Androgens modulate growth hormone-releasing factor-induced GH release from bovine anterior pituitary cells in static culture. Static primary cultures of bovine anterior pituitary (AP) cells were utilized to study the effect of sex steroids on basal growth hormone (GH) and GH-releasing hormone (GRF)-stimulated release of GH. The AP cells (5 x 10(5) cells/well) were allowed to attach for 72 hr and become confluent before treatments were imposed. Cells were incubated for an additional 24, 48 or 72 hr with either estradiol-17 beta (E2, 10(-11) to 10(-8) M), testosterone (T, 10(-8) to 10(-5) M), dihydrotestosterone (DHT, 10(-9) to 10(-6) M) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol, 10(-11) to 10(-8) M). Media were collected every 24 hr and GH concentrations determined by RIA. Incubation of calf AP cells with gonadal steroids did not affect (P > 0.05) basal GH released at 24, 48, or 72 hr. In another experiment, calf AP cells were incubated with the same concentrations of the steroids for 24 hr, media harvested, cells washed and challenged in serum-free media for 1 hr with bovine GRF 1-44-NH2 (10(-8) M). In non-steroid treated wells, GRF increased (P < 0.05) GH from 58 to 134 ng/ml. Incubation with E2 or 3 alpha-diol did not affect (P > 0.05) GRF-induced GH release; however, preincubation with T (10(-5) M) and DHT (10(-9), 10(-8) and 10(-7) M) increased (P < 0.05) GRF-induced GH release above control concentrations (195, 235, 190 and 185 ng/ml, respectively). At the doses tested, sex steroids did not affect basal release of GH, but androgens increased responsiveness of somatotropes to GRF.


Comparative morphometry and steroidogenic function of antral ovine follicles destined for ovulation or atresia. An experimental model was established in the ewe allowing one to predict with accuracy an antral follicle that coincidentally would either undergo ovulation (6-8 mm diameter) or atresia (3-4 mm diameter) following synchronization of luteal regression and the onset of the gonadotropin surge. Quantitative morphometric and hormonal criteria were used to make direct comparisons of such follicles collected throughout the preovulatory period. There were progressive alterations in percentages of granulosa cells exhibiting pyknotic nuclei, dispersion of granulosa cells, oocyte maturation, thecal vascular dynamics and extravasation of leukocytes. Nevertheless, no significant variations in temporal patterns were observed between follicular classification. The most notable anatomical distinction between preovulatory and atretogenic follicles was that the former had come into closer contact with the ovarian surface epithelium. The dominant follicle had a higher capacity than the subordinate follicle to produce estradiol before the gonadotropin surge; however, ensuing profiles of steroidogenic function (i.e., shift from the delta 5 to delta 4 pathway) occurred in parallel. Thus, in many respects the follicular mechanics of ovulation and atresia in the sheep appear analogous.


N-methyl-d,l-aspartate stimulates growth hormone and prolactin but inhibits luteinizing hormone secretion in the pig. The effects of n-methyl-d,l-aspartate (NMA), a neuroexcitatory amino acid agonist, on luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) secretion in gilts treated with ovarian steroids was studied. Mature gilts which had displayed one or more estrous cycles of 18 to 22 d were ovariectomized and assigned to one of three treatments administered i.m.: corn oil vehicle (V; n = 6); 10 micrograms estradiol-17 b/kg BW given 33 hr before NMA (E; n = 6); .85 mg progesterone/kg BW given twice daily for 6 d prior to NMA (P4; n = 6). Blood was collected via jugular cannulae every 15 min for 6 hr. Pigs received 10 mg NMA/kg BW i.v. 2 hr after blood collection began and a combined synthetic [Ala15]-h GH releasing factor (1-29)-NH2 (GRF; 1 micrograms/kg BW) and gonadotropin releasing hormone (GnRH; .2 micrograms/kg BW) challenge given i.v. 3 hr after NMA. NMA did not alter LH secretion in E gilts. However, NMA decreased (P < .02) serum LH concentrations in V and P4 gilts. Serum LH concentrations increased (P < .01) after GnRH in all gilts. NMA did not alter PRL secretion in P4 pigs, but increased (P < .01) serum PRL concentrations in V and E animals. Treatment with NMA increased (P < .01) GH secretion in all animals while the GRF challenge increased (P < .01) serum GH concentrations in all animals except in V treated pigs. NMA increased (P < .05) cortisol secretion in all treatment groups. These results indicate that NMA inhibits LH secretion and is a secretagogue of PRL, GH and cortisol secretion with ovarian steroids modulating the LH and PRL response to NMA.


Glucose and insulin metabolism in ruminating and veal calves fed high and low fat diets. Holstein male calves were maintained on conventional (milk to 6 wk of age, fed grain and hay after weaning) and veal (milk replacer only) diets to 16 wk of age. Within each of these 2 physiological states (ruminating or non-ruminating), calves were fed low or high fat diets (ruminating: 3 and 10%; veal: 10 and 18%). Glucose tolerance tests were undertaken at 8 and 16 wk of age in each group. Basal concentrations (4 hr postfeeding) and areas under the response curves for plasma glucose and insulin were higher in veal calves (P < .0001). Ruminating calves fed higher fat utilized glucose more readily (smaller areas under the curves for both glucose and insulin, P < .10) than those fed lower fat. Age did not influence basal glucose concentrations (P > .10), but older calves had higher basal insulin (P < .0001) and greater areas under the curves (P < .0005) for both glucose and insulin after a glucose challenge. Rate of clearance (k) was greater in ruminating calves (P < .001). Though rate of clearance in veal calves was slower, larger plasma pool size caused veal calves on average to utilize glucose at a 15% greater rate per kg body weight than ruminating calves. Whereas fat concentration in the diets did not influence glucose metabolism in veal calves, the high lactose content (> 50% of diet dry matter) of veal diets induced severe insulin resistance in these calves.


Advances in syncope: a combined approach utilizing head-up tilt testing and electrophysiologic evaluation. The electrophysiological evaluation of syncope of unknown origin yields a diagnosis in approximately 40% of patients. In the presence of structural heart disease ventricular tachycardia is the most common etiology accounting for 20% of cases. Over the past several years head-up tilt table testing with isoproterenol provocation has highlighted the syndrome of neurocardiogenic syncope. This syndrome accounts for an additional 30-40% of patients with syncope. There is compelling evidence that this syndrome involves the Bezold-Jarisch reflex with excessive stimulation of ventricular mechanoreceptors (C-fibers) located predominantly in the inferoposterior portion of the heart. Tilt table testing is now an established tool both for diagnosis of this syndrome and for guiding therapy with beta blockers, disopyramide, theophylline, or alpha-agonists. Tilt table testing combined with invasive electrophysiological testing significantly increases the diagnostic yield in the evaluation of syncope.


Arterial substitution in lower extremity trauma: autogenous vein vs polytetrafluoroethylene. This review article compares the two most commonly used grafts, autogenous saphenous vein and polytetrafluoroethylene (PTFE), for treatment of arterial trauma. Late graft occlusion is more common with PTFE, but PTFE may be better in situations where infection is a concern and extra-anatomic bypass is not possible. When infected, saphenous vein is much more of a risk because of its tendency to undergo sudden hemorrhagic disruption. PTFE grafts usually show only moderate suture line bleeding, which alerts the surgeon to the presence of a problem with the graft.


Case report: treatment of superior sagittal sinus thrombosis with urokinase. Sagittal sinus thrombosis (SSST) is a rare disease with high mortality. Definitive therapy is not known, but anticoagulation or addressing the underlying etiology have been the most often utilized approaches. We here report the second case of postpartum sagittal sinus thrombosis successfully treated with urokinase. Though there are no studies to support this therapy it may be safe and efficacious in refractory cases.


The multiload IUD--a U.S. researcher's evaluation of a European device. This evaluative review focused on the performance and safety of the Dutch-made Multiload copper IUD, primarily the Multiload-375 (MLCu-375) model which has a longer life expectancy (5 or more years) than the Multiload-250 (MLCu-250) model, usually cited for a life expectancy for three years. This copper-medicated IUD differs from the copper-T IUDs in shape and insertion technique. The review shows that (a) the MLCu-375 IUD seems to be slightly less effective in preventing pregnancies than TCu-380A IUD. Its efficacy is comparable to that of the Nova-T by two to three years of use; (b) the MLCu-250 IUD is similarly effective to TCu-200 but may be slightly less effective than TCu-220C; (c) no consistent differences were detectable in expulsion rates or in removal rates for bleeding/pain between the Multiload IUDs and comparative Copper-T IUDs; (d) the Multiload IUDs may perform better in nulliparous women than the T-shaped devices; (e) no or a very low incidence of uterine perforation is associated with insertions of the Multiload IUD; (f) ectopic pregnancy risks are similarly low in Multiload IUD users as in Copper-T-380A users; and (g) pelvic inflammatory disease (PID) risks are similarly low in Multiload IUD users as in users of T-shaped copper IUDs.


Risk factors for copper T IUD expulsion: an epidemiologic analysis. Little is known of the factors associated with expulsion of intrauterine devices (IUD). We conducted a nested case-control study to examine the risk factors for copper T IUD expulsion using data from a multicenter international clinical trial. We included 70 cases with expulsion and 1,536 controls, and we examined a variety of characteristics of the IUD wearers. The proportional hazards model showed that young maternal age, abnormal amount of menstrual flow and dysmenorrhea before IUD insertion are risk factors for copper T IUD expulsion. The risk of expulsion steadily increased as age decreased, and as the severity of dysmenorrhea increased.


What do women want during medical abortion? A questionnaire study was carried out to investigate the needs of women undergoing a medical abortion induced by mifepristone in combination with either gemeprost pessaries or oral misoprostol. One-hundred-and-eighty women undergoing medical abortion of pregnancy of up to 63 days amenorrhoea were randomised to treatment in the sitting-room (treatment room) or in the ward. Overall, 77% and 69% treated in the sitting-room and ward, respectively, would have preferred treatment in the sitting-room. Fifty-four per cent did not wish their partner or friend to be present and 76% would prefer to stay in hospital following administration of prostaglandin. Ninety-five per cent of the patients would recommend this method of abortion to their friends. Women who received misoprostol required significantly less analgesia than women who were given 1 mg gemeprost as a vaginal pessary. The requirement for opiate analgesia was not influenced by parity, gestation of pregnancy, history of dysmenorrhoea or the dose of mifepristone. Almost 100% of the patients were satisfied with this method of treatment. This study indicates that the majority of women undergoing medical abortion prefer to be treated in a group, a method which is highly cost-effective.


