Comparative thrombolytic properties of tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (u-PA) and K1K2Pu (a t-PA/u-PA chimera) in a combined arterial and venous thrombosis model in the dog. The chimeric molecule K1K2Pu, comprising the two kringle domains (K1 and K2) of tissue-type plasminogen activator (t-PA) and the COOH-terminal region with the serine protease domain (Pu) of urokinase-type plasminogen activator (u-PA), was previously shown to have a 5- to 10-fold reduced clearance rate with maintained specific thrombolytic activity, resulting in an increased thrombolytic potency in animal models of venous and arterial thrombosis. To document the thrombolytic potential of K1K2Pu, the thrombolytic potency and fibrin specificity were studied in a combined platelet-rich arterial eversion graft thrombosis and venous whole blood clot model in heparinized dogs (100 U/kg bolus and 50 U/kg per h infusion). Dose-response effects of bolus injections of K1K2Pu (0.032 to 0.25 mg/kg) were compared with those of recombinant t-PA (rt-PA) and of recombinant single chain u-PA (rscu-PA) (0.25 to 1.0 mg/kg each) in groups of five or six dogs, each given heparin with or without the thromboxane synthase inhibitor/prostaglandin endoperoxide receptor antagonist ridogrel. Heparin and ridogrel in the absence of a thrombolytic agent did not produce arterial reflow or venous clot lysis in five dogs. Addition of K1K2Pu, rt-PA or rscu-PA resulted in a dose-dependent induction of arterial reflow and of venous clot lysis in the absence of systemic fibrinolytic activation and fibrinogen breakdown. Consistent arterial reflow required 0.063 mg/kg of K1K2Pu and 0.5 mg/kg of rt-PA or of rscu-PA. The thrombolytic potency for venous clot lysis, expressed as percent lysis per mg compound administered per kg body weight, was (mean +/- SEM) 750 +/- 160 for K1K2Pu, 68 +/- 17 for rscu-PA (p less than 0.001 vs. K1K2Pu) and 110 +/- 29 for rt-PA (p less than 0.001 vs. K1K2Pu). The plasma clearance rates were significantly lower for K1K2Pu than for rscu-PA and rt-PA. In the absence of ridogrel, arterial reflow was significantly slower and was followed by cyclic reocclusion and reflow; however, venous clot lysis was unaffected. Template bleeding times were not significantly altered in the absence but were markedly prolonged in the presence of ridogrel. These results confirm and establish that, when given as a bolus injection, K1K2Pu has an approximately 10-fold higher thrombolytic potency for arterial and venous thrombolysis than does rt-PA or rscu-PA. Thrombolysis with K1K2Pu is obtained in the absence of systemic fibrinolytic activation and fibrinogen breakdown. These properties suggest that K1K2Pu offers potential for thrombolytic therapy by bolus administration in patients with thromboembolic disease.


Angle classification revisited. 1: Is current use reliable? The Angle method for the classification of malocclusion has been the standard in orthodontics for 100 years, but many academics and private practitioners find difficulty applying the Angle system to malocclusions in between fully Class II and fully Class III. To evaluate whether orthodontists are consistent in classifying malocclusions accordings to Angle's method, study models were selected of three patients with ideal buccal occlusions, two patients with mutilated occlusions, and five patients with varying degrees of Class II tendency. One buccal view was photographed of each study model, and a questionnaire was printed and sent to 347 orthodontists. The 77.8% response demonstrated significant interest in the subject of dental classification and significant disagreement among orthodontists in their classification response with all patients except the two obvious ideal occlusions. Respondents were given the opportunity to comment on Angle classification and their recommendations for improved classification techniques. Many of their comments are quoted.


Attitude change towards mental illness during nursing education--a cross-cultural study of student nurses in Korea, Republic of China and Japan. This is an initial report of a cooperative project by colleagues in Korea, the Republic of China (Taiwan) and Japan, involving the measuring of attitudes toward mental illness. The discussion mainly revolves around the influence of mental health education in nursing on attitudes towards mental illness. The subjects' attitudes were assessed by Wig's profiles. The attitudes of freshmen who had just entered nursing schools and seniors who had already finished clinical training in psychiatry were compared to measure the attitude change during the course of nursing education, if any. Non-medical students served as a control group. As a result, a seemingly "negative and pessimistic" attitude was demonstrated in the senior student nurses. The findings are examined and discussed.


Epidemiology of dengue/dengue hemorrhagic fever in Malaysia--a retrospective epidemiological study. 1973-1987. Part II: Dengue fever (DF). Dengue fever (DF) has been endemic in Malaysia since 1902 and reached epidemic proportions in 1973. The incidence rate of the disease in 1973 was 5.4 cases per 100,000 and reached 10.4 cases per 100,000 in 1987. The Chinese are the main ethnic community affected showing an overall morbidity rate of 9.0 cases per 100,000 followed by Malays 2.9 cases per 100,000 and Indians 2.4 cases per 100,000. The ethnic race ratio between Chinese, Malays and Indians which was 3.7:1:1.3 in 1975 reached 3.7:1:0.9 in 1987. The attack rates were observed to be higher in the males. The mean male:female ratio among Chinese was 1.1:1, while for Malays and Indians it was 1.5:1. The age-specific morbidity rate was highest in the 10- to 19-year age group followed by the 20- to 29-year age group. Epidemics of dengue fever were found to occur seasonally with the appearance of two peaks, viz. one in June and the other in August. Dengue fever, a rural disease before, has established itself as an urban disease.


Prevalence of hepatitis B surface antigen and antibody among health care employees in Negri Sembilan, Malaysia, 1989. This study was based on a hepatitis B screening program conducted in one of the states in Malaysia in 1989. The majority (84.6%) of the 2986 health employees were screened. One quarter (25%) was found to have serological markers for the Hepatitis B Virus (HBV); 2.1% had Hepatitis B surface Antigen (HBsAg) and 22.8% had antibody to the Hepatitis B surface Antigen (anti-HBs). The occurrence of HBsAg was higher in ethnic Chinese (6.3%) compared to Malays (1.8%) and Indians (0.9%), even when analyzed by sex, but not with age, type of institution and geographical locality. The distribution of anti-HBs was higher with ethnic Chinese (41.6%), male sex (27.2%) and age. There was a wide variation of the prevalence of serological markers among occupations and increased relative risks of HBsAg were found among medical assistants (RR3.7; 95% CI 1.4-9.1) and laboratory staff (RR 3.2; 95% CI 1-8.8), and that of anti-HBs among medical assistants (RR 2.8; 95% CI 1.8-3.7). The variations of HBsAg among occupations by type of institutions was marginal while that of anti-HBs was higher among attendants and midwives in hospitals, medical assistants in health departments, and assistant nurses and dentists in dental centers. The patterns of distribution of serological markers of HBV among health staff reflect the situation in the community with high endemicity and resemble specific occupational factors noted in previous studies in the West.


End-stage renal disease (ESRD) in Saudi Arabia. Information was collected on patients with End-stage Renal Disease (ESRD) receiving maintenance dialysis in all of the dialysis facilities in Saudi Arabia. Similar information was also collected from the Saudi Arabian government-sponsored patients with ESRD in the United States between December 1985 to March 1986. As of March 31, 1986, 806 Saudi patients were on maintenance hemodialysis and 16 on peritoneal dialysis in hospital-based dialysis facilities in Saudi Arabia. The prevalence rate of ESRD was 139/million at the completion of the study. The rates increased with age and were similar when compared on a regional basis, but were higher in the rural areas for both sexes in all regions except the Southern Region. Here, the prevalence rates for the female urban residents were higher than for female rural residents. Although primary health care services are available in rural areas, a delay was noted in seeking medical care. This was attributed to the possible lack of health education, knowledge of the disease and information on the availability of the health services. Upon completion of this study, it was concluded that a need exists for further research in all aspects to delineate the role of the various factors that affect ESRD in Saudi Arabia, with the universal goal of preventing development of the disease in the population.


Successful use of pooled sera to estimate HIV antibody seroprevalence and eliminate all positive cases. Pooling specimens when testing them in large numbers can save scarce resources and several earlier reports have indicated this to be a feasible strategy. In an HIV antibody mass screening test carried out in our laboratory, we used Dorfman's two-stage model. We sought to establish the optimal number of specimens in a pool, and to achieve maximum efficiency while maintaining both sensitivity and specificity. Before testing for HIV antibody, five positive samples were placed in a set of 1012 sera in a double blind manner, one positive sample into a second set of 1012 sera and none in a third set. The positive rate was assumed to be 0.2% for each set of 1012 sera. As indicated by our model, 22 individual serum samples were placed into each of 46 pools which, when tested by particle agglutination assays, lead to the identification of all positive samples. We concluded that the prevalence rate can be estimated in the first stage, 95% confidence intervals were given, and the efficiency rate could be calculated for the identification of all infected specimens in a large number of samples showing low prevalence rates.


Chronic arsenic poisoning from well water in a mining area in Thailand. Endemic arsenic poisoning manifested by palmoplantar keratoderma and hyperpigmentation was surveyed in a village in a tin and wolfram mining area in southern Thailand where two cases of Bowen's carcinoma had occurred. Nine percent of examined adults randomly selected from 58 households were found to have skin manifestations of arsenic poisoning. Also, children with typical palmoplantar keratoderma were recognized, the youngest being four years old. A seven-year-old with severe keratoderma also had neurological manifestations and appeared mentally retarded. Arsenic concentration in shallow wells varied between 0.02-2.7 mg/l (average 0.82), and piped water had 0.07 mg/l. A major source of the contamination of ground water probably was slag heaps positioned next to a stream that fed the village.


Maternal hair zinc and neural tube defects: no evidence of an association from a case-control study in Western Australia. In a case-control study of isolated neural tube defects in Western Australia, zinc was estimated by flame spectrophotometry in post-partum hair specimens from 54 mothers of infants with neural tube defects, and from 128 mothers of normal infants. The distribution of the estimates of zinc was divided into quartiles. Using the lowest quartile as the reference group, the crude odds ratios (and their 95% confidence intervals) for quartiles two through four were 1.07 (0.44, 2.59), 1.02 (0.41, 2.56), and 0.70 (0.28, 1.73). Adjustment for several potential confounding variables (parental country of birth, social class, previous pregnancy outcome, interval between previous and index pregnancy, pregnancy order, and interval from birth to interview) made little difference to the odds ratios. This study provides no evidence of an association between post-partum, maternal hair zinc and offspring with neural tube defects.


