Influence of DNA supercoiling on the loss of culturability of Escherichia coli cells incubated in seawater. The relationship between the loss of culturability of Escherichia coli cells in seawater and the DNA supercoiling level of a reporter plasmid (pUC8) have been studied under different experimental conditions. Transfer to seawater of cells grown at low osmolarity decreased their ability to grow without apparent modification of the plasmid supercoiling. We found that E. coli cells could be protected against seawater-induced loss of culturability by increasing their DNA-negative supercoiling in response to environmental factors: either a growth at high osmolarity before the transfer to seawater, or addition of organic matter (50-mg/l peptone) in seawater. We further found conditions where a DNA-induced relaxation was accompanied by an increase in seawater sensitivity. Indeed, inactivation of either one of the subunits A and B of DNA gyrase, which leads to important DNA relaxation, was accompanied in both cases by an increased loss of culturability of conditional mutants after transfer to seawater which could not be explained uniquely by the increase in the temperature required to inactivate the gyrase. Similarly, a strain harbouring a mutation in topoisomerase I, compensated by another mutation in subunit B of the gyrase, was more sensitive to seawater than the isogenic wild-type cell and this greater sensitivity was correlated to a relaxation of plasmid DNA. Again, in these different cases, a previous growth at high osmolarity protected against this seawater sensitivity. We thus propose that the ability of E. coli cells to survive in seawater and maintain their ability to grow on culture media could be linked, at least in part, to the topological state of their DNA.(ABSTRACT TRUNCATED AT 250 WORDS)


The identification of sex in the starling Sturnus vulgaris using a molecular DNA technique. Female birds can be identified through the presence of a W-chromosome. We describe a procedure for amplifying a W-linked DNA marker in the starling (Sturnus vulgaris) by the polymerase chain reaction (PCR) so allowing the diagnosis of sex in this species. The technique is sensitive, allowing even the smallest chicks to be sexed from a blood sample. The method possesses a positive internal control to ensure accuracy. It is also applicable to the spotless starling (S. unicolor) but not to two bird species outside the genus. The nucleotide sequence of the female-specific PCR product is given.


DNA stabilization and amplification from museum collections of extracts originally intended for allozyme analysis. Protein extracts originally prepared for isozyme electrophoresis two decades ago contain surviving DNA sequences susceptible to amplification by the polymerase chain reaction (PCR). Amplification was also possible after stabilization of such extracts on filter paper and immersion under mineral oil without refrigeration.


Islet cell surface antibodies in diabetic children determined with 125I-labelled anti-IgG as tracer. We have developed an assay for ICSA using fixed beta-cells as target cells and 125-I-Anti-IgG as tracer. Interassay variation was 9.5% and intraassay variation was 9.9%. For high titers of ICSA specificity was 100% but sensitivity then only 70%. Our technique enables a laboratory assistant to determine 200 samples in one week. Absorption of the samples with rat beta-cells as well as rat fibroblasts showed that ICSA are beta-cell specific and does not crossreact with rat fibroblasts. We found a significant difference in prevalence of high titer ICSA between healthy school children (4%) and newly diagnosed diabetic children (19%) (p < 0.001). That difference had disappeared after 18 months duration of IDDM when the B-cell mass and thus the amount of antigen had decreased. No difference was seen between healthy children and adult blood donors. There was no seasonal variation of ICSA titers in healthy children.


Intrinsic properties of FAD-linked glycerophosphate dehydrogenase in islets from normal and streptozotocin-induced diabetic rats. An acquired or inherited deficiency of FAD-linked glycerophosphate dehydrogenase activity in the pancreatic islet B-cell was recently proposed to represent a far-from-uncommon contributing factor in the pathogenesis of non-insulin-dependent diabetes mellitus. In the present study, it was investigated whether the postulated genomic defect coincides with the biosynthesis of an enzymic protein with altered catalytic properties and might concern an isoenzyme distinct from that found in extrapancreatic tissues. The activity of FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, was indeed severely decreased in islets from rats injected with streptozotocin. The intrinsic properties of the enzyme were preserved, however, as judged from the affinity for L-glycerol-3-phosphate, the ratio in reaction velocity using either FAD or iodonitrotetrazolium as electron acceptor and the activation of the enzyme by Ca2+. When the same kinetic parameters were compared in islet, liver and spleen homogenates from normal rats, significant differences were observed, however, between these three tissues, suggesting the possible existence of distinct isoenzymes.


Immunological and beta-cell-specific characteristics of diabetes-prone BB/OK rats and their congenic derivatives--a comparative study. In a comparative study congenic rat strains bearing either the genetic background of diabetic BB/OK rats and the MHC (RTla) of diabetes-resistant LEW.1A rats (BB.1A/OK) or vice versa carrying the genetic background of LEW.1A rats in combination with the MHC (RTlu) of diabetic BB/OK rats (LEW.1BB/OK) and their parental rat strains BB/OK and LEW.1A were checked for insulin secretion of pancreatic islets, for the number of splenic and peripheral blood mononuclear cells (MNC) as well as for the mitogenic response of splenic MNC. Glucose stimulated insulin secretion of isolated islets of Langerhans was not different in 50, 70 and 100 day-old congenic rats and the progenitor rat strains excluding an impact of the genotype on this beta-cell-specific function. The number of splenic and peripheral blood MNC was reduced in BB/OK and BB.1A/OK rats compared to LEW.1A and LEW.1BB/OK rats. Splenic MNC from BB/OK and BB.1A/OK rats displayed a strongly decreased total [3H]thymidine incorporation under basal conditions as well as upon mitogenic stimulation by ConA in comparison with MNC from LEW.1A and LEW.1BB/OK rats. Thus, the occurrence of lymphopenia and the impairment of mononuclear cell proliferation in BB/OK rats is not related to the RTlu haplotype of the MHC but is linked to non-MHC genes as indicated by the phenotypic expression of these traits in congenic BB.1A/OK rats.


Impact of dietary protein and fat source on the development of insulin-dependent diabetes in the BB rat. Epidemiological studies show a remarkable geographical difference in the prevalence of IDDM, suggesting a role for environmental factors such as diet, infection, or stress in the etiology of the disease. Dietary modification has already been shown to be effective in the prevention of autoimmune diabetes in the BB rat and NOD mouse. We studied the effect of protein and fat source in the prophylaxis of diabetes in the BB rat. Natural ingredient rat chow was consistently associated with a high expression of the disease, whereas a casein-based, defined diet significantly inhibited the development of diabetes. Substitution of casein with raw red lentils resulted in a markedly higher incidence. This is the first highly diabetogenic defined diet in the BB rat. Neither fish oil nor soy oil enhanced diabetes expression in the BB rat. Increased amounts of soy oil also did not influence the disease process. These results suggest a central role for dietary protein source in the pathogenesis of BB rat diabetes. We speculate that plant proteins containing anti-nutrients such as chemicals, lectins, enzyme inhibitors, and nonphysiologic amino acids may initiate or hasten the pathogenesis process via beta cell stress or immune response activation.


Aminoguanidine inhibits the modification of proteins by lipid peroxidation derived aldehydes: a possible antiatherogenic agent. The reaction of protein amino groups with lipid-peroxidation-derived aldehydes (LPDA) has been shown to play a key role in various pathological processes. Especially important is the reaction of LPDA with apolipoprotein B during oxidative modification of low density lipoprotein (LDL), which leads to its enhanced uptake by macrophages and, eventually, to atherogenesis. Since aminoguanidine, a drug which inhibits the advanced steps of glycation (probably by trapping reactive sugar-derived aldehydes), has been proposed as a therapeutic agent for the prevention of late diabetic complications, we have tested its ability to interfere with the modification of proteins by LPDA. LDL was incubated with cupric ions. Aminoguanidine at 5, 10 and 25 mM inhibited both the increase in electrophoretic mobility of LDL and the generation of thiobarbituric acid reactive substances (TBARS) (P < 0.001). It also inhibited the increase in electrophoretic mobility and 260-400 nm absorbance of bovine serum albumin incubated with malondialdehyde. These results suggest that aminoguanidine may have an antiatherogenic effect.


