway responsiveness in wildland fire fighters. The current study was undertaken to evaluate the effect of smoke on forced expiratory volumes and airway responsiveness in wildland fire fighters during a season of active fire fighting. Sixty-three seasonal and full-time wildland fire fighters from five U.S. Department of Agriculture Forest Service (USDAFS) Hotshot crews in Northern California and Montana completed questionnaires, spirometry, and methacholine challenge testing before and after an active season of fire fighting in 1989. There were significant mean individual declines of 0.09, 0.15, and 0.44 L/s in postseason values of FVC, FEV1, and FEF25-75, respectively, compared with preseason values. There were no consistent significant relationships between mean individual declines of the spirometric parameters and the covariates: sex, smoking history, history of asthma or allergies, years as a fire fighter, upper/lower respiratory symptoms, or membership in a particular Hotshot crew. There was a statistically significant increase in airway responsiveness when comparing preseason methacholine dose-response slopes (DRS) with postseason dose-response slopes (p = 0.02). The increase in airway responsiveness appeared to be greatest in fire fighters with a history of lower respiratory symptoms or asthma, but it was not related to smoking history. These data suggest that wildland fire fighting is associated with decreases in lung function and increases in airway responsiveness independent of a history of cigarette smoking. Our findings are consistent with the results of previous studies of municipal fire fighters.


Dust- and endotoxin-related respiratory effects in the animal feed industry. A cross-sectional study of 315 animal feed workers was undertaken in 14 animal feed mills in the Netherlands. Primary aims were to explore relationships between exposure to organic dust and respiratory symptoms and chronic lung function changes. The study comprised monitoring dust and endotoxin exposure, spirometric lung function measurements (FVC, FEV1, mean midexpiratory flow, and flow-volume parameters) and a questionnaire for respiratory symptoms. The exposure was measured in two periods, during spring and autumn. The average 8-h personal inspirable dust exposure was 9 mg/m3 grain dust (range, 0.2 to 150 mg/m3) and 25 ng/m3 endotoxin (range, 0.2 to 470 ng/m3) based on 530 personal dust measurements. On the basis of these measurements and the occupational history of the workers, the number of years "worked in dust" and an estimate of the cumulative dust and endotoxin exposure were calculated. The prevalence of most chronic respiratory symptoms tended to decrease with increasing years of exposure. The "healthy worker effect" is probably responsible for this finding. In general, a strong negative association between most of the exposure variables and lung function was found. The endotoxin exposure was more strongly related to decreases in lung function than the dust exposure. The estimated effects of an average (cumulative) endotoxin exposure on lung function were greater, with a higher statistical significance, than for an exposure to dust. These results suggest that endotoxin exposure is an important factor in the development of respiratory impairment. The lung function changes occur at endotoxin levels ranging from 0.2 to 470 ng/m3.


Exposures of older adults with chronic respiratory illness to nitrogen dioxide. A combined laboratory and field study. We combined field and laboratory experimentation to evaluate the effects of nitrogen dioxide in a panel of Los Angeles area residents with chronic respiratory illness, 15 men and 11 women aged 47 to 69. All had heavy smoking history, chronic symptoms, and low FEV1; some also had low FVC. During the fall-winter high-NO2 season, they monitored themselves for 2-wk periods using spirometers in the home, passive NO2 sampling badges, and diaries to record time and activity patterns and clinical status. In the middle of each self-monitoring week they were exposed in a chamber, once to clean air and once to 0.3 ppm NO2. Chamber exposures were double blind, lasted 4 h, and included four 7-min exercise sessions with average ventilation rates near 25 L/min. Symptom reports and hourly forced expiratory function tests showed no statistically significant differences between clean air and NO2 chamber exposures, although peak flow showed a approximately 3% loss with NO2 relative to clean air during the first 2 h of exposure only (p = 0.056). No significant overall differences were found between field self-measurements and measurements of lung function in the chamber or between field measurements in clean air and NO2 exposure weeks. Field data showed that group average lung function and symptom levels were worse in the morning than later in the day (p < 0.005) but otherwise were stable over 2 wk. Even though most subjects smoked and stayed indoors 80 to 90% of the time, personal NO2 exposures correlated significantly with outdoor NO2 concentrations as reported by local monitoring stations.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of steady-state and variable ozone concentration profiles on pulmonary function. Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Risk factors for increased airway responsiveness to methacholine challenge among laboratory animal workers. As a first step in a prospective study of the incidence of asthma to laboratory animals, a group of 364 adults 18 to 48 yr of age who were beginning employment with laboratory animals were evaluated in terms of their past history, health status, allergy, and airway responsiveness to methacholine. At entry to the study, 269 had previous occupational contact with animals, 109 had chest symptoms in the previous year, 168 had a history of allergic symptoms to laboratory animals (any with asthmatic responses were systematically excluded), and 118 had positive immediate skin tests (29 had positive skin tests to laboratory animals). When defined as a PD20FEV1 of 80 breath units or less, 18.4% of these young adults had methacholine hyperresponsiveness (HRA). Significant risk factors for HRA were found to be younger age, female sex, lower educational level, a history of allergic symptoms to laboratory animals, and a history of chest symptoms. Positive skin tests to laboratory animals were present in 8% of workers; this was not a significant risk factor for HRA although positive skin tests to pollen and household allergens were. Previous work experience was a risk factor, especially among those with allergic symptoms, and a trend toward self-selection was suggested in that the rate of HRA was lowest in workers with more than 2 yr of experience or with two or more previous jobs with laboratory animals.


Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma. To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS)


Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study. The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population.


Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air. We investigated the assumption that the efficacy of inhaled diuretics in asthma is dependent upon inhibition of the Na+/K+/2Cl- cotransporter. We compared the protective effect of acetazolamide, a diuretic without significant effect on the loop cotransporter, with the protection provided by inhaled furosemide in a cold, dry air hyperventilation model of asthma. Seven asthmatic subjects underwent a baseline bronchial challenge and then received a nebulized dose of 80 mg of furosemide or 500 mg of acetazolamide or saline placebo in a randomized, double-blind, placebo-controlled crossover design. Repeat challenges were performed immediately and at 2 and 4 h postnebulization. Acetazolamide caused a 47.2% increase in the amount of cold, dry air required to reduce the FEV1, by 20% (expressed in terms of respiratory heat loss as PD20RHL), from 0.79 multiplied or divided by (x/divided by) 1.13 kcal/min (geometric mean x/divided by geometric SEM) at baseline to 1.17 x/divided by 1.09 kcal/min postnebulization (p < 0.025). Furosemide increased the geometric mean PD20RHL by 53.9%, from 0.86 x/divided by 1.12 kcal/min to 1.33 x/divided by 1.12 kcal/min (p < 0.001). There was no significant change after placebo inhalation (0.81 x/divided by 1.15 kcal/min versus 0.87 x/divided by 1.10 kcal/min, NS). Airway responsiveness had returned to baseline by 2 h postnebulization on all 3 days. Furosemide also caused bronchodilatation, producing a 14.1% rise in the mean FEV1 (p < 0.005 versus prenebulization), whereas neither acetazolamide nor placebo altered airway tone significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Asthmatic subjects prone to nocturnal worsening demonstrate overnight recruitment of inflammatory cells into the airways. The influence of dose timing on the ability of corticosteroids to block circadian recruitment of inflammatory cells into asthmatic airways and attenuate the nocturnal worsening of asthma is unclear. In a double-blind, placebo-controlled, crossover design, we evaluated the response of seven asthmatic subjects with respect to overnight spirometry, blood eosinophil counts, and bronchoalveolar lavage cytology to a single variably timed 50 mg oral dose of prednisone given at 0800, 1500, or 2000 h. Compared to placebo, a single prednisone dose at 1500 h resulted in a reduction in the overnight percentage fall in FEV1 (-28.2 +/- 7.3 versus -10.4 +/- 4.5%, p = 0.04) and improvement in the 0400 h FEV1 (2.53 +/- 0.38 versus 3.43 +/- 0.38 L, p = 0.03). In contrast, neither a 0800 nor 2000 h prednisone dose compared to placebo resulted in overnight spirometric improvement. Also following the 1500 h prednisone dose, blood eosinophil counts were significantly reduced at both 2000 and 0400 h. Lastly, the 1500 h dosing resulted in a pan-cellular reduction in bronchoalveolar lavage cytology (p < or = to 0.05 for all cell lines compared to placebo), but neither alternative dose schedule significantly reduced any cell line. Our data support the relevance of timing of prednisone dose in altering the inflammatory milieu and spirometric decline associated with nocturnal worsening of asthma.


Bronchial exudation of bulk plasma at allergen challenge in allergic asthma. This study examined plasma exudation into the bronchial lumen after allergen challenge. A novel low-trauma technique was developed to challenge and lavage a medium-sized lingular or middle lobe bronchus. Eleven subjects with challenge-assessed pollen-sensitive asthma were allocated to fiberbronchoscopy in the supine position. In the control bronchus 0.5 ml diluent was instilled. The bronchus was occluded proximally 3 min later by inflation of a balloon, and lavage was carried out twice with 25 ml saline. Incremental doses of allergen solution (0.5 ml) were then instilled in the contralateral lung. The challenge continued until a clearly visible bronchial reaction occurred and was immediately followed by the same lavage as on the control side. The lavage liquids were analyzed for the presence of plasma exudation and mast cell activation indices. On the allergen-challenged side, tryptase, reflecting mast cell activation, was increased by 150% (p < 0.01) compared with the control side. Fibrinogen (mol wt 340,000), reflecting large protein exudation, was increased by 840% (p < 0.05), and N-alpha-tosyl-L-arginine-methyl esterase activity, reflecting both large protein exudation and mast cell activation, increased by 480% (p < 0.01). The level of albumin (mol wt 69,000), the major luminal protein under baseline conditions, increased but not significantly. We conclude that activation of mast cells and luminal entry of little sieved plasma exudates occur early after endobronchial allergen provocation in human subjects with allergic asthma.


Inhibition by L-NG-nitro-L-arginine of nonadrenergic-noncholinergic-mediated relaxations of human isolated central and peripheral airway. Human isolated central (5 to 12 mm) and peripheral (< 2 mm) bronchi were contracted with 3 microM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. NG-Nitro-L-arginine (L-NOARG) (10 microM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3-morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, alpha-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.


Excitatory role of axon reflex in bradykinin-induced contraction of guinea pig tracheal smooth muscle. To elucidate the role of the axon reflex in the airways, we studied the effects of atropine (10(-6) M) and tetrodotoxin (10(-7) M) on the bradykinin-induced contraction of guinea pig tracheal smooth muscle, with or without pretreatment of the animals with capsaicin. The concentration-response curves to bradykinin (10(-9) to 10(-5) M) were measured in the presence of both indomethacin and propranolol. In the guinea pigs not given capsaicin pretreatment, baseline tension values did not differ before versus after the application of atropine or tetrodotoxin. Tetrodotoxin reduced the bradykinin-induced contraction significantly, but atropine did not change the contraction induced by bradykinin. These observations indicate that bradykinin-induced contraction is potentiated by a neurally mediated action, but that is not mediated by acetylcholine released from the efferent vagal nerve terminals. The contractile response to bradykinin was significantly reduced in the animals treated with capsaicin as compared with those administered vehicle only. Furthermore, in the animals treated with capsaicin, tetrodotoxin did not affect the response to bradykinin. These observations indicate that bradykinin-induced airway smooth muscle contraction is mediated in part by tachykinins released from C-fiber endings, presumably via an axon reflex.


Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride. We established a model of asthma induced by trimellitic anhydride (TMA) in guinea pigs and assessed the role of sensitization in the development of their bronchial hyperresponsiveness, and relationship between bronchial responsiveness and bronchial inflammation. Fourteen guinea pigs (sensitized group) were administered 1 mg/0.5 ml of trimellity 36-bovine serum albumin intramuscularly and 0.5 ml of complete Freund adjuvant on Day 1 as the priming dose. Booster doses were repeated on Day 15. By Day 28, all of the sensitized animals showed a high passive hemagglutination titer against trimellityl 14-ovalbumin. On Day 29, they were challenged by an inhalation of TMA (150 mg/m3) for 30 min, and respiratory resistance (Rrs) was monitored by the oscillation method. In all sensitized animals, Rrs increased immediately upon challenge and returned to baseline within 6 h. The bronchial reactivity to acetylcholine (Ach), measured 6 h after TMA challenge in the sensitized animals, increased significantly (p < 0.01) compared with that measured 24 h before challenge; that measured 24 h later was not different from that before challenge. There was also a significant difference (p < 0.01) in the number of eosinophils in the lamina propria and the epithelium 6 and 24 h after the challenge inhalation in the sensitized group. The increased airway responsiveness to Ach in the sensitized animals was correlated with an increase in the number of eosinophils in the lamina propria and the epithelium. These observations suggest that humoral antibody and eosinophils are involved in the pathogenesis of TMA-induced asthma.


Metered-dose inhaler adherence in a clinical trial. We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits.


Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia? Inhabitants of the Metsovo area in Northwest Greece (population, 4,000) have been exposed to asbestos through the use of whitewash containing tremolite. This has resulted in endemic pleural calcifications (PCs) and increased incidence of malignant pleural mesothelioma (MPM). In order to evaluate the lung response to the fiber, bronchoalveolar lavage (BAL) was performed in 25 Metsovites; 14 with PCs, three with PCs and neoplasia, five without PCs, and three without PCs but with established neoplasia. There were no differences between the four groups with regard to age or exposure. Twelve Metsovites had lymphocytic alveolitis (BAL lymphocytes > 15%). Eleven belonged to the group with PCs and one belonged to the group without PCs. None of those with neoplasia had alveolitis. The lymphocytes were mainly helper T-cells, and activation markers were more frequent among those with PCs. We have previously reported on the relative absence of PCs in Metsovites with malignant pleural mesothelioma. This observation and the results of the present study suggest that lymphocytic alveolitis correlates with pleural calcifications, whereas both are rarely present in patients with neoplasia.


Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions. One hundred and thirty-five pleural effusions with definite etiology were analyzed by mucin-specific monoclonal antibody (17Q2)-derived enzyme-linked immunosorbent assay (ELISA). Twenty-four effusions were transudate, 45 were nonmalignant exudate, and 66 were malignant. Among the 66 malignant effusions, 52 were adenocarcinoma, and 14 were malignancies other than adenocarcinoma. Purified mucous glycoproteins from sputa of normal subjects were used as ELISA standard. Our results showed that the mean mucin concentration in malignant pleural effusions were significantly higher than that of benign exudates (8.41 +/- 13.48 ng/ml versus 1.09 +/- 0.82 ng/ml, p < 0.01). Mucin concentration in malignant pleural effusions caused by adenocarcinoma was also significantly higher than in non-adenocarcinoma effusions (9.96 +/- 14.81 ng/ml versus 2.66 +/- 1.74 ng/ml, p < 0.01). With the use of mean +/- 2 SD of mucin concentration in benign exudates as a cut-off value (2.73 ng/ml), the sensitivity of this assay for diagnosis of malignant effusions was 66.7%, specificity was 97.1%, and accuracy was 82.2%. High levels of mucin concentration were more specifically associated with adenocarcinoma. When the mucin concentration in pleural effusions was greater than 5 ng/ml, 93.1% (27/29) of patients were adenocarcinoma. If the mucin concentration was greater than 10 ng/ml, 100% (14/14) of patients were adenocarcinoma. Immunofluorescent staining by mucin-specific monoclonal antibody 17Q2 were also carried out in diastase-treated cell preparations obtained from 22 patients with malignant pleural effusions and 16 benign exudates. Nine of 14 adenocarcinomas (64.2%) were reactive with monoclonal antibody 17Q2, while none of the benign exudates, squamous cell carcinomas, and mesotheliomas were stained.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging. Magnetic resonance imaging (MRI) of a modified short-axis section of the heart, in 36 patients with chronic pulmonary diseases, consisting of 19 patients with pulmonary hypertension (PH group; mean pulmonary arterial pressure > or = 20 mm Hg) and 17 patients without pulmonary hypertension (non-PH group) was evaluated to study the configuration of the right ventricle. Parameters of right ventricular hypertrophy, including right ventricular wall thickness (RVWT) and the ratio of RVWT to left ventricular posterior wall thickness (RVWT/LVPWT), with this method were significantly larger in the PH group than in the non-PH group (p < 0.01). RVWT and RVWT/LVPWT correlated well with mean pulmonary arterial pressure (r = 0.90, p < 0.001 and r = 0.89, p < 0.001), total pulmonary resistance (TPR; r = 0.88, p < 0.001 and r = 0.85, p < 0.001), and pulmonary arteriolar resistance (PAR; r = 0.83, p < 0.001 and r = 0.81, p < 0.001). This method of setting a patient in a supine position and slicing with single-oblique sections may seem overly simple compared with Dinsmore's double-oblique short-axis section of the heart, but it is more convenient in practice. These results suggest that a modified short-axis section of the heart by MRI provides valid clinical configurational information concerning the right ventricle on which to base a noninvasive diagnosis of cor pulmonale.


CD3+ and CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis. To characterize the cells responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP), we depleted Micropolyspora faeni (M. faeni)-sensitized C3H/HeJ spleen cell (SC) cultures of CD3+, CD4+, or CD8+ cells before administration to recipients. We determined the length of time sensitization persists, the ability of cultured lung-associated lymph node (LALN) cells to transfer EHP, and the ability of cultured SC from animals subjected to two, four, or eight weekly intratracheal challenges of M. faeni to transfer EHP. The extent of pulmonary inflammatory response after challenge with intratracheal M. faeni was used to determine adoptive transfer. Depletion reduced the proportion of CD3+ cells from 21 to 1%, CD4+ cells from 15 to 3%, and CD8+ cells from 7 to 1% in the cultured SC population. The proportion of B cells exhibited reciprocal changes. Cultured SC could transfer EHP. Depletion of CD3+ and CD4+, but not CD8+ cells, ablated or diminished the capacity to transfer EHP. Sensitized cells persisted in recipients for at least 8 wk. Cultured LALN cells could transfer EHP. Recipients of cultured SC from 4- and 8-wk donors exhibited less extensive pulmonary abnormalities than recipients of cultured SC from 2-wk donors. The proportion of CD3+, CD4+, CD8+, B cells, and macrophages was the same in cultured cells from 2-, 4-, and 8-wk donors. We conclude that the active cells in SC cultures are CD3+, CD4+, and CD8- T cells, and there are differences in the ability of cultured cells to adoptively transfer EHP that are dependent on the nature of the donor but not on the phenotype of the cell population.


In vivo detection of a novel macrophage-derived protein involved in the regulation of mucus-like glycoconjugate secretion. We previously described a novel 68,000 D macrophage-derived protein (MMS-68) that can stimulate mucus-like glycoconjugate (MLGC) secretion from cultured human airways, respiratory epithelial cells, and the ishikawa adenocarcinoma cell line. To better characterize this mucus secretagogue, we generated monoclonal antibodies against MMS-68 by injecting crushed SDS-PAGE gel slices containing this protein into Balb-C mice followed by fusion with SP2/0, a nonsecreting mouse myeloma cell line. A panel of monoclonal antibodies was produced that identified the 68,000 D MMS by immunoblot analysis and immunoprecipitation. The monoclonal antibodies detected MMS-68 in normal peripheral blood monocytes and pulmonary macrophages by cytofluorographic analysis and in human airways as determined by immunohistochemistry. Utilizing the monoclonal antibodies, an antigen-capture ELISA assay was developed. Statistically significant elevations in levels of MMS-68 were detected in bronchoalveolar lavage fluid (BALF) of chronic bronchitic subjects and cigarette smokers and in monocyte culture supernatants from steroid-dependent asthmatic patients compared to normal control subjects. The 68,000 D MMS is a potent secretagogue and may play an important role in the regulation of mucus secretion, especially in chronic bronchitis and steroid-dependent asthma.


Bacterial tracheitis with upper airway obstruction in a patient with the acquired immunodeficiency syndrome. Bacterial tracheitis after an upper viral respiratory infection is a well-recognized entity in the pediatric literature. Bacterial tracheitis has only recently been reported in adults, and it is a potentially life-threatening illness. We report a case of bacterial tracheitis in a patient with AIDS.