Impact of Urban Basic Services on immunization coverage in a slum area of northern India. The Urban Basic Services (UBS) programme was launched in some of the urban slums in the major cities of India in the year 1986. The main objective of the Urban Basic Services (UBS) Program is to improve and upgrade the quality of life of the urban poor, particularly the women and children. The major thrust area under the UBS programme includes child survival and development, learning opportunities for women and children, water and sanitation, and community organization. The present study attempts to find out the impact of the UBS Program in terms of the immunization coverage carried out in slums covered by UBS and comparing it with non-UBS slums using the 30-cluster sampling technique as suggested by WHO. The percentage of fully immunized children was higher (16.2%) in the UBS slums compared to 10.9% in non-UBS slums. The immunization coverage of children was slightly better in the UBS slums for BCG, DPT and Oral Polio Vaccines, while for measles it was 18.6% in UBS slums and 11.9% in non-UBS slums. The dropout rates for I to III doses of DPT was much higher (36.4%) in non-UBS slums as compared to 28% in UBS slums. The availability of immunization cards was found to be higher in both mothers (16.7%) and children (22.4%) in UBS slums compared to the non-UBS ones (5.2% and 8.6% respectively). The slums thus covered under the UBS program have done marginally better in immunization but it appears that to assess the overall impact of UBS, all the components of services and not merely immunization should be assessed.


[Free radicals in silicosis].

[Free radicals in silicosis]. The prolonged inhalation of silicon powders induces an oxidative stress at respiratory system level, due to the formation of free radicals (FR). Free radical origin is either exogenous (as a result of the chemical structure of powders) or endogenous (result of the endocytosis of silicon powders). Bivalent Fe ions are implied in FR generation, and the substances with Fe chelating and antioxidizing actions block the evolution of silicosis.


[A subcutaneous thoracic abscess due to the aspiration of an ear of grain]. The paper deals with a child aged 9 years, with spastic then productive cough and moderate haemoptysis. X-ray picture shows a condensation process at the bottom of the right hemothorax. A subcutaneous abscess is registered 10 days after hospitalization. At the abscess incision, a wheatear inhaled previously by the child is found out.


[The characteristics of bacterial respiratory infections in patients with humoral immunodeficiencies]. The paper deals with 8 cases of different forms of bacterial respiratory infections (bronchiectasis, pleuropneumonia, tuberculosis), in which humoral immune deficits were noted: 2 dysgammaglobulinemia with IgA absence, 3 hypogammaglobulinemia with IgG deficit as well as IgA and IgM absence, 2 hypogammaglobulinemia with IgG and IgM deficit and IgA absence, and 1 hypogammaglobulinemia with IgA absence and IgM deficit. Stress is laid on the indications given by the antibody titer research, the pleural exudate hypoproteinemia being also added to those already known. A correct chemotherapy associated with the substitution treatment proved to by efficient.


HIV, international travel and tourism: global issues and Pacific perspectives. AIDS, like plagues throughout human history, has been blamed repeatedly on foreigners. This has heightened ramifications, from the personal to the geopolitical, in an era of escalating population movement and rapid international travel. By the end of 1990, the World Health Organization had estimated that the total number of AIDS cases worldwide was close to 1.3 million. Recent estimates suggest that by the year 2000, 38-100 million adults and over 10 million children will have been infected with HIV. Seventy-five to eighty-five percent of that number will be from the developing world. AIDS has rapidly become pandemic, with wide-ranging consequences for humankind. Human population movement is an important component in the natural history of AIDS. With respect to this, a central consideration is the relationship between AIDS and international travel, especially tourism. In this paper, after reviewing HIV in the Asia-Pacific region, we present the epidemiology of HIV in the Pacific Islands, discuss its impact with particular reference to population movement, and explore some of the specific challenges that the Pacific Island region faces.


[Pulmonary involvement in scleroderma].

[Pulmonary involvement in scleroderma]. The paper deals with 3 cases of sclerodermia with pulmonary determinations detected by clinical, radiological, functional and histopathological means, of diffuse interstitial fibrosis type. The association with bronchopulmonary cancer is pointed out in one case only.


[Diagnostic methods in allergic asthma]. Analysis of the allergic component in asthma results in a critical comparison of the data provided by the interview, skin tests, possibly completed by carefully selected immunological tests and/or bronchial or nasal stimulation tests. For some allergens, it is also possible to study the allergenic environment of these patients. The skin tests allow an easy analysis of the skin mastocytes carrying specific IgE and degranulating after the allergenic extract has been introduced. Among the in vitro tests, phadiatop represents a screening test of respiratory allergies which is more reliable than total IgE assays. Specific serum IgE assays should be reserved for difficult or conflicting cases. Bronchial allergen stimulation tests confirm the etiopathogenic role of an allergen. A few examples of diagnostic strategies are presented.


[The routine diagnosis of the distal obstructive syndrome (DOS)]. The diagnosis of distal obstructive syndrome (DOS) is based on the test of lung ventilation function. The tests applied (FEF25-75, MEF50, MEF25) are more sensible than in the routine spirography exploration (FEV1, FEV1.0 x 100/VC), because they evaluate the efficiency of ventilation in those conditions in which the force of the respiratory muscles plays a secondary part and, therefore, cannot hide a flow decrease caused by the obstruction of small pathways (less than 2 mm in diameter). FEF25-75 is measured on the same forced maximum expirogram as FEV1.0. MEF50 and MEF25 are parameters derived from the flow-volume curve. The introduction of these tests into the routine exploration of pulmonary ventilation will improve considerably the diagnosis of early COPD forms.


Increased plasma removal of microemulsions resembling the lipid phase of low-density lipoproteins (LDL) in patients with acute myeloid leukemia: a possible new strategy for the treatment of the disease. A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice.


Serum concentrations of insulin-like growth factor-I and proteoglycan synthesis rates in young rats: a comparative study between the regional diet of São Paulo state and casein diets. Insulin-like growth factor-I (IGF-I), also known as somatomedin-C, is an important mediator of growth regulation. Serum concentrations of IGF-I and proteoglycan synthesis rates in the tibial epiphysis, an estimate of the biological response to IGF-I in a target tissue, were compared in weanling Wistar rats fed ad libitum (group 1) and with 50% restriction (group 2) with the regional diet of São Paulo State (RDSPS--a mean diet consumed by low-income families with rice, beans, sugar, meat, milk, fruits and other vegetables) and in pair-fed animals fed with casein diets (groups 3 and 4). Data are reported as mean +/- SD for 8 rats in each group. Proteoglycan synthesis rates (cpm/mg) were significantly higher in rats fed with the RDSPS-based diet (groups 1 and 2: 210.8 +/- 58.8, 136.6 +/- 17.6) than in pair-fed animals fed with an 11% casein diet (groups 3 and 4: 62.9 +/- 11.6, 37.7 +/- 13.7) and in control animals fed ad libitum with a 20% casein diet (group 5: 58.1 +/- 22.7). Furthermore, these rates were higher in animals fed ad libitum than in those fed with the same diets but with 50% restriction. However, similar differences between groups 1 to 4 were not observed in serum concentrations (ng/100 microliters) of IGF-I (group 1: 44.1 +/- 7.1; group 2: 40.8 +/- 3.8; group 3: 46.0 +/- 3.6; group 4: 41.6 +/- 3.4, and group 5: 63.2 +/- 7.8). These results suggest that serum IGF-I levels are not reliable indicators of IGF-I status in this experimental model.


[The epidemiological aspects of tuberculous pleurisy in Romania]. The re-organization of the Tb network in Romania, which took place after 1948, made possible a gradual accumulation of a number of data on the epidemiological surveillance of the territory, including the tuberculous pleurisies. The incidence of tuberculous pleurisies showed a decrease from 30.7/100,000 to 4.2/100,000 between 1958 and 1985, followed by a "stagnation" at 4.3/100,000 for 1986-1989. In 1990, the incidence of Tb pleurisy reached 6.8/100,000. The weight of pleural localization among the respiratory ones was maintained 15%-13% for 1960-1980, with a subsequent diminution up to 7.9% in 1989. By age-groups, the incidence of Tb pleurisy was at its highest level (19.1/100,000) at the age of 20-24 years in 1990 (as well as in 1972, 1980 and 1985). The present time imperative is the improving of the etiological diagnosis of pleurisies by a larger accessibility to the histological (pleural biopsy puncture) and bacteriological investigations.


Phagocytosis of enteropathogenic Escherichia coli and Candida albicans by lectin-like receptors. 1. Ingestion of enteropathogenic Escherichia coli or Candida albicans by thioglycollate-elicited macrophages and polymorphonuclear leukocytes was investigated in vitro, 2. Goat antiserum against mannose receptors caused about 50% inhibition of E. coli phagocytosis and about 90% inhibition of C. albicans phagocytosis. 3. E. coli and C. albicans uptake was inhibited by about 60% and 98%, respectively, by plating the macrophages onto substrates coated with poly-L-lysine-mannan. Further addition of 50 mM mannose to the medium significantly increased the inhibition of phagocytosis of E. coli by macrophages from 60.7 +/- 1.5 to 79.8 +/- 13.1 and by polymorphonuclear cells from 58.9 +/- 3.7 to 88.7 +/- 4.9. 4. Preincubation of phagocytic cells with antiserum against substance A of human erythrocytes reduced E. coli ingestion by 95%, but this inhibition was not observed when the antiserum was incubated with N-acetylgalactosamine (50 mM) before being added to the phagocytes. The phagocytosis of C. albicans was not inhibited by anti-substance A antiserum. 5. The phagocytosis of E. coli was inhibited by about 25% by the addition of 7.8 micrograms/ml soluble mannan to the medium, and by about 50% by the addition of 50 mMN-acetylgalactosamine; when both substances were added to the medium, an additive inhibition of about 75% was observed. 6. These results indicate that mannose receptors on the surface of phagocytic cells mediate E. coli or Candida albicans uptake and that the binding of bacteria to N-acetylgalactosamine residues from the membrane of phagocytes is also involved in the phagocytosis of E. coli.