Pharmacokinetics of levonorgestrel in 12 women who received a single oral dose of 0.15 mg levonorgestrel and, after a washout phase, the same dose during one treatment cycle. The pharmacokinetics of levonorgestrel (LNG) was determined in 12 healthy women (age 21 to 33 years), following single dose administration of 0.15 mg LNG. The same preparation was also administered during one treatment cycle after a washout phase of 1 week. After single dose administration, maximum concentrations of LNG in the serum were 4.3 +/- 1.3 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.6 +/- 0.2 h and 13.9 +/- 3.2 h, respectively. The clearance was calculated to be 1.5 +/- 0.6 ml x min-1 x kg-1. The free fraction of LNG was 1.1 +/- 0.1% and the fractions bound to SHBG and albumin were 61.8 +/- 6.7% and 37.1 +/- 6.7%, respectively. There was a gradual decrease in serum trough levels of LNG from about 0.5 to 0.3 ng/ml during the cycle, and a concomitant decrease in SHBG concentrations in the serum by about 50%. Serum protein binding of LNG changed markedly during the treatment cycle. The free fraction increased to a value of 1.7 +/- 0.3%, the SHBG-bound fraction decreased to 42.0 +/- 11.4% and the albumin-bound fraction increased to 56.4 +/- 11.2%. Total serum clearance increased during the same time period from a mean value of 1.5 to about 2.5 ml x min-1 x kg-1. The clearance of unbound LNG, however, remained unchanged. An examination of the free LNG concentrations revealed the same time course of LNG trough levels during the cycle as the simulated curve. This was derived from the pharmacokinetic parameters which were obtained after single dose administration. Thus, the present study showed that the pharmacokinetics of LNG can be fully explained on the basis of single dose pharmacokinetics and the changes in serum protein binding which were caused by a reduction of SHBG levels in the serum during chronic treatment with LNG.


Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral contraceptive over a treatment period of 3 months and, after a wash-out phase, a single oral administration of the same contraceptive formulation. The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 9 healthy women (age 23 to 42 years), during a treatment period of three months with a low-dose oral contraceptive, containing 0.15 mg LNG together with 0.03 mg EE2 (Microgynon). After a wash-out period of 3 months, 8 of these women received a single administration of the same formulation. The results showed that there was an increase in serum trough levels of LNG, reaching steady-state in the second half of each treatment cycle. The LNG levels achieved were about 3 to 4 times higher than anticipated on the basis of single dose administration. At the end of treatment cycles one and three, the terminal half-life of LNG was in the range of 24-26 h, while a mean value of 20 h was observed following single dose administration. An EE2-induced increase in the SHBG concentration of about 50% as compared to pretreatment values was observed during a treatment cycle. Pretreatment values were reached following the drug-free interval of 7 days between two cycles. After single dose administration, the free fraction of LNG was 1.3 +/- 0.2% and the fractions bound to SHBG and albumin were 64.1 +/- 4.2% and 34.6 +/- 4.0%, respectively. Serum protein binding of LNG did not change during chronic treatment. An about 50% reduction in total and unbound clearance of LNG was observed during chronic treatment, as compared to single dose administration. Increased SHBG binding capacity and a reduced hepatic metabolic capacity were discussed as possible causes of accumulating LNG concentrations in the serum. On the last day of treatment cycles one and three, the AUC(0-24h) values of EE2 were 728 +/- 314 and 778 +/- 318 pg x ml-1 x h, respectively, and were in keeping with data reported from others.


The FlexiGard 330 ICC, an ultrasound evaluation. The FlexiGard 330 intrauterine copper contraceptive (ICC) was studied by ultrasound in 405 patients immediately following insertion and at each follow-up visit, for up to 5 years. The present study confirms the validity of the anchoring concept for the suspension of bioactive substances in the uterine cavity. The major conclusion from the study is that the anchor is non-migrating even when observed over a long period of time. Ultrasound examination is the method of choice to evaluate proper insertion technique as well as proper positioning of the device at follow-up.


Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen. The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.


Should we use prostaglandins, tents or progesterone antagonists for cervical ripening before first trimester abortion? Sixty-four women requesting first trimester termination of pregnancy were recruited into a comparative cohort study comparing the cervical ripening properties of a mechanical dilator (Lamicel; n = 17), prostaglandin, antiprogesterone and placebo control (n = 15), gemeprost; n = 17) and mifepristone; n = 15). Compared to the placebo group, all 3 active agents dilated the cervix (p < 0.02) and they significantly reduced the force required to dilate it to 8 mm Hegar (p < 0.001). Although Lamicel insertion resulted in the largest pre-operative cervical dilatation all agents are effective. Therefore the cervical priming agent of choice should be the most convenient to use and the one with least side-effects. The oral antiprogesterone, Mifepristone, is the easiest to administer and has less side effects.


Postoperative hypertension: a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside. To compare the efficacy and safety of iv nicardipine with sodium nitroprusside in the treatment of postoperative hypertension after both cardiac and noncardiac surgery. Multicenter, prospective, randomized, open-label study. Six tertiary referral medical centers (recovery rooms and surgical ICUs). A total of 139 patients with postoperative hypertension: i.v. nicardipine (n = 71), sodium nitroprusside (n = 68). Administration of i.v. nicardipine or sodium nitroprusside. Vital signs (BP, heart rate), hemodynamic variables, medication dosage, total number of dose changes, and time to achieve BP control were recorded. Both medications were equally effective in reducing BP in both the cardiac and noncardiac surgical groups. Under the conditions of the study, i.v. nicardipine controlled hypertension more rapidly than sodium nitroprusside (i.v. nicardipine 14.0 +/- 1.0 mins and sodium nitroprusside 30.4 +/- 3.5 mins, p = .0029). The total number of dose changes required to achieve therapeutic BP response was significantly less in the i.v. nicardipine-treated patients (i.v. nicardipine 1.5 +/- 0.2 vs. sodium nitroprusside 5.1 +/- 1.4, p < .05). Adverse effects were observed with both drugs (i.v. nicardipine 7% [5/71] and sodium nitroprusside 18% [12/68] [NS]). Intravenous nicardipine is as effective as sodium nitroprusside in the therapy of postoperative hypertension. Specific advantages have been identified. The use of i.v. nicardipine should be considered in the therapy of postoperative hypertension.


Effects of dopamine on T-lymphocyte proliferative responses and serum prolactin concentrations in critically ill patients. Dopamine is currently used in the ICU for its vasopressor, renal vasodilating, and cardiac inotropic properties. Animal studies have shown both endocrine and T-lymphocyte alterations with dopamine agonist administration. The relationships between exogenous dopamine and patient hormonal and lymphocyte proliferative responses have not been evaluated in the critically ill patient. These findings furnished the impetus for the present study. Prospective, controlled, clinical study. All patients admitted to the ICU at Truman Medical Center were evaluated for admission into the protocol, excluding patients whose medications or diseases produced effects in the study-dependent variables. Before institution of dopamine therapy, blood samples were taken for T-cell analysis and prolactin measurement. Daily, early morning blood samples were taken if the dopamine infusion was > 5 micrograms/kg/min for 4 hrs during that 24-hr period. An early morning postdopamine sample was taken on the first day after dosage discontinuation. Control blood samples for determination of T-cell and prolactin responses were drawn from ICU patients who did not receive dopamine. A severity-of-disease score (Acute Physiology and Chronic Health Evaluation [APACHE II] score) was recorded for all patients. Serum prolactin concentrations decreased > 90% (p < .001) within hours in all patients receiving dopamine infusions at study dose limit or above. The in vitro T-cell proliferative response to concanavalin A decreased (a transitory response) in patients receiving a dopamine infusion (p < .001). Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females. An immediate transitory decrease in patient T-cell response to concanavalin A stimulation in vitro was seen in patients receiving dopamine. The data suggest the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients.


Use of a combined right ventricular ejection fraction-oximetry catheter system for coronary bypass surgery. To evaluate the reproducibility and accuracy of a new pulmonary artery catheter system that provides both right ventricular ejection fraction and continuous venous oxygen saturation monitoring. Criterion standard study. University medical center. A consecutive sample of ten patients undergoing elective coronary artery bypass surgery provided informed consent for the study. Exclusion criteria included emergency surgery or clinically important preoperative tricuspid regurgitation as assessed by echocardiography. None of the patient sample was excluded. Catheter-derived mixed venous and arterial oximetry data were compared with simultaneous values obtained using conventional laboratory cooximetry methods. Measurements were performed before cardiopulmonary bypass and intermittently up to 48 hrs after cardiopulmonary bypass. The variability of cardiac output and computed right ventricular ejection fraction was also assessed concurrently with the oximetry analysis. A significant correlation was observed for mixed venous oxygen saturation between catheter-derived and laboratory cooximetry data (r2 = .81, p < .01). Similarly, arterial oxygen saturation values obtained from pulse oximetry and laboratory values were significantly related (r2 = .81, p < .01). The coefficient of variation for each set of five repeated measurements for cardiac output was 8%, and for computed right ventricular ejection fraction, it was 16%. The combined catheter system provides the means to monitor both mixed venous oxygen saturation and right ventricular ejection fraction. These data provide a reliable and detailed assessment of cardiopulmonary function that should prove beneficial in the critical care setting.