Hard metal pneumoconiosis and the association of tumor necrosis factor-alpha. Hard metal pneumoconiosis is a recently recognized occupational lung disease associated with the exposure to cobalt fumes in the workplace. Chronic exposure in susceptible individuals results in interstitial lung disease histopathologically manifested as interstitial fibrosis with an associated mononuclear cell infiltrate and the presence of "cannibalistic" multinucleated giant cells in the alveolar airspaces. The majority of patients present with symptoms of chronic cough and dyspnea. Interestingly, in addition, patients uniformly report significant weight loss out of proportion to their degree of respiratory impairment. In this case report we demonstrate the association of tumor necrosis factor-alpha (TNF) and hard metal (cobalt) pneumoconiosis and suggest that TNF may have a potential role in the etiology of the constitutional symptoms and the pathogenesis of interstitial lung disease.


Pulmonary and intestinal microsporidiosis in a patient with the acquired immunodeficiency syndrome. The microsporidian protozoan organism Enterocytozoon bieneusi has been found in enterocytes of the small intestine in patients infected with human immunodeficiency virus, and it has been recognized as an important cause of chronic diarrhea in this patient group. We report the first case of a 41-yr-old man with acquired immunodeficiency syndrome in whom microsporidia were detected in bronchoalveolar lavage fluid, transbronchial lung biopsies, stool specimens, and ileal biopsies. He experienced chronic diarrhea, wasting syndrome, chronic cough, and dyspnea. His chest roentgenogram showed a small left posterobasal infiltrate and a small left pleural effusion. The histologic pattern of microsporidia in his bronchial and ileal tissue and the cellular inflammatory reaction with intraepithelial infiltration by lymphocytes were identical to findings described in duodenal and jejunal Enterocytozoon bieneusi microsporidiosis. An association between the presence of microsporidia in the lung and the pulmonary symptoms has yet to be determined. It is not known whether pulmonary microsporidiosis was acquired by the aerosol route, by aspiration, or by hematogenous dissemination from the intestine.


Bronchial hyperresponsiveness and level of exposure in occupational asthma due to western red cedar (Thuja plicata). Serial observations before and after development of symptoms. Four workers from a cedar sawmill who developed red cedar asthma are described. They had serial measurements of lung function and nonspecific bronchial hyperresponsiveness (NSBH) several years before and after the development of chest symptoms. Measurements of dust concentration and specific IgE antibodies to plicatic acid-human serum albumin (PA-HSA) conjugate were also carried out before the onset of disease. NSBH developed in parallel with the development of asthma and was not present in any of the workers beforehand, indicating that it is not a predisposing host factor. Nasal symptoms preceded chest symptoms in three workers, suggesting that this may be an early marker of the disease. Although dust concentrations for jobs located both inside and outside the sawmill were low, jobs associated with somewhat higher exposures were associated with the initiation of asthma symptoms.


Hypercapnic ventilatory response in recipients of double-lung transplants. Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR.


Bicarbonate concentration in rhesus monkey and guinea pig fetal lung liquid. Fetal lung liquid secretion is essential for the normal growth of the lung in utero. Previous studies of fetal lung liquid secretion, mostly performed in lambs, have demonstrated that it has high Cl and very low HCO3- concentrations relative to plasma values. Because it is unknown whether primates have a similar electrolyte profile in their lung liquid, we sampled the lung liquid from rhesus monkeys (Macaca mulatta) at 127 to 128 days gestation (0.8 gestation). Although we found that lung liquid Cl concentration was higher than plasma values (p < 0.05), the HCO3- concentration was the same as in the plasma. This indicates that nonhuman primates, relative to lambs, have different cellular mechanisms for regulating fetal lung liquid HCO3- concentrations.


Control of tuberculosis in the United States. American Thoracic Society. TB continues to be a major public health problem in many areas of the United States. Elimination of this disease will require coordinated efforts of public health agencies, voluntary health associations, health-care providers, and community groups. TB controls is comprised of a variety of activities. Identification and treatment of patients with clinically active disease should be the highest priority for all TB control programs. Identification and preventive treatment of infected contacts and persons with tuberculous infection at greatest risk for developing disease (eg, HIV-infected, young children) should also receive high priority. Attention should then be given to identifying other high-risk groups and administering preventive therapy to those infected. While TB control occurs in many different settings, the health department TB control program plays a pivotal role in providing clinical services, and performing contact investigations, tuberculin-testing and prevention activities, surveillance, and evaluation of the community's overall progress in TB elimination. Health departments should receive strong and continuing support from medical care providers, voluntary health organizations, and community groups if TB elimination is to be achieved.


Effectors of hypercarbia during experimental pneumoperitoneum. Hypercarbia occurs during laparoscopy with carbon dioxide (CO2) insufflation. This may be due to increased ventilatory dead space after expansion of the peritoneal cavity with impairment of diaphragmatic excursion, or to increased absorption of CO2 from the peritoneum. To separate these effects, the authors examined the consequences of different insufflating gases and of diminished tissue perfusion on hypercarbia and dead space during pneumoperitoneum. Helium was chosen as an alternate insufflating gas because it is both inert and minimally absorbed. Eight swine (18 to 20 kg) were anesthetized, paralyzed, and mechanically ventilated at constant minute volume. Pneumoperitoneum with helium was maintained at 15 mm Hg for 45 minutes. After desufflation and stabilization for 1 hour, pneumoperitoneum was repeated with CO2. The sequence was again repeated after hemorrhagic shock to constant mean arterial pressure of 50 mm Hg. Data was analyzed by analysis of variance; significance levels are P < 0.01 unless otherwise listed. Arterial PCO2 increased significantly with CO2 insufflation within 15 minutes in normotensive animals and within 30 minutes during hypotension. Arterial pH decrease with CO2 pneumoperitoneum was significant in both groups at 30 minutes. Mixed venous PCO2 also increased with CO2 pneumoperitoneum within 30 minutes. Hypotension did not alter these changes. No significant changes were seen with helium pneumoperitoneum. Neither helium nor CO2 pneumoperitoneum significantly altered dead space. The authors make the following conclusions: 1) Absorption of CO2 from the abdomen during CO2 pneumoperitoneum produces respiratory acidosis, which is not seen with helium insufflation; 2) Pneumoperitoneum does not significantly increase dead space with either gas; 3) Transperitoneal absorption of CO2 is only partly related to perfusion because significant hypercarbia occurs during hemorrhagic shock.


A new method for microvascular anastomosis: report of experimental and clinical research. Principles of microvascular anastomotic surgery are uncertain in contrast to the standardized suture methods for the repair of large arteries. Complications of early thromboses or late stricture at the microvascular anastomotic line can be related to the inherent biologic response of these delicate tissues to penetrating needle and suture. A new method for microvascular reconstruction based on the principle of flanged, nonpenetrated, intimal approximation by an arcuate-legged clip has proven biologically and technically superior to the penetrating microsuture. These conclusions are based on extensive testing in multiple surgical laboratories of the following parameters: long- and short-term patency, morphology of wound repair, and burst and tensile strength. Details of the new surgical system and experimental studies are described.


