Correlative effects of quinidine on ECG pattern and serum cholesterol concentration in Acridotheres tristis. Antiarrhythmic drug quinidine, administered daily at the rate of 10 mg/kg for 7 days in A. tristis produced an increasing effect on the amplitude and duration of different waves and intervals. Heart rate was decreased from 478.40 to 444.47 beats/min. Serum cholesterol level was reduced from 86 to 54.30 mg/100 ml. The data of the effect of quinidine on the ECG pattern and serum cholesterol were analysed and the values of the correlation coefficient and their significance were computed. The values of the correlation coefficient computed between the level of serum cholesterol (Y) and P-R interval (X) comes out to be significant at 5% level of significance. A linear regression line Y on X was fitted to the above data and the line is found to be: Y = 2535.897 X -62.858. This regression line may be used to determine the level of serum cholesterol on the basis of changes in the P-R interval of the ECG tracing in the quinidine treated birds.


Nitroimidazoles, Part XXIII--activity of satranidazole series against anaerobic infections. A large number of nitroimidazoles have been examined for in vitro activity against three anaerobes - Bacteroides fragilis (Bf), a strain of Bf resistant to metronidazole (16a) and Clostridium perfringens and many found to be active. Among these may be mentioned 1-methyl-5-nitroimidazoles carrying N - bound hetetocycles at position 2, such as satranidazole 1a, 1b, 1c, 1k, 1n and 1v which are at least twice as active as metronidazole (16a), ornidazole (16b) and tinidazole (16c). Even more active are 5-nitroimidazolyl benzimidazole 5d, -thiazolidinone 6b and thiadiazolidine dioxide 8a. Many other types of compounds derived from 1-methyl-2-amino-5-nitroimidazole are feebly active. Among 5-nitroimidazoles with a carbon substituent at position 2, 16a, 16b and 16c are equiactive while dimetridazole 14f is more active than 16a against Bf. Some 2-vinyl derivatives are very potent, with 18f and 18i being outstanding. Activity better than that of metronidazole is seen for nitroimidazooxazepines, e.g. 29d. 5-Nitroimidazoles are more active against anaerobes than 4-nitro isomers. Antianaerobic and antiamoebic activities generally run parallel in these classes of compounds. The study has led to the elaboration of the antianaerobic profile of satranidazole 1a.


Inhibition of cytokinesis by lead (Pb2+) in a centric diatom. Effect of inorganic and organo lead has been studied on the mitosis of a centric diatom Cyclotella meneghiniana f. unipunctata. Binucleate cells were formed in the presence of different concentrations of Pb2+ (1.0, 2.0, 3.0 and 5.0 mM) due to inhibition of cell plate formation. Lead at 5.0 mM concentration was more inhibitory than the other concentrations. Organo lead was a powerful depressant of cytokinesis than inorganic lead. Failure of cytokinesis might be due to disruption of microtubules. Formation of distinct nuclei delayed post incubation cell divisions suggest partial damage of mitotic spindles.


Late effects of cyclophosphamide treatment of neonatal mice. Swiss mice surviving early onset of wasting disease at 4-6 weeks following cyclophosphamide administration at birth suffer from delayed effects of this immunosuppressive drug. The late wasting syndrome developing at 6-8 months post-inoculation is characterized clinically by loss of weight, hunched posture, ruffled fur and diarrhoea. Lymphocyte and granulocyte levels are raised. The lymphocyte/granulocyte ratio is significantly inhibited. The development of various pathological lesions in thymus, spleen, lymph nodes and bone-marrow is frequently observed. Infiltration of lymphoid tissue in lungs, liver and kidneys is a common feature. It is hoped that further experimental studies would provide more insight into the delayed adverse effects of cyclophosphamide therapy.


In vitro influence of hormones on transport of glucose and glycogen in liver and muscle of pinealectomised pigeons, Columba livia Gmellin. To substantiate the increased peripheral utilization of blood glucose by pineal in wild pigeons, an in vitro study on the ability of liver and muscle slices of intact and pinealectomised wild pigeons (C. livia) in terms of uptake and release of glucose, and deposition and depletion of glycogen, in presence of insulin, acetylcholine, glucagon and adrenaline has been undertaken. A total insensitivity of liver and muscle of pinealectomised birds for glycogen deposition and insensitivity of liver for glucose uptake has been observed. Increased glucose release from liver in response to adrenalin has been observed. The results are discussed in terms of involvement of pineal in metabolic regulation associated with breeding activities.


Effect of nicotine on glycosaminoglycan metabolism in rats. Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major components of cigarette smoke which is believed to be partly responsible for the deleterious effect of cigarette smoke. There was significant alteration in the concentration of glycosaminoglycans (GAG) in rats exposed to cigarette smoke. Administration of nicotine to rats has been found to decrease many of GAG fractions in the aorta, liver and heart and increase in the lungs. The increase in GAG now observed in lung tissue in rats administered nicotine and those exposed to cigarette smoke may be involved in the increased incidence of lung cancer in smokers. Increased activity of many of GAG hydrolysing enzymes indicates increased degradation of GAG. Sulphate metabolism in the liver is also significantly altered by nicotine. Thus administration of nicotine to rats caused alteration in the metabolism of GAG which are similar to those observed on exposure of rats to cigarette smoke, indicating that nicotine content of the tobacco smoke may partly be responsible for the effect on GAG observed on exposure to cigarette smoke.


Oocyte maturation in Clarias batrachus: in vitro effect of various gonadotropins and homologous pituitary homogenate. The effects of five different gonadotropins and homologous pituitary homogenate (HP) on germinal vesicle breakdown (GVBD) were investigated in vitro using folliculated oocytes of Clarias batrachus. Among all the gonadotropins, salmon gonadotropin (SG-G100) was the most potent in vitro inducer of oocyte maturation. At concentrations of 1, 0.1, 0.01 and 0.001 microgram/ml it induced 86.98 +/- 2.71, 68.74 +/- 2.85, 44.56 +/- 1.75 and 25.90 +/- 2.36% GVBD. Next to SG-G100 in inducing GVBD was luteinizing hormone (LH) which was consistently found to be effective at all the concentrations used. Human chorionic gonadotropin was also found to be effective at all the concentrations but when compared to SG-G100 and LH, it was less effective. Follicle stimulating hormone and pregnant mare serum gonadotropin were found to be effective at higher concentrations but were ineffective at the lowest concentration. HP treatment resulted in a significant number of GVBD at all the three concentrations used.


Effect of prolactin on accessory sex organs of prepuberal male albino rats: an in vitro study. The in vitro studies on the effect of hypophysial gonadotropins (PRL, FSH, LH) on the maturation events of accessory sex organs in prepuberal male rats revealed that prolactin (PRL) alone has both direct as well as androgen mediated effect on the maturation activities. The effect of PRL is age dependent and it had higher activation on the gland system than the duct system.


Salmonella typhi cell wall protein showing antigenic similarity to transferrin. Antiserum to cell wall proteins of S. typhi showed immunoprecipitin lines of identity with homologous antigen, normal human serum and human transferrin. Also, anti-transferrin antibody showed immunoprecipitin band with S. typhi cell wall proteins and agglutinated S. typhi whole cells, but not Eschericia coli. It is speculated that transferrin or a transferrin-like protein present in the cell wall may play a role in iron-uptake by S. typhi.


Reversal of endothelin-1-induced contractions by isoproterenol without myosin dephosphorylation in tracheal smooth muscle. Effects of isoproterenol on isometric force, and 20,000 Da myosin light chain (LC20) phosphorylation were examined in smooth muscle fibre strips from lamb trachea stimulated with endothelin-1 (ET-1). ET-1 induced a rapidly rising isometric tension which was coupled with a multiple site phosphorylation of LC20. Isoproterenol addition at the time of peak isometric force resulted in a brisk relaxation of the fibre strips. Myosin light chain phosphorylation, however, remained unaffected.


Fibrinolytic activity in bleeding associated with intrauterine contraceptive devices. A prospective study was conducted to assess endometrial fibrinolytic activity before and after insertion of copper 250 (Multiload) and after removal of the IUCD. Fibrinolytic activity was measured on the fibrin plate in the form of zone of lysis. Sixty two women in the control group had fibrinolytic activity of endometrium in the range of 0.3-9.5 cm2 (mean +/- SD 1.77 +/- 1.27), 40 women who wanted to have the IUCD removed, because of reasons other than bleeding had a range of 0-9.5 cm2 (mean +/- SD 2.28 +/- 1.88) while 48 women who had the IUCD removed because of subjective menorrhagia had a range of 2.24-7.56 cm2 (mean +/- SD 4.75 +/- 1.20) which was higher than in the other two groups.


Post-coital antifertility activity of the marine plant, Achrostichum aureum L. in rat. The ethanolic extract of A. aureum and its fractions were evaluated for postovulatory antifertility activity in female rats. The water soluble fraction of ethanolic (95%) extract prevented (100%) pregnancy when administered to female rats on days 1-7 postcoitum. This fraction was found devoid of both estrogenic and antiestrogenic activities.