A comparative study of resistance to MHV3 infection in genetically homogeneous and heterogeneous mouse populations. Resistance to MHV3 infection was investigated in genetically homogeneous inbred (A/J, BALB/c) and genetically selected (High, Low) mouse lines. The A/J and L lines are resistant and the BALB/c and H mice are susceptible. The genetic analysis was performed on the F1 hybrids, as well as on the genetically heterogeneous F2 populations and backcrosses bred from HxL and A/JxBALB/c lines. The mortality rates of the F1 hybrids showed codominance of susceptibility and resistance characters. The results indicate that the same MHV3 susceptibility genes are present in isogenic and selected lines and corroborate previous results showing that at least two major genes are involved in the control of this response.


[The therapeutic prospects of patients with bronchopulmonary cancer]. By means of a retrospective analysis on 405 cases found out as having bronchopulmonary cancer, the therapeutical possibilities on fixing the diagnosis were evaluated. The therapeutical attitude indicated by pre-established criteria and the therapeutical line adopted were also analysed. The low percentage (25%) of cases with favourable therapeutical perspectives at case finding, as well as the high percentage (75%) of cases found out in stages therapeutically beyond treatment are pointed out. Several non-concordances between recommended and applied therapies are discussed.


Anti-anaphylactic and anti-inflammatory effects of ternatin, a flavonoid isolated from Egletes viscosa Less. Ternatin, a tetramethoxy flavone isolated from Egletes viscosa Less (Compositae), was tested for its efficacy in modulating mouse passive cutaneous anaphylaxis (PCA) and rat carrageenan-induced pleurisy. Ternatin (12.5, 25 and 50 mg/kg, ip) caused a dose-dependent inhibition of IgG antibody-mediated 1.5-h homologous PCA as well as IgE antibody-mediated 48-h homologous PCA in 2-month old mice (N = 5 per group). The inhibitory activity of ternatin was more potent on IgE-mediated PCA (47-79%) than on IgG (45-59%). In the rat carrageenan pleurisy test, ternatin (25 and 50 mg/kg, ip) reduced the response to carrageenan at 5 h both by decreasing exudate volume (33-40%) and leukocyte number (60%) in 5-6-month old rats (N = 6 per group). In contrast, indomethacin (2 mg/kg, po), a known cyclooxygenase inhibitor, showed greater potency in the inhibition of exudate volume (57%) and leukocyte number (77%). These results show that ternatin has both anti-inflammatory and anti-anaphylactic properties and suggest that it may be a useful alternative to anti-allergic drugs of the disodium cromoglycate (DSCG) type for use in bronchial asthma.


[The efficacy of ethambutol compared to streptomycin in the initial quadruple phase of short-term regimens]. In order to test comparatively SM and EMB efficacies within quadruple regimens of short-term chemotherapy, two groups of patients with pulmonary tuberculosis at first treatment, sputum positive under microscopic examination, were constituted through randomization. One group (59 cases) was submitted to the standard regimen RHSZ 2/7, and the other (61 cases) to RHZE 2/7. Group structure was homogeneous from the standpoint of case repartition, according to the anatomo-radiological form, therapeutical regimen, and sensitivity to Tb drugs. Both bacteriological and radiological clinical evolutions show, even in the conditions of a short-time interval (2 months), a similar efficacy of SM and EMB within the quadruple regimens in the initially intensive phase of anti-Tb treatment. It is possible that the results may be dependent upon the concomitantly bactericidal action of: rifampicin, hydrazide and pyrazinamide. Therefore, a further testing of the comparative efficacy of the triple regimen RHZ 2/7 with the quadruple RHSZ 2/7 and RHZE 2/7 during a longer follow-up is required.


Canatoxin induces activation on mice peritoneal macrophages. Canatoxin (CNTX), the toxic protein from Canavalia ensiformis seeds, injected into the peritoneal cavities of mice (10 micrograms/cavity) induced a significant neutrophil migration (10.5 +/- 0.5 x 10(6) cells/cavity) after 4 h. A later migratory effect (48 h) on mononuclear cells, predominantly macrophages, was also observed (controls: 7 +/- 0.9; CNTX: 17 +/- 2.0 x 10(6) cells/cavity). These CNTX-elicited macrophages, when compared to resident cells (R) or cells elicited by thioglycollate (TG), had an increased content of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (R: 4.5 +/- 0.5; TG: 7.2 +/- 1.0; CNTX: 20.2 +/- 3.0 mU/10(6) cells) and a greater (> or = 100%) phagocytic activity. The data suggest that CNTX-stimulated macrophages presented some characteristics of activated cells.


Effects of mercury on the contractility of isolated rat cardiac muscle. The effects of increasing concentrations of mercury (Hg2+) chloride (1, 2.5, 5 and 10 microM) were studied on isometrically contracting papillary muscles from female rats (Wistar, EPM strain) weighing 150 to 180 g. Hg2+ promoted an increase of 12.7 +/- 2.2% in the developed force at 1 microM. At 2.5 microM, force values were similar to control, decreasing progressively as Hg2+ concentration increased to 5 (-13 +/- 6.4%) and 10 microM (-37 +/- 12.3%). Potentiated post-rest contractions (PRC) were also determined after 15-, 30- and 60-s pauses. There was a progressive reduction of the potentiated PRCs relative to their respective steady-state control contractions with increasing concentrations of HgCl2. Since in several tissues including myocardium Hg2+ inhibits the activity of Ca2+ and Na(+)-K(+)-ATPases the results described here suggest that Hg2+, at lower concentrations, could increase force by inhibiting Na(+)-K(+)-ATPase, while at higher concentrations Hg2+ would decrease relative PRC potentiation by inhibiting sarcoplasmic reticulum Ca(2+)-ATPase.


[The incidence of the loss of work capacity in chronic respiratory diseases within the area of Hunedoara County]. Within the highly polluted area of the Committee for medical valuation of work ability--Deva, with 186,563 inhabitants out of which 73,046 wage earners (43% of them in industry), the percentage of disabled persons (through chronic respiratory diseases except tuberculosis) is 8%. In a group od 161 chronic respiratory disease patients pensioned in 1985-1989 and representing 0.44/1000 of all wage earners (0.35/1000 in urban and 0.71/1000 in rural areas), most of them (1.03/1000) came from the extractive and mining industry, 67% over 51 years of age. On the first places of disablement causes there are mentioned: COPD (34%), malignant tumours (23%), bronchial asthma (17%), and on the last place--post Tb-syndromes (3%). Proposals of retirement come--in their majority--from the Department of Internal Diseases. The study shows that the incidence of retirements (for disease) is an important index of the epidemiological situation of these diseases and of the severity in the evolution of some of them (cancer, COPD), that treatments and recovering methods are little efficient, and the pneumophysiology departments and sanatoria are not correspondingly involved in the control of such diseases. Pneumology sections or compartments as well as units provided with adequate and equipment are required, at least in the areas polluted with noxious powders and chemical substances.


[The incidence of chronic respiratory diseases in Hunedoara County and the cases of disease hospitalized in the Pneumophthisiology Department of Deva Hospital]. The structure of the incidence of chronic respiratory diseases is analysed within the district of Hunedoara for the last two decennia (1970-1991), and the low percentage of pulmonary tuberculosis as compared with the other respiratory diseases (8.75% for the last five years) is emphasized. A comparison is performed between the figures of Tb and of non-Tb disease cases hospitalized in the Pneumophysiology Department, District Hospital, Deva (27.6% non-Tb diseases) from 1987 to 1991. Attention is drawn to the obligation of pneumophysiologists to take over the medical assistance and follow up of non-Tb respiratory diseases, as a result of the Ministry of Health legislation on "pneumophysiology" (a specialty replacing the old "physiology").


In vitro action of vasopressin on water absorption by rat colon. The action of vasopressin on water absorption was studied in vitro in the colon of rats, weighing approximately 250 g. Everted sacs of intestinal segments (ascending and descending colons) prepared with mucosa only were used. Vasopressin (10 mM) significantly stimulated water absorption in both the proximal (4.85 +/- 3.78 vs 1.51 +/- 1.16 ml/mg) and distal (10.39 +/- 3.52 vs 7.22 +/- 3.58 ml/mg) colon, which corresponds to an increase of 220% and 50%, respectively. The results indicate the need for a study of the possible physiological function of vasopressin in enhancing intestinal water absorption, when it is released in response to plasma hyperosmolarity.


Vagal and sympathetic control of heart rate during exercise by sedentary and exercise-trained rats. 1. The present investigation was undertaken to study the vagal and sympathetic effects of an acute bout of exercise on ten sedentary (S) and nine trained (T) rats. The exercise training was performed 5 times a week for 13 weeks on a motor treadmill, at 1.0 mph, 15% grade for 60 min. 2. Heart rate (HR) was recorded at rest and during exercise, 15% grade at 0.5, 0.8 and 1.0 mph, for 3 min per stage. Vagal and sympathetic effects were studied after the administration of methylatropine (3 mg/kg) and propranolol (4 mg/kg). 3. Exercise training significantly attenuated cardiac acceleration at 0.8 (441 +/- 8 vs 486 +/- 9 bpm in S, P < 0.05) and 1.0 mph (466 +/- 12 vs 508 +/- 6 bpm in S, P < 0.05). The vagal effect was significantly increased in the T group at 0.8 (72 +/- 5 vs 32 +/- 10 bpm in S, P < 0.05) and 1.0 mph (46 +/- 8 vs 15 +/- 7 bpm in S, P < 0.05). The sympathetic effect was significantly decreased in the T group at 0.8 (73 +/- 9 vs 112 +/- 9 bpm in S, P < 0.05) and 1.0 mph (96 +/- 11 vs 125 +/- 7 bpm in S, P < 0.05). The intrinsic HR behavior was not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial collagen remodeling and left ventricular diastolic function. 1. The myocardial collagen matrix is an active participant in determining ventricular architecture and diastolic function, and myocardial structural integrity and mechanical properties. It consists of a network of fibrillar collagen which is intimately related with the myocyte, myofibril and muscle fiber as well as the coronary vasculature. Consisting primarily of collagen types I and III, this material exhibits a high tensile strength which, even though normally present in relatively small amounts, plays an important role in the behavior of the ventricle during diastole. 2. Removal of less than half of the normal amount of collagen results in a dilated ventricle with increased compliance. Collagen degradation of this magnitude and similar myocardial and ventricle with increased compliance. Collagen degradation of this magnitude and similar myocardial and ventricular histologic and functional alterations are evident during ischemia and in dilated cardiomyopathy. Thus, it would appear that a chronic change in the shape and size of the heart must be preceded by alterations in the interstitial collagen matrix. 3. With elevations in the circulating levels of angiotensin and/or mineralocorticoids, the hypertrophic response of the myocardium to the accompanying hypertension includes a progressive remodeling of the collagen component. Typically there is an increase in collagen concentration, thickening of existing fibrillar collagen and the addition of new collagen at all levels of the matrix. The consequences of this remodeling are an adverse alteration of the passive mechanical properties of the myocardium and LV diastolic dysfunction. This pathophysiologic aspect of the hypertrophic process is independent of the concomitant remodeling of the myocyte.(ABSTRACT TRUNCATED AT 250 WORDS)