Glucose intolerance in critically ill surgical patients: relationship to total parenteral nutrition and severity of illness. The authors evaluated the relative influence of severity of illness and total parenteral nutrition (TPN) on glucose intolerance in critically ill surgical patients. Records of TPN administration, serum glucose measurements, and the simplified acute physiology score (SAPS) were extracted from the surgical intensive care unit (SICU) and hospital clinical information systems (CIS) for all patients admitted to the SICU from October 1, 1989 through March 31, 1990. Critical hyperglycemia was defined as glucose > 400 mg/dL and critical hypoglycemia as < 40 mg/dL. During the study period, 1,129 patients received 3,054 days of care, including 88 patients who received 705 days of TPN. Of 4,985 glucose determinations performed during the study period, 48 (0.96%) were critically abnormal. Critical hyperglycemia occurred in 1.7 per cent of blood samples from TPN patients, compared to 0.7 per cent in non-TPN patients (P < 0.005). However, the mean admission and daily and maximum severity of illness scores were significantly higher in TPN patients compared to non-TPN patients (all P < 0.0005). Mean glucose levels rose with increasing SAPS in both TPN and non-TPN patients. When stratified by severity of illness, TPN patients did not have significantly higher glucose levels than non-TPN patients except for the SAPS = 15 category. The authors conclude that the glucose intolerance noted in critically ill TPN patients reflects their underlying severity of illness rather than TPN administration per se.


Subcapsular hematoma as a predictor of delayed splenic rupture. Over the past 46 months at a level I trauma center, 966 computed tomography (CT) scans were performed for blunt abdominal trauma. Eighty-three (8.6%) demonstrated splenic injury, and 31 (3.2%) of these showed a subcapsular hematoma with or without associated parenchymal damage. Of the 31 patients, 23 were managed conservatively, based initially upon surgeons' preference (14 patients) and after March 1990 to conform to the authors' splenic trauma protocol (nine patients). The eight patients operated upon were hemodynamically stable and all underwent splenectomy. Subcapsular hematoma, as diagnosed by preoperative CT scan, was confirmed in each of the eight celiotomies. Parenchymal involvement, which had also been identified in these eight patients by CT, was evident at operation in all, and hilar involvement occurred in three. None of the 23 observed patients developed delayed splenic rupture. All were discharged home with outpatient follow-up in surgical clinic to at least 1 month without further complication. The authors came to the following conclusions: 1) Subcapsular hematoma is neither a predictor for delayed splenic rupture, nor by itself an indication for operative management of the injured spleen in the hemodynamically stable patient; 2) Degree of parenchymal injury based on CT morphology, specifically hilar involvement, signifies the need for laparotomy with splenectomy; 3) Splenorrhaphy has a reduced role in splenic trauma because most injuries now operated upon are severe.


A critical analysis of blood transfusion requirements in children with blunt abdominal trauma. Over the past 2 years, 178 children with blunt abdominal trauma were admitted for observation. Fifty-five patients (31.5%) had intra-abdominal injury confirmed by computerized tomography (CT) scan, laparotomy, or postmortem examination. Forty-four children (80%) were managed with observation only; nine had other operations. Eleven patients (20%) required an operation for their intra-abdominal injuries. Thirteen patients died, ten from head or spinal injuries and three from intra-abdominal injuries (5.5%). Of 35 children with intra-abdominal injuries observed without any type of operation, 27 (77%) were not transfused (mean Pediatric Trauma Score [PTS] 8, Injury Severity Score [ISS] 19.3, average low hemoglobin [ALH] 10.1). The other eight were transfused an average of 49 cc/kg (mean PTS 4.5, ISS 26.5 ALH 6.1). Twenty children had operations. Eleven 11 (20%) of these were laparotomies; nine were transfused an average of 200.6 cc/kg (mean PTS 6, ISS 33, ALH 9). Nine had neurosurgical/orthopedic procedures (mean PTS 6.2, ISS 27.7), with six transfusions averaging 84.9 cc/kg (ALH 8.9). There were no significant complications. Blood transfusion was necessary only for 33 per cent of the observed cases, usually with multiple injuries. Blood should be transfused only to maintain hemodynamic stability (normal vital signs and tissue perfusion). Hemoglobin levels as low as 7 gm% do not mandate transfusion in children who are hemodynamically stable.


Continuous intra-arterial oxygen monitoring: accuracy and reliability in the surgical intensive care unit. The accuracy and reliability of an invasive intra-arterial oxygen sensor catheter was evaluated in 20 critically ill surgical intensive care unit (SICU) patients. All patients required continuous arterial blood pressure monitoring, at least 72 hours of ventilator support, and intermittent arterial blood gas sampling for clinical management. The intra-arterial sensor provided continuous PO2 (PsO2) values on a bedside electronic monitor. PsO2 values were sampled every 60 seconds and automatically stored on a bedside personal computer. Arterial blood gas (ABG) PaO2 values were collected and matched by collection time with corresponding PsO2 values. During 1,238 hours of continuous intra-arterial monitoring, 74,280 PsO2 values and 246 ABG PaO2 values were collected. Of the 246 PaO2 results, 175 (71.3%) had a matching PsO2. Regression of matched PsO2 and PaO2 values yielded a correlation coefficient of 0.58 and standard error of the estimate (SEE) of 33.1 (P < 0.0005). Even though matched PsO2 and PaO2 measurements demonstrated a linear relationship, only 34 per cent of the variation in PsO2 could be attributed to changes in PaO2. Technical sensor or instrument problems affected PsO2 monitoring in 17 of 20 patients and 28 of the 33 sensors tested. The authors conclude that continuous intra-arterial monitoring of PsO2 is a novel idea, but technical issues limit its use in acutely ill, conscious SICU patients.


Occult traumatic pneumothorax: immediate tube thoracostomy versus expectant management. Occult pneumothorax is pneumothorax identified by computed tomography but not seen on conventional chest radiographs. Twenty-seven occult traumatic pneumothoraces in 26 patients were identified retrospectively at the authors' level I trauma center. Of these, 24 patients survived to discharge or transfer; 2 died of brain injury. Eleven patients were treated immediately with tube thoracostomy (TT) and 13 were observed with interval chest radiography. The authors' data support the conclusion that it is safe to withhold immediate TT in patients who are hemodynamically stable. Close clinical observation and interval chest radiography can identify those patients who require subsequent TT. Prospective study of larger numbers of patients is needed to confirm the safety and cost efficacy of this approach.