Basal intermediary metabolism in impaired glucose tolerance and morbid obesity. The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.


Monoclonal antibodies raised against semi-purified preparations of human islets define subpopulations of pancreatic cells. Monoclonal antibodies were produced from fusions between splenocytes from BALB/c mice immunised with purified human islets and the mouse myeloma cell line NS-0/Uncl. Supernatants from uncloned hybrids were screened by immunohistology on frozen sections of human pancreas. The range of specificities appeared to reflect the relative purity of the human islet preparations used. Eight monoclonal antibodies were investigated further, four of these bound to islet cells, two to acinar cells, one to ductal cells and one to occasional cells. The antigens recognised by these antibodies were characterised by immunohistology using a number of different tissues, as well as haemagglutination, immunoblotting and radioimmunoassay for insulin. Seven of the eight antibodies studied were IgM. One acinar cell antibody (IgG2a) precipitated proteins of 200Kd and 11OKd molecular weight. None of the antibodies bound directly to insulin. Seven of the antibodies appear to have defined previously unreported epitopes in the pancreas and will prove useful in further studies of human pancreatic cells.


A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus. Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC) virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation. The infection resulted in mild insulitis and the destruction of pancreatic beta cells at 1 week after inoculation and led to a significant reduction in the insulin content of the pancreas, but there was no ketonuria. The insulin content of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16 micrograms/g pancreas at 12 weeks, although the latter value was still significantly lower than that of the control mice (P < 0.05). Under microscopy, mild and partial infiltration of mononuclear cells was observed in about half the pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we believe we have established a new model of noninsulin-dependent diabetes mellitus using the NDK25 variant of EMC virus.


Plasma alanine and lactate concentrations following glucose ingestion in normal and NIDDM subjects. Conflicting evidence has been reported on the metabolic fate of glucose following oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as alanine, predominantly produced by muscle, and lactate after an oral glucose load in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases in plasma alanine observed, whereas a significant increase in plasma lactate was observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour in plasma alanine and lactate between normal and NIDDM subjects was found, in NIDDM significantly higher levels of plasma alanine and lactate were found at each time. From these observations we conclude: 1) when glucose is ingested under post-absorptive conditions, since plasma alanine levels do not change concurrently with lactate increase, muscle tissue does not play a predominant role in glucose disposal 2) after an oral glucose load, the pattern of gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM subjects may be due to an overproduction of alanine as well as lactate.


Serum lipoprotein Lp(a) in obesity.

Serum lipoprotein Lp(a) in obesity. Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for cardiovascular disease (CVD), whose incidence is greater in obese subjects. There are few data available on the serum Lp(a) concentrations in obese individuals with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non obese diabetic men and 17 healthy men as controls. We measured serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, insulin, was found; only a significant positive correlation between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude that hyperglycemia may influence the levels of serum Lp(a) facilitating its glycosylation in the liver with the consequence of a decline in its catabolic rate.


Amelioration of dermal lesions in streptozotocin-induced diabetic rats by aminoguanidine. As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various tissues, we have histologically and biochemically evaluated AG effects on the skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats. HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were maintained about two times higher than those in control rats during the 10 weeks of the experiment. Histological findings revealed that the dermis in diabetic rats was thin and edematous, associated with swelling and degeneration of collagen fibers. Necrobiotic changes were seen in the lower dermis. These changes were greatly improved in AG-treated diabetic rats. Skin glucose contents in diabetic and AG-treated diabetic rats were about 10 times higher than those in the controls, whereas there was no difference in the sorbitol contents between three groups. Dry weight of the skin and collagen content was well correlated (r = 0.9044) and collagen represented 78.0 +/- 2.3% of the dry weight. By SDS-PAGE analysis of cyanogen bromide digests it was shown that high molecular weight peptides were increased in diabetic rats, but were decreased in AG-treated diabetic rats. The mean of glycosaminoglycan (GAG) contents of diabetic skin was 54% of that in the controls (1.58 +/- 0.09 vs. 2.94 +/- 0.39 micrograms/mg dry weight, P < 0.0025), which increased significantly in AG-treated diabetic rats (1.75 +/- 0.07 microgram/mg dry weight, P < 0.01 vs. diabetic).(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of antibodies against both isoforms of glutamate decarboxylase in BB/OK rats by western blotting and immuno trapping enzyme activity assay. The GABA-producing enzyme glutamate decarboxylase (GAD) is a prominent autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against GAD were found with a high prevalence in IDDM patients and in animal models for IDDM. The aim of this study was to detect autoantibodies against both isoforms of GAD in diabetic and non-diabetic but diabetes-prone BB/OK rats by Western blotting and to test their specificity to GAD by an immuno-trapping enzyme activity assay. Eighteen diabetic and 18 non-diabetic BB/OK rats (age 121 +/- 20 days) were investigated. In 10/18 (56%) of the diabetic and 13/18 (72%) of the non-diabetic BB/OK rats autoantibodies against at least one GAD-isoform were detected by Western blotting. In the immunotrapping enzyme activity assay, the mean value of the diabetic (1151 +/- 552 cpm, n = 11) and nondiabetic BB/OK rats (1978 +/- 1213 cpm, n = 10) was significantly (p < 0.01) increased compared to the LEW. 1A control rats (581 +/- 274 cpm, n = 12). 7/10 (70%) individual sera of the non-diabetic and 5/11 (45%) of the diabetic BB/OK rats were positive in this test. In conclusion, the prevalence of GAD autoantibodies in BB/OK rat is connected with the genetic susceptibility to IDDM but is not a predictor for the onset of the disease in BB/OK rats.


[Determinism and indeterminism in the study of risk factors for disease]. In epidemiology "risk" is stated as a probability. This statement implies adopting a definite position regarding the concept of probability in science: whether it has to be intended as a lack of knowledge or a casual component of biological phenomena. On this fundamental premise the authors discuss the epidemiological implications on the issue of "determinism" of the recent developments of chemical, physical and biological sciences, particularly the quantum mechanics and the theories of complexity. The authors suggest three major interpretations of the relationship between risk factors and disease: strong determinism, weak determinism and dualism determinism/indeterminism. For each one of these positions they discuss the consistency, affinity and implications on epidemiological work.


[Development of an integrated system of family medicine--pathologic anatomy service to start epidemiologic studies on tumors occurring in an area of southern Italy. First results]. In Italy there are eight tumor Population-Based Registries (PBRs) that publish incidence data, and only one of them (Ragusa) provides data for Southern Italy. Usually, PBRs are based on data collection from Pathologists and medical records. Our integrated system differentiates from traditional PBRs because the information comes from the General Practitioners (GPs) and is completed with the diagnosis provided by the Pathologists (Ps). During two years we have registered 1,057 new cancers on a middle period population of 212,644. GPs and Ps signed 395 and 879 incident cases, respectively. GPs alone provided 16.8%, Ps alone 62.6%, and either source 20.6% of total cases. After excluding non melanotic skin cancers and bladder carcinoma, the GPs-Ps integrated system counted 828 new cases in two years. These incidence data are the first in our region (Puglia). The 178 cases signed by GPs alone should have been lost if the informations of our PBR had been based only on local Ps' records. Moreover, 94 of GPs cases (11% of total cancers registered) were subjects who moved outside the area for diagnosis and treatment. Even if this article evaluates the effect of under-registration attributable to Ps or GPs, the cancer incidence data and the active involvement of GPs indicate that they could be usefully involved in the registration of cancer data.


[Anti-rubella vaccine coverage in women 11-28 years of age: data on 5 local socio-health units of Veneto]. Selective rubella vaccination in the 11 years old girls, has been carried out in the Regione Veneto (Venetian Land) since 1974. The rubella immunization rate in teh women born between 1962 and 1978, in five sanitary districts, is 68.25%; the trend of increasing vaccination is continuing. Important differences in the organization of vaccination campaign were found among the five districts.