Can the need for a physician as part of the pediatric transport team be predicted? A prospective study. To evaluate the quality of objective information obtained during telephone requests for the transport of pediatric patients. To evaluate the ability of subjective judgment, the Pediatric Risk of Mortality (PRISM) score, and the presence of tachycardia for age to predict the need for a physician on as a member of the pediatric transport team. Prospective data collection. The pediatric transport program of a children's hospital. All 129 infants and children transported over a 4-month period. We defined an objective measure of the need for a physician's presence during the transport of a pediatric patient, based on either the necessity for procedural or medical interventions during the time of transport or on direct admission to the pediatric ICU after transport. At the time of initial telephone contact, a physician's subjective opinion of the need for physician presence was recorded, a PRISM score was derived, and the presence of tachycardia (adjusted for age) was determined. Subsequently, the vital signs recorded on the record of this request were compared with those vital signs charted at the referring hospital at the time of the initial telephone request. A total of 96% of vital signs obtained during the initial telephone contact were consistent with those percentages in the referring hospital medical records. Fifty (39%) of 129 transported patients required procedural or medical interventions or pediatric ICU admission. Subjective judgments predicted physician need with a high sensitivity (0.98), but with a low specificity (0.18). PRISM score predicted 62 (48%) of 129 transports to be "physician-required" (sensitivity = 0.72; specificity = 0.67). There was no statistical association between tachycardia for age and the objective need for a physician's presence. Objective information obtained during request for transfer was reliable. At the time of request for transfer, subjective judgment, PRISM score, and the presence of tachycardia did not predict the need for a physician presence during transport.


Pediatric risk of mortality scoring overestimates severity of illness in infants. To validate Pediatric Risk of Mortality (PRISM) scoring in infants and children admitted for intensive care. Validation cohort. A five-bed pediatric ICU and three cots providing intensive care for surgical neonates, within a 159-bed tertiary care children's hospital. All patients admitted for intensive care during an 18-month period, January 1990 to July 1991. Admission (first 24 hrs) PRISM scoring was introduced as a routine procedure. Discretion was allowed in requesting arterial blood gas measurements and clotting studies. All other parameters were intended to be measured on all patients. PRISM scores were obtained on 380 (88%) of 433 patients. Median age was 15 months. A complete PRISM score was obtained in 24% of cases and a score as intended (i.e., allowing discretionary omissions) was obtained in 56% of patients. Comparison of observed and predicted mortality rates using chi square goodness-of-fit tests showed a significantly better observed outcome for all patients (chi 2(5) = 12.04, p < .05). In-depth analysis indicates that the model works well for children (chi 2(5) = 1.80, p > .75), but that observed outcome is significantly better than predicted for infants (chi 2(5) = 17.46, p < .01). Underscoring of children is not the cause of this finding. In our center, PRISM scoring overestimates severity of illness in infants. PRISM scoring is not institutionally independent and therefore, at present, a comparison between units may not be justified. A reappraisal of the parameter ranges for infants is suggested.


Intensive care unit outcome in the very elderly. To determine if age, previous functional status, or acute severity of illness affect the acute and long-term mortality rates and functional status of the very elderly (> or = 85 yrs) after an ICU admission. Cohort study (retrospective entry for the first year of the study and prospective entry thereafter with prospective follow-up throughout). An ICU in a community teaching hospital with follow-up at home or at a skilled nursing facility. All (n = 105) patients > or = 85 yrs admitted to the ICU over a 2-yr period. ICU, 30-day posthospital discharge, and 1-yr mortality rates, activities of daily living scores, organ system failure score at the time of ICU admission. The ICU, 30-day posthospital discharge, and the 1-yr mortality rates were 30%, 43%, and 64%, respectively. Mortality rates significantly increased between the ICU stay or 30 days posthospital discharge and 1-yr follow-up periods. Of those patients who lived up to 6 months after hospital discharge, 86% survived to 1 yr with little change in functional status from baseline. In the patients with > or = 2 organ system failures, there were 88% 30-day posthospital discharge and 100% 1-yr mortality rates. Severity of illness, as measured by the number of organ system failures, was associated with increased ICU (odds ratio 3.38; 95% confidence interval, 1.51 to 7.60; p < .005) and 1 yr (odds ratio 5.76; 95% confidence interval, 2.49 to 13.29; p < .0001) mortality rates, while age within this group and preadmission functional status were not. Within the very elderly population, acute severity of illness is the most significant predictor of mortality after an ICU admission. For most very elderly patients, surviving 1 yr after an ICU admission, there is little change in functional status.


Acute continuous hemofiltration with dialysis: effect on insulin concentrations and glycemic control in critically ill patients. To quantitate insulin losses and glucose absorption during acute continuous hemofiltration with dialysis and to assess the clinical importance of these changes. Prospective collection of serum and ultradiafiltrate fluid in patients receiving acute continuous hemofiltration with dialysis. Measurements of serum and ultradiafiltrate insulin and glucose concentrations. Calculations of insulin excretion and glucose absorption. Correlation of findings with patient outcome. University medical center. Sixteen ICU patients with acute renal failure. The mean serum glucose concentration before acute continuous hemofiltration with dialysis was 178 mg/dL (9.9 mmol/L) (95% confidence interval 112 to 244 mg/dL [6.2 to 13.6 mmol/L]), increasing to 257 mg/dL (14.3 mmol/L) (95% confidence interval 167 to 347 mg/dL [9.3 to 19.3 mmol/L]) after 4 hrs of acute continuous hemofiltration with dialysis, and stabilizing at 207 mg/dL (11.5 mmol/L) (95% confidence interval 160 to 254 mg/dL [8.9 to 14.1 mmol/L]) at 24 hrs. Mean plasma insulin concentration before acute continuous hemofiltration with dialysis was 34.4 mU/L (95% confidence interval 8.6 to 60.2 mU/L), increasing to 54.4 mU/L at 4 hrs (95% confidence interval 25 to 83.8 mU/L; NS). There was no significant decrease in mean insulin concentration across the filter (51.8 mU/L before filtration vs. 51.9 mU/L after filtration). Insulin was detected in the ultradiafiltrate but its overall mean clearance rate was only 6.2 mL/min, with mean daily losses of 689 mU/day (95% confidence interval 325 to 1053 mU/day). During acute continuous hemofiltration with dialysis, glucose absorption through the filter averaged 134 g/day (95% confidence interval 96.2 to 171.8 g/day). Plasma insulin concentrations were significantly (p < .05) lower in survivors than nonsurvivors (51.7 vs. 123.6 mU/L). Significant glucose absorption occurs during acute continuous hemofiltration with dialysis and is coupled with minor insulin losses (< 1 U/day) through the filter. These events do not appear to have major clinical impact. A low plasma insulin concentration is associated with diminished mortality rates in this group of patients.


Alterations in oropharyngeal flora in patients with a nasogastric tube: a cohort study. To determine whether or not the presence of a nasogastric tube causes a change in the bacterial flora in the oropharynx. Cohort (prospective) design with concurrent control. General Surgical and Ear, Nose, and Throat Units of a tertiary care hospital. Sixteen patients with and 14 patients without a nasogastric tube. Patients scheduled to undergo surgery under general anesthesia with endotracheal intubation were eligible for inclusion in the study. From these patients, a study cohort of 16 consecutive patients who were to have nasogastric tube intubation and 14 patients who were not to have nasogastric intubation were enrolled. All patients had a high oropharyngeal swab taken for bacteriologic culture just before surgery. The swab of the oropharynx for culture was repeated after 48 to 72 hrs. The type of organism grown was identified and compared between and within the two groups. There was a significant increase in the frequency of colonization of the oropharynx by pathogenic Gram-negative bacteria after 48 to 72 hrs of nasogastric intubation in comparison with the preintubation level (p < .01) as well as in comparison with the group that did not have nasogastric intubation (p < .001). The pathogens included Pseudomonas, Klebsiella, Proteus and Escherichia coli. There was also a tendency for suppression of normal flora. There was no significant change in the flora of the control group of patients who did not have nasogastric intubation. The two groups were comparable with respect to age, gender, severity of underlying illness, and use of prophylactic perioperative antibiotics. The presence of nasogastric tubes in patients predisposes to colonization by Gram-negative pathogenic bacteria within 48 to 72 hrs.


Evaluation of the consistency of Acute Physiology and Chronic Health Evaluation (APACHE II) scoring in a surgical intensive care unit. To determine the applicability of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in a Swiss ICU, and to evaluate its utility in evaluating data from 2 yrs of consecutive admissions to show that the predictability of outcome is similar to that predictability observed by Knaus et al. in 1985 (in 5,815 patients), with the provision that large numbers of patients are studied. Prospective clinical trial over 2 yrs, with statistical analysis of the Swiss patients, and between the Swiss patients and the patients studied by Knaus et al. Receiver operating characteristic curves were calculated. Surgical ICU in a Swiss university hospital. A total of 2,061 consecutive patients admitted to the surgical ICU who were classified as postoperative (elective or emergency) and nonoperative. Hospital mortality rate was considered. Patients were 53 +/- 16 yrs of age. Mean APACHE II score was 10.5 +/- 7.0. The mean APACHE II score was significantly (p < .001) lower in the 1,813 survivors (9.0 +/- 5.2) than in the 248 nonsurvivors (21.5 +/- 8.5). The mortality rate was higher among the Swiss patients when compared with the patients studied by Knaus et al. who had postoperative scores of 20 to 29 and nonoperative scores of > 24. The distribution of the scores and mortality rates were stable during the two study periods, as were the differences in mortality rates between the Swiss population and that population studied by Knaus et al. Sensitivity and specificity of the scores were highest in the emergency surgery group (87% and 78%), and lowest in the elective surgery group (76% and 73%). The APACHE equation underestimated the risk of death. The APACHE II score, because of its consistency over time and the stability of the mortality rates, can be used in our surgical ICU without modification. The calculated risk of death gives no additional information.


Prospective evaluation of residents and nurses as severity score data collectors. To determine the interobserver reliability of residents and nurses collecting Acute Physiology and Chronic Health Evaluation (APACHE II) data and the subsequent effect of these data collections on individual patient mortality prediction. In a prospective study, residents and nurses independently collected data to derive APACHE II scores. When their scores differed, a standard score was determined by one of the investigators. A general medical and surgical ICU. A total of 120 consecutive patients were included; of these patients, 79 had standard scores determined because resident and nurse scores differed. There was overall agreement between the residents and nurses with no significant difference between mean APACHE II scores or mean predicted mortality rates. Intraclass correlation coefficients confirmed good overall agreement between observer groups for predicted mortality rate: resident vs. nurse r2 = .94, resident vs. standard r2 = .94, and nurse vs. standard r2 = .90. However, clinically significant lack of agreement was demonstrated in 5% of the patients by the 95% confidence limits of agreement: resident vs. nurse -14 to +14%, resident vs. standard -10 to +14%, and nurse vs. standard -14 to +20%. While interobserver variability between resident and nurse data collection has minimal effect on derived predicted mortality rate with large patient groups, significant variability may occur in individual patients. Residents were more accurate data collectors than nurses.