Incidental preclinical hyperparathyroidism identified during thyroid operations. The entity of preclinical hyperparathyroidism has never been clearly investigated. The authors believe that the incidence of pathologic abnormalities of the parathyroid glands before the development of any symptoms or hypercalcemia (serum calcium > 12.0 mg/dl) is more frequent than has been reported. Over a 14-year period, parathyroid glands were examined during thyroid operations in over 800 patients. Serum calcium and phosphorous levels were measured in all patients preoperatively. Thirty-six patients had additional parathyroid operations for a preclinical form of hyperparathyroidism, defined by abnormal appearing parathyroid glands at the time of thyroid surgery. None of the 36 patients had symptoms of hyperparathyroidism preoperatively. Nine patients had borderline hypercalcemia (serum calcium 10.6 to 12.0 mg/dl), and the remainder were considered normocalcemic. The average age was 53 (range 21 to 75) with a male to female ratio of 1:3. Nine of the 36 patients had thyroid cancer. There were eight patients with parathyroid adenoma and 28 patients with parathyroid hyperplasia. Of 13 patients who had a history of neck irradiation, five had parathyroid adenoma and eight had parathyroid hyperplasia. Only two patients with parathyroid hyperplasia remain on calcium medication. Since preoperative normocalcemia does not preclude the presence of parathyroid pathology, the authors urge careful identification and examination of the parathyroid glands during thyroid operations. It adds little time to the procedure. Excision of parathyroid disease along with the thyroid gland can be performed safely and prevents the need for further operation with its associated morbidity.


Seroma prevention after modified radical mastectomy. The most common mastectomy-associated complication is seroma formation. Seromas can be associated with other more serious complications such as skin flap necrosis, delayed wound healing, infection, and lymphedema. The flap tacking procedure that closes the axillary fossa dead space and tacks the mastectomy flaps to the chest wall has been suggested as one potential technique to reduce the incidence of postmastectomy seromas. This institution-wide study of modified radical mastectomies demonstrated a significant decrease (P < 0.0381) in the incidence of seroma when flap tacking was performed. Women who developed a seroma, compared to those who did not, averaged nearly twice as any office visits in the first 2 months after the operation. Distribution of office visits between the seroma patients and nonseroma patients was significant (P < 0.0001). When practiced by several surgeons, the flap tacking procedure 1) reduces postmastectomy seromas and 2) reduces the amount of postoperative patient office visits and care.


Simple surgical treatment of nonparasitic hepatic cysts. Benign nonparasitic liver cysts are uncommon lesions. Incidental diagnosis is increasing with the advent of routine abdominal computed tomography and ultrasound scanning. Cysts that attain massive proportions often become symptomatic and require therapeutic intervention. Surgical resection and Roux-en-Y cystojejunostomy drainage have been the treatments of choice, but simpler unroofing techniques without drainage have recently been employed with success. Three patients with symptomatic, large, nonparasitic cysts were surgically treated in such a fashion without complication and form the basis of this report. The technique of wide unroofing involves excision of the nonhepatic cyst wall with oversewing of communicating biliary radicals. No recurrences have been detected in follow-up screening. Wide unroofing is a simple and yet reliable surgical option for the treatment of symptomatic hepatic cysts.


Immunohistochemical determination of the estrogen receptor content of gastrointestinal adenocarcinomas. Recently there have been several reports documenting the presence of estrogen receptors (ERs) in human gastrointestinal (GI) malignancies, raising the possibility that these cancers may be hormonally manipulated. To test this hypothesis, 68 frozen GI tissue specimens were examined for the presence of ERs within the cell nuclei by immunohistochemical staining. There were 51 cancers (25 gastric, 26 colon) and 17 normal tissue specimens (six gastric, 11 colon). Tissue sections 4 to 6 microns thick were incubated with monoclonal antibody H222SP psi, then stained by the peroxidase-antiperoxidase technique for visualization of the ER. The staining was semiquantitatively graded from 0 to 3+ depending on both the intensity of staining and the percentage of cell nuclei stained. A breast cancer specimen known to be strongly positive for the ER was used as a positive control. The 30 male and 21 female cancer patients had a median age of 59 years. All tumors were adenocarcinomas. Eight per cent of the gastric cancers were poorly differentiated, while 94 per cent of the colon cancers were moderately well to well differentiated. Using weak staining of at least 20 per cent of the cell nuclei as the minimum requirement for an ER positive tumor (1+, 0/51 tumors and 0/17) normal specimens were positive for ER. Only three out of 25 (12%) gastric tumors, and two out of 26 (8%) colon tumors demonstrated any staining; each exhibited weak staining of only five to ten per cent of the tumor nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of acute appendicitis by technetium 99 HMPAO scanning. The diagnosis of acute appendicitis can be difficult. Barium enemas, computed tomography (CT) scans, ultrasound examinations and Indium scans are used to aid in making the diagnosis with varying degrees of success. This blinded, prospective study reports the use of a Technetium 99-m Hexamethylpropyleneamineoxide (HMPAO) labelled white blood cell scan in 30 patients with suspected appendicitis. Autologous white blood counts from 25 cc of whole blood labelled with Tc-99 HMPAO were reinjected into patients. Abdominal imaging was performed at a half hour postinjection and repeated at 2 to 4 hours postinjection. A positive study showed an increased isotope uptake in the right lower quadrant. Nineteen patients had histologically proven appendicitis. Three of these patients were excluded because they were operated on before scan completion. Thirteen of the remaining 16 patients with appendicitis had positive studies (false negative rate = 19%). All patients without appendicitis had either negative scans or scans that detected other intra-abdominal diseases, such as diverticulitis, tubo-ovarian abscess, or small bowel infarction (false positive rate = 0%). Overall, this Tc-99 HMPAO study had a sensitivity of 81 per cent, a specificity of 100 per cent and an overall accuracy of 89 per cent. The 4-hour Tc-99 HMPAO WBC scan is a useful, noninvasive test for confirming the clinical diagnosis of acute appendicitis, but it may prove more valuable as a diagnostic study to rule out appendicitis in patients that have abdominal pain of unclear etiology.


Iatrogenic bile duct injuries. The real incidence and contributing factors--implications for laparoscopic cholecystectomy. Laparoscopic cholecystectomy has achieved wide acceptance as the preferred treatment for symptomatic gallbladder disease. Yet there are alarming reports of iatrogenic bile duct injuries. To establish a comparison standard, the incidence of iatrogenic bile duct injury during conventional cholecystectomy has to be known. A single institutional retrospective review of 1,617 consecutive open cholecystectomies between 1980 and 1989 was performed. Eight patients (0.49%) sustained iatrogenic bile duct injury in this study. Inflammation, anatomic variation, or both were contributing factors in all injuries. Operative cholangiography identified the injury at the initial operation in three patients. Treatment consisted of either primary ductal repair, ductal repair over a stent, or ductal-enteric anastomosis. There were no late complications after surgery (follow-up 26 to 97 months; mean 50.9 months). The implications for laparoscopic cholecystectomy are apparent. Iatrogenic bile duct injuries are associated with acute inflammation and/or variant ductal anatomy; routine operative cholangiography assumes increased importance; and immediate repair of the injury minimizes long-term complications.