[Colorectal adenocarcinoma in patients with familial anamnesis positive for malignant neoplasms of the large intestine]. Familial aggregation of colorectal cancer occurs also among sporadic cases that are not part of defined genetic syndromes. First degree relatives of patients with "sporadic" colorectal cancer have a 3-4 fold increased risk of the same cancer. The aim of the present study is to investigate the relationship between a first degree family history of colorectal cancer and pathological and clinical features of the tumor (site, Dukes' stage, age at diagnosis, sex and survival of patients). 461 patients with colorectal cancer were evaluated (250 males and 211 females) after obtaining informations about their family history of cancer. 52 (11.25%) of them reported to have at least one close relative affected by intestinal cancer. Sex, age and stage of the disease are the only parameters that significantly affect survival. No relationship between family history of colorectal cancer and prognostic variables was observed.


[Analysis of the quality of death certificates for neoplasms in the province of Ragusa]. The reliability of the death certificates issued in Ragusa for 379 of the 909 cancer patients registered in 1986 by the Ragusa Cancer Registry, who had died within 31 october 1988, was investigated. Data were available for 365 cases deceased. A consistent proportion (32.8%) of disagreements between diagnosis of the Registry and cause of death reported on death certificate was observed, concerning errors of the second and third digit of ICD-9 (21.9%) and for lack of mention of cancer in the death certificate. The main causes of the loss of information were the issuing of the certificate by a M.D. of the permanent medical ward and not by the family doctor, and the lack of the document released by the hospital upon discharge of the patient, usually containing indication on diagnosis and treatment.


[Mortality and care level of very low birth weight newborn infants. A population study]. A population study on 314 very low birth weight infants (VLBW) was carried out in 1987 in the Lazio Region of Italy to investigate the relation between the availability at birth of neonatal intensive care and infant mortality. Fifty-two percent of VLBW infants did not survive the first year of life. The mortality Odds Ratios, adjusted for four potential confounding variables, did not show a beneficial effect of Maternity units with neonatal intensive care (level 3) compared with those with special (level 2) and normal care (level 1). The overall high crude mortality rate together with the homogeneity of odds ratios among the different levels of care suggest that, when a regionalized perinatal care system is missing, as in Lazio region, the availability of neonatal intensive care, per se, does not improve the survival on this group of infants.


[Diffusion of smoking habit in the commune of Florence in 1989]. The results of a study on smoking habits of Florence inhabitants (14 years of age or more) are reported. A random sample of general population of the town (1744 males and 1977 females) was recruited throughout the registration office and interviewed by mail or telephone. General compliance was approximately 85%. Thirty-seven percent of males and 25% of females were current cigarette smokers, 29% of males and 11% of females were ex smokers. Males were heavier smokers both as concerns duration of the habit and daily amount of cigarettes. In males born after 1930 the smoking prevalence decreased gradually by period of birth, while it increased in females born before 1960. As a result the smoking habits of younger cohorts were similar in males and in females. In each sex age-adjusted smoking prevalence showed important differences by educational groups and in respect to national averages.


Postmarketing surveillance-one of the key issues in drug development. The terms "postmarketing surveillance" or "human phase IV studies" are applied to all those examinations which are performed with a drug following its registration. The principles, methods of these examinations are discussed on the basis of international experiences. The authors also give some examples from Hungarian practice referring to this subject. They consider postmarketing examinations to be as important as the clinical pharmacological examinations preceding the introduction of a drug. The usefulness, role of a drug in the therapy may be definitely determined on the basis of the results of these studies.


Hormone therapy in breast cancer.

Hormone therapy in breast cancer. Means and the currently accepted principles of hormone therapy of breast cancer have been summarized on the basis of data from references. Fields of application and adverse effects of anti-oestrogens, aromatase inhibitors, gestagens, gonadotrophin-releasing, and androgenic hormones have been analysed. Drugs with various mechanisms of action and available in Hungary have been discussed.


Local antiphlogistic treatment with Apulein cream. The effectivity of two topical steroids, Apulein cream and Hydrocortisone ointment, was compared in women suffering from vulvitis and other superficial inflammations. The basic properties of budesonide and data from references have been discussed. In the examined cases Apulein cream proved to be a more effective and more rapidly acting antiphlogistic as compared to Hydrocortisone ointment. The adjuvant and symptomatic role of corticosteroid therapy and the importance of adequate target-specific treatment in cases of infection is emphasized.


Use of Dormicum sleeping pills in everyday practice. Dormicum is a rapidly absorbed up-to date hypnotic of 3-4 hours' duration of action physiologically influencing the phases of normal sleep. In the course of the examination of 26 patients, 21 found the hypnotic action of 7.5-mg or 15-mg Dormicum doses to be highly effective. The drug proved to be an effective hypnotic also in the group of patients above 60 years of age (14). It is of special importance in the everyday practice of a general practitioner that the intake of Dormicum in the evening did not influence the physical and mental activity of the patients the next day.


Evaluation of the antiemetic effect of domperidon in patients treated with cytostatic drugs. Forty patients with various neoplastic syndromes received domperidon as a drug reducing nausea and vomiting. The drug prevents in the daily dose of 30 mg completely the occurrence of nausea and vomiting in 30% of the patients and in 58% considerably reduces their intensity. The dose of 60 mg abolishes nausea and vomiting in 60% of the patients and alleviates in 35%. The drug had been administered through the whole period of chemotherapy without any side effects which may be attributed to its antagonist action to dopamine.


Clinical examination of nitroglycerin spray (EGIS) in angina pectoris patients. On the basis of our examinations it may be stated that the new product of EGIS Pharmaceuticals Nitromint aerosol seems to be effective and well tolerable in the course of clinical examinations. The drug action develops significantly more rapidly as compared to Nitromint tablet. Significant difference was not found when comparing the duration of action of the two products. The adverse effects are the same as the undesired effects of other short-acting nitrate preparations. Mostly local unwanted effects were observed. It can be recommended in all forms of angina pectoris for controlling pain syndrome and in effort angina for prophylactic purposes. In acute left heart failure it may be used in urgent cases. Because of its effectiveness and easy applicability the patients prefer Nitromint aerosol to Nitromint tablet.


Clinical observations with Paxirasol aerosol in patients suffering from chronic bronchitis accompanying silicosis. Paxirasol aerosol applied in daily 3 x 5 puff doses in the treatment of silicosis patients is found to be a well tolerated drug form. In the course of the 21-day therapy especially coughing and chest pain were moderated, but the product also controlled, the catarrhal coat formation on the mucosa. It influenced abundant expectoration and dispnoea beneficially. During the therapy the laboratory parameters did not change. The objective respiratory parameters improved but the change was non-significant. Paxirasol aerosol is found useful in the treatment of chronic bronchitis accompanying silicosis. Evaluable side-effects were not registered.


The relation between atypical migraine and multiphasic oral contraceptives. Data in references referring to the relation between atypical or menstrual migraine and the use of oral contraception have been reviewed. The authors own observations are discussed on this subject. Motilium and Voltaren have been successfully used for controlling vascular headache developing as a side-effect of contraceptive tablets. In case of migraine associated with dysmenorrhoea and/or premenstrual tension the management with triphasic hormone proved to be of therapeutic value. The authors call attention to the concurrent high incidence of these latter symptoms and suggest the further analysis of this problem. They collect evidence regarding that in the major part of cases atypical migraine is hormone dependent.


Use of Klion suspension in paediatry and gynaecology. Klion suspension was given to 42 girl and woman patients suffering from vaginal trichomoniasis. Negativity for Trichomonas was recorded in 73.8% of the cases in response to the first 10-day cure, and in 90.5% of the patients following repeated cures. The therapy had no notable side-effects. The liquid form of the medicine proved to be advantageous especially in the treatment of young girls but the possibility to take the drug diluted in soft drinks also facilitated the treatment of the partner.


Leukotriene B4 and peptido-leukotriene levels during radiographic contrast media infusion. The pathogenic mechanisms of radiographic contrast media (CM) reactions are still not well understood. Recently it has been proposed that leukotrienes (LT) may be involved in CM reactions. We measured plasma LTB4 and peptido-LT levels in 20 subjects undergoing urography with 2 low osmolality CM (ioxaglate and iopamidol) in order to elucidate if CM infusion determines LT release in plasma. LTB4 and peptido-LT did not change significantly during infusion of the 2 CM. Blood pressure, heart rate, and the number of circulating granulocytes were not affected by CM infusions, further evidence that LT release did not occur. We conclude therefore that LT are not released during infusion with the CM studied.