Immunosuppression by human seminal plasma as evaluated by effect on natural killer cell cytotoxicity. Re-examination of earlier observations of the suppressive role of oxidized polyamines and their cytotoxic products, has suggested that immunosuppression by seminal plasma (SePl) observed in in vitro assays employing culture medium supplemented with serum containing amine oxidase is 'artefactual'. Investigation of the relevancy of this suggestion to immunosuppression of natural killer (NK) cell activity by SePl as related to NK cell viability was made. NK cells in various culture regimens were preincubated in SePl and medium supplemented with 10 per cent foetal bovine serum, a source of amine oxidase, without and with 0.2 mM hydroxylamine, an amine oxidase inhibitor, and 10 per cent normal human AB serum, virtually devoid of amine oxidase, and examined for viability up to 72 h by trypan blue dye exclusion and lytic activity in a 4 h 51chromium-release microcytotoxicity assay. Viability to NK cells varied with the concentration of SePl, culture medium and time of incubation. At 18 and 24 h, times corresponding to preincubation and completion of the NK cell assay, viability was greater than or equal to 75 per cent for the optimum inhibitory concentration of SePl, irrespective of the culture medium. Comparison of the lytic activity of NK cells preincubated with the optimum inhibitory concentration of SePl in the various culture regimens did not disclose significant (P less than 0.05) differences.(ABSTRACT TRUNCATED AT 250 WORDS)


Socio-economic differentials in mothers at risk based on pre-pregnancy weights & heights. Data on heights and weights of women measured as part of a longitudinal study on maternal and child health in Tamil Nadu state, south India are presented and discussed in relation to various socioeconomic and demographic factors. The mean (+/- SD) heights in rural and urban women were 151.2 +/- 5.4 cm and 150.8 +/- 6.6 cm respectively. The mean weights were 42.6 +/- 5.4 kg; and 44.0 +/- 7.9 kg respectively. The mean BMI were 18.6 +/- 2.2 and 19.4 +/- 3.5 respectively. The differences were statistically significant. Forty two per cent of rural and 48 per cent of urban women were less than either 145 cm in height or 40 kg in weight. The need to identify and care for such women as part of the "Risk Approach" in maternal and child health programmes is emphasized.


Distribution of iodine in marine foods from different regions of India. The iodine content of fresh and processed marine fish collected from different parts of coastal India was analysed. It was found that Indian marine fish are rich in iodine content (mean of 193 +/- 82 micrograms/100 g on wet weight basis). Also the iodine contents of shell fish and crabs (0.7-2.5 mg/100 g on wet weight basis) were higher than that of other fish. No significant regional differences were noted in the iodine content of marine fish. Further, no differences were observed in case of either salted or sun-dried fish indicating that curing did not influence the iodine content.


Inhibition of aflatoxin production & growth of Aspergillus flavus by eugenol & onion & garlic extracts. Efficacy of natural non-toxic materials including extracts of onion and garlic as well as eugenol was tested against aflatoxin production by A. flavus in liquid SMKY medium and in maize grains. Maximum inhibition in the mycelial growth occurred with garlic extract (61.94%), whereas inhibition of aflatoxin production was highest (60.44%) due to onion extract. Eugenol was most suitable for inhibiting aflatoxin production (60.35%) on maize grains.


Peroxidative changes in experimental diabetes mellitus. Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.


Psychological assessment of blood related renal donors. The impact of kidney donation on the psychological health of 31 living related donors was assessed by administering certain psychological tests before and after the operation (for donating the kidney). The results indicated a significant rise in the somatization subscale of the Middlesex Hospital Questionnaire (MHQ) from a mean of 1.61 to 3.23. There was no significant change in the other variables of these instruments or in the locus of control score. Only about one-fourth of the donors had prior knowledge of renal transplant. In almost all cases, the decision to donate had been voluntary and immediate, motivated by a concern for the recipient; there was virtually no second thoughts or regrets subsequently, which was apparently partly related to the opinions of other relatives who positively valued the act of donation.


Antibiotics & glycosaminoglycan metabolism in rats. The administration of antibiotics to rats resulted in significant alteration in the metabolism of glycosaminoglycans (GAG). The concentrations of the total GAG and most of the fractions increased in the aorta and liver in rats given tetracycline and cephalosporin, but decreased in ampicillin and streptomycin treated groups. The activity of biosynthetic enzymes of GAG in the liver increased significantly with all the antibiotics administered, except streptomycin. The pattern of change in the activity of many of the degrading enzymes of GAG in the liver and aorta was not uniform in different antibiotics administered groups. The changes observed in the activities of biosynthetic and degrading enzymes of GAG in the liver and aorta in different antibiotics administered groups may account for the alterations in the level of GAG observed in different experimental groups.


Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate. A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age-pigment, lipofuscin, can be accepted as an index of cellular ageing.


Confidence intervals in medical research. The utility of confidence intervals in a wide variety of situations in the medical field is re-emphasized, with examples drawn from controlled clinical trials, disease control programmes, vaccine trials and laboratory studies. It is shown that the confidence interval approach is more informative than a mere test of statistical significance, and should therefore be employed as an useful adjuvant. Since proportions are widely quoted in medical literature and as the determination of the exact confidence limits for a binomial proportion is iterative and time-consuming, an assessment is made of 15 published methods which provide approximate confidence limits; the 'Square root transformation' method is recommended since it is accurate and the computation of limits is relatively easy. In the case of a difference between two proportions, the usual method may be employed if sample sizes exceed 75; for smaller sample sizes (even for sizes of 5), the Jeffreys-Perks method is very satisfactory and is therefore recommended.


Bacterial enteric infections and vaccine development. There is a great need for effective vaccines against the major bacterial enteropathogens. Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease and several million deaths annually in developing countries. Diarrhea caused by a bacterial enteric infection is also the commonest illness experienced by international travellers. Studies of pathogenesis have established the importance of specific ligand-receptor interactions between the enteropathogens and the intestinal epithelium, resulting in attachment and colonization of the bacteria and production of disease through either invasive mechanisms or production of toxins. Studies of protective immune mechanisms have emphasized the importance of secretory IgA antibodies and mucosal memory for protection against noninvasive, enterotoxigenic infections such as cholera and ETEC diarrhea and also drawn attention to the possible protective role of IFN-gamma production by intestinal T cells in these secretory diarrheas. In invasive dysenteric and enteric-fever infections caused by such organisms as Shigella and Salmonella, optimal protection may depend on a combination of mucosal and systemic immunity. On the basis of this knowledge, several new vaccines have been developed and proved to be efficacious in large field tests. These include an oral killed B-WC vaccine and a killed WC-alone vaccine against cholera, and both a live attenuated oral vaccine (Ty21a) and an injectable Vi antigen vaccine against typhoid fever. In addition, a killed oral ETEC vaccine and live attenuated oral Shigella vaccines have begun to be tested in phase 1 and phase 2 studies in humans. The properties of the new vaccines against bacterial enteric infections give promise that these vaccines should be useful both in control programs in developing countries and for immunoprophylaxis against travellers' diarrhea.


Cells and cytokines in mucosal immunity and inflammation. The mucosal immune system consists of a number of compartments that are populated with a different assortment of cells and serve different functions. The cytokines produced by the cells in each of these compartments are currently being defined. This is best understood in relation to B cells, whose proliferation and maturation is guided by a sequence of cytokines. PP are inductive sites that preferentially stimulate IgA production. At least in part, this preference seems to be due to the T cells located in PP, which have been shown to stimulate switching to IgA production by cognate interactions and production of TGF-beta. Postswitch B cells expressing surface IgA respond to IL-5, a cytokine produced by T cells in GALT. Terminal differentiation to IgA-producing plasma cells in the lamina propria may be driven by IL-6, which can be produced by a variety of cells in the lamina propria and by epithelial cells. T cells in the lamina propria have an assortment of surface markers consistent with both activation and memory and appear to produce a variety of cytokines in the local environment that presumably act in normal host defense. IEL consist mainly of CD8+ T cells. They have been shown to produce IFN-gamma and, very likely, other cytokines that presumably act in a paracrine fashion on local enterocytes. How these cells and cytokines are perturbed during intestinal inflammation is currently being defined. A certain assortment of cytokines are greatly increased in IBD. This assortment, including IL-1, IL-6, and IL-8, is elevated in a wide variety of chronic inflammatory states in other tissues as well. A critical requirement for cytokines to exert their effects is the expression of specific receptors on target cells. Virtually nothing is known about this aspect of mucosal immunity, but receptor expression on mucosal cells must be defined before we will be able to understand the complex interactions among lymphoid cells, the cytokines they produce, and the local stromal and epithelial cells.


The mucosal barrier, IgE-mediated gastrointestinal events, and eosinophilic gastroenteritis. The "mucosal barrier" plays an important role in regulating immune responses in the gastrointestinal tract. Although the precise mechanisms controlling mucosal immune responses have not been defined, when an abnormal response such as IgE production is initiated, a variety of complex and incompletely understood pathophysiologic events occur and can result in gastrointestinal pathology. This article attempts to present the complexity of such abnormal responses. Although more questions have emerged than were answered, in recent years our knowledge of the pathophysiology of IgE-mediated events in the gastrointestinal tract has advanced significantly. Our understanding of the pathophysiology of these events will ultimately allow the development of more directed and effective therapeutic interventions for allergic gastrointestinal diseases. In addition, through further clinical and basic research, we should begin to unravel the more enigmatic conditions affecting the gastrointestinal tract, such as EG.