High-dose magnesium sulfate attenuates pulmonary oxygen toxicity. Rats rapidly develop respiratory distress when exposed to 100% oxygen and die within a few days. Autopsy of the lung shows severe histologic damage characteristic of the adult respiratory distress syndrome. The purpose of this study was to evaluate the effects of magnesium sulfate loading in a rat model of acute oxygen toxicity. Thirty-four rats were divided into three groups. Group 1 (n = 18) served as a control (no magnesium therapy), while group 2 (n = 8) and group 3 (n = 8) received varying amounts of magnesium sulfate. All animals were exposed to 100% oxygen for 96 hrs or until death. Lung damage was quantitated by measuring the lung injury score on histologic examination. Administering magnesium sulfate in moderate doses at infrequent intervals to rats (group 2) resulted in less severe oxygen-induced lung damage than that which occurred in rats not receiving magnesium (control group). However, the difference was not statistically significant. Rats (group 3) given doses of magnesium sulfate in amount and frequency adequate to maintain a serum magnesium concentration recognized as therapeutic in eclampsia significantly reduced oxygen-induced lung damage. High-dose magnesium sulfate therapy can reduce lung injury caused by acute oxygen toxicity in rats.


Selective decontamination of the digestive tract prevents secondary infection of the abdominal cavity, and endotoxemia and mortality in sterile peritonitis in laboratory rats. This study was undertaken to find out whether translocation of bacteria to the abdominal cavity and endotoxemia in rats with sterile peritonitis could be prevented by selective decontamination of the digestive tract. Sterile peritonitis was caused by the intraperitoneal injection of either 100, 150, 200, or 300 mg of zymosan suspended in paraffin. The frequency of infection of the abdominal cavity depended on the dose of zymosan given, ranging from 20% in rats receiving 100 mg to 89% in rats receiving 300 mg of zymosan. In rats not receiving antibiotics for selective decontamination of the digestive tract (the control group). Gram-negative bacilli were isolated from the digestive tract in all rats, and Gram-negative bacilli were isolated from the abdominal cavity in ten of 19 rats. In rats receiving antibiotics for selective decontamination of the digestive tract, Gram-negative bacilli were isolated from the digestive tract in none of the 14 rats, and likewise, Gram-negative bacilli were isolated from the abdominal cavity in none of the 14 rats (p < .005). Moreover, in rats receiving antibiotics for selective decontamination of the digestive tract, endotoxin levels in feces and plasma were significantly lower, as compared with rats not receiving antibiotics for selective decontamination of the digestive tract. Selective decontamination of the digestive tract prevents translocation of Gram-negative bacilli to the abdominal cavity, and endotoxemia and mortality in rats with sterile peritonitis.


Rethinking brain death.

Rethinking brain death. To evaluate whether current criteria for the diagnosis of brain death fulfill the requirement for the "irreversible cessation of all functions of the entire brain, including the brainstem." Clinical, philosophical, legal, and public policy literature on the subject of brain death. We advance four arguments to support the view that patients who meet the current clinical criteria for brain death do not necessarily have the irreversible loss of all brain function. First, many clinically brain-dead patients maintain hypothalamic-endocrine function. Second, many maintain cerebral electrical activity. Third, some retain evidence of environmental responsiveness. Fourth, the brain is physiologically defined as the central nervous system, and many clinically brain-dead patients retain central nervous system activity in the form of spinal reflexes. We explore options for resolving these inconsistencies between the conceptual definition and the clinical criteria used to make the diagnosis of brain death. Brain death is a valid conception of death because it signifies the permanent loss of consciousness. Brain death criteria should therefore be based on the diagnosis of the permanent loss of consciousness rather than that of the loss of vegetative brain functions. Revision of our current "whole brain" definition of brain death to a "higher brain" standard should be considered.


Critical care: how should we evaluate our progress? Review of the history and accomplishments of the Society of Critical Care Medicine (SCCM) to determine appropriate directions for the future. Historical documents of the SCCM, Critical Care Medicine, bioethics and healthcare financing literature, Instant Library of Quotations. Identified (by the author) material containing specific statements concerning goals and objectives at the time of the founding of the SCCM and at intervals. Material supporting and criticizing predictive indices were identified and bioethical treatises concerning patient autonomy and quality-of-life decisions were chosen. Presidential addresses of the first three SCCM presidents, material relevant to preservation of life and alleviation of suffering from bioethical and healthcare financing perspectives. Relevant quotations. Initial goals and objectives were identified. Societal and economic factors changing critical care were analyzed for their effect on current and future SCCM directions and objectives. The founding members set important goals for critical care and patient care, research, education, and organization. From a perspective of what was foreseeable, these goals have been accomplished to an admirable degree. The SCCM has responded to these goals by providing educational programs and fostering research, especially in its annual meetings and through the publication of guidelines in Critical Care Medicine. The SCCM members would do well to read the first three presidential addresses to experience the eloquence and foresight firsthand, particularly with respect to the founders' spirit, considerations of training, scope of care, humanism, organization and relations within and outside of critical care, integration of care, and development of the scientific process at the bedside. There have been major changes in society since the SCCM was founded: the maturation of the concept of patient's autonomy; recognition of quality-of-life values; healthcare financing; and legal and ethical aspects of care. The critical care profession in general, and the SCCM specifically, should seek to develop effective cost-containment strategies and severity of illness or predictive indices. The SCCM should also educate the professions with respect to ethical issues and provide information directly to the public, especially in the areas of advance directives and withholding and withdrawing care. Through these contributions, the SCCM can assume its proper leadership role within medicine, but, of greater importance, in society. In doing so, societal myths and misunderstandings of the capabilities, futility, role, and limitations of critical care can be corrected. The organization and structure of the SCCM are well developed to accomplish these ends. The SCCM leaders are both able and willing. The objectives seem reasonable and should be attainable.


Extrahepatic bile duct cancer. Report of 106 cases. Extrahepatic bile duct cancers (BDC) are still frustratingly difficult lesions to deal with at present. 106 cases of BDC treated between January 1986 and December 1990 were reviewed retrospectively. The resectability rate of the entire series was 18.9%. Hilar (upper third) BDC accounted for 51% of the entire series and its resection rate was 14.8%. Lymph node metastases occurred in 40.9% of the cases and were mostly seen in the middle 1/3 of BDC. 32% of the cases had liver metastases, frequently occurred in hilar BDC. Sixty-four patients had specimens histologically studied. Of them, adenocarcinomas accounted for 90.6% (58 cases) and adenosquamous carcinomas 4.7% (3). Among the adenocarcinomas, 32 (55.2%) cases were well differentiated and 26 (44.8%) poorly differentiated.


Extracorporeal shock wave lithotripsy and methyl tert-butyl ether for gallbladder stones. Twenty-one patients with gallbladder stones of 1.1-2.6 cm in diameter were treated by extracorporeal shock wave lithotripsy (ESWL) combined with dissolution using methyl tert-butyl ether (MTBE). In 18 of 21 patients, ESWLs were followed by MTBE instillation through a catheter placed percutaneously via the liver and the gallbladder bed under ultrasonographic and fluoroscopic guidance. As a result, 15 of the 18 patients were cleared of their stones after 54 minutes to 3 hours of dissolution. In the other three cases initially treated by MTBE, ESWLs were added because of no dissolution or poor efficacy. Consequently, after additional 3-5 hours of instillation, complete dissolution in one and subtotal dissolution in two were achieved. Our preliminary results indicated that ESWL followed by MTBE dissolution in the management of cholesterol gallbladder stones was reasonable. On the one hand, ESWL can enhance dissolution by increasing the surface area of stone, and on the other hand MTBE can instantly clear the fragments created by ESWL, so that long-term bile acid intake and potential side effects caused by fragment migration might be avoided.


Surgical treatment of hilar bile duct carcinoma. Clinical and pathological studies. Resection of the extrahepatic bile tract for hilar bile duct carcinoma was performed at the PLA General Hospital, with a resectability rate of 62% (31/50) and no operative mortality. Hepatic lobectomy was performed at the same time in 16 cases (51.6%). Reoperative resections were successfully done in 5 cases; 4 cases are still living 1-4 years after the second operation. The cause of late death was mainly biliary infection due to local recurrence and bile duct obstruction. The median survival period was 15 months. 32 cases were studied pathologically, of which 27 were resected surgical specimens and 5 autopsies. The tumors were histologically classified into 4 types: papillary adenocarcinoma (6 cases); well differentiated adenocarcinoma (21); poorly differentiated adenocarcinoma (3); and simple carcinoma (2). The importance of early diagnosis of hilar bile duct carcinoma at its subclinical stage before appearance of clinical jaundice is stressed.


Interventional chest radiology.

Interventional chest radiology. Radiologically guided percutaneous drainage procedures are commonly performed to manage a variety of intrathoracic collections. As a natural extension of similar procedures performed for abdominal and pelvic collections, these procedures use both the conventional and cross-sectional imaging modalities to detect intrathoracic collections and to guide safe percutaneous diagnostic aspiration and drainage. The high-resolution images obtainable on current computed tomographic and ultrasound units allow detection of lung abscesses, empyemas, malignant effusions, and infected mediastinal fluid collections that are amenable to percutaneous drainage. Advances in catheter design and introduction techniques have allowed drainage of collections previously managed by open procedures. The ease of fluoroscopically guided catheter placement for treatment of spontaneous or biopsy-induced pneumothorax has provided a safe, effective, and comfortable alternative to blind large-bore surgical tube placement. Transthoracic needle biopsy of lung, mediastinal, and pleural or chest-wall masses has resulted from the availability of image intensifiers and cross-sectional imaging modalities useful in guiding needle placement and tissue sampling. Equally important has been the development of cytopathology as a subspecialty that can provide diagnoses of malignant and benign thoracic conditions from needle aspirates. This technique has had a major impact on the preoperative evaluation of the patient with a solitary pulmonary nodule and has eliminated unnecessary surgery in a significant percentage of such patients. Transcatheter arterial embolization has made a significant contribution to the management of the patient with massive hemoptysis and is the procedure of choice for treatment of pulmonary arteriovenous malformations. A thorough knowledge of the vascular anatomy of the thorax and expertise in catheterization and embolization techniques are prerequisites for the safe performance of these procedures.