Fixed dose combination short course chemotherapy in the treatment of pulmonary tuberculosis. In this study two highly effective chemotherapeutic regimens of 6 and 8 months duration were studied and compared with the standard 12 month therapy under full supervision at the National TB Centre and St. Peter's TB Hospital in Addis Abeba. Patients with direct smear positive pulmonary tuberculosis were admitted to hospital during the initial phase of treatment for two months. At two months, sputum conversion rates, by direct smear and culture respectively, were 82% and 80% on Rifater, and 86 or 88% and 86% on the regimens containing separate preparations of isoniazid rifampicin and pyrazinamide, compared to 60% and 30% on the standard regimen. It was concluded that short course regimens of six or eight months with drugs either in combined form or separate preparations are more effective than the standard regimen.


[Duodeno-biliary reflux during T-tube drainage: a clinical study]. The relationship between duodeno-biliary reflux and bile bacterial contamination was studied in 28 consecutive cases of T-tube drainage after cholecystectomy and choledochotomy. Patients were randomly divided into two groups of 14 each. Group I treated with positive pressure drainage (PPD), with the pressure in T-tube 0.3-0.5 kPa higher than that created by sphincter resistance. Group II treated with traditional negative pressure drainage (NPD). It was found that the amount of duodenal reflux in group II was obviously larger than that in group I. We conclude that the traditional T-tube drainage incurs inevitably contamination of bacteria to bile by way of duodenal reflux. It is the consequence of bile flow dynamic disorder. PPD raises the bypass outflow resistance against the duodenal reflux and is thus superior to NPD.


Effect of acupuncture on gastric acid secretion in healthy male volunteers. Six randomized, placebo controlled studies were performed to investigate the effect of electroacupuncture on gastric acid output in 38 healthy males. Electroacupuncture decreased basal acid output when compared to placebo acupuncture [from 3.50 +/- 0.59 mmol/hr to 2.54 +/- 0.56 mmol/hr (P < 0.05)] as well as sham feeding-stimulated acid output [from 18.52 +/- 2.25 mmol/hr to 5.38 +/- 2.11 mmol/hr (P < 0.005)], but had no effect on the pentagastrin stimulated acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid output was not affected by local anesthesia of the acupoint, but was prevented by a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin levels (20.7 +/- 7.6 micrograms/liter, vs control 21.2 +/- 7.2 micrograms/liter) but naloxone increased it (26.1 +/- 14.5 micrograms/liter) (P < 0.05). We conclude that the antisecretory effects of electroacupuncture do not result from decreased gastrin release or decreased parietal cell sensitivity to gastrin, but are mediated through naloxone-sensitive opioid neural pathways and vagal efferent pathways.


Calcium supplementation prevents hypertensive disorders of pregnancy. Preeclampsia, a hypertensive disorder of pregnancy, is a major cause of fetal and maternal morbidity and mortality. Epidemiologic studies have shown an inverse relationship between dietary calcium intake and gestational hypertension. A recent large-scale, randomized, double-blind, placebo-controlled clinical trial has shown that supplementation of pregnant women with 2 g calcium per day from the twentieth week of gestation to term can significantly lower the incidence of hypertensive disorders of pregnancy. The beneficial effect of calcium supplementation was apparent as early as the twenty-eighth week of gestation. The mechanism responsible for the effects of calcium on gestational hypertension is unknown.


Valproic acid-induced placental and teratogenic effects in rats. Studies on teratogenicity and pathology of the cenceptus were conducted in Sprague-Dawley rats treated with 600, 800, and 1,000 mg/kg valproic acid po on day 13 of pregnancy. Each of the three doses was maternotoxic and caused (1) resorptions and/or abortions, reduction in the number of live fetuses per litter and mean fetal weight, and defects of the tail, rib and phalanx; and (2) degenerative changes in the labyrinth (thrombosis, angiectasis in the maternal lacunar network, necrosis of cytotrophoblasts and suppressed proliferation of fetal capillaries), reduced diameter nearing obliteration of umbilical vessels, with or without karyorrhexis of embryonic tissues. The lesions in the placental labyrinth were specific but, in the embryonic tissues, they were generalized. It was postulated that the vascular lesions in the labyrinth and umbilicus may have influenced embryonic development by reducing maternoembryonic gaseous and nutritional exchange.


Plasma lipid concentrations in hyperlipidemic patients consuming a high-fat diet supplemented with pyruvate for 6 wk. We evaluated the effects of a three-carbon compound, pyruvate, on plasma lipid concentrations in hyperlipidemic patients consuming a high-cholesterol (560-620 mg), high-fat (45-47% of energy; 18-20% of energy as saturated fatty acid), anabolic diet (0.11-0.12 MJ/kg body wt) for 6 wk. Forty subjects consumed the diet, randomly supplemented with 36-53 g pyruvate (n = 19) or 21-37 g polyglucose (placebo, Polycose, n = 21) as a portion of carbohydrate energy. Plasma cholesterol and LDL-cholesterol concentrations were unchanged in the placebo group, but decreased by 4% and 5%, respectively, in the pyruvate group (P < 0.05 vs placebo). Plasma HDL-cholesterol, HDL3-cholesterol, and triglyceride concentrations were similar in both groups. Resting heart rate, diastolic blood pressure, and rate-pressure product were unchanged after 6 wk of therapy in the placebo group, but decreased by 9%, 6%, and 12%, respectively with pyruvate supplementation (P < 0.05 vs placebo). We conclude that pyruvate supplementation of a high-fat, high-cholesterol, anabolic diet will decrease plasma cholesterol and LDL-cholesterol concentrations without affecting the HDL-cholesterol concentration.


Precision of biological standardization of allergenic preparations. Biological standardization (BS) aims at equilibration of the activity of allergen preparations from different types of allergen source materials. The biological unit (BU), proposed in the Nordic guidelines for 20 patients, has been found reproducible among different countries in Europe, but to be relatively imprecise, with a 95% confidence interval of about one power of 10. A more precise estimate of the biological activity of allergens or difference in sensitivity between populations would be of value. We used Ch, i.e. the concentration of allergen eliciting a wheal of the same size as histamine in the individual patient, estimated by regression line analysis. The Ch of 36 patients included in a BS trial was used. One of the 36 Ch-values was drawn randomly, and then sent back to the sample. This procedure was repeated 10, 20, 30, 40 and 60 times to create "samples" of different sizes. Ten samples of each size were produced. With 60 "individuals", the 95% confidence interval of the sample and the confidence interval of the medians were reduced to less than a factor of 2, i.e. to 74 to 128% of the median of the medians.


Reducing distress associated with pelvic examinations: a replication. A previous study of the effect of a new examination gown on patients' experienced discomfort during pelvic examination demonstrated that the gown was effective. This study replicated the previous study with a younger group of subjects. It was hypothesized that the new gown would reduce reported distress. Subjects were 147 patients at a university student health center. Age ranged from 18 to 31. Informed consent was obtained and patients were randomly assigned to either the experimental gown or the standard drape condition. Following examination, subjects completed questionnaires assessing demographic characteristics, state and trait anxiety, desired changes in pelvic examination procedures, and reactions to the examination. The attending nurse recorded blood pressure. Results supported the hypotheses. Experimental subjects rated the gown as more comfortable than control subjects rated the drape. Results indicate that this simple stimulus control intervention reduces one source of distress associated with pelvic examinations.


Segmental absence of small intestinal musculature. Three instances of segmental absence of small intestinal musculature are described. Based on their clinical and pathological features and on the 12 cases previously described in the English literature, these can be classified into two groups: primary and secondary. In the primary group, the etiology is unknown, the onset of symptoms is acute, and there are no pathologic findings in the remaining layers of the small bowel except for superimposed perforation, or intussusception. In the secondary group, there is a longer history of intestinal symptoms and of multiple surgical procedures. Histologically, there may be ischemic necrosis of remaining layers, fibrosis, calcification, chronic inflammation, and presence of macrophages. These findings indicate secondary destruction of muscle layers due to ischemia and/or infarction, interruption of the blood supply, or trauma.