Potassium channel opening drugs and the airways. 1. Potassium channel opening drugs (KCOs) include benzopyrans such as cromakalim, cyanoguanidines such as pinacidil and tetrahydrothiopyrans such as RP 49356. 2. While clinical trials have indicated that cromakalim may be of benefit in the treatment of nocturnal asthma, it remains to be determined whether KCOs will find a place in our armamentarium of clinically useful anti-asthma agents. 3. KCOs inhibit the spontaneous tone of airways smooth muscle in vitro, an action associated with membrane hyperpolarization towards the potassium equilibrium potential and with the promotion of 86Rb+ or 42K+ efflux from the muscle cells. KCOs suppress spasm of airways smooth muscle evoked by low (< 40 mM) but not high (> 40 mM) concentrations of KCl. Their relaxant effects in airways smooth muscle can be attenuated by a variety of agents (including sulphonylureas) known to inhibit the opening of plasmalemmal K(+)-channels. 4. The KCOs open an ATP-sensitive K(+)-channel (KATP) in the plasmalemma. KATP is not open under normal circumstances and does not play an important role in determining the strong outward rectifying behavior of the cell membrane. The biochemical mechanisms by which the KCOs promote the opening of KATP remain to be elucidated but probably do not involve channel phosphorylation consequent to the intracellular accumulation of cAMP. 5. By causing hyperpolarization of the plasmalemma, the KCOs inhibit the cellular influx of Ca2+ through voltage-dependent channels. Relaxation follows both as a direct consequence of the fall in cytosolic free Ca2+ and also as a consequence of reduced production of phosphoinositide second messengers. The KCOs may also inhibit Ca2+ uptake by, and hence Ca2+ release from, the sarcoplasmic reticulum. 6. KCOs can inhibit cholinergic and non-adrenergic, non-cholinergic (NANC) excitatory neuroeffector transmission in the airways by glibenclamide-sensitive mechanisms which may involve inhibition of neurotransmitter release. The KCOs do not attenuate NANC inhibitory neuroeffector transmission, suggesting that KATP may not be expressed in neurones of this type. 7. The active enantiomer of cromakalim has been found to be effective in alleviating nocturnal asthma at plasma concentrations just threshold for relaxing human airways smooth muscle in vitro. The clinical efficacy of cromakalim may therefore depend on an action other than the direct relaxation of airways smooth muscle. Animal studies indicate that KCOs can reduce airway hyper-reactivity at sub-bronchodilator doses. The mechanism of this effect remains to be elucidated and may not crucially depend upon inhibition of neurotransmitter release within the lung.


Competitive parabolic inhibition of bovine trypsin by bis-benzamidines. 1. Competitive parabolic inhibition, a rare type of inhibition of one-substrate enzymes, is described for alpha- and beta-trypsin. The enzymes were so inhibited by two bis-benzamidines, 4-4'-diazoamino-bis-benzamidine, Berenil (DABB) and its platinum complex, DABB-PtCl2, acting on acyl-amino acid and -peptidyl nitroanilides (Nan) substrates, when inhibitor concentrations exceed 10 mM and approach the millimolar range. 2. The type of nonlinear inhibition observed requires ternary complex formation between one enzyme molecule and two inhibitor molecules (M.E.M), and also permits the formation of the mixed ternary complex (M.E.S). Binding of the first DABB molecule to the active center of trypsin takes place with Ki values of ca. 1.50 microM for both alpha- and beta-trypsin. The secondary binding site binds the inhibitor with dissociation constants Ki2 close to 0.25 mM for both forms of the enzyme, as determined with different substrates. 3. The dissociation constants of the ternary mixed complexes (Ksi and Kis), however, depend on the structural features of the substrates, which are of negligible importance for Bz-Arg-Nan, but significant for Ac-Phe-Arg-Nan and D-Val-Leu-Arg-Nan, reflecting subsite interactions between S1-S3 and S'2. 4. Pentamidine, a diamidino-4,4'-diphenoxy-alkane with a flexible chain, behaved as a strict competitive inhibitor. This implies that the triazene moiety of DABB is involved in the interaction between the inhibitor and the secondary binding site of the enzyme.


Hormonal and metabolic study of a case of adiposis dolorosa (Dercum's disease). A case of a 43-year-old nonobese woman with adiposis dolorosa (Dercum's disease) is reported. Muscle glucose uptake and oxidation before and after ingestion of 75 g of glucose were similar to control group values, although a greater insulin release (16,578 vs 6,242 +/- 1,136 microU/3 h) occurred simultaneously. In vitro studies of abdominal normal and painful subcutaneous adipose tissue of the patient revealed lower responsiveness to norepinephrine and lack of response to the antilipolytic effect of insulin in the painful adipose tissue (0.98 vs 1.43 microM FFA/10(6) cells at 5.0 microM of norepinephrine). The disease was not correlated with the HLA system and there were no alterations in hormonal secretion at the pituitary, adrenal, gonadal, and thyroid levels. These findings indicate the presence of peripheral insulin resistance in this patient with adiposis dolorosa.


Virulence of nonpathogenic zymodemes of Entamoeba histolytica isolates from asymptomatic subjects in Calcutta, India. 1. The zymodeme and virulence of 31 Entamoeba histolytica isolates obtained from asymptomatic human subjects in Calcutta, India are described. 2. Virulence was measured by the extent of lesion diameter (mm) induced by each isolate in the liver of golden hamsters and resistance of isolates to non-immune hamster sera in vitro. 3. Two nonpathogenic zymodemes, III (N = 17) and IV (N = 14), were detected among 31 isolates by isoenzyme electrophoresis. Most of the zymodeme III isolates were moderately to highly virulent while a quarter of the zymodeme IV were invasive although with low virulence. 4. The virulence of the isolates was found to have a significant positive correlation (r = 0.96, P < 0.001) with their greater resistance to complement-mediated lysis. 5. The data suggest that the virulence of E. histolytica is probably not related to its zymodeme.


Immunochemical detection of purified crotoxin from Crotalus durissus terrificus venom in the motor end plate of striated muscle in CBA/J mice. Electrophysiological studies of crotoxin, a potent neurotoxic fraction from Crotalus durissus terrificus venom, have shown a pre- and post-synaptic action. In order to determine the specific site of this activity, we performed an immunohistochemical analysis on striated muscle from CBA/J mice, injected with crotoxin (5 LD50), iv, using a single-step immunoperoxidase assay with peroxidase-conjugated antibodies to whole venom. Control muscle and muscle obtained from treated animals 15 min after injection showed no staining. However, 30 min after injection, the neuromuscular motor end plate of mice who received crotoxin was clearly stained, including thin terminations, without any morphological alteration. Sixty min after administration, the motor end plate was no longer intact, but only roughly formed stained areas without clearly identifiable structures were present. These data show specific crotoxin binding to neural end plates in striated muscle, with a subsequent toxin-induced degeneration of this structure.


Increasing the efficiency of lipid-conjugated antibodies incorporation into the membrane of antigen presenting B cells. We have introduced some modifications in the technique called "cell decoration" in order to increase the amount of lipid-conjugated antibodies which can be incorporated into the membrane of B cells. As shown by FACS analysis, we have obtained an approximately 4-fold increment in the amount of specific antibodies incorporated into the cell membrane. The procedure, which consists of successive changes of the medium that contains the lipid-conjugated antibodies, avoided changes on parameters that interfere with cell viability. The proposed modification resulted in an approximately 2-fold enhancement of the ability of decorated B cells to act as antigen presenting cells for specific T hybridomas.


A toxoid prepared from cholera toxin by iodination. A cholera toxoid was prepared by iodinating purified cholera toxin having an activity of 25 Limit of blueing (Lb) doses/1 microgram with 0.8 mumol of iodine monochloride per mg toxin, and the residual lesion capacity was tested in mice. The blueing dose (BD) test was strongly positive for the native toxin, and completely abolished in the iodinated toxoid when tested at up to 25 times on Lb dose. The dermal microscopic lesions with intradermal doses of 1 microgram virulent toxin presented intense leucocyte infiltration, proteinaceous edema and active hyperemia, whereas none of these effects was observed with the same amount of toxoid. To determine antigenicity, two groups of mice received toxin or toxoid, 8.5 micrograms adsorbed to aluminum hydroxide, followed by a booster of 17 micrograms in saline 21 days later. Measurement of antibodies by ELISA at day 28 indicated that the toxoid was 2.5 times more antigenic than the toxin. These data show that iodination converts cholera toxin to an effective toxoid.


Inhibitory sidebands in multiple angular frequency filters in the human visual system. The view of multiple spatial frequency channels to characterize spatial factors determining the processing of contrast and brightness information has been mostly based on studies using sine wave gratings. In a study of angular frequency filtering, we demonstrated the presence of multiple peaks reflecting inhibitory activity in the measurement of a 24-cycle angular frequency filter (Simas MLB & Dodwell PC (1990). Spatial Vision, 5: 59-74). We now report sensitivity functions for angular frequency filters at 2, 4, 9, 13, 16, and 47 cycles, and have included new data for 24 cycles using the same method and analogous equipment to allow comparisons with our previous study. The present findings consistently show inhibitory effects flanking the filter's specific test frequency and, in every case, much weaker or almost no inhibition occurs at the specific test frequency for the given angular frequency filter.


Effects of age and isolation on the evolution of catalepsy during chronic haloperidol treatment. Sixteen young (5 months) and 16 old (20-24 months) male Wistar rats, housed together or in individual cages were observed for cataleptic behavior 10, 20 and 30 days after the beginning of chronic haloperidol treatment (1.0 mg/kg, twice daily, for 30 days). Catalepsy was measured by the bar test. Age increased the duration of haloperidol-induced catalepsy of isolated and group-housed rats in the three observation sessions (old-isolated = 7.4 +/- 0.2; old-group housed = 7.5 +/- 0.1; young-isolated = 6.3 +/- 0.2; young-group housed = 6.8 +/- 0.2 In seconds in session 1, for example). Conversely, isolation did not modify the sensitivity to the cataleptic effect of haloperidol. Even more important, no differences in duration of haloperidol-induced catalepsy were observed among the three sessions for each group. The results indicate that under the experimental conditions employed the animals did not develop tolerance nor sensitization to haloperidol-induced catalepsy. In addition, neither age nor isolation modified the absence of effects of repeated haloperidol treatment on the catalepsy behavior of rats.


Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats. 1. The participation of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). 2. Microinjection of noradrenaline (12.5 to 100.0 nmol/microliters) into the LHA promoted a significant decrease in proximal sodium reabsorption (controls, 86.5 +/- 1.3; 12.5, 81.4 +/- 2.0; 25.0, 72.6 +/- 2.4; 50.0, 75.4 +/- 1.8 and 100.0, 77.2 +/- 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 +/- 1.6; 12.5, 18.4 +/- 1,25.0, 26.9 +/- 2.9; 50.0, 24.1 +/- 2.7; 100.0, 22.1 +/- 1.9%) with no significant changes in creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/microliter. Beyond this concentration, a smaller but progressive increase in fractional sodium reabsorption was observed in the post-proximal segment. 3. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation.


Influence of calcium on the blood pressure and renal effects of stevioside. 1. The effects of verapamil (V, 0.015 mg/min, i.v.) or CaCl2 (800 mEq/l, 0.025 ml kg-1 min-1, i.v.) on renal function and mean arterial pressure (MAP) were evaluated in male Wistar rats weighing 280-320 g during treatment with stevioside (S, 16 mg kg-1 h-1, i.v.). 2. Verapamil administered to 10 rats significantly increased the hypotensive effect of stevioside on MAP (control, 124 +/- 0.77; S, 96 +/- 1.50; S+V, 67 +/- 0.70 mmHg) and on fractional sodium excretion (control, 0.76 +/- 0.05; S, 1.56 +/- 0.10; S+V, 2.72 +/- 0.25%). Urinary flow, reported as percent glomerular filtration rate (V/GFR), and renal plasma flow (RPF) increased slightly but not significantly during stevioside plus verapamil administration. 3. In contrast, infusion of CaCl2 in 10 rats pretreated with stevioside induced a marked attenuation of MAP (control, 119 +/- 1.83; S, 70 +/- 1.12; S+CaCl2, 109 +/- 1.60 mmHg) and RPF (control, 16.73 +/- 3.76; S, 34.33 +/- 2.55; S+CaCl2, 17.20 +/- 2.87 ml min-1 kg-1). The diuresis and natriuresis induced by stevioside were also inhibited by simultaneous administration of CaCl2. 4. These data are consistent with the view that stevioside acts on arterial pressure and renal function as a calcium antagonist, as is the case for verapamil.


Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats. Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.


Possible role of the submandibular glands in the control of glucose metabolism in mouse enterocytes. We evaluated the effect of sialadenectomy on hexokinase activity and on rates of lactate formation and of [U-14C]glucose decarboxylation in 3 cellular fractions of the small intestine epithelium from male adult mice. The surgery was carried out under ether anesthesia and a sham-operated group was used as control. Three cell fractions were obtained by shaking the inverted small intestine: 1) tip of the villus, 2) villus and 3) villus and crypt cells. Five days after sialadenectomy, hexokinase activity was reduced in fractions 1 (3.53 +/- 0.65 vs 1.98 +/- 0.25 nmol min-1 mg protein-1, expressed as mean +/- SEM for 7 mice) and 3 (5.01 +/- 0.55 vs 3.15 +/- 0.42 nmol min-1 mg protein-1, mean +/- SEM for 7 mice). After removal of the submandibular glands, the rates of lactate formation were decreased in fractions 2 (4.16 +/- 0.54 vs 2.30 +/- 0.25, mean +/- SEM for 10 and 11 mice, respectively) and 3 (1.74 +/- 0.24 vs 0.87 +/- 0.14, mean +/- SEM for 13 mice) and the rates of [U-14C] glucose decarboxylation were reduced in fraction 1 (1.14 +/- 0.12 vs 0.61 +/- 0.10, mean +/- SEM for 11 and 12 mice, respectively). We conclude that the secretion of submandibular glands plays a physiological role in the control of glucose metabolism in enterocytes.


Development of a hospital ethics committee: lessons from five years of case consultations. The development and consultation experience of an ethics committee in an urban community hospital has been presented, and various approaches to case consultation have been considered. Our committee has concentrated on the clinical evaluation model. As expected, most consultations have centered on issues of withdrawing or limiting medical care. Most patients evaluated have been unable to clearly express their wishes concerning further treatments, highlighting the need for promoting advance directives. When resorting to substituted judgment, our committee has supported continued care in a majority of cases. Limitation of the consultation process to the attending physician has, in our experience, actually served to increase the credibility of the committee and has promoted acceptance of its recommendations. The committee's most useful function seems to be in assisting physicians and their patients in defining realistic goals and limitations of treatment. Within this context, the coming decade may find ethics committees concerned less with promoting the autonomous wishes of individual patients than with defining the limits of that autonomy against the competing demands of the larger society. Such a shift should be approached with caution.


Char syndrome (unusual mouth, patent ductus arteriosus, phalangeal anomalies). A mother and son are described with unusual facies, patent ductus arteriosus, fusion of distal interphalangeal joints and mild learning difficulties. The facial features include hypertelorism, strabismus, flat nasal bridge, short philtrum and a triangular mouth. This autosomal dominant syndrome has been reported in one other family by F. Char (1978).


Acrorenal syndrome: further observations. A 23-year-old female patient with the acrorenal syndrome is described. In addition to acral and renal malformations, she had anomalies of the gastrointestinal and genital tracts. An annular pancreas had caused duodenal obstruction and had been associated with malrotation of the bowel. Secondary sexual characteristics were absent; no ovaries were identified by pelvic ultrasound, and endocrine investigations were compatible with non-functioning ovaries.


Ramon syndrome with diabetes mellitus and vascular skin lesions in two sibs. Two sibs are reported with Ramon syndrome with the previously undescribed associations of insulin dependent diabetes mellitus and vascular skin lesions.


Multisystem disorder of Punjabi children exhibiting spontaneous dermal and submucosal granulation tissue formation: LOGIC syndrome. We describe a multisystem disease that affects children of Muslim families originating in the Punjab region of Pakistan and India. An altered cry due to vocal cord thickening, skin ulceration, nail abnormalities, and conjunctival scarring appear in the first few months of life. Progression and spread of the disease in these sites may be accompanied by involvement of other epithelial surfaces. The teeth may exhibit defective enamel formation. Histology reveals the formation of simple granulation tissue arising in the dermis and submucosa which become massively thickened and ulcerated. There is good evidence for an autosomal recessive gene defect, but the actual mechanism of the disease is not known. Medical and surgical therapy have been ineffective in altering the course of this devastating and usually fatal condition. We suggest the term LOGIC (laryngeal and ocular granulation tissue in children from the Indian subcontinent) for this newly established disease.


Encephalocele, radial defects, cardiac, gastrointestinal, anal, and renal anomalies: a new multiple congenital anomaly (MCA) syndrome? We present two unrelated female patients with a complex pattern of congenital malformations including encephalocele, oesophageal atresia, abnormal lung lobation, congenital heart defects, anal anomalies, liver, spleen and radial defects. Clinical variability between the two cases can be seen as a result of variable expression. The pattern of anomalies in these two unrelated patients suggest that they may represent the same, as yet unknown, syndrome.


Microgastria-hypoplastic upper limb association: a severe expression including microphthalmia, single nostril and arhinencephaly. Report on a female infant with iris coloboma on the right and microphthalmia/orbital cyst on the left, single nostril, radial defectis, abnormal lung lobation, congenital heart defect, hypoplastic spleen, absent gallbladder, microgastria, unilateral renal aplasia, arhinencephaly and fused thalami. This case represents an unusually severe expression of a probably rare association recently reviewed by Lueder et al. (1989).


Fetus with unbalanced translocation involving chromosomes 2 and 11. We report a fetus with an unbalanced translocation between chromosomes 2 and 11, the product of a paternal balanced reciprocal translocation, fetal karyotype 46, XX, -11, +der(11)t(2;11) (q35;q24.1)pat. The fetus had unusual facial features. The relevance of this case to mapping of the type I Waardenburg syndrome gene is discussed.


New dysmorphic syndrome with choanal atresia in siblings. We report five children from three families who presented with bilateral choanal atresia associated with a spectrum of additional malformations including cardiac defects, deafness, defects of the external ear, eyes and eye lids and a characteristic dysmorphic appearance. The children were of normal intelligence. This syndrome is distinct from CHARGE association.


Cardiofaciocutaneous syndrome.

Cardiofaciocutaneous syndrome. A boy aged 6 years 10 months with dysmorphic features of the cardiofaciocutaneous syndrome is reported. This patient had early total alopecia, persistent hypotrichosis and an inflammatory hyperkeratotic dermatosis with psoriasiform features occurring predominantly on the scalp, extensor surfaces of limbs and trunk. Bilateral progressive femoral valgus deformity culminated in unilateral hip subluxation. Previously undescribed neuro-ophthalmologic findings are reported.


Setleis (bitemporal 'forceps marks') syndrome in a German family: evidence for autosomal dominant inheritance. The Setleis syndrome is a rare disorder characterized by predominantly facial findings, including bitemporal skin changes resembling forceps marks. Autosomal recessive inheritance of this distinct condition has been proposed. We report on a typically affected German boy whose father shows a much milder expression, thus suggesting autosomal dominant inheritance.


Chondrodysplasia punctata: further evidence of heterogeneity. We describe a patient with chondrodysplasia punctata. He had stippled epiphyses and coronal clefting of the vertebral bodies. No peroxisomal abnormalities were detected. His facial appearance and X-rays were suggestive of the Sheffield type of chondrodysplasia punctata. This type of chondrodysplasia punctata appears to be a heterogeneous group.


Hairy throat: a dominant trait affecting seven members of a family. Hypertrichosis was noted on a confined area of skin in the midline of the throat, just cranial to the laryngeal prominence, in three males and four females through three generations of a Japanese family. The proband, an 11-year-old girl, in addition had a 46 X,i(Xq) karyotype, short stature and other stigmata of the Turner syndrome. Her mother and one younger brother both had a hairy throat on examination. On the mother's side, the proband's grandmother, aunt, uncle and a male cousin, all reportedly had a hairy throat. No instance of male-to-male transmission was present. The trait was thus inherited as either an autosomal or X-linked dominant.