Celiac disease. A gastrointestinal disease with environmental, genetic, and immunologic components. In summary, research in immunogenetics, protein chemistry, and molecular biology is leading to a greater understanding of the contribution of genetic, environmental, and immunologic factors to the etiopathogenesis of celiac disease. Taken together, the findings discussed in this article suggest that understanding of the contribution of a major genetic factor to celiac disease susceptibility is closer at hand. Thus, the pathogenesis of celiac disease appears to involve an interaction between the gene products of the HLA class II D region on chromosome 6 and the gliadin proteins, possibly because of their homology with an intestinal viral protein. A logical extension of these findings would predict that T cells, particularly CD4 T cells, play a key role in the pathogenesis of celiac disease by virtue of their recognition of a gliadin or viral peptide in conjunction with the HLA class II D-region gene products. Nonetheless, the precise mechanisms by which the HLA class II genes and their products contribute to celiac disease is not known. Further, the precise peptide sequence in gliadin that interacts with the relevant HLA class II D-region molecule is not known. Finally, the role of CD4 T cells in the pathogenesis of celiac disease, either directly or indirectly by their ability to regulate other T-cell subsets and antibody-producing B cells, remains to be defined. The lessons learned and to be learned from celiac disease will substantially increase our understanding of the mechanisms that are important in this disease as well as in other intestinal and HLA-associated autoimmune diseases.


Immune disorders of the liver and bile duct. Several hepatobiliary diseases appear to be mediated by the host immune response. They can be subdivided into those in which the immune reaction is against an infectious agent such as hepatitis viruses, those in which the immune reaction appears to be against an autoantigen expressed on hepatobiliary cells, and those due to alloimmunity. The existence of autoimmune liver diseases indicates a breakdown in the mechanisms responsible for self-tolerance. In HBV infection, the hepatocellular necrosis appears to be mediated by the host immune response against viral antigens expressed on the membranes of infected hepatocytes. Autoimmune chronic active hepatitis can be subdivided on the basis of differences in circulating autoantibodies. In classic type I autoimmune chronic hepatitis, autoantibodies are directed against non-organ- and non-species-specific antigens. Thus, they are unlikely to be involved in pathogenesis. In contrast, type II autoimmune chronic hepatitis is characterized by antibodies against specific cytochrome P-450 isoenzymes that appear to be expressed on the surface membrane of hepatocytes. Immunogenic cytochrome P-450 also can be induced by drug metabolism and haptenation. This indicates that environmental or medicinal xenobiotics may initiate autoimmune liver damage. Primary biliary cirrhosis is characterized by T-cell-mediated inflammation and destruction of interlobular and septal bile ducts and antibodies specific for epitopes of the 2-oxo-acid dehydrogenase multienzyme complex of mitochondria. The histopathologic lesion NSDC also is observed in alloimmune-mediated diseases such as CGVHD and rejection of liver allografts. PSC may be mediated by an immune response against endothelial cells of the peribiliary capillary plexus, with secondary reactions to bile duct epithelial cell antigens. The pathogenesis of alcoholic liver disease is multifactorial, but one component involves an immune response to acetaldehyde-protein adducts. Secondary sensitization of cell-mediated effector mechanisms, endothelial damage, and secretion of noxious cytokines appear to be involved in pathogenesis.


The role of the mucosal immune system in inflammatory bowel disease. Continued delineation of the major factors that lead to intestinal inflammation will provide critical insights into many of the pathophysiologic events leading to tissue destruction in IBD. The exploration of exciting and important new areas, such as the role of adhesion molecules, proinflammatory cytokines, and the activation of lymphocytes and phagocytes, will contribute significantly to a better understanding of the mechanisms that sustain the intestinal inflammatory process. Determining the mechanisms of amplification and perpetuation of intestinal inflammation as well as learning more about the natural suppression of intestinal inflammation by the normal cellular and cytokine networks of the mucosal immune system will open exciting new therapeutic approaches. It is encouraging to see realistic and testable working models emerge from the combined efforts of many committed investigators who have been engaged in studying the role of the mucosal immune system in the pathophysiology of IBD. A great deal more remains to be learned in this rapidly advancing area, and we can look forward with confidence to continued advances in the study of IBD.


Ambulatory blood pressure monitoring and circadian variation of cardiovascular disease; clinical and research applications. Ambulatory blood pressure monitoring is an evolving technology. It has an established role in the diagnosis of hypertension, the clinical management of selected patients, and in the evaluation of new medication. From continuous recording much has been learned about the circadian nature of blood pressure and heart rate. Future research holds promise for a greater understanding of the mechanisms and treatment of cardiovascular disease. The purpose of this short review is to describe the development of ambulatory blood pressure monitoring, and outline some of its important contributions to date; and also to explore the research potential and clinical utility of advanced intravascular monitoring techniques, such as the continuous recording of pulmonary artery pressure in ambulant patients.


Dynamic changes of the QRS complex in unstable angina pectoris. Despite intensive medical treatment to control chest pain, about one-third of patients with unstable angina have an unfavourable outcome within a period of 1 to 2 months. Holter monitoring can identify patients with silent myocardial ischaemia that are at a high risk of sustaining a major cardiovascular event. The present paper describes the use of dynamic, continuous, computerized on-line vectorcardiography for real-time monitoring of QRS-complex and ST-segment changes in patients with unstable coronary disease. In many patients a pattern of frequent repetitive episodes of QRS change was observed, with or without concomitant ST change. Whereas no patient had episodes of ST-vector change without also having episodes of significant QRS change, 15 patients had several episodes of QRS changes without any episode of significant ST change. The number of episodes of significant increase of the QRS vector difference correlated weakly but significantly with the number of episodes of significant ST-vector magnitude change (r = 0.34, p less than 0.05). The present study suggests that myocardial ischaemia will influence the QRS complex as well as the ST segment. The mechanism behind the QRS changes observed is not clear but episodes of QRS change without ST change or chest pain, may reflect sudden depressions of left ventricular function, as has been reported by others to occur in patients with coronary artery disease. Dynamic vectorcardiography offers the opportunity to monitor all parts of the QRST complex in real time.


Correlation of reciprocal ST-segment depression after acute myocardial infarction with coronary angiographic findings. We studied 266 consecutive patients with acute myocardial infarction to assess the significance of electrocardiographic "mirror images". Ninety-four (group A) had anterior wall and 132 (group B) had inferior wall infarction. Thirty-one group A patients had stenosis of the right coronary artery greater than 85% in diameter (subgroup A1), and 63 either had a normal right coronary artery or less than 85% stenosis (subgroup A2). Of group B patients 62 had greater than 85% stenosis of the left anterior descending (subgroup B1) and 70 had a left anterior descending or less than 85% stenosis (subgroup B2). ST-segment depression was significantly greater in depth and duration in subgroup A1 than A2 (p = 0.02) and in subgroup B1 than B2 (p = 0.02, p = 0.01, respectively). Left ventricular ejection fraction was lower in subgroup A1 than A2 (p less than 0.001) and in B1 than B2 (p less than 0.001). There was a strongly positive correlation between depth and duration of ST-segment depression and the Gensini index (r = 0.78, 0.84) for anterior and inferior infarction, respectively. In conclusion, increased depth and duration of ST-segment depression opposite the infarct are indicative of ischemia, and are related to the extent of coronary artery disease, the degree of stenosis of the vessels supplying the opposite wall and of left ventricular dysfunction.


Recombinant tissue plasminogen activator in acute myocardial infarction in the Chinese in Hong Kong. Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue plasminogen activator (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 h after onset, and intravenous heparin or dipyridamole therapy started at 3 h, were studied prospectively. Their mean age was 59.6 +/- 10.6 yr. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion were seen in 63 patients (70.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%) majority of which are related to reperfusion and self-remitting, haematoma around vascular access sites (23.6%), melaena (3.3%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 h, including a decrease in fibrinogen by 64.2% and an increase in fibrin degradation products by 47 times. The changes in haemostatic variables were not related to body weight or bleeding complications. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure and reinfarction. Angiogram at 14 days confirmed TIMI 2 or 3 patency of infarct-related arteries in 63 out of 73 (86.3%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promise of recombinant tissue plasminogen activator for acute myocardial infarction in the Chinese were confirmed.


Ventriculoarterial coupling during exercise in normal human subjects. To examine the relative roles of ventricular contractility and loading conditions for cardiovascular adjustment during exercise, 10 normal human subjects were studied using a framework of ventriculoarterial coupling. Anaerobic threshold was evaluated to determine the work rates of aerobic and anaerobic exercise. Ventricular contractile properties were quantified by the slope of the end-systolic pressure-volume relationship (ventricular elastance) and arterial system properties were expressed by the end-systolic pressure-stroke volume relationship (arterial elastance). During aerobic exercise, left ventricular end-diastolic volume and stroke volume were increased by 14 and 33%, with plasma norepinephrine levels being doubled. Arterial elastance was reduced by 30%, but ventricular elastance did not change significantly. During anaerobic exercise, ventricular end-diastolic volume returned to the resting value, while stroke volume remained increased by 31%. In contrast to aerobic exercise, ventricular elastance rose substantially by 89% in association with about a 10 times increase in plasma norepinephrine. Arterial elastance remained the same as in aerobic exercise. Thus, the increase in stroke volume was primarily mediated by changes in loading conditions during aerobic exercise and by enhanced contractility during anaerobic exercise.


Isolated right ventricular infarction.

Isolated right ventricular infarction. The literature on isolated right ventricular infarction is reviewed and local experience is reported. Chronic lung disease is an important risk factor. Chest pain and breathlessness are common. Syncope and sudden collapse can also occur. Rhythm disorders include sinus bradycardia, atrial fibrillation and ventricular tachycardia or fibrillation. Atrioventricular block is rare. Hypotension and a right-sided fourth heart sound are common. Cautious use of slow-release nitroglycerin is not hazardous in the absence of hypotension. High doses of steroids and anticoagulants can be helpful. The prognosis is usually good, although sudden collapse can occur due to ventricular fibrillation, rupture of the right ventricular free wall or massive pulmonary embolism.