Three-year occlusal wear of posterior composite restorations. The specific aims of this study were to: 1) measure the occlusal wear of four different dental composite materials placed in the posterior teeth of adults; and 2) evaluate the effect of the clinical parameters, cavity class and tooth type on occlusal wear. Four different visible light-cured composite materials were used to make the restorations in this study. The restorations placed for this randomized clinical trial were scored through the use of an indirect evaluation system (M-L scale). The total sample size per recall ranged from 90 to 142 restorations from baseline to 36 months. The mean wear at 36 months for Heliomolar, J&J Experimental (Adaptic II) and P-30 was 45-54 microns, which is rather low compared to the recently reported wear of other composite materials. Marathon exhibited significantly greater wear with a mean of 174 microns at 36 months. The data also showed that cavity class and tooth type had no significant effect on the occlusal wear of the restorations made with the three low wear-rate materials, while restorations composed of the high wear-rate material exhibited more wear in molars than premolars; this effect was again not statistically significant. These data support the hypothesis that the overall wear of a composite restoration is more dependent on the material's properties than clinical parameters such as cavity class and tooth type.


Persistent hypotension associated with hypermedullipinemia: a new syndrome. A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin 1. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.


Fibrosis of the human heart and systemic organs in adrenal adenoma. In experimental animals, chronic mineralocorticoid (MC) excess is associated with fibrosis of the myocardium and systemic organs, where both a reactive, i.e. interstitial and perivascular, and reparative, i.e. microscopic scarring following cardiac myocyte necrosis, fibrosis are found. We sought to determine if a similar fibrous tissue response was present in human myocardium and systemic organs in association with adrenal adenoma. Postmortem specimens of heart, adrenals, pancreas, lungs, kidney and liver were obtained from 5 patients (age 67 +/- 5 years) with autopsy-proven adrenal adenoma. Documented histologically normal tissue from age-matched patients was used for comparison. Tissue sections were stained with the collagen specific stain Sirius Red F3BA and analyzed using normal and polarized light. Reactive and/or reparative fibrosis was found in the heart, pancreas, adrenal glands and lungs, but not in the kidney or liver. These observations support a link between chronic MC excess and fibrosis of the heart and systemic organs in humans with adrenal adenoma.


Plasma atrial natriuretic peptide (ANP) concentration in patients with pheochromocytoma. The interaction between catecholamines (CA) and ANP is not clearly established. The effects of excess endogenous CA on ANP secretion can be investigated in patients with pheochromocytoma. We studied 27 patients with surgically and histologically proven pheochromocytoma (P) aged 19-70 years. In 16 of these patients plasma ANP study was repeated after surgical removal of the tumour. The control group (C) consisted of 20 healthy volunteers aged 21-48 years. Moreover, 42 patients with uncomplicated mild to moderate essential hypertension (EH) aged 18-48 years were also studied. In P higher plasma ANP concentration versus C, EH was found (51.9 +/- 8.1; 25.5 +/- 1.5; 19.3 +/- 1.5 fmol/ml, respectively). In 16 patients with P, increased plasma ANP level (mean 63.3 +/- 12.6 fmol/ml) declined after surgical removal of the tumour (mean 22.4 +/- 2.9 fmol/ml). In the P patients no relationship was found between plasma ANP and hormonal patterns of the tumour or between plasma ANP and plasma catecholamines, whereas significant positive correlations between plasma ANP and both systolic and diastolic blood pressure and heart rate were demonstrated. These results suggest that excess CA produced by the chromaffin tumour induce ANP secretion via stimulation of adrenergic receptors. However, influence of the haemodynamic changes evoked by CA cannot be excluded. It is suggested that increased secretion of ANP may be of some importance in maintaining blood pressure homeostasis in patients with pheochromocytoma.


Effect of ketoprofen on blood pressure, endocrine and renal responses to chronic dosing with captopril in patients with essential hypertension. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/- 11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.


The stroke preventive effect in elderly hypertensives cannot fully be explained by the reduction in office blood pressure--insights from the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). To study whether the cardiovascular preventive effect of antihypertensive therapy can be explained solely by the reduction in office blood pressure, and to what extent the risk of stroke and cardiac events is associated with in-study diastolic blood pressure (DBP) and systolic blood pressure (SBP). The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. The study group comprised 1,627 elderly patients (mean blood pressure 195/102 mm Hg; mean age 75.7, SD 3.7; 63% females). The average follow-up was 25 months (range 6-65 months). No patient was lost to follow-up. We applied a Poisson model taking current age, sex, treatment, DBP and SBP into account for all patients in the study. The constants of the model were estimated by the maximum likelihood method. The risk of stroke was significantly lower (42%, p = 0.0402) for a patient on active therapy than for a patient on placebo having the same blood pressure level, age, and sex. There was a corresponding, non-significant, reduction in cardiac events of 21%. In the whole study group the risk of stroke increased by 3% per mmHg (p = 0.0247) with increasing diastolic blood pressure for a given systolic pressure. The corresponding value for cardiac events was 2% per mmHg (p = 0.0376). In STOP-Hypertension we found a substantial risk reduction in stroke in actively treated patients, which was not solely explained by the blood pressure reduction obtained by treatment with beta-blockers and a potassium-sparing diuretic combination.


Influence of early antihypertensive treatment on vascular and cardiac design in SHR with and without renal hypertension. The present study was designed to explore to what extent pressure reduction by antihypertensive therapy and pressure elevation by renal hypertension are able to affect structural vascular and cardiac changes in young spontaneously hypertensive rats (SHR). Pressure elevation in SHR was induced by means of superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13 weeks of age in both clipped and unclipped SHR. Vascular structure of the skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation and left ventricular dimensions were calculated from pressure-volume relationships of isolated hearts arrested in diastole. Induction of renal hypertension in SHR resulted, besides augmentation of arterial pressure in a marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness to internal radius ratio. Likewise, in renal hypertensive SHR, a structural adaptation of the skeletal muscle vascular bed occurred, reflected as elevations of minimal vascular resistance and maximal generated perfusion pressure. Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented mean arterial pressure from increasing further in SHR, and in SHR with superimposed renal hypertension by approximately 15% (p < 0.001 for both). In renal hypertensive SHR, felodipine partly prevented the development of exaggerated structural changes, both in the heart and in the skeletal muscle vascular bed, as reflected by reduced wall thickness to internal radius ratio and reduced minimal vascular resistance by 22% and maximal pressure response by 10% respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)


Radioimmunoassay of endothelin in human plasma. A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1 (ET-1) in human plasma has been developed. Antibodies were raised in rabbits using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies obtained were used at a final dilution of 1:300,000 yielding maximum binding of 61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose 50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2 was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18 cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was 1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1. Extracts of normal human plasma subjected to high performance liquid chromatography on a reverse phase C18 column showed one peak of immunoreactivity co-eluting with the standard for ET-1. From these data it is concluded that the immunoreactive material measured in normal plasma with the present RIA is identical to ET-1.


[The significance of lobular inflammation in chronic active hepatitis]. Authors have performed an anatomo-clinico-biological comparison of two groups of hepatitis with lobular inflammation: group I with a simple lobular inflammation, called lobular hepatitis, and group II with a lobular inflammation associated with portal and periportal hepatitis, called chronic active hepatitis (CHA) with lobular hepatitis. Furthermore, a comparative study of these forms with a group of CHA without lobular inflammation was performed. Both forms of lobular inflammation appeared in young patients, the large majority of whom were infected with the hepatitis B virus; in 5 cases of CHA with lobular hepatitis the presence of the delta agent in the liver, possibly responsible of the lobular inflammation, was detected. The two forms of lobular hepatitis are differentiated by: the fivefold increase of ALAT over the normal value, with usually normal gamma-globulins and albumin, in the first group; in the lobular hepatitis, HBsAg was present in 33% of cases in the first group and in none of the patients of the second group, suggesting the integration of HBsAg within the hepatocytic genome; the clinical picture was generally asymptomatic in the first group and noisier, with hepatomegaly, in the second group; the period elapsed since the acute hepatitis was shorter in the first group (4-11 months) in 8 of 15 patients and longer in the second group. The clinical course of these forms of hepatitis if unforeseeable and the diagnosis is established on the basis of the morphological examination.