Campomelic dysplasia without overt campomelia. We describe a newborn girl with virtually all the characteristics of campomelic dysplasia except for overt campomelia. This observation and similar cases previously reported indicate that campomelia is a variable feature in campomelic dysplasia. In contrast, hypoplasia of the scapulae is a constant finding and should be regarded as a diagnostic significant sign.


Recessively determined chylous ascites--a case report and possible mouse model. A male infant, whose parents were first cousins, was born with tense chylous ascites, mild generalized oedema and facial dysmorphism. The baby initially seemed well but subsequently probably aspirated, developed septicaemia and finally died at 26 days from a bleeding diathesis, possibly secondary to liver dysfunction. No cause for the chylous ascites was found at post mortem. This case is presumed to represent an example of recessively determined chylous ascites. The mouse mutant Chy may be an homologous condition.


Agnathia-holoprosencephaly with tetramelia. Agnathia is a rare malformation which may occur in isolation or with holoprosencephaly, situs inversus or visceral anomalies. A fetus is described with the lethal malformation complex of agnathia-holoprosencephaly in whom tetramelia was also present.


Pathogenesis of retinoid-induced hindbrain malformations in an experimental model. Among the findings associated with the human Retinoic Acid Embryopathy are hindbrain defects including the Arnold-Chiari malformation. The human Arnold-Chiari malformation (ACM) is a malformation complex where the cardinal feature is herniation of the caudal hindbrain into the vertebral column; it is frequently accompanied by lumbosacral myelorachischisis and hydrocephalus. Mice exposed to all-trans-retinoic acid or etretinate on day 8.25 of pregnancy, produce offspring with hindbrain herniation and caudal lumbosacral myelorachischisis in addition to a variety of other craniofacial and caudal malformations. Several experimental animals were observed to lack the caudal myelorachischisis proving that this lesion is not required to generate hindbrain herniation. We provide evidence that the cranial malformations, including hindbrain herniation, result from primary damage to the neural crest and the rhombencephalon. The vulnerability of these sites appears to be correlated with the presence of normal physiological cell death. While these experimental animals differ in many respects from the typical human Arnold-Chiari malformation, they may provide some insight into the pathogenesis of the latter.


Autosomal dominant transmission of acrodysostosis. A mother and daughter with acrodysostosis are described. This documented parent-to-child transmission supports the hypothesis of autosomal dominant inheritance of acrodysostosis. The daughter exhibited many features of acrodysostosis by two months of age, demonstrating that acrodysostosis may be diagnosed in infancy.


Familial acrodysostosis: can it be distinguished from Albright's hereditary osteodystrophy? A girl, who presented initially to the orthodontist because of anterior and posterior open-bite, was noted to have short stature and facial dysmorphism suggesting the diagnosis of acrodysostosis. Her father had similar features, though less marked. Photographs of the paternal grandfather showed short stature and a similar facies. This family presents a further example of autosomal dominant inheritance of acrodysostosis and highlights the difficulty in distinguishing between acrodysostosis and pseudohypoparathyroidism.


Disproportionate short stature, type E brachydactyly and exostoses of tibiae in a patient with an XYY karyotype. A 'new' syndrome? An 18-year-old male with an XYY karyotype is reported with short stature, normal intelligence and normal personality, in contrast to the XYY syndrome which can be characterized by tall stature, mental subnormality and aggressive behaviour. The patient, in addition, had exostoses of the tibiae bilaterally and type E brachydactyly; this association has not previously been described in patients with the XYY karyotype.


New autosomal recessive chondrodysplasia--pseudohermaphrodism syndrome. Two siblings with a previously undescribed syndrome are presented. They both have severe dwarfism, antenatal in origin, with generalized chondrodysplasia, severe microcephaly with cerebellar vermis hypoplasia, a hypoplastic iris and a papillous coloboma (Coloboma of the optic disc). The first sibling has a 46,XY karyotype despite normal female internal and external genitalia. She has moderate mental retardation. Gestation of the second sibling was interrupted after antenatal diagnosis. The fetus was 46,XX and very similar to the first case.


Three cases of oblique facial cleft: etiology, tomographic evaluation and reconstruction. Three cases of oro-ocular clefts from different families are presented. Two of the cases had a normal chromosomal constitution. The defects in each case were evaluated by computerized tomography computerized tomography prior to surgery. The theories concerning etiology and classification of oblique facial clefts are discussed in the light of computerized tomography scan findings. One of the cases had a history of maternal bromocriptine mesylate usage for prolactinoma, suggesting a teratogenic effect, but no similar cases have been reported in the medial literature.


Neurological complications in one of a sibpair with aplasia cutis congenita. We describe two sibs with aplasia cutis congenita, one of whom has developed moya-moya disease resulting in severe physical handicap and mental retardation. The presence of aplasia cutis congenita should at least alert the clinicians to the possibility of a co-existing central nervous system lesion.


Topical acetylsalicylic acid in the treatment of allergic pollinosic conjunctivitis. The pharmacological treatment of allergic conjunctivitis includes the use of topical antiinflammatory drugs, i.e. steroids and NSAIDs (nonsteroidal antiinflammatory drugs), such as acetylsalicylic acid (ASA). However, steroids are not suitable in prolonged treatment, as well as in pollinosis in the Mediterranean area, because of their side effects. The present double-blind study evaluates the topical use of acetylsalicylic acid eye drops (1% solution) compared to placebo in the treatment of patients with seasonal allergic conjunctivitis during the period June-July 1990. The patients were randomized and treated with ASA eye drops or placebo eye drops, both applied as one drop in each eye q.i.d. for 14 days. The severity of symptoms was evaluated before and after treatment by the investigator and the patient. An overall judgement of therapeutic response was expressed independently by the patient and the investigator at the end of the treatment. The ASA-treated group improved significantly compared to the placebo-treated group. No serious side effects were observed. The results confirm the clinical efficacy and safety of topical ASA in the treatment of pollen-induced allergic conjunctivitis.


Aspirin-induced urticaria--a clinical study. This paper describes the clinical characteristics of patients with aspirin-induced urticaria. The group of 71 patients (49 women and 22 men), with a mean duration of symptoms of 32.5 years, underwent allergological, laryngological and histamine dihydrochloride inhalation tests. Nasal polyps were found in 2 patients (2.8%), atopic disease in 23 (32.3%) and at least one feature of atopy in 37 (51.9%). Forty-nine patients (69%) suffered from urticaria which was not associated with aspirin. In 22 patients, urticaria developed solely due to aspirin. Urticaria not associated with aspirin has been present from 2 weeks to 30 years before the onset of sensitivity to aspirin. The authors conclude that aspirin-induced urticaria results from two different concomitant phenomena, i.e. sensitivity to aspirin and urticaria not associated with ingestion of the drug.


Respiratory allergies and skin test reactivity in high school students in Tenerife, Canary Islands, Spain. The prevalence of skin test reactivity to 22 aeroallergens and of allergic respiratory diseases was determined in 501 high school students on the island of Tenerife, Spain. Two hundred seventy-seven students (55.2%) had at least one positive prick skin test (wheal > or = 2 mm). Two hundred sixteen students (43.1%) had symptoms of upper or lower respiratory tract allergies [24 (4.7%) had asthma with or without rhinitis and 192 (38.3%) seasonal or perennial rhinitis alone]. Two hundred eighty-five students (56.8%) were asymptomatic. One hundred per cent of the students with asthma, 87.5% of the students with rhinitis and 27.7% of the asymptomatic students had at least one positive skin test. The prevalence of positive skin tests was significantly higher in symptomatic than in asymptomatic students (p = 0.0001). One hundred seventy students (33.9%) had a family history of respiratory allergic diseases. The prevalence of positive skin tests among these students was significantly higher than in students without such history (p = 0.0001). Thus, there is a high prevalence of allergic respiratory diseases and skin test reactivity to aeroallergens among high school students in Tenerife. Significant correlations were found between family history, positive skin tests and respiratory allergic symptoms.


Subacute cutaneous lupus erythematosus--clinical, histopathological and immunophenotypical study of five cases. Subacute cutaneous lupus erythematosus (SCLE) is a recently described distinct subset of lupus erythematosus (LE) having characteristic clinical, serological and genetic features. The clinicopathological and serological findings of 5 patients are reported. From a clinical point of view, we describe two types of cutaneous lesions: psoriasiform and annular pattern. ANA were present in 80% of the cases, anti-Ro was present in 60%, and anti-La in 20%; anti-RNP was positive in 1 patient. Circulating immune complexes were detected in 2 patients, and low levels of complement factors (C3, C4) in another 2 patients. The B- cell alloantigens HLA-A2, HLA-Bw4 or HLA-DR3 were present in 60% of the cases. The cutaneous histopathology revealed important changes in the epidermis. Our findings are similar to those described by most other authors. Also, we would like to emphasize the low disease activity and benign course of our patients.


Intolerance to sodium metabisulfite in children with steroid-dependent asthma. Oral challenge tests were carried out with sodium metabisulfite solution doses of 5, 10, 25, 50 and 100 mg, dissolved in 20 ml of citric acid, and administered to 20 children aged 7-14 years with steroid-dependent bronchial asthma. A single-blind challenge protocol was performed initially and the positive responses were confirmed by double-blind challenge. Initially, 6 of 20 presented a positive reaction, confirmed in 4 of 20 by double-blind challenge. Only 1 child was clinically suspected of exhibiting intolerance to this agent. The prevalence of the challenge test using sodium metabisulfite in children with steroid-dependent bronchial asthma was 20%.


IgE antibodies against Neisseria flavescens. Bacterial allergy is still a matter of controversy. We sustain that this name should be employed only in the presence of a specific IgE against antigens from bacteria. In 100 atopic patients and 100 healthy controls with Neisseria flavescens in their pharyngeal exudates, we performed type I immediate skin tests with Neisseria flavescens and IgE-RAST throughout 1 year. Positive wheal and flare reactions were elicited in 8 of 100 atopic patients as well as in 3 of 100 nonatopic subjects. IgE-RAST/anti-Neisseria flavescens was found in 6 of the former group and in 1 of the latter. Neither late-phase nor Arthus-like reactions were recorded. Neisseria flavescens is a non-pathogenic commensal of the oropharynx with scarce antigenic properties and seems not to play an important role in these conditions (rhinitis/asthma). Bacterial immunotherapy should be considered only in the presence of specific IgE antibodies with careful selection of the bacteria or their antigens.