Resting blood pressure and cardiovascular response to sympathetic stimulation in adolescents. The prevalence of significant hypertension in childhood may be higher than expected. We have measured sitting blood pressure in 168 11-yr-old children attending a pre-high school in the Neapolitan area on four occasions over a 3-month period. We have also measured blood pressure and heart rate during a mental arithmetic test and during isometric exercise. Prevalence of significant hypertension (diastolic blood pressure 82-90 mmHg) was 13% at the first visit and decreased to 6.5% at the last visit; prevalence of severe hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased from 5.4% to 1.2% from the 1st to the 4th visit. No sex-related difference was observed. A more frequently positive family history of hypertension (50% vs 30% in the fifth and first quintile of blood pressure, respectively) and higher body weight (body mass index = 21.4 vs 19.3 kg/m2) were found in children in the 5th quintile of blood pressure distribution. Blood pressure increased during mental arithmetic by 10/13% of the resting values in the first quintile and by 6/11% in the last one during mental test; during handgrip the increase was of 20/37% and 24/46%, respectively: differences between quintiles did not reach statistical significance. These data show that about 8% of a Neapolitan sample of school population have high blood pressure levels, while no difference in vascular reactivity to sympathetic stimulation was detected in children with higher blood pressure.


The hypertrophied myocardium and coronary disease. Structural changes in patients submitted to aortocoronary bypass surgery. Seventeen patients with coronary disease submitted to myocardial revascularization were studied. Ten patients had a hypertrophied ventricle, and 7 had normal ventricular mass. Myocardial biopsies were obtained before ischemia and at the time of reperfusion and were assessed for: volume fraction of fibrous tissue, myocyte diameter, morphometric mitochondrial studies and ultrastructural changes. The volume fraction of fibrous tissue in patients with hypertrophied ventricle was 1.9 +/- 0.04, and in patients with normal ventricular mass was 0.9 +/- 0.01 (p less than 0.05). The diameter of the myocyte was 23 +/- 0.3 microns and 18 +/- 1.2 microns for patients with hypertrophied and normal ventricular mass, respectively (p less than 0.01). The value of volumetric density for pre-ischemia samples in patients with a hypertrophied ventricle was 23 +/- 2.2 and in patients with normal ventricular mass was 35 +/- 2.7 (p less than 0.02). Grades 3 and 4 of damaged mitochondria were significantly increased in reperfusion samples from patients with a hypertrophied ventricle compared to pre-ischemia samples. Collagen growth was increased in hypertrophied hearts which were also more sensitive to the ischemia/reperfusion mechanism.


Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study. An analysis of the Coronary Artery Surgery Registry (CASS) was performed to determine the occurrence of stroke after coronary artery bypass surgery in patients entered into the Coronary Artery Surgery Study Registry. Of the 10,098 patients having coronary artery bypass surgery at the Coronary Artery Surgery Study participating sites during the period July 1974 through May 1979, a total of 348 patients (or 3.4%) sustained a stroke during the first year after coronary bypass surgery. Fifty-nine strokes occurred on the day of surgery, and an additional 129 strokes occurred during hospitalization for coronary bypass surgery. Thus, 188 patients (1.9%) of the entire surgical group sustained a stroke during initial hospitalization for coronary artery bypass surgery. Logistic regression analysis was used to predict stroke on the day of surgery, during the hospitalization for surgery, and during the first year after surgery. The most powerful predictors of stroke on the day of coronary artery bypass surgery were: 1) older age (n = less than 0.0001); 2) use of alpha-adrenergic drugs after bypass (n = 0.0001); and 3) longer duration of cardiopulmonary bypass (n = 0.002). For those strokes occurring at least 1 day after coronary artery bypass but during the initial hospitalization, age and duration of cardiopulmonary bypass were the most powerful predictors of stroke. An analysis of predictors of stroke within 1 yr after hospital dismissal for initial coronary bypass surgery revealed that the most powerful predictor was a history of previous cerebrovascular disease (n less than 0.0001) and a history of hypertension (n less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


Pacing termination of spontaneous ventricular tachycardia in the coronary care unit. We reviewed our experience with the use of pacing techniques in the acute treatment of spontaneous ventricular tachycardia occurring outside the context of acute myocardial ischaemia. Over a consecutive 18 month period 23 patients (20 male, aged 38-76 yr) admitted to our coronary care unit experienced a total of 75 episodes of haemodynamically tolerated sustained ventricular tachycardia. Pace termination was attempted in 18 patients in a total of 58 episodes of ventricular tachycardia using a standard temporary external pacemaker. Pacing was successful in 32/58 (55%) attempts vs 13/49 (27%) with intravenous antiarrhythmic drug therapy p = 0.003. The superior success rate of pacing was apparent whether or not patients were receiving chronic antiarrhythmic drug therapy. Pace termination should be considered in the treatment of haemodynamically tolerated spontaneous ventricular tachycardias.


Life-threatening pulmonary hypertensive crises occurring preoperatively. A 10-week-old infant with left atrial isomerism and a primum atrioventricular septal defect presented with life-threatening episodes of collapse. They proved due to paroxysmal pulmonary hypertension, although her pulmonary artery pressure was virtually normal between attacks. The pulmonary hypertensive crises persisted early but resolved late after surgical correction. Labile pulmonary vascular resistance may prove a problem preoperatively if the ventricular septum is intact.


Patency of Blalock-Taussig shunt assessed by Doppler colour flow imaging. A neonate with pulmonary atresia and intact ventricular septum underwent a modified right sided Blalock-Taussig shunt. Following the procedure, the patient developed a right sided haemothorax, which required drainage. A murmur was not audible subsequently. Echocardiography with colour flow imaging enabled identification of patency of the right sided shunt. It was then possible to discontinue intravenous prostaglandin medication.


Pericardial effusion as a result of cardiac rhabdomyoma. A 34-yr-old patient is presented who suffered from chronic pericardial effusion. Surgical exposure revealed a right atrial rhabdomyoma.


Are late potentials operative in arrhythmias following methylprednisolone pulse therapy. We have evaluated 11 patients for the presence of late potentials in an attempt to investigate whether pulse methylprednisolone exerted its arrhythmogenic effect via this mechanism. All patients received pulse steroid therapy for their glomerulopathies. One of the patients developed bradycardia, no electrocardiographic abnormalities were present in the rest of these patients. Late potentials were not detected in any of the patients. Thus, in this preliminary study we have not been able to demonstrate that pulse steroid therapy plays a role in the genesis of late potentials.


Post-operative left ventricular to right atrial shunt: detection by colour Doppler echocardiography. A 24-yr-old man, who underwent combined mitral and aortic valve replacements for rheumatic valvar heart disease, was detected to have a left ventricular to right atrial fistula 3 months after surgery on routine cross-sectional and colour Doppler echocardiography. This complication of valve replacement is reported because of its rarity.


Implantation of a dual chamber pacemaker in a patient with persistent left superior vena cava. A patient underwent dual chamber pacemaker implantation by puncture of the left subclavian vein. During the procedure we observed persistence of the left superior vena cava. An active fixation atrial lead was required to prevent instability induced by the odd course of the electrode and produced excellent long term pacing and sensing.


Perigraft seroma diagnosed by echocardiography: a complication following Blalock-Taussig shunt. Perigraft seroma is a specific clinicopathologic entity, which is a collection of clear, sterile fluid, confined within a nonsecretory fibrous pseudomembrane surrounding a vascular graft. Serous leaks and/or seroma formation from polytetrafluoroethylene grafts have been reported in peripheral arteriovenous anastomoses, arterial grafts and subclavian pulmonary anastomoses. We present a case of seroma formation which developed after a Blalock-Taussig shunt operation constructed with a polytetrafluoroethylene graft in a child with tricuspid atresia and which was diagnosed by echocardiography.


Effects of MPTP and vitamin E treatments on immune function in mice. The effects of treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and vitamin E, an antioxidant, on immune functions were examined. Male C57/B1 mice were fed daily with natural vitamin E for 12 weeks, subsequently injected i.p. with MPTP or its vehicle, and sacrificed 1 week later. Control mice received the stripped corn oil vehicle daily, in place of vitamin E. Oral vitamin E feeding increased cerebral vitamin E content by 60% (P = 0.05). However, MPTP attenuated this rise in cerebral vitamin E content when measured 1 week after treatment with the neurotoxin (P = 0.05). MPTP also produced an 80-90% reduction in striatal dopamine content in both the stripped corn oil control group and the vitamin E-treated group (P = 0.0000). One week after MPTP injection, the numbers of peripheral blood lymphocytes and the percent of spleen T-cells, but not B-cells, were decreased in those groups receiving MPTP alone or MPTP plus vitamin E (P less than 0.05 and 0.02, respectively). The Con A-induced IL-2 production of spleen cells was decreased in all treated groups (P less than 0.005). There was no difference in the mitogenic stimulative response to PHA, Con A or LPS. However, the response to PWM was increased in both MPTP and MPTP plus vitamin E-treated groups (P less than 0.05 and 0.001, respectively). On the other hand, the one-way mixed lymphocyte response of the splenocytes from the MPTP-treated group was increased (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Combined effects of selected insecticides on humoral immune response in mice. Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone.