[An association between ankylosing spondylitis and rheumatoid polyarthritis; comments on 3 cases]. The article is an analysis of 3 clinical cases, characterized by the presence of the lumbosacral axial involvement, with the radiological evidence of a bilateral sacroiliitis and a peripheral polyarthritis displaying a rheumatoid picture, with rheumatoid factors in the serum and in 2 of the cases also in the articular fluid. These cases belong to the HLA-27 B histocompatibility type, a feature which could be, according also to the data of literature, an explanation of the association of these two diseases.


[Lethal midline granuloma in Senegal. (Apropos of 15 cases)]. African authors, other than senegalese, have not paid enough attention to lethal granuloma, a terrible disease. This series is about a series collected between 1975 and 1990. It is particularly high compared to other series in the world. If diagnosis is easy for the clinician, much care must surround the pathological answer. Those diagnosis problems and difficulties of treatment (represented by 11 deaths) are studied.


[Fungi in the hospital environment and infectious risk]. Using petridishes at hospital in services with risk patients, we have isolated Aspergillus (41.5%), Penicillium (26.4%), Candida (12.2%), Fusarium (7.5%), Mucorales (5%), Scopulariopsis (5%), Scytalidium (0.8%), Tricothecium (0.8%), Ulocladium (0.8%). Several fungi grew at 37 degrees. These saprophytic fungi could give opportunistic mycoses in immunodeficient patients.


[Non-infectious complications of treatment of hydrocephalus by shunt]. From january 1975 to december 1988, 234 hydrocephalus cases of newborn and infant treated by ventriculo-peritoneal or ventriculo atrial shunt have been studied at Dakar CHU (University Teaching Hospital) neuro-surgery clinic. The non infectious complications of this type of surgical treatment using inert material, have been observed in 52 patients or 22 per cent even though infectious complications can be noted in 34 per cent of the cases. Among these non infectious complications the extra-cranial mechanical are the most frequent. Fistula or subcutaneous collection of CSF (13 cases), cutaneous necrosis (12 cases), shunt material disconnection (9 cases), obstruction (8 cases). Chronic subdural hematoma has been proved rare and cranio-stenosis secondary to drainage, exceptional. The treatment of mechanical complications by simple revision emphasizes the maintenance of shunt material in place contrary to the treatment of infectious complications that occurs almost always the removal of a material already expensive associated with a long standing antibiotic chemotherapy. Successive revisions and reinsertion of material can raise technical difficulties which will lead to delayed infection. Careful technical procedure of shunting constitutes the best mean prevention against these non infectious complications.


[Aerobic capacity training in heterozygote sickle cell athletes]. Two sport groups, all training physical educational and sports teachers at the H.N.I.P.S.S. of Dakar have been tested by measure of maximum consumption of oxygen (VO2max) before and after a three month aerobic training. The first group contained 10 abnormal hemoglobin (AS) subjects. The second group 11 normal hemoglobin (AA) subjects. The results do not show any difference in the reaction of adaptation between the two groups.


[Antithrombin ii in eclampsia: estimation of predictive value]. We have observed in our study that antithrombin III activity decreases very significatively in eclampsia (p < 0.0001). A level of 90% was defined as a threshold. All the rates which are under or equal to 90% have 78.3% as a positive predictive value and those over 90% have a 98.7% as a negative predictive value for the overcoming of eclampsia. We have concluded that the 90% antithrombin III activity represents the alarm level for over coming eclamptic crises. The determination of the antithrombin III activity must be systematically done in every hypertensive pregnancy with proteinuria.


[Dispersion of biochemical analysis results in Dakar: preliminary results]. Now and then, the conflicting character of results of some analyses is prejudicial to patients (financial and particullary psychological repercussions), to the laboratories (renown) and to the practitioners (difficulties of interpreting). After a study of the dispersion of some analyses results, the authors propose a creation of an Interlaboratory Quality Control in Clinical Biochemistry in Senegal.


[Diagnosis and follow up of the development of a large left intraventricular thrombus. Apropos of 1 privileged case]. The authors report a rare observation of left intraventricular thrombus in a 39 years old senegalese man with a dilated non-obstructive cardiomyopathy. With the echocardiographic follow-up, it was possible to follow the regression of the clot. Echocardiographic diagnosis and evolutive problems of such left intraventricular thrombus are reviewed.


[Effect of water fasting on sport performances in the laboratory]. 15 sport men heart rate and central temperature were measured at rest and at the end of a progressive maximal exercise. Maximum consumption of oxygen (VO2 max) was estimated after the effort. The experience began in the morning from 9 to 11 a.m. and the afternoon from 4 to 6 p.m. In the first time subjects had a normal alimentation and in the second they observed a rigorous fast. The comparison of the results doesn't show difference induced by fast on VO2 max and maximal heart rate. However heart rate at rest and capacity of work decrease during fast and permit to think that a more intensive and long exercise in more strenuous climates than this one should give significative modifications.


[Rational prescription if protein evaluation in the diagnosis and follow up of protein-energy malnutrition]. In our countries, a good prescription of analysis would help to reduce hospital costs without modifying the efficiency of the diagnosis approach. In this work, the authors establish a bond between medicos and biologists by a good indication of protein check-up in the diagnosis and follow up of protein-energy malnutrition (PEM). After a discriminant analysis of all the results of protein check-up, two groups of markers are individualized depending on whether the PEM is accompanied or not by inflammatory complications. Finally, they recommend a systematic prescription of the useful group in case of inflammation associated with PEM, because infectious and parasitic diseases are almost constant among our malnourished infants.


[Preparation and characterization of a monoclonal antibody directed against bovine leukocytes]. A monoclonal antibody (MAb-M25) was obtained by immunizing BALB/C mice with tumour cells isoled from a familial thymic lymphosarcoma observed in Friesian cattle. The specificity of this MAb was assessed using PBL, lymphoids organs (lymph node, spleen, tonsil, Pleyer's patch) and non lymphoid tissues (liver, skin) from clinical normal cattle. Immunofluorescence and immunohistochemistry methods were used to characterise this monoclonal antibody. It reacted with 27% of peripheral blood lymphocytes and a large proportion of mononuclear cell in the lymphoid organ, in the thymic cortical, in the dermis and in the liver. It also stained lymphocytes of the mantle of follicules and thymocytes of the thymus cortex. The tissue distribution of M25 have a similarity with the human CD1c Mab and the bovine 20-27 MAb.


[Christopherson's tumor. Review of the literature apropos of a retroperitoneal localization]. Alveolar soft-part sarcoma is rare, and its retroperitoneal localization in psoas major muscle, exceptional. Concerning a case occurred in a young woman, the authors focus on the characters of this tumor of unknown histogenesis which affects predominantly young adults, mainly females. This disease, which symptomatology is poor and which evolution is particularly long for such a neoplasm, leads inexorably to death despite surgical treatment that represents to date, the unique efficient therapeutic modality.


[Sacro-ilial tuberculosis (sacrococcygeal). Apropos of 1 case]. In a single case review the authors recapitulate the different methods for the presentation of sacro-ilial infectious and underscore imagery techniques which are of prime importance in diagnostic work. X-rays can only reveal advanced sacro-ilial bone joint lesions which are under-evaluated. In the absence of HI-Tech imagery, surgical biopsy must be widely recommended to identify the germ and allow early diagnosis.


[Problems linked to trismus in a dental office]. The objective of this report was to know the most frequent etiology of trismus we meet in our dental office as well as the different treatment set up. The question is an observation of 58 cases of trismus that we received in two different dental clinics: Odontology and Stomatology Institute and Social Hygen Institute of Dakar. The results we got show that trismus is an odontologist's daily problèm. Although its treatment is relatively easy, it is good to remember that etiologies other than dental exist.