Magnetic resonance imaging in a patient with X-linked agammaglobulinemia and chronic meningoencephalitis. The case of a boy with congenital agammaglobulinemia is reported. In spite of regular immunoglobulin replacement therapy (fresh plasma transfusion from family donors--20 ml/kg/month), he developed chronic meningoencephalitis (ME). Besides characteristic clinical signs of ME, he also presented at cerebrospinal fluid analysis pleocytosis with lymphocyte predominance and class II cytomorphology, and delta and theta waves in the EEG. Computerized tomography showed dilatation of the ventricles and marked cortical fissures (sulci). Magnetic resonance imaging showed a disease affecting white and gray matter. After diagnosis of ME, replacement therapy with Sandoglobulin (700 mg/kg every 2 weeks) was started. His condition gradually worsened, and coma and death occurred after a follow-up of 18 months. The etiological agent could not be identified.


Immunotherapy by inhalation of allergen in powder in house dust allergic asthma--a double-blind study. The authors report the analysis of clinical and immunological parameters during local immunotherapy (LI) by inhalation of an extract in powder in patients with allergic asthma due to D. pteronyssinus (DP). The study was double-blind and lasted 24 months. Twenty-four patients were randomly assigned on a double-blind basis to receive by inhalation increasing doses of a micronized, freeze-dried DP extract in powder (14 patients, active therapy) or capsules of lactose (10 patients, placebo group). Results showed a statistically lower symptom score, a significant increase in bronchial tolerance to the allergen and significant levels of DP-specific IgG in actively treated patients compared to those treated with placebo.


Reagent strip for semiquantitative total and specific IgE measurement: a comparison to radioisotopic methods. Determination of total and specific IgE using reactive test strips may afford a useful screening method in the in vitro diagnosis of allergens owing to easy use and possible correlation with established methods. T.D. LETI reactive strips for the semiquantitative determination of total IgE is a method combining classical fundamentals (sandwich anti-IgE-IgE-labeled anti-IgE) and the use of strip methods. It also permits determination of specific IgE levels in a wide range of Mediterranean and food (10) allergens. In a preliminary assessment, this method was correlated with isotopic PRIST for total IgE and with Phadebas RAST for specific IgE. The most important features are: a) no additional equipment besides serum or whole blood; b) cheaper and faster than PRIST for total IgE; c) correlation coefficient of 0.88 in the proposed range (n = 20) and 0.91 (n = 25) in the 10-500 U/ml range for PRIST/T.D. LETI for total IgE; d) specific IgE determination strips present sensitivity and specificity of 88 and 91%, respectively, in 180 allergens assayed in relation to Phadebas RAST. In conclusion, the in vitro diagnosis of allergens using reactive strips is currently a practical and simple method. By optimizing the top of the scale for total IgE and reducing the volume and/or time in specific IgE, it may prove to be an important screening method.


A one-year case study of farmers with storage mite allergy. Four farmers with a positive bronchial challenge test to either L. destructor or T. putrescentiae had bronchial histamine challenge every second month during a year. In the same year, monthly samples of house dust, grain, straw and hay were analyzed for their content of house dust mites and storage mites. The exposure to house dust mites and storage mites differed between farmers. Significant changes in histamine reactivity were found, but no association with time of year or mite counts was observed.


Study of mold allergy in asthmatic children in Hungary. We studied the change in sensitivity to propagating aerogenic fungi (spores, conidia) in extrinsic asthmatic children living in an urban environment from 1977 to 1988. According to the skin test, 10.6% of those examined in 1977 were sensitive to the fungi, the proportion being 30.4% in 1985 and 38.5% in 1987/88. The increase may be explained by the increasing frequency of sensitivity to Alternaria alternata and Phoma betae. In skin tests with Bencard allergens, reaction to both types was frequently observed. Of those sensitive to P. betae, 83% were also sensitive to A. alternata, and 87.5% of those sensitive to A. alternata were also sensitive to P. betae. The frequency of cross-reactions observed both with skin tests and specific IgE determinations suggests the presence of a common allergen, or epitope. The effect of environmental factors was analyzed with computer techniques. P. betae allergy was not related to detectable mold, humidity or number of pot plants in the home. The living conditions changed during the study period as follows: 1) housing conditions improved; 2) energy-saving building technologies were generally accepted; and 3) air pollution increased, also affecting the vegetation. The sensitizing masses of spores and conidia originated most likely from molds living on plants weakened and diseased by environmental pollution.


Autoantibodies in splenectomized patients as a consequence of abdominal trauma. The presence of autoantibodies was examined in 100 adult patients splenectomized because of abdominal trauma and without systemic disease, and the results were compared with those observed in a healthy control group. Thirty-seven percent of the patients studied presented some type of autoantibody. Those observed were antinuclear, anti-smooth muscle and, in 1 case, anti-reticulin. Patients with antinuclear antibodies have no antibodies against native DNA, but in 5 cases, anti-Ro (SS-A) and anti-La (SS-B) antibodies were observed. Rheumatoid factors were also found, but their incidence was similar in patients and controls. The incidence of autoantibodies proved not to be related to either the period of time since splenectomy or to age of the patient; they were observed in patients many years after splenectomy and in individuals of both sexes and all ages. Although the presence of autoantibodies seemed to have no effect on our patients, all of whom were asymptomatic, it is important to be aware of this phenomenon when evaluating the laboratory results obtained from splenectomized patients.


Immunoregulatory properties of seminal plasma: perspective and prospective considerations. Perspective and prospective considerations of the immunoregulatory properties of seminal plasma and their biological and/or clinical relevance are presented. Further understanding of the interactions of the immune system with exocrine products of the male reproductive system may contribute to improvements in reproductive health and to an understanding of the antithetical aspects of the immune response represented by such biological phenomena as insemination, pregnancy and malignancy.


Chronic urticaria: humoral and clinical diagnosis of its morphological variables. Thirty adult patients with a diagnosis of chronic urticaria were attended as outpatients at the Allergology Service, Clinical Surgical Hospital "Hnos. Ameijeiras". An accurate clinical history was made, humoral parameters such as erythrosedimentation, total eosinophil count, serum levels of immunoglobulins and complement fractions were measured, and a skin biopsy was done. Most of the patients with urticarial vasculitis showed almost permanent papulous reactions with fever and arthralgias. Duodenal smear was positive for Giardia lamblia in a high percentage of patients with urticarial vasculitis. Paraffin-embedded skin biopsy was very useful for measuring morphological variables, and it is recommended that this technique be used in recent reactions (< 24 h evolution).


Bronchial challenge of tropical asthmatics with Ascaris lumbricoides. Despite the fact that helminthic parasites can stimulate strong immediate hypersensitivity reactions, it is uncertain whether these are relevant to the development of allergic disease in infected patients. In order to examine this possibility, we tested 20 informed chronic asthmatic patients from an Ascaris-endemic area by bronchial challenge with a partially purified extract of this parasite. Sequential measurements were made of both the forced expiratory volume in the first second (FEV1) and the peak expiratory flow rate (PEFR) up to 6 h postchallenge, then of PEFR from 6 to 14 h and at 24 h. These were compared to the effect of control inhalations of saline. Extremely low doses of Ascaris antigen that did not exceed 10 PNU (6 x 10(-7) g of protein) induced significant reductions (> 20%) in FEV1 within 30 min in 3 (15%) patients, and in PEFR in 5 cases (25%). By 6 h postchallenge, 5 (25%) subjects showed significant alterations in FEV1, and 10 (50%) in PEFR. Significant changes in PEFR were recorded between 6 and 24 h in 12 (60%) patients. The challenge of nonasthmatic subjects from the same Ascaris-endemic area did not produce notable changes in pulmonary function, and although asthmatics with no evidence of prior contact with the parasite showed a certain degree of immediate bronchial reactivity to the parasite extract, the late responses were significantly less frequent than in the infected patients. No correlations were detected between the bronchial responses and skin test reactivities to the Ascaris extract, or serum levels of specific IgE or IgG antibody.(ABSTRACT TRUNCATED AT 250 WORDS)


Peripheral blood T-lymphocyte subsets in autoimmune thyroid disease. Interest in T-lymphocyte subsets has arisen because of their involvement in the autoimmune process. Contradictory results have been published in the literature about the number of peripheral blood lymphocyte subsets in autoimmune diseases. In order to investigate the number and distribution of peripheral blood lymphocyte subsets in autoimmune thyroid disease, the levels of total T-lymphocytes (CD3), T-helper (CD4) and T-suppressor/cytotoxic (CD8) lymphocytes were determined in 44 patients with Graves' disease (1), multinodular goiter (2) and Hashimoto's thyroiditis (3). All patients had high levels of antithyroglobulin and thyroid antiperoxidase (antimicrosomal) antibodies. The T subset levels were related to the functional thyroid status, measured as serum free thyroxine (FT4) and thyrotropin (TSH). Our data show the existence of a strong influence of functional status on CD3, CD4 and CD8 levels, as reflected in the significant correlations obtained with FT4 (negative) and TSH (positive). A significant decrease in all populations was observed in Graves' disease hyperthyroid patients. A decrease in the CD4/CD8 ratio in Hashimoto's thyroiditis hypothyroid patients was observed, in contrast to an increase in the ratio in autoimmune hyperthyroid patients. This points to the CD4/CD8 ratio as a differential characteristic between the two autoimmune (hypothyroid and hyperthyroid) entities, independent of free thyroxine levels. No significant correlation was found between antithyroid antibody levels and peripheral blood T-lymphocyte subsets or serum levels of FT4 and TSH.


The ability of granulocytes to absorb latex particles and Staphylococcus aureus in patients hypersensitive to aspirin. An examination of the ability of granulocytes to absorb latex particles and Staphylococcus aureus was performed in 32 patients with atopic asthma, 27 patients with atopic asthma and hypersensitive to aspirin, and 20 patients hypersensitive to aspirin only. The control group included 20 healthy subjects. The results of our investigation demonstrate a defect of the ability of granulocytes to absorb latex particles and S. aureus in patients with atopic asthma and hypersensitivity to aspirin.