IL-2 responsiveness of lectin-induced lymphoblasts: soluble IL-2 receptor release and differential in vitro effects of immunosuppressants. We examined the mode of action of different immunosuppressants on the responsiveness of phytohemagglutinin (PHA)-induced lymphoblasts further stimulated by recombinant interleukin-2 (rIL-2). The stimulation of PHA blasts with rIL-2 resulted in an enhancement of tritiated thymidine ([3H]TdR) incorporation and of soluble interleukin-2 receptor (sIL-2R) release. Cyclosporin A (CsA) and prednisolone inhibited in different ways the responsiveness of PHA pre-stimulated blood mononuclear cells (PBMC) to rIL-2, as measured by [3H]TdR incorporation. The addition of CsA resulted in considerable enhancement of the release of sIL-2R, whereas the addition of prednisolone was associated with a similar enhancement only when the higher concentrations of rIL-2 were employed. EGTA, a calcium (Ca2+) chelator, and verapamil, a Ca2+ channel blocker, inhibited [3H]TdR incorporation in a concentration-dependent manner. EGTA inhibited sIL-2R release in the same manner when used alone, and reversed the CsA- and prednisolone-induced enhancement of sIL-2R release by rIL-2 induced lymphoblasts, when used in combination with CsA or prednisolone. Verapamil had a similar but less striking effect. The effects of CsA and prednisolone were also studied in PHA-induced blasts originating from purified CD4+ or CD8+ lymphocytes. Stimulation of these blasts with rIL-2 resulted in higher [3H]TdR incorporation by CD8+ blasts than by CD4+ blasts: however, no sIL-2R release was detected in supernatants of either CD4+ or of CD8+ blasts. Both CsA and prednisolone inhibited the rIL-2-induced enhancement of [3H]TdR incorporation by both T-cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)


Humoral responses following immunization with Leishmania infantum (ex. Oklahoma): a comparison of adjuvant efficacy in the antibody responses of Balb-C mice. Adjuvants are commonly used in immunization protocols for the purpose of augmenting immune responses to antigens. The antigenic profile of Leishmania infantum (ex. Oklahoma) is described and the efficacies of three adjuvants delivered coincidentally with killed promastigotes are compared, by measuring relative serologic responses of Balb-C mice to specific antigenic determinants. Western blotting techniques were employed to visualize humoral responses to isolated antigens; serologic profiles were compared and contrasted. Four immunization protocols utilizing Freund's complete adjuvant, glucan adjuvant, lipovant adjuvant or phosphate-buffered saline, in conjunction with killed L. infantum (ex. Oklahoma) promastigotes were executed in parallel. All groups receiving adjuvant protocols developed enhanced serologic responsiveness. Similar profiles were observed in mice treated with glucan or lipovant. Animals receiving promastigotes in Freund's complete adjuvant also developed strong humoral responses, binding cross-reactive epitopes not recognized by other groups. Our findings indicate that glucan and lipovant present effective adjuvant alternatives, to Freund's complete adjuvant and may be of value in immunization against visceral leishmaniasis.


Potentiation by thiopurines and sulfhydryl-reactive agents of the inhibition by 3-deazaadenosine of mononuclear phagocytes. Combination effects of 3-deazaadenosine (c3Ado) on antibody-dependent phagocytosis in mouse resident peritoneal cells and human peripheral blood monocytes precultured with cytotoxic thiols, azathioprine (AZA) or 6-mercaptopurine (6-MP), and thiol-reactive agents, 2-cyclohexene-1-one (2-CH) or ethacrynic acid (ETA), are described. In the mouse cell preparations, a non-inhibitory concentration of 10 microM AZA or 6-MP potentiated the inhibition by 5 and 10 microM c3Ado of phagocytosis. Higher concentrations of AZA or 6-MP (50, 100 microM) and c3Ado (40, 50 microM) were needed to achieve similar effects in human monocytes. Both 2-CH (50 microM) and ETA (25 microM) inhibited mouse cell phagocytosis and acted synergistically with c3Ado. Precultivation of mouse cells with an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO, 50 microM) caused no inhibition of phagocytosis and no potentiation of the inhibition by c3Ado, although BSO potentiated the inhibition by 2-CH (50 microM). In human monocytes, non-inhibitory concentrations (10 and 25 microM) of gold sodium thiomalate (GST), AZA, and c3Ado, but not 6-MP, potentiated the inhibition by 2-CH (25-37.5 microM) of phagocytosis. Results are discussed in connection with the possible modulation by endogenous sulfhydryl-reactive metabolites of phospholipid turnover of the effects of c3Ado.


Enhancement of murine alveolar macrophage functions by orally administered beta-glucan. The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on alveolar macrophage (AM) functions of CDF1 mice was examined. SSG administered orally (20, 40, 80 or 160 mg/kg) for 10 consecutive days enhanced the lysosomal enzyme activity of AM. The greatest enhancing effect was observed at 80 mg/kg of SSG. Multiple oral administrations of SSG (10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity and interleukin-1 (IL-1) production of AM were also augmented by oral administration of SSG, and the kinetics of the activated state differed depending on the kind of activity. However, H2O2 production of AM was not affected by SSG. Orally administered SSG also (40 or 80 mg/kg, 10 consecutive days) increased the number of AM and the greatest increment was observed 14 days after the first administration. On the other hand, the supernatant of Peyer's patch (PP) cells from mice administered SSG (80 mg/kg) orally stimulated the lysosomal enzyme activity of AM in vitro, and enhanced colony stimulating activity (CSA) was detected from this supernatant. These results demonstrate that SSG given by the oral route can activate murine AM both qualitatively and quantitatively, and it would mediated, at least in part, by the activation of PP cells in the intestine.


Role of hydrolysis in the association of leu-enkephalin to peripheral blood mononucleate cells. The possible hydrolysis of labelled leucine enkephalin in the presence of peripheral blood mononucleate cells and its association with the same cells have been investigated. Results obtained indicate that under experimental conditions leu-enkephalin is rapidly hydrolysed in the presence of model cells. Under the same conditions, the radioactive label is partially associated with the cells. The presence of protease inhibitors reduces both enkephalin degradation and association of the radioactive label with the cells. The hypothesis that the associated species is intact leu-enkephalin is not supported by the relative kinetics of enkephalin hydrolysis and of association of the radioactive label with the cells, nor by the statistically significant correlation between these data, nor again by the effect of proteolysis inhibitors. The same data agree with the hypothesis that the radioactive label associated with the cells is represented by one, or several, of the fragments formed by enkephalin hydrolysis, not by the intact molecule. However, results obtained in the presence of hydrolysis-stable DADL indicate association with the cells of the intact peptide. Moreover, antigen stimulation has opposite effects on the two peptides: with leu-enkephalin, hydrolysis and association are increased, with DADL association is decreased by stimulation. The sum of these data seems to suggest the co-existence in PBMC of two phenomena, i.e. internalization of one, or several, of the fragments formed by the enzyme degradation of enkephalin and binding to membrane receptors of the intact pentapeptide.


Model of bronchial allergic inflammation in the brown Norway rat. Pharmacological modulation. Exposure of non-sensitized Brown Norway (BN) rats to a 10%-ovalbumin aerosol induced an increase in the number of neutrophils in the broncho-alveolar lavage (BAL) fluid 3 and 6 h later but with no change in number of cells at 24 h. When the BN rats were actively sensitized (i.m. injection of 10 mg/kg ovalbumin and i.p. injection of killed Bordetella pertussis) and exposed 12-14 days later to a 10%-ovalbumin aerosol there was an increase in the number of eosinophils in the BAL fluid, maximal 24-48 h after the anaphylactic reaction. The increase in the number of neutrophils in the bronchial lumen 3 and 6 h after the anaphylactic reaction was larger than that obtained in non-specific inflammation and in contrast to this was still present 24-48 h after ovalbumin exposure. In passively sensitized BN rats exposed to ovalbumin aerosol, no inflammation appeared in the BAL fluid 24 h after the anaphylactic reaction. Various drugs, administered twice, 5 min and 5 h after the anaphylactic reaction, have been evaluated for their effects on the 24-h inflammation obtained in actively sensitized rats. Dexamethasone acetate (0.08 mg/kg i.p.) and theophylline (50 mg/kg i.p.) decreased the number of eosinophils and neutrophils. Ketotifen fumarate (12.5 mg/kg), cetirizine dihydrochloride (12.5 mg/kg), salbutamol (2 mg/kg), disodium cromoglycate (50 mg/kg) all given intraperitoneally, reduced the number of eosinophils. Tioxamast decreased the number of eosinophils at 12.5 mg/kg i.p. and by the oral route.(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement in the proliferative capacity and natural killer cell activity of murine spleen lymphocytes by thyrotropin. In the present study we investigated the effect of thyrotropin (TSH) on both the proliferative capacity and the natural killer (NK) cell activity of murine spleen lymphocytes. It was found that TSH at various concentrations significantly increased the proliferative response of mouse lymphocytes to both concanavalin A (Con A) and phytohemagglutinin (PHA). This increase was particularly evident when suboptimal concentrations of mitogens were used (40-50% increase). The administration to cell cultures of TSH alone could not induce a significant stimulation of proliferative capacity. In order to provide a better knowledge about the mechanism by which TSH improved the mitogen-induced lymphocyte proliferation, the effect of the pituitary hormone on lymphocytes directly stimulated with recombinant interleukin-2 (RIL-2), was examined. It was observed that there was a great increase in IL-2-induced lymphocyte proliferation by TSH. The improvement in proliferative capacity of lymphocytes was particularly evident by using suboptimal rIL-2 concentrations (25-30% increase). The studies carried out on the cytotoxic activity of NK cells showed that TSH was able to significantly increase the IL-2-induced NK cell activity without modifying the basal levels of cytotoxicity. The results support the immunoregulatory role of TSH and contribute towards understanding the mechanisms of interaction between neuroendocrine and immune systems.