[Anatomic study of the anterior interventricular artery (Ramus interventricularis anterior). Apropos of 200 anatomical samples]. The coronary system has been studied on the basis of 200 hearts taken during necropsies and treated by injection of a synthetic resin followed by corrosion. Sixty samples were used for the study of the L.A.D. and one hundred and fifty were used for studying intercoronary anastomosis on L.A.D. The study highlighted the following particularities: the left coronary is the most common origin of L.A.D. (90 per cent cases); the L.A.D. irrigates: all the left ventricle ventral wall, the right apical part of both ventricles and the upper portion of the interventricular septum; out of 92 anastomoses, 49 were located on the L.A.D. which could protect against ischemia.


[Drug prescription in Dakar and outskirts]. Drugs are very important to human life due to their human mission and to the essential role they play in modern society through their real social function. When used in certain conditions, drugs are expensive, ineffective and can even become dangerous and the source of poisoning with serious consequences. In order to minimize risks and accidents, special attention is paid to drugs from their conception to their elimination by the body, resulting inter alia in a severe control of their prescription. In Dakar, where are can find the greatest number of prescribers in Senegal, this control is rarely respected. This situation can be fraught with serious consequences for the health of populations.


[Biological diagnosis of hepatitis e. Completion of a test for detection of infected patients]. The aim of this study is to set up a biological method for diagnosing hepatitis E using an immunoenzymatic technique. This technic attaches specific IgM of a monkey experimentally infected with the Hepatitis E virus to a solid phase. These antibodies capture the HEV antigen (AgHEV) present in the stools of patients with hepatitis E. Antigen was then revealed using purified and labelled IgG from the same monkey. Using this method, we were able to: prove the existence of sporadic cases of hepatitis E in Dakar, biologically confirm the diagnosis of hepatitis E in 53.33% of patients suffering from hepatitis during an epidemic in Constantine and in 26.3% of patients in Bangkok who contracted oral-fecal transmitted hepatitis. Confirmation by inhibition and control reactions demonstrated the specificity of this test and its usefulness as a tool for the biological diagnosis of hepatitis E.


[Bacteria associated with diarrheic episodes in young camels in Niger]. During diarrhoeic episodes of young camels in Niger, bacteria such as Salmonella enteritidis, E. Coli, Staphylococcus sp., Clostridium perfringens and other bacteria were isolated from stool samples. Bacteria roll in this pathology is discussed, and a treatment is proposed, compared with antibiogram results.


[Hypertrophic pyloric stenosis of the infant. Apropos of 8 cases]. Eight cases of Infantile Hypertrophic Pyloric Stenosis collected in 10 years (1980-1989) in the Pediatric Surgery Unit of the Surgical Clinic of Dakar are reported. The rarity of this pathology among Blacks and a male predominance are noted. The clinical onset occurred after an average period of 3,25 weeks marked by food vomiting. At the start of the surgical management the age of patients was 6 weeks. X-ray examination following a barium meal showed no passage of contrast in 3 cases. However a narrowed and elongated pyloric canal was noted in 5 cases. Abdominal sonography was used in 3 cases and showed gastric stasis with a hypertrophy of pyloric muscle. A rammstedt pyloromyotomy was performed after a period of few hours to 13 days of resuscitation. A duodenal perforation complicated the operation twice and was subsequently repaired. In the post operative period, two patients died within 2-3 days. One of them had duodenal perforation. Six patients made a good recovery.


[Evaluation of Vibrio cholerae isolation over 10 years in CHU Fann]. A retrospective study, concerning ten thousand five hundred and sixty five (10,565) stool samples examined from 1981 to 1990, was done at the Bacteriology Laboratory of Fann University Hospital, Dakar (Sénégal). One thousand and six hundred and eighty (1680) enteropathogen agents were detected (15.9%), five hundred ninety two (592) of which were vibrio cholerae. The quasi totality strains of the vibrio cholerae (99.8%) belonged to the Ogawa serotype; they were isolated mainly during the hot and raining season. Young male adults were the most infected. Most of the strains revealed sensitive to Sulfamids and Tetracycline.


[Mycetoma with neurological manifestations. Inherent therapeutic difficulties in these localizations. Apropos of 5 cases]. The authors report five cases of mycetomas with an original localization, cranio-encephalic and vertebro medullary. Four times it concerned a dorsal or cervical mycetoma with deep enlargement responsible for compression of the spinal cord. In the 5th case, scalp infection reached the dura mater. All patients have got histopathological diagnosis. Therapeutic difficulties are evocated about these singular localizations in a pathology for which greater amputation stands as the rule.


[Cylindroma of the epiglottis].

[Cylindroma of the epiglottis]. The observation of an exceptional laryngeal localization of an adenoid cystic carcinoma allows authors to review diagnostic, therapeutic and increasing problems of this glandular carcinoma. The reported case constitutes a histologic surprise. An economical removal has allowed to obtain a long remission without recurrence, nor metastasis; this never put back the principle of the broad surgery to institute when faced this type of cancer, but just emphasize the interest of an early treatment.


[Bacteriology of shigella isolated in a tropical zone CHU]. From 1981 to 1991, five hundred eighty one Shigella's strains were isolated in the Laboratories of the CHU Fann of Dakar. They represent 24.8 per cent of enteropathogen agents and 4.3 per cent of diarrhoeae causative agents. Shigella flexneri was predominant (71%), following by Shigella dysenteriae (14.5%), Shigella sonnei (11.4%) and Shigella boydii (2.5%). In pediatric hospital 90 per cent of strains were isolated between 1 and 5 years age; in adults, the pic was found from 20 to 30 years. Five of the 13 tested antibiotics had inhibited 89 to 96 per cent of strains. The isolation of multiresistant strains will be in rapport with the antibiotic resistant plasmide portage.


[Ureteral-pelvic junction syndrome in the child. Apropos of 8 cases]. Eight cases of uretero-pelvic junction syndrom collected in the ten past years are reported. They are 4 males and 4 females ranged from 18 months to 15 years with a mean age of 4.5 years. This age too late is probably due to the misknowlege but also to the lack of information about the pathology. The main characteristics of this syndrome are analysed according to the literature. All patients except one underwent nephrectomy because the irreverible lesions of the kidney. The authors emphasize the importance of early diagnosis done by antenatal echography but it can be made with a good clinical examination followed by the results of I.V.P. It is necessary for them to make parents, general practitioners and paediatricians sensitive to that pathology to avoid such operating act whose consequence are very serious where as it is benign.


[Surveillance of heavy metal pollution of mangrove oysters in Senegal]. Joal-Fadiouth, located in department of Mbour (region of Thies), 118 kilometers from Dakar, the capital of Senegal, is an area where one can find a large swamp with mangroves whose self-propagating roots serve as growth support for young oysters. The importance of those oysters, both on the domestic and foreign markets and the ever greater threat of pollution of our coasts led us to search for and measure out heavy metals. In fact, it is well know that the accumulation of those elements in the food chain can be at the origin of severe poisoning. It appears, in the light of the results obtained that the level of pollution by heavy metals in this part of the senegalese coast has not yet reached alarming limits.


[Spinal meningiomas. Apropos of 14 cases]. Fourteen cases of spinal meningiomas were reviewed. There were 5 males and 9 females, with an average age of 40 years who underwent surgical treatment at the Neurosurgical Division of Dakar University Teaching Hospital. The thoracic spine was involved in 10 cases. The location of the tumor in the spinal canal was epidural in 6 cases and subdural in 8 cases. 7 patients (50%) had marked improvement or stabilization: 4 patients died and in 3 cases, a recurrence was noted. The authors emphasize diagnostic difficulties encountered in the epidural forms.


[Male sterility through hormonal insufficiency in Cameroon]. At the Gyneco-obstetric service of the Yaounde CHU, we have studied 361 cases of couple sterility. In 38%, the man was responsible. Among these patients, less than 50% had a complete hormonal checkup. The hormonal cause of sterility was confirmed in 63 patients by static tests using the radio-immunologic method. These hormonal abnormalities were most the result of a primary testicular insufficiency (23.8%) and seminifer tube abnormalities (38.5%).