Role of monoconjugated bilirubin in pathogenesis of gallstones. In order to explore the substantial role of monoconjugated bilirubin (MCB) in gallstone formation, bile pigment precipitation and hemolytic jaundice, three experimental protocols have been studied, namely, (1) MCB and dietary induced pigment gallstone model, (2) MCB in human gallstone and incubated bile precipitates and (3) MCB in hemolytic jaundice. It was found that doubly increased MCB accounted for 1/3 of the total pigment in lithogenic guinea pig and CDCA plus glycine possessed certain protective effect from gallstone development; MCB was found in human gallstones both in bilirubinate and cholesterol type, and an unknown pigment, possibly an isomer of MCB, was found in black stone. During experimental hemolytic jaundice model preparation, both MCB and UCB were elevated, and MCB was found increased by 10 times, even exceeding the concentration of DCB when the injected bilirubin was about 4 mg/kg of body weight. It is reasonable to consider that MCB as a coprecipitant with UCB and a precursor of UCB played an essential role in the pathogenesis of gallstones.


Effects of glutathione depletion using buthionine sulphoximine on the cytotoxicity in mammalian cells and human tumor cells in vitro. An inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), was used to deplete the endogenous thiols in mammalian cells in vitro. In this study, the cytotoxicity of BSO and BSO combined with the hypoxic cell radiosensitizer misonidazole (MISO) was investigated. Both aerobic and hypoxic cytotoxicity of MISO was found to be increased. The concentration of BSO required to reduce the colony forming ability to 50% (Cc) for the chronic cytotoxicity on V79 cells was 0.03 mmol/L under aerobic condition, while the Cc for the acute cytotoxicity on V79 cells under hypoxic and aerobic conditions was 0.4 and 0.5 mmol/L. The growth inhibition rate of human tumor cells K562 and SGC-7901 by BSO was 6.89-26.06% and 12.01-55.69%, respectively. Enhanced cytotoxicity activity was observed when BSO was used in combination with cis-dichlorodiamino Pt(II) or 5-fluorouracil.


Optimal low dosage of acetylsalicylic acid (ASA) for the prevention and treatment of ischemic cerebrovascular disease in geriatric patients. A series of 108 geriatric patients with ischemic cerebrovascular disease were treated with low dose aspirin (acetylsalicylic acid, ASA). Daily doses of 100 mg, 50 mg and 25 mg were administered to three groups of 36 patients. Changes in platelet aggregation responses were dynamically observed in 64 (22 normal subjects, 42 patients). Monitoring of 22 normal subjects revealed inhibition of platelet aggregation at a dose of 300 mg or 100 mg which could last as long as 7 days. This suggests that 100 mg or less could be clinically effective. Satisfactory inhibitory effects on platelet aggregation were observed in all three groups, with 14 patients in each group given daily doses of 100 mg, 50 mg and 25 mg during four weeks' observation. The most effective inhibition was obtained in the 50 mg group. Therefore, the authors recommend 50 mg/d as the optimal dosage for low dose aspirin therapy in geriatric patients.


Value of CT myelography in differential diagnosis of spinal extradural tumors. Twenty-three cases of spinal extradural tumors were differentiated with CT myelography. In 16 benign tumors, the proximal and/or distal widened extradural space was filled with adipose tissue, whereas in 7 malignant tumors, the widened extradural space showed soft-tissue density. This difference is helpful in evaluating the nature of the tumors.


Anisodamine inhibits acetylcholine-induced endothelium-dependent relaxation of canine femoral artery. The effects of anisodamine on acetylcholine-induced endothelium-dependent relaxation were studied in organ chambers and under bioassay conditions. In organ chamber experiments, both acetylcholine and bradykinin induced an endothelium-dependent relaxation of norepinephrine-contracted canine femoral arteries in a concentration-dependent manner; the relaxation induced by acetylcholine, but not that by bradykinin, was inhibited by anisodamine or atropine in a concentration-dependent manner. In bioassay experiments, a denuded ring of left circumflex coronary artery was superfused with perfusate passed through segment of femoral artery with endothelium or a direct superfusion line. Acetylcholine induced the release of relaxing factor(s) from the segment with endothelium causing a relaxation of bioassay ring and the relaxation was eliminated by anisodamine infused into the perfusion line above, but not below, the perfused segment. The results suggest that anisodamine, like atropine, is able to inhibit acetylcholine-induced endothelium-dependent relaxation by blocking endothelial muscarinic receptors which activate the release of endothelium-derived relaxing factor(s).


Effect of heparin on the anionic sites of glomerular basement membrane in adriamycin nephrosis in rats. The effect of heparin on the anionic sites of glomerular basement membrane (GBM) in adriamycin-induced nephrotic rats was studied by means of calculating the polyethyleneimine (PEI) stained particles under electron microscope. The results showed that treatment with heparin under the anticoagulant effect markedly reduced the loss of anionic sites within lamina rara externa (LRE) of GBM and also the urinary protein excretion in nephrotic rats. The results demonstrated that one of the mechanisms of heparin in preventing the structural damage of glomeruli in kidney diseases was the reduction of the loss of anionic sites within LRE, indicating that changes in biomembrane charge played an important role in the pathogenesis of nephrotic syndrome. The results provided a scientific basis for the use of heparin to treat glomerular diseases.


Hepatic stimulator substance from human fetal liver for treatment of experimental hepatic failure. The authors previously reported the successful reversal of lethal D-Gal induced hepatic necrosis in rats by human hepatic stimulator substance (hHSS), a liver specific growth factor partially purified from human fetal liver cells, which promoted hepatocyte proliferation. In this study, they further investigated the mechanism of hHSS in improving survival of experimental acute hepatic failure. Our results demonstrated that the level of alanine transaminase and endotoxin in the plasma and lipid peroxides in the liver of chemically poisoned rats were reduced by hHSS to different extent at different periods of observation compared with the saline control group. The apparent recovery of liver function and the increase of 3H-TdR incorporation into hepatic DNA correlated with the morphologic changes observed under light and electron microscopes, showing that the damages inflicted on the cellular and subcellular structure in the liver of hHSS-treated rats were greatly alleviated and rapidly repaired. Therefore, hHSS, which can prevent liver deterioration and promote hepatocyte regeneration, may be a new hepatic stimulator factor readily available for clinical use.


Changes in hepatic energy metabolism in experimental acute pancreatitis. The changes in the cellular concentrations of ATP, ADP, AMP and oxidative phosphorylation of mitochondria in the liver were investigated experimentally in rats with acute pancreatitis (AP). The energy charge (ATP + 1/2ADP)/(ATP+ ADP+ AMP) of the liver decreased from 0.866 to 0.806 (P < 0.05) at 24 hours after onset of AP, and continuously decreased to 0.769 (P < 0.01) at 48 hours. On the other hand, the mitochondrial phosphorylative activity increased rapidly to 130% and 157% in the controls at 12 hours and 24 hours respectively and then decreased rapidly at 48 hours. The blood ketone body ratios were paralleled to the hepatic energy charge level in AP rats. These findings suggest that the nature of the derangement of the hepatic energy metabolism initiated by AP is that the effects of mitochondria damage result in a significant decrease in liver energy charge level, leading ultimately to hepatocellular impairment, and the measurement of the blood ketone body ratio is useful in evaluating the energy status of the liver in AP patients.


[Continuously alternating prone and supine positioning in acute lung failure]. Acute respiratory failure is still one the main problems in surgical intensive care. Unknown pathophysiological mechanisms permit only symptomatic therapy. Today ventilatory strategies by using PEEP und IRV are established to improve gas exchange and FRC by recruiting collapsed alveoli, decreasing intrapulmonary shunting and returning V/Q matching to normal. Furthermore different studies have shown the effects of supine and lateral decubitus posture in patients with acute respiratory failure. There are only rare reports on using the prone position, which doesn't require two-lung ventilation in difference to lateral position. We have studied 16 patients with acute respiratory failure by using continuous changing between prone and supine position under mechanical ventilation. All were male, aged 41.3 years in the middle and showed an average "Injury Severity Score" of 30 (13-50). 15 were trauma patients with blunt chest trauma in 11 cases. We have used prone position on threatening or manifest ARDS. In all patients we observed an increment of PaO2 during prone position on to 48 mmHg so that FiO2 could be reduced on an average of 0.2 within the first 48 h since changing patient's position. Posture changing depends on blood gas analysis, specifically on decreasing PaO2 after previous increment. Patients remained in prone and supine position at a mean of 6.3 (4.5-20) h and posture changing was proceeded over a period of 15.4 (7-32) days. No problems recording to blood pressure or mechanical ventilation appeared during prone position. 11 of 16 patients survived (68.8%), 5 died of cardiac (2) and multi organic failure (3) in connection with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)


[Use of internal fixator in injuries of the thoracic and lumbar spine]. Between 1984 and 1989 51 patients with spinal traumata received surgical treatment by means of Fixateur interne. The results of patients' postsurgical check-up were as follows: Cases with incomplete neurological dysfunctions (levels Frankel B-D)-especially lumbar-showed improvements of neurological deficiencies up to three levels Frankel after emergency decompression and stabilization. The majority of cases with complete paraplegia-especially thoracic-did not subside. This holds true even for the results of a second check-up after about three years. A correlation between the degree of stenosis of the spinal canal and the neurological dysfunctions could not be established. The results of segmental stabilization by means of internal fixator and of definitive spondylodesis by means of autogenous spongiosa were positive, as was the spine proof and the patients' postsurgical function.