Modulation of IgM to IgG class switch by protein A. The Fc binding property of soluble protein A (SpA) from Staphylococcus aureus has been utilized to form IgG-SpA complexes which enabled an increase or decrease of IgG from the host depending on the dose of SpA administered. When 5 micrograms SpA was administered the IgG-SpA complexes were rapidly catabolized and, hence, low plasma IgG levels were observed. In contrast 25 micrograms SpA resulted in a significant increase in the IgG level in the host plasma. Based on these observations, the present investigation attempted to study the effect of IgG depletion/increase on the primary and secondary B-cell response to sheep erythrocyte (SRBC) antigen in Balb/c mice. Introduction of 5, 10 and 25 micrograms SpA at the time of the primary antigenic challenge inhibited both the primary IgM and the secondary IgM and IgG responses in a dose-dependent manner. Administration of 5 and 10 micrograms SpA at the time of the secondary antigenic challenge enabled the host to maintain the otherwise depressed secondary IgM response equivalent to the normal primary response. In contrast, 25 micrograms SpA at the time of the secondary antigenic challenge inhibited both the IgM and IgG PFC responses. These results extend our understanding of the mechanism of switch in immunoglobulin class expression during antigen driven maturation of the B-cell response.


Increased oxidative metabolism in PMA-activated lymphocytes: a flow cytometric study. Flow cytometry and the fluorescent dyes DCF and R123 were used to examine oxygen metabolite production in human leukocytes and T-lymphoblastoid Jurkat cells, activated by PMA or by FMLP. When unseparated leukocytes were activated by PMA, oxidative products were generated not only in PMN and monocytes but also to a lower extent in lymphocytes. These responses were correlated with protein kinase C activation. PMA did not, however, induce the synthesis of reactive oxygen species in isolated lymphocytes. FMLP did not affect lymphocyte oxidative metabolism when added to the whole leukocyte mixture, but activated only the phagocyte populations. Similarly, Jurkat cells which alone were unresponsive to PMA, became strongly fluorescent when they were mixed with PMN and treated with this activator. In all cases, they did not respond to FMLP. Superoxide dismutase and catalase addition did not prevent the lymphoid cell response in the presence of phagocytes, whereas Desferal did. These data indicate that under physiological conditions, activated lymphocytes are capable of oxidative metabolism and also evidence some close relation between the leukocyte populations. We discuss the putative mechanism of oxygen metabolite generation in lymphocytes and the role of these metabolites in the immune response.


In vitro effects of retinoid RO 10-9359 on lectin-induced activation and proliferation of T-lymphocytes. RO 10-9359 has been shown to cause a dose-dependent (0.05-50 micrograms/ml) inhibition of proliferation of rat thymocytes after in vitro activation by PHA and Con A. In experiments designed to dissect the effects of the drug on various aspects of proliferation it was demonstrated that RO 10-9359 did not inhibit IL1 production by macrophages, nor the IL1-dependent events of T-cell activation, i.e. the IL2 production and the acquisition of IL2-receptors. However, the capacity of exogenously supplied IL2 to stimulate the proliferation of T-cells that had previously acquired IL2-receptors was suppressed by RO 10-9359 in a dose-dependent manner. Thus, it appears that retinoid RO 10-9359 does not interfere with the early events of T-cell activation, but inhibits lectin-induced proliferation by affecting the later phase of proliferative activity after T-cell triggering.


Tumor-specific L3T4+ and Lyt-2+ lymphocytes in mice primed to mutagenized cell variants. We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non-specific tumoricidal effects.


In vitro effects of three iron chelators on mitogen-activated lymphocytes: identification of differences in their mechanisms of action. The effects of three iron chelators (ADR-529/ICRF-187; omadine/pyrithione; and a newly synthesized pyridoxal-based iron chelator, SAG-15) on cultured BALB/c murine lymph node cells stimulated with phorbol myristate acetate and ionomycin have been investigated. All three agents were found to inhibit [3H]-thymidine incorporation after 66-72 h incubation. Pretreatment of ADR-529 and omadine with Fe(III) or Fe(II) ions did not prevent their inhibitory effects. However, pretreatment of SAG-15 with Fe(II) or Fe(III) ions led to a significant increase in the ID50. Time-course studies of cell viability and thymidine incorporation demonstrated that the inhibitory effect of omadine was attributable to cell killing while for ADR-529 and SAG-15 there were both cytostatic and cytotoxic effects. Cell cycle analysis showed that treatment of cells with ADR-529 led to arrest in G2/M while treatment with SAG-15 led to a G0/G1 arrest. Iron has an obligatory role in T-lymphocyte activation that may be related to the formation of reactive oxygen species. SAG-15 is a new iron chelator that will help in the elucidation of the precise role of iron in lymphoproliferation. Since SAG-15 is an extremely effective iron chelator in vivo it has potential as an immunosuppressive agent.


Immunosuppression induced by non-reducing acylated monosaccharide subunits of lipid A. Synthetic acylated glucosamine monosaccharides, representative of the non-reducing subunit of lipid A, were compared for their ability to induce non-specific suppression of antibody forming cells. Five of nine analogs were found to be functional in this respect, indicating that these compounds, carrying a phosphate at C4 and acyl substituents at C2 and C3 are the smallest synthetic analogs of lipid A capable of eliciting non-specific immunosuppression. A comparison of the analogs inducing suppression with those testing negative revealed that (i) a single 3-hydroxymyristoyl group at C2 is common to 4/5 analogs inducing suppression; (ii) addition of an oxytetradecanoyl group to the 3-hyroxymyristoyl group at either C2 or C3 negated suppression; and (iii) extreme specificity was exhibited in suppression induction such that substitution of either lauric (C12) or palmitic (C16) for myristic acid (C14) at C2 voided transmission of the suppressive signal.


Mudi-chood: an unusual tropical dermatosis. Mudi-chood is an unusual dermatosis seen in India. It affects the nape of the neck and the exposed part of the upper back in girls and young women. It is characterized by mildly pruritic pigmented papular lesions. It probably represents the comedogenic activity of various oils applied to the hair, which is aggravated by the typical climatic conditions. We present three cases of mudi-chood.


Basal cell carcinoma in tropical Australia. A survey of people with skin cancer in tropical Australia detected a change in site of the prevalent cancer. In the post-war generation more basal cell carcinomas are occurring on the back and fewer on the head and neck. A reversal of the sex ratio was also detected, with more women being afflicted.


Post-kala-azar dermal leishmaniasis in the Sudan: peripheral neural involvement. Four patients developed post-kala-azar dermal leishmaniasis and neuritis (PKDL) 1 to 6 months following apparently successful treatment of kala-azar. The duration of the lesion varied between 1 month and nearly 5 years. The lesions were macules, papules, or nodules affecting the face, extremities, and trunk. The diagnosis was made by demonstration of the parasite in slit smear and biopsies and by a positive direct agglutination test (DAT). Histologically, the patients were found to have neuritis affecting the cutaneous nerves in the lesion only. The nerves showed a lymphohistiocytic infiltration and occasionally parasites. There was no impairment of sensation. Response to sodium stibogluconate was good. PKDL may simulate leprosy both clinically and pathologically.


Liver biopsy versus ultrasound in methotrexate-treated psoriasis: a decision analysis. Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis.


Immunohistochemical identification of Penicillium marneffei by monoclonal antibody. We present an experimental study on the immunohistochemical identification of Penicillium marneffei in paraffin-embedded, formalin-fixed tissue. The monoclonal antibody EB-A1 detects a specific galactomannan that appears to have at least one epitope identical in P. marneffei and Aspergillus sp. This immunohistochemical approach could be useful in the diagnosis of a rare diseae, penicilliosis marneffei, which proves to be difficult to identify by conventional microscopy.


Melasma-like (pigmented) actinic lichen planus. Four patients suffering from pigmented actinic lichen planus were studied. Clinically, the lesions are melasma-like, affecting mainly the face and exacerbating in summer and spring time. The histopathologic and immunofluorescence studies showed typical changes of actinic lichen planus. The possibility of pigmented actinic lichen planus should be considered in every patient with facial melanosis.


Worldwide strategy for skin health care in a financial strait-jacket. In consideration of the year 2000, dermatologists must take up the challenge of "Health for All." This paper draws attention to the scope of dermatology, the nature of its work force, the qualifications that are desirable, and the deficiencies and impediments that characterize dermatologic solutions worldwide. It suggests that the future of dermatology depends on achieving appropriate and essential staffing, technology, drugs, and learning materials, within available financial resources. To achieve this, dermatologists must talk more persuasively to those who govern and some centralization of resources into regional training centers may be desirable. Delegation of skin care to purpose-trained auxiliaries, nurses, or medical assistants is essential if costs are to be contained while enlarging the work force.


Ofloxacin versus cephalexin for treating skin and soft tissue infections. Patients with acute localized skin or soft tissue infections were randomized to receive either ofloxacin (300 mg orally, b.i.d.) or cephalexin (500 mg orally, b.i.d.). Among 401 enrolled patients, 382 were evaluable for safety and 148 for microbiologic response. Microbiologic cure occurred in 93.4% of ofloxacin-treated patients and in 94.0% of those treated with cephalexin. Clinical cure or improvement, respectively, was found in 85.2% and 11.1% of patients treated with ofloxacin, and 83.6% and 14.9% of patients receiving cephalexin. Adverse effects (primarily associated with the gastrointestinal tract and central nervous system) were considered to be drug-related in 7.9% of those receiving ofloxacin and 4.8% of those receiving cephalexin. Thus, ofloxacin is as effective and well tolerated as cephalexin and a good alternate antibiotic for treating skin and skin structure infections caused by a variety of pathogens.