Gastroduodenal intussusception secondary to a gastric lipoma: a case report and review of the literature. Gastroduodenal intussusception is an extremely uncommon condition usually caused by the prolapse of a benign gastric tumor into the duodenum with subsequent invagination of a portion of the stomach wall. A rare case of this condition associated with a gastric lipoma is presented. Clinical manifestations may mimic many other disease entities and are nonspecific. Diagnosis, however, can often be made preoperatively with noninvasive tests, which are usually associated with more specific signs. Treatment involves reduction of the intussusception and surgical excision of the lead point, either endoscopically or through a formal laparotomy.


Herpes simplex virus: a possible etiologic agent in some gastroduodenal ulcer disease. There is increasing evidence that the herpes simplex virus may account for some gastric ulcer disease. To examine this possibility, 62 tissue biopsies from 21 patients were obtained during esophagogastroduodenoscopy for gastroduodenal ulcer disease and from one operative specimen during the procedure for perforation of a gastric ulcer. The samples were collected from the base and rim of the ulcer, as well as from apparently healthy tissue adjacent to the lesion. When the DNA was extracted from these tissues and hybridized to a herpes simplex virus-specific DNA probe, positive results were obtained with 9.5 per cent (2 out of 21) of the patients with benign ulcers. Positive signals were obtained only with ulcer-associated tissues and never with healthy tissue. Hybridization also occurred with DNA from one ulcerative carcinoma in the study. These data suggest that a subset of ulcer disease may be caused by herpes simplex virus or that this virus may be secondarily associating with these lesions.


Cyst of the falciform ligament of the liver: a rare cause of right upper quadrant pain. Cysts of the falciform ligament are rare. Only a dozen cases have been reported in the English literature, with the first reported case in 1909. The etiology of these cysts is diverse but can be classified into primary and secondary causes. No specific complex exists and their presentations vary among persons. Physical examination may demonstrate a mass in the right upper abdomen. Although rare, they should be considered in the differential diagnosis of right upper quadrant abdominal pain. They are treated through excision.


Carcinoma arising in a duplicated colon. One case of adenocarcinoma arising in a duplicated transverse colon is presented. Its unusual feature was the site of the carcinoma origin, which was the true colonic segment and not the duplication.


Vesico-diverticular fistula: a rare complication of Meckel's diverticulum. Enterovesical fistulas usually result from diverticulitis, Crohn's disease, or colorectal cancer. A perforated Meckel's diverticulum can also result in an vesico-diverticulum fistula, as noted in three previously reported cases. In all three cases, bladder or bowel disease was associated with the fistula. Herein, the authors describe a previously healthy, 23-year-old man who presented with an enterovesical fistula. Exploratory laparotomy revealed a vesico-diverticular fistula resulting from a perforated Meckel's diverticulum. Pathologic examination revealed that the diverticulum did not contain ectopic gastric or pancreatic tissue and that the perforation was secondary to an enterolith. The patient underwent a diverticulectomy and had an uneventful postoperative course. Unlike any of the three previously reported cases, the authors' patient had no coexisting bowel or bladder disease occurring with his vesico-diverticular fistula. To the authors' knowledge, this is only the third reported case of a vesico-diverticular fistula resulting from a perforated Meckel's diverticulum that did not contain ectopic tissue. It represents the first case where the perforation was secondary to an enterolith.


Surgical treatment of the enterogastric reflux syndrome: preoperative and postoperative estimation by 99mTc-HIDA scintigraphy. Twenty-nine patients with enterogastric reflux syndrome after anti-ulcer gastric surgery underwent a revisional Roux-en-Y gastrectomy. The diagnosis of enterogastric reflux syndrome was based on symptomatology and endoscopy in the first eight patients. The latter 21 patients had, in addition, a 99mTc-HIDA scintigraphy for the documentation and measurement of reflux. An enterogastric reflux index > 20 per cent is considered to justify symptoms due to reflux. Three of the first eight patients continued postoperatively to experience the same symptoms as before. These symptoms were eventually attributed to other than enterogastric reflux syndromes. The latter 21 patients were relieved from their preoperative symptoms and classified as Visick I and II (18 patients) and Visick III (3 patients). The authors conclude that enterogastric reflux syndrome must be documented on scintigraphy before the patient is subjected to revisional anti-reflux surgery in order for failures due to misdiagnosis to be avoided.


Malignant lymphoma of the breast: a review of 13 cases. Thirteen cases of primary malignant lymphoma of the breast are reported from a 15-year retrospective review of records. The ages ranged from 19 to 75 years. One patient had nodular sclerosing Hodgkin's disease and 12 had non-Hodgkin's lymphoma. Eleven patients were treated with local excision, followed by radiotherapy, chemotherapy, or both. One patient had mastectomy and chemotherapy, and one had local excision only. Four patients died 6 months to 7 years after initial diagnosis. One patient was alive and with disease 5 years later. The remainder were alive and free of disease 24 months to 9 years after presentation. Prognosis depended on the clinical stage and histologic grade of the lesion. Five-year survival was 72 per cent, which was slightly better than that observed in mammary carcinoma.


[Fever and petechial exanthema in children]. In an attempt to determine clinical and analytical predictive parameters of a possible grave disease, we have carried out a retrospective study of 172 children admitted to our hospital with fever and petechiae as initial symptoms. The ages ranged between 1 month and 10 years. Even though we have not found a clinical symptom or analysis sufficiently sensitive as to predict all grave diseases, the general clinical state of the child associated with either a high or low white cell count and an abnormal coagulation study should be alert signals for a serious infectious disease. On the contrary, if the clinical and analytical parameters are within normal limits the risk of a grave disease is low. We emphasize the high incidence of meningococcal disease (26%).