[External fixator in complicated tibial fracture. Effect of various fixation systems on fracture healing and rate of complications]. In a retrospective analysis 93 external fixations with different rigidity after open tibial shaft fractures have been reviewed and compared concerning complications and healing time. Fracture consolidation was attained in fixation with unilateral frame after 14 weeks, with bilateral v-shaped fixator after 19 weeks and with triangular configuration in about 28 weeks. Subsequent internal fixation or extension to v-shaped fixation was necessary in about 33% after initial unilateral half-pin frame, whereas 90% of the two rigid systems could be left in situ until fracture consolidation was achieved. Cancellous bone grafts were performed in 58% after triangular, in 40% after v-shaped, and 28% after unilateral fixation. Pin infections were observed in 36% after triangular, 25% after bilateral v-shaped, and in 15% after unilateral fixation.


[Histologic reactions of the bone-implant zone and cortical bone area after long-term hip replacement]. 29 femora with cemented hip endoprostheses and 17 age related controls were analyzed regarding different histological criteria. All specimens were processed to undecalcified ultra thin grindings and in addition a few to surface stained block-grindings. The reactions at the bone implant interface in cases without loosening of the implant are: accumulation of macrophages and multinucleated giant cells, fibrous tissue membranes with a mean thickness of 103 microns and mineralization defects near the cement. The mean rate of direct bone/bone-cement contact is 2.7% of the whole cement surface. The phenomenons at the interface were explained as being the result of micromovement and resulting from wear and tear. The cortical bone demonstrates a remarkable loss of bone (up to 60% after 12 years) following an increase of osteoclastic resorption with no change of osteoblast activity. The localization of the bone loss indicates a relation to the new load situation after implantation.


[Defect coverage of the extremities with distal pedicled flap-plasty]. Clinical consideration of anatomy of skin vascularity led to the establishment of distally pedicled flaps in the extremities. In certain situations, distally pedicled flaps are a quick and safe alternative to free microvascular tissue transplantation or distant pedicled flaps. However, an exact indication for this method as well as exact planning and performance of the operation is necessary for success. A synopsis of clinical applications of distally pedicled flaps is given.


[Intraosseous ganglion in the area of the wrist]. In the differential diagnosis of cystic lesions in bones, the intraosseous ganglion must be included. These tumor-like lesion is rare in the carpus, but often the cause of therapy-resistant pain. Four patients with intraosseous ganglion in the carpus are presented. This bone disease is treated by curettage and bone grafting. Postoperative prognosis is good.


[Simplified surgical technique and decreased radiation exposure in dorsal stabilization of spinal fractures]. The dorsal approach for reposition and stabilisation of dorsal and lumbal spine fractures is widely accepted. It is much easier for the surgeon and with lower risk for the patient. For placement of the pedicle screws 3 steps with X-ray fluoroscopy in transversal and anteroposterior direction are necessary: K-wire placement in the pedicle, drill for opening the pedicle and finally screw placement. With the use of two fluoroscopes and a central cannulated drill which is placed over the K-wire the operation gets much shorter, easier and the fluoroscopy time can be reduced significantly.


[Total hip joint endoprosthesis in osteopetrosis]. Albers-Schönberg disease (osteopetrosis) is a rare condition, and it very seldom occurs that a patient requiring a hip endoprosthesis is also suffering from this disease. The report describes the difficulties which may confront a surgeon unprepared for such a case and the author illustrates the problem taking the case history of a 46-year-old patient with X-rays and histological tests as an example. The reasons for implantation of either a cemented or cementless endoprosthesis are discussed.


[Carcinoma metastasis in cutaneous osseous metaplasia. Differential diagnosis of osseous tumor metaplasia]. The formation of metastases in heterotopic ossifications is a very rare finding. The example of a 63-year old male who underwent Billroth II procedure because of recurrent duodenal ulcers 30 years ago and median laparotomy of the upper abdomen because of blunt abdominal trauma 9 years ago shows the formation of metastasis of a carcinoma found in the gastroenteral anastomosis in a focus of heterotopic ossification, which was located in the scar of the upper abdominal laparotomy.


Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry. The study of the role of apoptosis in thymocyte development has been hampered by the lack of a means of directly immunophenotyping cells undergoing the early phase of apoptosis. This restriction has been overcome by single laser flow cytometry in which apoptosis is detected by Ethidium Bromide (EBr) staining and cell phenotype by binding of FITC-labelled antibody. The initial phase of apoptosis is observed as a cell population that stains faintly with EBr preceding the characteristically bright EBr-staining normally associated with cell death. Here we directly demonstrate using single laser flow cytometry that CD4+ CD8+ CD3low/CD3intermediate thymocytes undergo apoptosis in vitro in response to glucocorticoid treatment.


Noise, sensitivity, and resolution of flow cytometers. The sensitivity and resolution of flow cytometers are functions of the signal produced by a given particle as well as by the noise in the presence of which the signal is detected. The noise is primarily due to the fact that emission of light as well as its detection by photoelectric devises are stochastic processes. This fact leads to equations describing how resolution and sensitivity are limited by the magnitude of the signal, the background, and the photoelectron quantum yield of the detector. The equations are pointing to a method by which the signal and noise of a flow cytometer can be measured in absolute terms, as well as a way to determine fluorescence sensitivity without having to extrapolate to the noise level. The equations appear to be validated when applied to measuring data obtained with two different flow cytometers.


Quantification of inter- and intra-nuclear variation of fluorescence in situ hybridization signals. This study aims at the quantification of specific DNA sequences by using fluorescence in situ hybridization (ISH) and digital imaging microscopy. The cytochemical and cytometric aspects of a quantitative ISH procedure were investigated, using human peripheral blood lymphocyte interphase nuclei and probes detecting high copy number target sequences as a model system. These chromosome-specific probes were labeled with biotin, digoxigenin, or fluorescein. Quantification of the fluorescence ISH signals was performed using an epifluorescence microscope equipped with a multi-wavelength illuminator, and a cooled charge coupled device (CCD) camera. Specific image analysis programs were developed for the segmentation and analysis of the images provided by ISH. The fluorescence intensity distributions of the ISH spots showed large internuclear variation (CVs up to 65%) for the probes used. The variation in intensity was found to be independent of the probe, the type of labeling, and the type of immunocytochemical detection used. Variation in intensity was not caused primarily by the immunocytochemical detection method, since directly fluorescein-labeled probes showed similar internuclear variation. Furthermore, it was found that different white blood cell types, which harbor different degrees of compactness of the nuclear chromatin, showed the same variation. The intra-nuclear variation in intensity of the ISH spots on the two chromosome homologs within one nucleus was significantly smaller (approximately 20%) than the inter-nuclear variation, probably due to more constant local hybridization conditions. Due to the relatively small intranuclear variation, copy number polymorphisms of the satellite DNA sequence on chromosome 1 could readily be quantified.(ABSTRACT TRUNCATED AT 250 WORDS)


Fluorescence ratio measurements of double-labeled probes for multiple in situ hybridization by digital imaging microscopy. To expand the multiplicity of the in situ hybridization (ISH) procedure, which is presently limited by the number of fluorochromes spectrally separable in the microscope, a digital fluorescence ratio method is proposed. For this purpose, chromosome-specific repetitive probes were double-labeled with two haptens and hybridized to interphase nuclei of human peripheral blood lymphocytes. The haptens were immunocytochemically detected with specific antibodies conjugated with the fluorochromes FITC or TRITC. The FITC and TRITC fluorescence intensities of spots obtained with different double-haptenized probes were measured, and the fluorescence ratio was calculated for each ISH spot. Combinations of different haptens, such as biotin, digoxigenin, fluorescein, sulfonate, acetyl amino fluorene (AAF), and mercury (Hg) were used. The fluorescence intensity ratio (FITC/TRITC) of the ISH spots was fairly constant for all combinations used, with coefficients of variation between 10 and 30%. To study the feasibility of a probe identification procedure on the basis of probe hapten ratios, one probe was double-labeled with different ratios, by varying the relative concentrations of the modified nucleotides (biotin-11-dUTP and digoxigenin-11-dUTP) in the nick-translation reaction. Measurement of the FITC and TRITC intensities of the ISH spots showed that the concentration of modified nucleotides used in the labeling procedures was reflected in the mean fluorescence intensity of the ISH spots. Furthermore, the ratio distributions showed little overlap due to the relatively small coefficients of variation. The results indicate that a multiple ISH procedure based on fluorescence ratio imaging of double-labeled probes is feasible.


Quantification of fluorescence in situ hybridization signals by image cytometry. In this study we aimed at the development of a cytometric system for quantification of specific DNA sequences using fluorescence in situ hybridization (ISH) and digital imaging microscopy. The cytochemical and cytometric aspects of a quantitative ISH procedure were investigated, using human peripheral blood lymphocyte interphase nuclei and probes detecting high copy number target sequences as a model system. These chromosome-specific probes were labeled with biotin, digoxigenin, or fluorescein. The instrumentation requirements are evaluated. Quantification of the fluorescence ISH signals was performed using an epi-fluorescence microscope with a multi-wavelength illuminator, equipped with a cooled charge couple device (CCD) camera. The performance of the system was evaluated using fluorescing beads and a homogeneously fluorescing specimen. Specific image analysis programs were developed for the automated segmentation and analysis of the images provided by ISH. Non-uniform background fluorescence of the nuclei introduces problems in the image analysis segmentation procedures. Different procedures were tested. Up to 95% of the hybridization signals could be correctly segmented using digital filtering techniques (min-max filter) to estimate local background intensities. The choice of the objective lens used for the collection of images was found to be extremely important. High magnification objectives with high numerical aperture, which are frequently used for visualization of fluorescence, are not optimal, since they do not have a sufficient depth of field. The system described was used for quantification of ISH signals and allowed accurate measurement of fluorescence spot intensities, as well as of fluorescence ratios obtained with double-labeled probes.