Psychic change: insight or relationship? The phenomenon of psychic change has been a subject of interest since the beginning of psychoanalysis. The author presents clinical material from a four-year analysis of a 50-year-old man, including a verbatim session, which illuminates two questions raised about psychic change. (1) What criteria may be used to evaluate psychic change and how do those criteria relate to the concept of 'structural change'? (2) Is it insight or the effects of a new object relationship that is most responsible for the changes that a patient is able to achieve? The search for a single mechanism of psychic change is doomed to frustration. But the author argues that insight is crucial to psychoanalytic change, both for its own sake and for its role in maintaining an understanding relationship.


Psychic change and its clinical evaluation. The author looks at the question of psychic change from the viewpoint of difficulties involved in this change, starting with a short historical overview. He discusses 'the difficult patient as a specialist in resisting change' and describes the clinical characteristics of such patients over and above their psychopathological diagnoses. Some specific clinical cases are described to clarify the theoretical ideas. The author then covers the nature of changes best studied within the field of transference and countertransference. Finally, he examines change as a process of change and suggests that qualitative differences exist between psychic functions relating to 'traumas' in narcissistic constraints. These differences are apparent in psychic content. The connexions between interpretation, insight, anxiety and change are described. The nature of the negative therapeutic reaction is discussed. The notion of an underlying deficiency in the development of genuine egoistic resources required to bring about psychic change is examined.


Some changes observed in a clinical case. The author presents clinical material from a 36-year-old female patient with depressive and hysterical traits, whose personal history shows her psychosexual development to be at a pregenital level. It is intended to demonstrate the type of clinical interpretations that enabled a change towards an oedipal transference in order to reach a psychoanalytic approach. Some of the psychoanalytic interpretations during the treatment process are described, related to several behavioural changes and a discrete structural change.


Marc, or the solder's journey. The elaboration of passivity as a factor of change. Change during analysis is here understood as the possibility of elaborating the 'biological bedrock' described by Freud as the repudiation of femininity in both sexes. The analysis of a man with anxiety hysteria permits us to show how temporal regression induced by the analytic setting enables the elaboration of passivity in its fantasy and object-related aspects. The return of this patient seven years after the end of the analysis in a moment of strange coincidence for the analyst, gave rise to a consideration of the difficulties and the issues in topographical and formal regression during analysis: the necessity of working on the dynamics of the narcissistic double and on the anxieties relating to the danger of non-representation and the loss of the capacity for investment. The working through of this primordial passivity, corresponding to active work, concerns analyst as well as analysand in their common work and constitutes the final point which all analyses should reach to achieve a durable change in its topographical, dynamic and economic aspects.


Psychic change: some perspectives.

Psychic change: some perspectives. I have not attempted in this paper to discuss psychic change in general, nor the aims of change as such, but rather an approach to achieving psychic change. I discuss the way in which both patient and analyst bring into the analytic relationship their own way of looking at things, their own vertex, and how the converging and separating out of these vertices is part of the movement within the analytic relationship, in the session, where it is experienced by both participants and is basic to the stuff of insight and to psychic change.


Psychic change: development in the theory of psychoanalytic techniques. 37th IPA congress overview. This paper addresses some of the methodological problems in assessing and understanding change in psychoanalysis, including the twin difficulties of not knowing precisely what transpires in an analytic session and not knowing to which of the many aspects of psychoanalytic process any particular change should be assigned. There are alternate models for understanding change. The most commonly used model is that of psychoanalytic growth with the analyst acting as a fostering maternal figure. An alternate model of change is of psychic repair with the analyst in a more physicianly role. Analysts also work with alternative models of trauma. In one model danger stems from the infant's own overwhelming affective states, while in the other model danger comes from parenting failures. Analysts also differ regarding the importance assigned to interpretation and insight rather than to the new relationships and altered experience. This paper elaborates these models and their implications for psychoanalytic technique and our understanding of psychic change.


Psychic change: the analytic relationship(s) and agents of change. Psychic change, the agents of change, and the theory of technique have gradually changed pari passu with other changes in the field. Rather idealized concepts of structural change have been supplanted by current emphasis on experience-near clinical and functional change. There are varied processes and agents of change, but interpretation and insight are crucial to psychoanalysis. Attention to noninterpretive agents of change includes contemporary theoretical and technical interest in the analytic relationship(s). As analyses become much longer, the real relationship expands, and may impede the analysis of inter-weaving transference and countertransference ramifications. The ambiguous concept of 'new object' primarily refers to the analyst's analytic attitude, role, and analysing functions. Analysis progresses with internalization of the analytic process, but internalization of the analytic relationship and experience may also contribute to psychic change. The analyst should have a stable analytic attitude and identity, and be able to change with new knowledge and experience.


Psychoanalytic contributions to Holocaust studies. The purpose of this presentation is to provide a comprehensive overview to a wide audience of how effects of trauma incurred by victims of Nazi persecution during the Holocaust may affect survivors and their children. In doing so, one has to accept that powerful defences employed by survivors themselves and the world about them led to a 'latency period' which delayed investigation of the late sequelae of Holocaust trauma. Bridging the gap was stimulated by the passage of indemnification legislation by the Federal German Republic which enabled mental health professionals to investigate these possible effects. Psychoanalytic theories of trauma had to be reconsidered in the light of these inquiries. Further study revealed that the effects of massive and cumulative trauma may be transmitted to the second generation. Recurrent themes and conflicts in children of survivors have been described. Clinical illustrations have been provided to illuminate some aspects of problems encountered in treating members of a traumatized group. Finally, issues involving unresolved mourning and questions of commemorating the Holocaust have been considered.


Does psychoanalysis heal? A contribution to the theory of psychoanalytic technique. Beginning with Freud's controversial admonition to psychoanalysts to model themselves on the surgeon who 'dresses the wound, but does not heal it', the author attempts to explore the limits of the therapeutic effect of psychoanalysis. After briefly reviewing the role of projective identification in the transference, and the origin of the analyst's need to be a healer in his anxieties about the strength of his own destructive impulses, he describes certain emotional difficulties that arise in the analyst when he accepts the fact that he can only do analysis. He goes on to suggest that, while psychoanalysis is able to reduce the psychic distance between parts of the patient's mind that have been separated by splitting, this in itself does not provide the patient with a corrective emotional experience, mitigate the severity of his superego, or guide him along the correct developmental path. He further suggests that the analyst's acknowledgement of this limitation--which is equivalent to acknowledging that he can help the patient to grow, but he cannot 'grow' him--is part of a state of mind that the analyst must have to do analysis, and that this state of mind helps to distinguish the practice of psychoanalysis from that of other psychotherapies.


Inductive reasoning in clinical psychoanalysis. It is argued that clinical observations can be used to test psychoanalytic theories. Psychoanalysis cannot use controlled experiments but it can use the standard canons of inductive reasoning to test the reliability of conflicting theories. Conflicting hypotheses concerning narcissism and object relations are analysed to identify crucial observations that can be used for testing. If these experiments in theory testing are reliable they show that psychoanalysis is not limited to being a hermeneutic discipline but rather has legitimate claims to be a natural science.


Psychic change in child analysis.

Psychic change in child analysis. The paper describes a period of analysis of a 5-year-old boy as an illustration of some ideas about psychic change. Psychic change is approached in terms of emotional growth, which is directly associated with the degree of flexibility of the defensive system and its capacity to absorb and re-integrate lost parts of the ego and to be open to new emotional experiences. It is described how, through interpretations, the child's internal objects and relationships changed. In particular, his representation of his bad-analyst, bad-father, bad-self changed from being a gorilla to the Incredible Hulk to the whale and finally to Superman crying. When the analysis was interrupted, the patient was showing clear indications that the basis had been laid for establishing a more stable internalized object capable of containing and transforming his anxieties and feelings of despair into more tolerable ones, which gave him a better chance of being fed by good experiences.


Psychic change and developments in the theory of technique in adolescent analysis: the handling of perverse levels of transference. The paper presents some of the characteristics of the analytic process in an adolescent with homosexual behaviour. The technical peculiarities of this kind of treatment are compared with those of adult patients with similar pathologies. The difficulties arising from complex acting-out behaviour in which the family take an active part, the role of secrecy, and the handling of the erotization of the transference through the verbal interchange are discussed on the basis of the clinical material presented. The characteristics of a strongly split transference, with a dissociated perverse level, imply specific difficulties in maintaining a workable analytic setting; the strategic choices with which the analyst is faced to be able to attain it, and its clinical implications are discussed.


Psychic change in the analyst.

Psychic change in the analyst. This paper addresses the use of one's mother tongue as a means of facilitating access to splitoff regions of the mind. It also looks at the different situation of strong emotional impact for the analyst which requires, upon recognition, careful reflection and analysis in order to separate the analyst's own transference from the counter-transference. The latter is taken as the total of all the analyst's reactions towards what the patient is and what he/she brings into analysis.


Ambiguity as the route to shame.