[Nutritional status in HIV infection in infancy]. The physiopathology of malnutrition among AIDS, ARC and HIV infected children was reviewed. One-hundred eight-three newborns were studied, 152 of which were born at "La Fe" Maternity Hospital. Of these patients, 29% were LBW and 28% preterm. Transfused and hemophiliac patients were excluded from the study. Anorexia, vomiting, fever, infections of the respiratory and GI tracts and drug therapy were the most frequent factors affecting the nutritional status. Fifty-three newborns were infected with the HIV (29%). The children were classified into three groups (G). Group-I was formed by HIV+children > 18 months of age, G-II, P-2 class by children < 18 months of age and G-III was formed by those children that died of AIDS. The most common symptoms were chronic diarrhea and infections of the respiratory tract. Of the HIV+children > 18 months of age, 65% had a weight < the 10th percentile and 61% were < the 10th percentile for height. Of the children that died of AIDS, 80% were in the lower 10th percentile for both weight and height. Hemoglobin, T4/T8, total proteins, seroalbumin and calcium were also negatively affected. Those most severely affected were the dead patients, followed by P-2 < 18 months and finally the HIV+ > 18 months of age. The differences between G-I and G-II-G-III were statistically significant, p < 0.01. The biochemical quantification of the nutritional status was difficult due to the limited amount of blood available. HIV infected children require nutrition supplementation to maintain an adequate nutritional status. Among these patients, malnutrition is a multifactorial phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)


[Patterns of breast feeding and study of interfering factors in a primary health care facility]. The present study aims to evaluate the patterns of breast-feeding in a population of children depending on a Primary Attention Team. Its duration and any factors which may interfere with it were also studied. The breast-feeding period of 114 boys and 119 girls is reviewed. We found the following data: 85.2% of the mothers started to breast-feed their children. By the third month, 42.1% of them persisted with exclusive breast-feeding, whereas only 5.6% reached the sixth month. Commercial formulas were introduced as a result of health reasons in only 43.3% of the cases. The time of exclusive breast-feeding was significantly shorter (p < 0.05) in the children who required hospitalization during the breast-feeding, in the cases of mothers that smoke, when commercial formula was introduced at the mother's will and in those children who had a smaller weight at their birth and a smaller gestational age. After introduction of commercial formulas we observed a statistically significant increase in weight (p < 0.05). Nevertheless, the standard score of weight at six months of age, compared with that previous to the introduction of lacteal supplements, did not differ significantly.


[High frequency ventilation in the newborn. Study of 27 cases]. The clinical histories of 27 neonates ventilated with high frequency respirators (Volumetric Diffusive Respirator VDR-2) have been analyzed in order to evaluate the efficiency of this type of ventilation in neonatal pathology. The average gestational age of these patients was 32 +/- 4 weeks. Most of them (70%) presented respiratory distress due to hyaline membrane disease. Of the remaining cases, three (11%) presented with congenital diaphragmatic hernia, two with pulmonary hypertension, two with meconium aspiration syndrome, one with Group B Streptococal sepsis/shock and one with case diaphragmatic agenesia. Between two and six hours after initiation of high frequency ventilation (HFV), pH, paCO2 and pO2 improved significantly in relationship to former values (p < 0.05- p < 0.001), reaching values in the normal range at 6.5 +/- 14 hours regarding pH, 30 +/- 50 hours regarding paCO2 and 6.5 +/- 10 hours regarding paO2. No hemodynamic modification could be attributed to this procedure. The principal complications were ectopic air (62%) and necrotizing tracheobronchitis (TBN) (25%). Bronchopulmonary dysplasia (BDP) was diagnosed in 20% of the cases, ductus (DAP) in 33% of the cases and intracraneal hemorrhage in 25% of the cases. Mortality was 70%. High frequency ventilation is an alternative procedure to conventional ventilation in this group of neonates. It produces an important number of favorable responses, but has complications that can not be overlooked.


[Vertical transmission of HIV infection: descriptive epidemiology, risk factors and survival]. The basic epidemiological characteristics of HIV infection and AIDS among children are described with a particular reference to HIV vertical transmission. The HIV transmission pattern identified in our community is described according to the WHO classification scheme. To describe the epidemic, as well as its temporal evolution, 1.933 cases reported to the population based registry of Catalonia and 287 seropositive children and their mothers are used. We have quantified the importance of intravenous drug usage by the parents in relationship to HIV transmission; 54.7% of the mothers of HIV positive children were intravenous drug users. We predict that during the coming years there will be a continuous increase in AIDS cases as a result of vertical transmission.


[Non-Hodgkin's lymphoma in childhood: 19-year experience in a pediatric oncology unit]. Ninety-one patients with Non-Hodgkin's Lymphoma (NHL) were treated in our Pediatric Oncology Unit during a 19 year period. The median age at diagnosis was 5.8 years and there was a higher incidence in males. All patients were classified according to Murphy's stages and Rappaport's modified classification. Advanced disease and non-lymphoblastic histology were prevailing. Chemotherapy was the preferred treatment. Forty-seven patients (54%) are alive with a median follow-up period of 6.2 years. Actuarial survival rate at 5 years is 0.6. Advances in chemotherapy led to an increase in NHL patient's survival. Twenty patients died because of the disease and 21 because of fatal complications.


[Biologic rhythm of respiratory rate in the first trimester of life]. This study was designed to address the following objectives: 1) To record the respiratory rate in a population of newborns and infants. 2) To verify the existence of a rhythm in each population group, as well as the organization and maturing process of these rhythms. 3) To determine the possible influence of environmental factors on these rhythms. The study population consisted of the following groups and ages: A) 1 day (21 cases); B) 7 (15 cases); C) 15 (10 cases); D) 30 (17 cases); E) 60 (17 cases); F) 90 (18 cases). Respiratory rate was continuously monitored and recorded, as well as environmental light, noise and temperature. Rhythmometric analysis of the data was done by simple Cosinor test and analysis of variance. The zero amplitude test showed statistically significant differences in the circadian rhythm of groups E and F (p < 0.005). An ultradian rhythm of 3 hours was detected in groups D and F. Environmental factors also showed a circadian rhythm. The appearance of an ultradian rhythm suggest the maturation in a rhythm. To evaluate physiological parameters, reference to time series must be considered.


[Clinical profile, course and outcome of gastroesophageal reflux in 10 infants under active medical treatment]. We have studied the clinical profile, cause and outcome of 105 infants with the diagnosis of gastroesophageal reflux. In most cases, pharmacological treatment managed to control the symptoms in 9 out of 10 infants followed in our series. Complications were described in 26.2%, of which esophagitis and chronic respiratory disease were the most common. Corrective surgery of the reflux was indicated in those cases in which pharmacological treatment was not successful. This managed to control the reflux in 90% of all cases. Morbidity was scarce. In all, 75% of the infants were considered to be medically cured within 15.5 months from the time that they were diagnosed and within 18.5 months after the appearance of the first symptoms.


[Acute meningococcal disease. Study of auditive sequelae]. We have examined the auditory function in 49 children that have survived an acute meningococcal disease (AMD). Functional auditory exploration consisted of: ABR; tonal liminal audiometry or behavioral audiometry (Peep-show method, Suzuki-Ogiba ROC) depending on the age and collaboration of the patient; and impedanciometrical techniques (tympanometry, ipsi and contra-lateral stapedial reflex). Three months later, altered tests were repeated in patients that had been evaluated at a time greater than 90 days after their first day of hospitalization (n = 18). All tests were repeated in those patients that had been evaluated before 90 days from the first day of hospitalization (n = 31). No transmission or neurosensory hearing impairments were detected as a result of AMD. We consider the absence of neurosensory hearing impairment, despite the presence of significant risk factors, an important finding. These results suggest that the risk of hearing impairment could be reduced to a minimum by the early establishment of antibiotic treatment.