Comparison of BrdUrd and [3H]TdR incorporation to estimate cell proliferation, cell loss, and potential doubling time in tumor xenografts. In this study, two different methods of estimating cell proliferation were compared: cell loss and potential growth rate of xenografted head and neck cancer grown in nude mice based on the detection of DNA incorporation of bromodeoxyuridine (BrdUrd) in one method, and [3H]thymidine ([3H]TdR) in the other. The 21-d-old xenografts were labelled in vivo, either with BrdUrd or [3H]TdR and excised at intervals during 65.5 h. In tumors containing BrdUrd, the percent labelling was measured in mid-S and mid-G1 phase windows of cytograms from bivariate DNA flow cytometry (FCM). In [3H]TdR-labelled tumors, the percent labelled mitoses (PLM) was determined by light microscopy evaluation of autoradiographs. With a computer program based on a theoretical model, the percent labelling versus time after injection was used to analyze cell cycle time, cell loss, tumor growth fraction, and potential doubling time. The values calculated from DNA incorporation with BrdUrd agreed well with those obtained from labelling with [3H]TdR, i.e., cell cycle time 2.3 vs. 2.4 d, and growth fraction 67 vs. 70%. The estimated potential doubling time was 3.1 d and cell loss factor 40% by both methods. Flow cytometry analysis of BrdUrd-labelling is considerably faster than the evaluation of [3H]TdR-labelling, and the present results provide further support for the BrdUrd labelling method as a promising alternative to the PLM method in cell cycle studies designed to evaluate the relevance of cell proliferative properties in relation to biological behavior in xenografted head and neck cancer.


Intercalation of anthracyclines into living cell DNA analyzed by flow cytometry. Anthracyclines (ANT) are used in the treatment of leukemia and other cancers. These drugs have been shown to intercalate between the strands of DNA. In the present study, we show that the amount of ANT intercalated into DNA can be determined by measuring the fluorescence resonance energy transfer (FRET) between Hoechst 33342 (H33342) and ANT bound to DNA. The transfer efficiency was found to depend on the amount of disposable ANT but was independent of the amount of H33342 bound to DNA over a wide range of H33342 concentrations. The method was adapted for flow cytometric measurement of FRET in whole living cells and was used to evaluate the degree of intercalation of daunorubicin (DAU) and idarubicine (IDA) into DAU-sensitive and DAU-resistant leukemic cell lines. ANT intercalation into DNA was affected by factors which modify the intracytoplasmic concentration of ANT, and it was shown that the action of ANT and the resistance to ANT could not be attributed solely to the intercalative effect of the drugs. The method has advantages over previously described methods and represents a useful complementary tool in studies on the mode of action of ANT and the mechanisms of chemoresistance.


DNA quantification of squamous cell carcinoma of the oesophagus by flow cytometry and cytophotometric image analysis using formalin fixed paraffin embedded tissue. This is the first comparative study of DNA quantification of oesophageal squamous cell carcinoma by flow cytometry (FCM) and image cytometry (ICM) using formalin fixed paraffin embedded tissue. The potential advantages of ICM include the identification of a reliable control cell population; avoidance of non-tumour stromal and inflammatory cell nuclei, nuclear fragments, degenerate cell nuclei and doublets, triplets etc., which are not possible with FCM using archival tissue. Twenty-eight cases, all of the same stage (stage 2a) and similar grade (well or moderately differentiated) were analysed. The cases were separated into two groups, those that had succumbed to tumour in less than 18 months (group A) and those that were tumour free at least 18 months post-resection (group B). Using ICM all 28 tumours yielded interpretable histograms by comparison to 25 of 28 using FCM. Aneuploidy was identified in 100% of cases in group A using ICM (in comparison to 73% by FCM) and in 73% of group B using ICM (in comparison to 44% by FCM). Any tumour aneuploid by FCM was also aneuploid by ICM. Nine cases aneuploid by ICM were euploid by FCM. The mean 5C exceeding rate (% of cells whose nuclei contain a DNA mass equivalent to > 5 sets of 23 chromosomes) was 21% in group A and 14% in group B (P < 0.01). Euploidy was confined to tumours of those patients disease free for more than 18 months. The conclusions of this study are that: firstly, ICM is superior in its yield of interpretable histograms to FCM using formalin fixed paraffin embedded tissue; secondly, ICM is more sensitive in the identification of aneuploid stemlines than FCM; and thirdly, euploid tumours (as detected by ICM) appear to have a better prognosis than aneuploid tumours of similar stage and grade.


Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease. The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia-related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in 10(3) to 10(4) cells. Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia-associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102). We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia.


[Laparoscopic cholecystectomy: ERCP as standard preoperative diagnostic technique]. In a prospective study 250 patients with proven cholelithiasis and clinical, biochemical and ultrasound indications for laparoscopic cholecystectomy (LC) underwent endoscopic retrograde cholangiography (ERCP) and (if bile-duct stones had been shown) endoscopic papillotomy (EPT). The biliary system was demonstrated in 229 patients (91.6%). Biliary tract stones were confirmed in 18 of 68 patients in whom they had been suspected clinically. In addition, ERCP revealed small stones in the bile-duct in eight of 154 patients with normal biochemical results and unremarkable ultrasound imaging, and in seven patients bile-duct anomalies which required EPT or open cholecystectomy. However, in retrospect five of the patients with cystic duct anomalies could have been treated by LC. The complication rate of ERCP/EPT was 3.2%. It is concluded from these results that, in view of the cost and potential risk to the patient, ERCP before LC can be limited to patients suspected of having bile-duct stones, even though small stones may be missed.


[Diabetic gastroparesis and gallbladder disease. Ultrasound diagnosis after multiple-component meals]. Thirty insulin-dependent diabetics (16 women, 14 men, mean age 37.7 [17-74] years) and 12 controls (eight women and four men; aged 20-58 years) were studied by real-time ultrasound before and after each of three meals to assess gastric and gallbladder motility. The diabetics were grouped according to the results into those without (n = 17) and those with diabetic autonomic neuropathy (n = 13). Antral cross-section provided the criterion for gastric emptying. It decreased significantly more slowly in diabetics with autonomic neuropathy than in the other two groups. The difference during the postprandial observation period of 240 min became the greater the longer the interval after the test meal (multivariance analysis: P < 0.001). Gallbladder emptying, too, was slowest in diabetics with autonomic neuropathy (P < 0.05). These results indicate that abnormalities of gastric and gallbladder emptying in diabetics can be recognized by measuring antral cross-section and longitudinal gallbladder area on fasting and 180 min after a test meal.


[Patent foramen ovale and platypnea after pneumonectomy]. Six months after a pneumonectomy for myeloma, which had preoperatively been indistinguishable from bronchial carcinoma, a 50-year-old man presented with shortage of breath, cyanosis and episodes of syncope on standing or walking, symptoms which improved on lying down (platypnea). On one occasion these symptoms necessitated controlled artificial ventilation, but even at an inspiratory oxygen saturation of 100%, blood gases only partially improved (pCO2 27 mm Hg, pO2 67 mm Hg, O2 saturation 93%). Right heart catheterization in recumbency revealed a right to left shunt at atrial level of 37% of systemic flow. Contrast medium injection into the inferior vena cava near the heart demonstrated cardiac displacement and rotation. Part of the inferior vena cava flow passed into the left atrium via a patent foramen ovale: it is likely that this shunt increased in the upright position. After surgical closure of the patent foramen ovale and partial relocation of the heart (with a vicryl net) the patient has now remained free of symptoms for 5 years.


[Preventive tetanus immunization and avoidance of side effects of booster immunization]. Prevalence of antibodies against tetanus toxoid (tetanus antitoxin titre) was measured in 5,235 males aged 17-60 years, 3,069 (59%) aged 20-22 years. Taking as criterion a threshold value of 0.1 IU/ml, 5,071 (97%) had adequate tetanus immunity. 1,301 of 4,355 aged 21-30 years (30%) actually had antibody concentrations above 6.3 IU/ml. Booster injections are especially contraindicated in this latter group because of the danger of side effects with further toxoid doses. Thoughtless routine booster immunization should therefore be avoided.


[Incidence, frequency and resistance characteristics of methicillin-oxacillin resistant Staphylococcus aureus strains in Germany]. In a multicentre study, the methicillin-resistant Staphylococcus aureus (MRSA) isolates in 19 large clinics in Germany were recorded, and the resistance characteristics of these strains were studied. Oxacillin-mannitol-salt agar plates were distributed to all participants to ensure uniformity of screening, and each laboratory used these plates to investigate 200 consecutive Staphylococcus aureus isolates for oxacillin-methicillin resistance. Of the 3,794 evaluable Staphylococcus aureus isolates, 71.5% were penicillin and 3.7% (142) oxacillin resistant; four study centres reported methicillin-oxacillin resistance rates of more than 5%. Of the MRSA isolates, 75% were also resistant to ciprofloxacin, 61% to fosfomycin, 52% to imipenem, 50% to trimethoprim/sulfamethoxazole and 36% to clindamycin. All isolates were sensitive to vancomycin and teicoplanin. Of the Staphylococcus aureus strains isolated from patients in intensive therapy units, 10.4% were methicillin-oxacillin resistant. Drains and catheter tips (9.8% and 5.2% respectively) were the materials with the highest proportions of MRSA. Of the MRSA isolates in this study, 58.2% belonged to lysis group II.


[Bronchobiliary fistula in carcinoma of the hepatic duct bifurcation]. Carcinoma of the hepatic duct bifurcation was diagnosed in a 67-year-old women with obstructive jaundice. As metastatic spread could not be demonstrated the carcinoma was removed with a view of achieving a cure (hemihepatectomy, resection of the hepatic duct and the bifurcation, cholecystectomy and hepatojejunostomy). Histological examination indicated adenocarcinoma of the biliary tract. Seven months postoperatively the patient was found to be cachectic and cough up greenish liquid sputum. Bilirubin concentration in sputum was 500 mumol/l. There was no jaundice and total bilirubin concentration was 33 mumol/l. Alkaline phosphatase was 508 U/l, but GOT and GPT were normal (23 U/l and 21 U/l). Computed tomography confirmed the clinical diagnosis of a biliobronchial fistula. The patient died 9 days after renewed hospitalization of tumour cachexia. The biliobronchial fistula was found at necropsy.


[Intracerebral gliofibroma].