Functional evaluation of human neutrophils. Is the bactericidal activity correlated with nitroblue tetrazolium reduction? The cytochemical nitroblue tetrazolium (NBT) reduction test continues to be used in clinical laboratories to detect defects in the oxidative metabolism of phagocytes. However, the specificity of the test is controversial, and it is not clear whether NBT reduction really reflects the microbicidal activity of these cells. In the present study, we evaluated the killing of Staphylococcus aureus by neutrophils from healthy adult individuals and from patients with phagocyte dysfunctions using a fluorochrome phagocytic assay, and compared the results with those obtained with a cytochemical NBT test performed simultaneously. The ability of neutrophils to reduce NBT (expressed as percent reducing neutrophils) with or without a lipopolysaccharide stimulus was not correlated with the bactericidal activity of these cells (expressed as percent killed bacteria per 100 neutrophils). The age and sex of the healthy adults did not influence the results of either assay. It seems that the superoxide anion played a small role in NBT reduction by normal neutrophils, since superoxide dismutase did not significantly inhibit this reaction. Only the absolute absence of NBT reduction reflected the low bactericidal activity of neutrophils, as seen in patients with chronic granulomatous disease (CGD). We conclude that the only clinical usefulness of the NBT test is for the screening of CGD, and that bacterial phagocytic assays are more appropriate for assessing the microbicidal function of neutrophils.


Multicenter double-blind comparative study of terfenadine and cetirizine in hay fever. The efficacy and safety of terfenadine in the management of hay fever were compared with those of cetirizine in a multicenter, double-blind, parallel-group study, carried out during the 1990 spring pollen season. The patients were randomly assigned to one of two groups of treatment, 70 patients being given terfenadine 120 mg, and 72 patients cetirizine 10 mg, once daily for 7 days. The severity of the main symptoms was evaluated at baseline and after treatment by a 4-point rating scale. In addition, the overall symptom severity was recorded daily by the patient on a diary card. Both terfenadine and cetirizine produced significant relief of symptoms by the end of treatment, with a decrease in symptom severity ranging from 46 to 69% for terfenadine and from 40 to 55% for cetirizine. Adverse effects experienced by terfenadine- and cetirizine-treated patients were mainly drowsiness, with minor differences between the two groups. The results of this study confirmed previous experiences, showing that both terfenadine and cetirizine once daily should be regarded as effective drugs for the management of hay fever.


Bronchial asthma due to sensitization to chloramine T. Chloramine T, an organic, highly reactive derivative of chlorine with potent bactericidal properties, is used as a disinfectant in the food industry. Described as an occupational sensitizer in 1945 for the first time, it produces late or dual asthma, occasionally accompanied by fever and leukocytosis, which is mediated by IgE. We present the case of a male dairy worker who, after 4 years of exposure to the product, developed rhinitis and asthma. Skin tests with chloramine T were positive at a concentration of 10 mg/ml, while all other allergens tested negative. RAST detected specific IgE at 12 PRU and bronchial provocation induced immediate and late bronchoconstriction.


Immunochemical properties of the antigens of Triatoma infestans. Taxonomically related to the cockroach Periplaneta americana (Pa), Triatoma infestans (Ti) is an insect that parasitizes two-thirds of Argentina and acts as a vector for American trypanosomiasis. The glycoproteins obtained by a Sephadex G-150 column fractionation from the whole-body extract prepared with the chitinous structures revealed antigenicity in rabbits, which developed specific IgG after 8 weeks of immunization, as detected by several serological techniques. Atopic patients living in the northern provinces of Argentina--Santiago del Estero and Chaco (endemic area for Ti)--with rhinitis/asthma showed immediate positive skin tests to Ti and its fractions, as well as an IgE-RAST-anti-Ti in 30-36% of them. Healthy nonatopic adults of the same area and other atopics and nonatopics from Buenos Aires (non-endemic area) were selected as controls and showed negative type I skin tests, as well as specific RAST. The existence of common epitopes between Ti and Pa was confirmed by absorption techniques, RAST inhibition, IEF and STIF-RAST. These findings have clinical and epidemiological connotations.


Effect of flunisolide on nasal eosinophils and IgE, and symptom score in children with allergic rhinitis. We evaluated the effect of treatment with flunisolide nasal spray (100 micrograms/day for 3 months) in 24 children with allergic rhinitis on the following parameters: clinical symptoms, absolute number of peripheral and nasal eosinophils, and total IgE levels in nasal secretion. Therapy with flunisolide induced a significant reduction of clinical symptoms (p < 0.001), nasal eosinophils (p < 0.001) and nasal IgE concentration (p < 0.02), while it did not affect the number of peripheral eosinophils. These results indicate that flunisolide can reduce the allergic inflammation of the nasal mucosa.


Urticaria/angioedema-type sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. Diagnostic value of anamnesis and challenge test with acetylsalicylic acid. The aim of this study was to determine the value of challenge tests with acetylsalicylic acid in the diagnosis of ASA-induced urticaria. The study was performed in 71 patients with suspected urticaria/angioedema-type sensitivity to ASA. Anamnesis confirmed sensitivity in 67 patients (94.4%) and showed that sensitive patients usually suffered from extensive urticaria (37 patients, i.e 55.5%) after ingestion of ASA. Eight patients (12%) reacted with loss of consciousness and 4 (6.0%) with edema of the larynx. Oral challenge test with acetylsalicylic acid was performed in 53 patients, in 49 (92.4%) of whom it was positive. Threshold doses of acetylsalicylic acid ranged from 40 to 300 mg. In 11 patients, the test was repeated and in 8 it was performed 3 times. It was observed that both the threshold acetylsalicylic acid doses and the time of appearance of sensitivity symptoms were variable. All ASA-sensitive patients reacted to indomethacin in a similar manner as to ASA. Paracetamol, on the other hand, was well tolerated by all 25 evaluated patients with urticaria/angioedema-type sensitivity to ASA.


Variations of intracellular histamine basophil levels after treatment with ketotifen. As reported in previous studies, ketotifen modifies the number of basophils in peripheral blood, most likely inhibiting their degranulation, which correlates with the lack of exercise-induced respiratory manifestations. In this study, we attempted to measure the approximate amount of intracellular histamine in patients with bronchial asthma sensitized to Dermatophagoides pteronyssinus when they were treated with ketotifen, and compare the values with those of an untreated group and a control group, in order to determine if ketotifen stabilizes the cellular membrane, with the subsequent increase of intracellular mediators. We found that untreated patients had 57% less histamine per basophil than the control group, while treated patients had only 17% less than the controls. This shows that ketotifen acts as a membrane stabilizer, thus inhibiting degranulation and increasing the amount of intracellular mediators.


Allergy to pomegranate (Punica granatum). We present the case of a 7-year-old IgE-dependent asthmatic child who, moments after ingesting several pomegranate seeds, showed a clinical condition of bronchospasm which responded to treatment with inhaled salbutamol. Cutaneous tests using the prick-by-prick techniques with extract of the fresh fruit were positive and the RAST for pomegranate was 0.8 PRU/ml. In the literature studied, we have found few specific references to allergy to pomegranate.


A study of the aeromycoflora of Cádiz: relationship to anthropogenic activity. We describe a quantitative and qualitative study of the fungal spores found in the air of Cádiz during 1989 using a Cour-type trap. The results of this study can be extrapolated to other coastal cities of southern Europe with a Mediterranean climate. The spores identified have been classified into 25 taxonomic categories. The most abundant were Cladosporium, Chaetomium and Ustilago, and the most frequent, in addition to those mentioned, were Alternaria, Ascophyta and Venturia. The great abundance of Cladosporium is in accordance with the coastal situation of the city. Cladosporium, Alternaria, Curvularia and Stemphylium reached maximum concentrations jointly in October, 1989. They showed mutual cross-reactions. Ustilago and Nigrospora appeared during the period of cereal harvesting and storage.


Experimental models of hypersensitivity pneumonitis. Experimental models of hypersensitivity pneumonitis are important tools for the study of the pathogenesis of this disease. In this paper we review the characteristics of the main animal models developed until now. The HP models in rats seem to be particularly appropriate for studying pigeon fancier's disease and the HP induced by chemicals, as well as for studying mediators of acute lesions induced by immunocomplexes. However, the HP models developed in rats are of less value in the evaluation of other aspects of the pathogenesis of this clinical entity in humans. The murine models of HP offer several advantages: the ease and simplicity of intranasal administration, the ability to produce acute and subacute pulmonary lesions similar to those found in humans, the possibility of reproducing lesions similar to those of nonaffected exposed subjects and the possibility of pharmacologically modulating the process. Their disadvantages lie in the different pulmonary lymphocyte response and the difficulty in reproducing a model of chronic fibrosis. The HP models in rabbits are extraordinarily useful for evaluating the immunological mechanisms through which subjects repeatedly exposed to the antigen do not develop clinical manifestations. However, the rabbit has several immunological differences when compared to humans, and the effect of some immunomodulators in this animal is different. The models of HP in guinea-pigs have as advantages the ease in handling the animals, the possibility of pharmacological manipulation, and the ability to induce an acute phase that is very similar to that observed in humans. The drawback, however, is the low lymphocyte response and the striking eosinophilic reaction that contrast with the bronchoalveolar data found in HP in humans. In conclusion, there is no ideal model to reproduce all the findings observed in humans, suggesting that the experimental animal and the method of developing HP should be selected on the basis of concrete research aims.


Diagnostic capabilities of penicillin-based structures as tools in the in vitro diagnosis of penicillin allergy. Various penicillin-based structures attached to paper disks were used in the radioallergosorbent test (RAST) to measure concentrations of circulating specific IgE antibodies in sera from subjects suspected of having penicillin allergy. The structures used were penicilloyl, penicillanyl, penicoyl and penicanyl groups prepared from benzylpenicillin (PG), phenoxymethylpenicillin (PV), amoxicillin (AX) and 6-amino-penicillanic acid (6-APA). The efficacy of these structures was evaluated using serum samples from 53 subjects who, on clinical grounds, were considered to have had adverse reactions to penicillins. The results showed the presence of IgE antibodies specific to the penicillin side-chain in certain patients, whereas others had IgE antibodies specific to the penicilloyl or penicillin basic structure (penicillin nucleus), which led to clinical cross-reactions between penicillins. The results showed that the use of several penicillin-based structures in a new test system increased the positive rate observed to 54.7% from 37.7% utilizing penicilloyl G, penicilloyl V and amoxicilloyl Phadebas RAST. Thus, the prepared species improve the capabilities of the in vitro diagnosis of penicillin allergy.