Ambiguity as the route to shame. In patients who have been exposed to extreme conditions, shame is connected with a dilemma of identity: it is indicative of the patient's conflict over his alienation, his adaptation to and familiarization with the conditions offered by an unacceptable frame. Bleger's (1967) theoretical model, with the concepts of the symbiotic link, ambiguity and the ambiguous position (which precedes the classical Kleinian positions), dynamically combines the problem of the frame or context with that of the capacity of discrimination between the ego and its objects. Ambiguity is characterized by the adaptability, malleability, permeability and non-conflictuality which it confers on the personality. Shame appears as an alarm signal concerning ambiguity, connected with the ego's need to maintain its internal conflictuality, its capacity for integration and its sense of continuity. Experiences of dependence and passivity, or ones which touch upon the dilemma between true and false, private and public, ethics and aesthetics, etc., may give rise to feelings of shame. In this paper it is suggested that a common denominator for the many different factors of shame may be found in the dynamics of ambiguity.


An anatomical commentary on the concept of infantile oral sadism. Although this paper is entitled 'An anatomical commentary on the concept of infantile oral sadism' it is also an attempt to examine hypotheses regarding the sources of oral sadism. Freud did not explicitly refer to an oral sadistic phase of development in early infancy, believing as he did that sadism was a component instinct. Abraham postulated that oral sadism arises when the teeth erupt and the jaw muscles function. Melanie Klein, however, came to claim that oral sadistic impulses operate from birth and arise from the infant's innate potential for fantasy. This hypothesis is akin to Freud's theory of primal fantasies. The anatomical record supports Abraham's theory of the source of oral sadism.


Countertransference: the analyst's retreat from the patient's vantage point. As analysts, we may agree with certain basic tenets: we should not impose our truths, whether or not theory-laden; we should maintain the focus on the patient's inner reality, not on how he or she lives in the world--out there; we should be prepared to be surprised, to learn something that hadn't occurred to us; we should look for multiple cues in the clinical data, pay attention to affect and state as may be expressed within the moment, and listen for subtleties that may convey something about how we are being experienced in the transference. But again and again, we fail to adhere to these precepts. Despite our best intentions, we seem to have a fundamental disinclination to maintaining these positions. I have tried to consider some reasons for this difficulty and its relation to the countertransference. Drawing upon several clinical examples, I have attempted to examine ways of enhancing our attunement to verbal and non-verbal cues from the patient which may direct us, sooner, to dimensions of our counter-transference responses otherwise overlooked.


[Prevalence of dental caries among school children: a cross-sectional survey in the city of Barcelona]. The results of a cross-sectional survey performed in the spring of 1990 in a sample of 533 twelve-year old schoolchildren in the city of Barcelona (Spain) are presented. The proportion of children with caries is 49.2%, with a DMFT index of 1.34 (1.09 for boys and 1.50 for girls). 63.4% of permanent decayed teeth were filled, and 2.2% were missing. There is a socioeconomic gradient in dental decay, with more caries among the lower socioeconomic strata, where missing teeth concentrate. The comparison of these results with those of other studies suggests a decline in caries incidence in school age in Spain, and greater use of dental care services.


Induction of invasive and experimental metastasis potential in BALB/c 3T3 cells by benzo(a)pyrene transformation. A clone of BALB/c 3T3 cells (A-31), which is highly resistant to spontaneous in vitro transformation, was treated with the carcinogen benzo(a)pyrene [B(a)P]. This agent was capable of inducing in vitro transformation in the presence of S9 activating system and 6 weeks after treatment large foci were detected. Transformation frequency in solvent control groups was very low. Three foci from a single plate of two different experiments were pooled and the cells tested for their in vitro invasive properties and in vivo tumorigenic and metastatic potential. B(a)P-transformed 3T3 cells grew in soft agar and were highly tumorigenic when injected s.c. in nude mice (75% incidence within 7 weeks). Untreated cells were poorly tumorigenic (0/4 mice had tumors within 7 weeks), though they also gave rise to neoplasms after a longer latency. Spontaneous metastasis incidence was low for both controls and treated cells; however, almost all animals (15/16) injected i.v. with B(a)P-transformed cells had pulmonary nodules in the experimental metastasis assay. A few nodules in some of the animals in the control group were detected (4/16). B(a)P-transformed cells were able to invade a thin coating of matrigel in the chemoinvasion assay and also grew in matrigel showing an invasive, branching morphology. Untreated cells did not grow or invade. Our data suggest that a single treatment with a chemical carcinogen can increase tumorigenicity as well as confer invasive and experimental metastasis potential in BALB/c 3T3 cells. This work provides evidence for a role of chemical carcinogens in tumor progression.


[Sampling limitations in studies of primary care: comparison of 4 sampling designs]. Different sampling methodologies have been used to avoid the great amount of information which arises in Primary Health Care. The objective of this study is to compare the estimates of four sampling schemes, analyzing variables of utilization, referral activity and diagnostic morbidity, based on data obtained from consultations in a health centre over a one-year period. The percentage of error between each sample estimation and the real value for the whole data set was obtained. Sampling schemes using week periods showed the worst results (40% of error in the estimation of chronic consultations, 18% of error in the percentage of radiology requests and more than 13% in the estimation of morbidity). The findings of this study suggest that some of the sampling schemes usually applied in primary care studies have important limitations, showing the need for more research in this field.


[Prevalence of tobacco consumption in Mallorca]. The prevalence of tobacco consumption has been estimated in the population of Mallorca, by means of a survey based on interviews of a random sample of 300 individuals between the ages of 18 and 75, selected from the 1986 electoral census of the Island. From the 297 valid questionnaires, the prevalence of smokers was 34%; 15% were ex-smokers and 50% non-smokers. Among women younger than 40 years old the prevalence of smokers was 60%. A direct relationship between level of education and prevalence of smokers was observed for women. Immigrants from the mainland of Spain formed a major proportion of smokers (44%) compared to the Mallorcans (30%), and also among those living in the main city (41%) with respect to those living in other areas (25%). The prevalence of tobacco consumption in Mallorca shows a similar pattern to that of other geographical and cultural areas with similar characteristics.


Invasion in vitro of malignant hamster brain tumor cells is influenced by the number of cells and the mode of malignant progression. We investigated the capacity of two glial tumor cell lines (CxT24neo3 and CxT3Cl5) to invade through reconstituted basement membrane (Matrigel, MG). The purpose of our experiments was to establish whether the number of cells or the mode of malignant progression would quantitatively modify the invasion of a brain tumor cell population. To accomplish this goal, we used a vital-dye method to assess the fraction of cells that invaded through 30 micrograms MG coated on a polycarbonate filter (8 microns pore size). Our experiments demonstrated that the fraction of invasive CxT24neo3 and CxT3Cl5 cells in vitro reproducibly differed as a function of the number of initially seeded cells. This showed that invasion through MG was subject to quantitative changes caused by the number of cells present. Since CxT24neo3 and CxT3Cl5 became malignant by transfection with different oncogenes, the results also indicated that the type of quantitative change was influenced by the mode of malignant progression.


Endothelial injury causes degradation of adjacent basement membranes and promotes their invasion by A549 carcinoma cells. Experiments in vivo have demonstrated that endothelial cell injury promotes the local arrest of circulating, intravascular cancer cells and the subsequent formation of metastatic tumors. The experiments described here were performed to test the hypothesis that injury of the endothelium also causes damage to the adjacent vascular basement membrane, which in turn facilitates the passage of cancer cells across the vessel wall. Confluent monolayers of bovine pulmonary artery endothelial cells were incubated with 3H-2-deoxyglucose or 3H-proline to label the endothelial cells or the basement membrane, respectively. After adding H2O2 to these cultures, damage of the endothelium and basement membrane was detected by release of the isotopes into the culture medium. The kinetics and magnitude of basement membrane degradation correlated with the damage to the endothelial cells. Evidence for involvement of endothelial proteases in basement membrane injury included identification of a 63-kD gelatinase in the culture medium, inhibition of injury by protease inhibitors and the inability of H2O2 to cause 3H-proline release when applied directly to basement membranes. Scanning electron microscopy demonstrated that a greater number of A549 lung adenocarcinoma cells attached to the basement membrane and endothelium at points of endothelial retraction. However, this was not due to an increase in the adhesive properties of the basement membrane. The media from injured endothelial cultures stimulated the motility of A549 cells in a Boyden chamber assay. Furthermore, in a 24-hour invasion assay, a greater number of A549 cells migrated through injured basement membranes than through control membranes. We conclude that endothelial cell injury can cause enzymatic damage to the underlying basement membrane and postulate that this can facilitate the transvascular passage of cancer cells in vivo.


[Meta-analysis in epidemiology (2): quantitative methods]. The main goal of this paper is to offer an introduction to the quantitative methods of meta-analysis used in epidemiology/public health, emphasizing on the most widespread used. We give also a brief reference of the methods to recognize publication bias. The limitations and advantages of the methods commented on are discussed.


[Should general practitioners consider the costs of their prescriptions? Reflections stemming from the "White Paper" and an opinion survey]. The British government proposal to introduce drug budgets will compel general practitioners to consider the financial consequences of prescribing. In our country, the practitioner neither in the past nor now has an incentive to consider the cost of his prescription, and few efforts have been made to influence it, if we exclude the pharmacy industry. In the present article, the situation of both countries is analyzed and the answers of the general practitioners of Girona and Scotland to questions that examine their predisposition towards considering costs when prescribing are compared. The reduction of the prescription costs must be formulated as a part of a rational prescription and should employ a combination of approaches: education, feedback, administrative changes, and incentives. The procedures to encourage a more efficient use of medicines require an active participation of the practitioners in managing the resources of their practices.