[Intracerebral gliofibroma]. A 14-month-old girl had three epileptiform attacks in the course of 6 months, each consisting of rhythmic movements of the right arm and right hand of 5 minutes' duration, followed by a 15-minute period of weakness. There were otherwise no abnormal neurological signs. Prenatal and perinatal development had been uneventful and the mother was healthy. Computed tomography showed a tumour in the left frontoparietal region. Surgery revealed an intracerebral tumour 7 cm in diameter with two large cysts; it was not sharply demarcated from the brain parenchyma, had no connection with the dura and was not infiltrating the ventricular system. The tumour was completely removed and at follow-up 18 months later there was no evidence of recurrence. Histological and immunohistochemical investigations showed that the tumour consisted of closely interwoven astrocytes and fibroblasts, two different cell types the latter of which does not normally occur in the brain. Exact immunohistochemical analysis of the components of a tumour is important because, unlike pure glial tumours, gliofibromas have a good prognosis after complete resections.


[The helminth fauna of the red fox (Vulpes vulpes LINNE, 1758) in Nordhessen and Ostwestfalen. 2. Nematodes]. Between November 1989 and June 1990 a total number of 397 foxes were examined for the presence of nematodes in the stomach and the small intestine and 403 foxes for the presence of Trichinella spiralis larvae. The animals came from the districts of Kassel, Arnsberg and Detmold. In 32.7% of the foxes infections with Toxocara canis were found, in 11.1% Toxascaris leonina, in 3.8% Ancylostoma caninum, in 3.5% Uncinaria stenocephala and in 2.3% Capillaria species. In most cases the number of nematodes per fox was low. Only Toxascaris leonina was frequently found with more than 20 specimen per animal. Trichinella spiralis larvae were not found in any of the foxes.


Comparative studies on hydatidosis in farm animals in Egypt. A survey on the frequency of hydatid disease in animals slaughtered in Cairo abattoir revealed that the percentage in camels, sheep, pigs, cows and buffaloes attained 31.0%, 1.33%, 4.62%, 0.0% and 0.0% respectively. In camels and pigs the lungs were the main predilection sites of hydatid cysts, while in sheep the liver was the most infested organ. The wall thickness of the cysts was different according to the host species and the location of the cyst. The parasitic membrane of the cysts collected from camels consisted of two layers, an outer layer rich with mucopolysaccharides, and an inner germinal layer; some of its cells were rich with glycogen others were charged with lipids; the latter were mainly concentrated at the origin of the brood capsule. Hydatid cysts from camels showed a large number of calcareous bodies which stained deeply with both von Kossa stain and alcian blue stain. The majority of the examined cysts from sheep showed non-fertile germinal membranes. The most characteristic feature observed in the cysts collected from pigs was the presence of large amounts of fat droplets.


[Comparison of IgG determination in foals using commercially available rapid tests]. The three tests (EQUI Z-Test, AGLUTINADE FOAL IMMUNITY, CITE Foal IgG-Test) were evaluated for their accuracy and usefulness in the field. Single radial immunodiffusion was used as reference method. All tests were easily and rapid to perform and results were obtained within a few minutes. It was easy to get the results of the CITE Foal IgG-Test, but use of the EQUI Z-Test and the FOAL AGLUTINADE IMMUNITY-Test needed some practice to get correct results. Results obtained by the CITE Foal IgG-Test correlated to single radial immunodiffusion in 94%, those obtained by FOAL AGLUTINADE IMMUNITY-Test in 74.1% and those obtained by EQUI Z-Test in 57.1%. Best results with a correspondence of 97.1% (CITE Foal IgG-Test) and 100% (EQUI Z-Test) were seen in the group having > 800 mg IgG/100 ml and in the group having < 200 mg IgG/100 ml with 93.3% (CITE Foal IgG-Test) and 82.1% (EQUI Z-Test). The AGLUTINADE FOAL IMMUNITY-Test had the same accuracy in all groups (70.9%-77.8%).


[Sonography during the pregnancy of sheep. I. Fetometry for the determination of the stage of gestation and prediction of the time of parturition]. Transrectal and transcutaneous ultrasonography was performed on 187 pregnant Merino ewes to measure the growth of fetal parameters (fetometry) such as the diameters of the eye, braincase and trunk, the width of one rib with its intercostal space and the crown-rump-length (CRL). In the ewes, cross and longitudinal diameters of the intrauterine lumen around the embryo and fetus were determined. Trunk diameter and crown-rump-length of embryos and fetuses were sonographically determined from Day 26 and size of eyes, braincase and ribs were measured from Day 52 to 66 of gestation. Embryonic resp. fetal parameters and uterine diameters showed almost linear growth rate. Relationship between the measured parameters and days of pregnancy is described by regressions and correlation coefficients. Correlation coefficient between gestational stage and the diameter of the trunk was very narrow (r = 0.98) and between gestational stage and the crown-rump-length resp. eye diameter equalled 89% (r = 0.89). These fetal parameters are appropriate to assess gestational age and growth of ovine fetuses. It can be concluded that sonographic fetometry in the ovine can be valuable for the evaluation of fetal development, the estimation of gestational age and the prediction of parturition dates.


[The relationships between the internal and external pelvic measurements of Schwartzbunt cows]. 1118 Friesian cows and 101 Friesian heifers were investigated in internal pelvic measurements and their relationships to external measurements. The mean of the pelvic vertical and the medium diagonally diameter of the pelvis are 19.8 cm and 18.3 cm. 363.9 square centimetres and 76.3 centimetres were found for the pelvic surface and pelvic circumference. The difference between the biggest and smallest pelvis was 295.0 square centimetres. Medium to high coefficiences of correlation were detected between the internal pelvic measurements but relationships between internal and external pelvic measurements were low. From determined external pelvic measurements only the hip breadth provides usefull informations of the pelvic shape.


[Birth weight and measurements of various body parts of stillborn calves of a large dairy cattle herd]. Stillborn calves (80 animals) originating from one dairy herd were used for studies on allometric measures in newborn calves. In the first approach some factors were neglected and only the effect of the calves' sex was considered. Differences in mean birthweight between male and female calves were reflected in organ and other body constituent weights too, but with different relations between them. Enlarged thyroid glands could be observed in both sexes but more often in female calves meaning that there is no correlation between thyroid size and body weight. Strong correlations of bones, muscles and outer body measures and looser ones of internal organs (thymus, liver, lung, kidneys, spleen) and endocrine glands (adrenal glands) with body weight were found especially in male calves. In some calves the sometimes enlarged liver looked like a fatty liver with its pale yellowish appearance and crumbly consistency.


[Campylobacter as the cause of diarrhea in calves]. The modified Preston medium allows the isolation of C. jejuni, C. coli and C. fetus subsp. fetus from intestinal samples of calves at an incubation temperature of 37 degrees C. In the first series of investigation, Campylobacter excretion in calves (n = 7) was followed up to the age of 4 months. In the first 4 days of life, these bacteria could not be detected in any of the animals. Thereafter first C. coli we found in all calves. In 4 animals, only strains of this species were isolated during the whole investigation period. In 3 animals C. fetus subsp. fetus could be detected repeatedly, however C. coli and sometimes C. jejuni were found, too. In the second series of investigation, isolation of Campylobacter from different parts of the gastrointestinal tract or organs was successful in 19 out of 25 diarrhoeal, moribund calves. 16 out of 19 positive animals harboured large amounts of these gramnegative bacteria in the distal jejunum and ileum. In 10 animals out of these 16, the germ colonized also the proximal jejunum and abomasum. From 6 calves, C. fetus subsp. fetus was isolated, and C. jejuni from 7 calves. C. coli was relatively rare. From the lymph nodes of the proximal and distal jejunum, Campylobacter (exclusively C. jejuni) were isolated from 5 animals. Due to the Campylobacter presence in the small intestine of diarrhoeal calves, a contribution of this bacteria within the pathogenesis of calf diarrhoea is possible. Final evaluation of their pathogenesis importance is only positive by means of virulence tests.


[Skeletal muscle samples from slaughtered bodies of swine in student laboratories for the study of muscle physiology]. Viable, excitable and contractile samples from gracilis muscle of pig carcasses were used in our student laboratory of muscle physiology. Samples were taken about 20 minutes after stunning. Sampling, transport of the samples and equipment are described. Some examples of registered isometric contractions are shown.


Monensin poisoning in dromedary camels.

Monensin poisoning in dromedary camels. Four female fistulated camels (Camelus dromedarius), 4-5 years of age, were each given two grams of 10% monensin intraruminally daily for six days to study the effect of monensin on the rumen fermentation pattern. Signs of toxicity appeared on the sixth day, and included depression, anorexia, muscular weakness, inability to stand, salivation and regurgitation of ruminal contents. On the eighth day, two animals died. The ruminal contents were replaced in the survivors, but they died on the tenth and eleventh day from the start of the experiment.


[An unusual tumor of the nictitating membrane gland of dogs-- a case report]. A tumor of the third eyelid gland was diagnosed in a 13 year old female Chihuahua. Histopathology of the excised tissue revealed an apocrine adnexoma with squamous metaplasia. The literature regarding prolapse and tumors of the third eyelid gland was reviewed. No case with similar morphology to this tumor was described to our knowledge.


Successful pretreatment/therapy of soman, sarin and VX intoxication. Chemical pretreatment is effective against a 2 LD50 challenge of soman, sarin or VX or a 5 LD50 challenge of tabun. Chemical pretreatment followed by post challenge therapy should be effective against greater levels of agent. Such tests in guinea pigs are reported here; pretreatment regimens (PRGs) consisted of physostigmine (0.15 mg/kg, im) and an adjunct. The adjuncts [mg/kg, im] used were aprophen [8], atropine (AT)[16], azaprophen (AZA)[5], benactyzine [1.25], benztropine (BT) [4], scopolamine [0.08] and trihexyphenidyl [2]. Pretreatment was given 30 min before, and atropine (16 mg/kg, im) and 2-PAM (25 mg/kg, im) therapy (T) at one min after, 5 LD50s of agent. Results indicate that, all of the PRG+T regimens, except BT-not tested with T, prevent lethality by soman; trihexyphenidyl and scopolamine (the only adjuncts used therein) regimens each prevent lethality by sarin and VX. Against soman, all PRG+T regimens (vs PRG only) may shorten the median recovery time to 2 hrs or less. Even without therapy, the PRGs containing AT, AZA or BT prevent lethality by 5 LD50s of soman; however, used alone, only the PRG containing AZA reduces the incidence of convulsions at this level of soman.