[Conjugal sterility at Dakar CHU: epidemiological profile and evaluation limits apropos of 429 cases]. The writers draw up the outcome of the medical management of infertiles couples at Dakar's teaching hospital over a period of 7 years (1983-1989). Restrictives factors (low rate incomes, social and psychological obstacles) make that médical management difficult. The responsibilities are shared among the couple with sex ratio of 1 man for 3 women. Among the women the etiologies dominated are the sterility of the Phaloppe tubes (81%) among men with the oligo and the azoospermy (32 and 27%). Sterility within married couples is a problem of public health that becomes more acute every day. A better handling of this problem through preventive medicine and elementary sanitary training is necessary.


[Congenital cystic dilatation of the choledochus: apropos of a case diagnosed in an adult Senegalese women]. The authors report a case of congenital cystic dilatation of the choledochus diagnosed on a 37 years old senegalese woman. It is an uncommon affection in Africa. The clinical presentation with various signs is reviewed. Ultrasound or cholangiography confirms the diagnosis. Surgical excision of the cystic dilatation is the best treatment because of the high risk of cancerisation.


[Seroprevalence of anti-Delta antibodies in hospital workers in Dakar]. 708 hospital workers in CHU of Dakar were tested to HBs antigen: among them 128 were positive and tested to Delta antibody by ELISA Abbott kit. Seven men and one woman were positive; however the positivity to Delta antibody is neither linked to sex, nor to age. 87% of the Delta antibody carriers were found among the trainees, and 50% of them studied in the Odonto-Stomatology Institute.


[Central temperature and its circadian rhythm in men acclimated to the intertropical zone]. The central temperature has been measured at rest over 623 black men who are between 18 and 78 years old, and perfectly fit to warm weather in the intertropical areas. The measures have been taken according to two protocols: dealing with the ambiant temperature and the humidity (ambiant temperature varying from 20 degrees C to 42 degrees C, the humidity from 70% to 80%). dealing with the daily cycle: The central temperature was recorded every 3 hours by 24 hours at two different periods in the year, on June (the ambiant temperature varying from 28 degrees C to 42 degrees C and the humidity from 33 to 42%), and on December (the ambiant temperature varying from 21 degrees C to 25 degrees C and the humidity from 70 to 90%). On the one hand, the results showed an influence of the external temperatures on the circadian curves of the central temperature (maximal central temperature taken in the afternoon was 37.2 degrees C in winter and 37.6 degrees C in summer). On the other hand, there's a linear relation between central temperature and ambiant temperature, at least on certain limit and apart from the weather. In spite of two modifications, the thermoregulator system of some designed individual remain efficiency but would work rather than according to the mechanism of the "following" systems.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diagnosis of tuberculosis by specific DNA amplification directly in samples]. The polymerase chain reaction (PCR was used to identify M. tuberculosis in specimens from patients with suspected pulmonary tuberculosis. A segment of the IS 6110 sequence and of the Cro EL gene were amplified and identified by hybridization with specific probes labeled with peroxidase. The results are in agreement with those obtained using standard microbiological techniques or clinical criteria. The PCR method allowed the detection of M. tuberculosis in 22 out of 58 samples that were acid fast staining negative. The number of patients with at least one positive sample by PCR was much higher in the group with suspicion of tuberculosis (14/28) than in the control group (3/23). This demonstrates the possibility of using PCR technology in endemic areas for tuberculosis.


[The plague: disease and vaccine?].

[The plague: disease and vaccine?]. Plague has existed in Madagascar since 1896, with epidemic control achieved by GIRARD with an EV vaccine in 1937. Plague persists in Madagascar, however, due to the large animal reservoir. With a predilection for nodal tissues, Yersinia pestis is a virulent bacteria that is potent inducer of antibody synthesis. Immunity mechanisms stimulated by infection were studied: 1. In human by immunoenzymatic methods 2. In mice by seroprotection and vaccinating tests. Induced immunity for people in endemic and endemic-epidemic areas, is significant, affecting approximately 70% of these populations. In non endemic areas, immunity is found in only 33% of the population, perhaps this explains the persistence of epidemic? In all cases, this immunity is a quick onset (6 days), is persistent (> 2 years), and has demonstrable serious recognition of YOP (Yersinia Outer Proteins) by Western Blot method. Human antibodies were shown to be protective for mice. Animals vaccinated by YOP were protected equally well, when compared to animals infected with Yersinia pestis and subsequently treated with antibiotics. Finally, YOP aerosols were also shown to induce antibodies. In conclusion, plague is a vaccinatable bacterial disease and YOP can be used as an animal vaccine to permit plague control in the rat reservoir.


[Cysticercosis in Madagascar: diagnostic and therapeutic improvement]. Human cysticercosis is linked to infection by the larval stage of Taenia solium: Cysticercus cellulosae and was identified in Madagascar since 1901. Neurocysticercosis constitute, when parasite is localized in cerebral vesicles, a disease with important neurologic symptoms: epilepsia, spasms... This disease would be diagnosed before parasite calcification and this diagnosis permit Praziquantel treatment indication, with good results in many cases. We have developed cysticercosis diagnosis permitting: stage definition of the disease: Elisa and Western Blot tests, therapeutic following by enzyme immunoassay capture of serum cysticercosis antigens. We have observed: disease prevalence of 18% proving high rate of circulating parasite, in the countries studies, significative variation of circulating antigens and/or antibodies, one month after one or two Praziquantel treatment, in 82% of 130 patients. This disease seems to be important in Madagascar in neurologic syndromes, but the solution of this problem would result in prophylactic and concerted actions by public health means.


[Epidemiology and prognosis of cervix cancer. Experience of the University Gynecology and Obstetric Clinic Ignace Deen of Conakry in 10 years: 1982-1991]. The cancer of the cervix is a tumor that can be detected at an early stage. Unfortunately, it is still detected lately in our service. Thus, it is the underlying cause of death by gynecological affection. After a preliminary work in 1982 about 35 case histories, the authors undertake a 10 years retrospective study where they showed that: the cancer of the cervix is the primary gynecological cancer (78.7%), it obtains between 25 and 65 years, the most often associated factors are early sex, (28%), poor living conditions (22%), cercivitise (17%), metrorrhagias (24%) and leucorrhoea are the most frequent signs. buding lesions are the dominant macroscopic form (68%) epidermoid carcinoma is the most important histological type, 98.7% cancer cases are detected at advanced stages (T3 and T4), the prognosis is dramatic: most patients die at home. This is a great public health issue the solution of which implies the collective action of decision-markers, health personnel and the communities themselves in order to promote early detection.


Renal transplantation in infants, a therapeutic option? Renal transplantation is widely accepted as the treatment of choice for endstage renal failure in childhood. Since dialysis is regularly applied to infants with renal failure, the question logically arises, can infants also receive renal transplants and what are the outcomes? A review of the literature and the clinical experience at the University of Minnesota supports the performance of renal transplantation in infancy. Present patient and graft survival rates for infants are indistinguishable from those of older children. While living adult donors are preferred, adult cadaveric kidneys have also been successfully transplanted. Following successful transplantation, the infants have generally enjoyed "catch-up" growth and accelerated psychomotor development. While there may be problems related to fluid and electrolyte balance in these smallest patients, the majority of the problems encountered mirror those seen in any child undergoing transplantation. Renal transplantation is regularly successful in infancy and should be considered an integral component of the therapy for any child with chronic renal failure.


Paediatric aspects of renal transplantation: experience of a single centre. From 1970 to 1991 a total of 244 renal transplantations were performed in 203 children at the Medical School in Hannover. The mean patient age was 10.4 years with a range between 11 months and 16.9 years. Fifty-nine children received a living donor graft from one parent and 144 received cadaveric grafts. Forty-two children were transplanted without prior dialysis treatment. After 20 years the overall survival rates were 86% for the patients and 39% for the first grafts. Grafts from donors below 5 years of age had a less favourable survival (44% after 5 years). Pre-emptive transplantation yielded comparable results with the benefit of a shorter period of uraemia. Hypertension developed in 80% of transplanted patients. Only children with living related donor grafts had significantly less hypertensive problems independent of the immunosuppressive regimen. Post-transplantational growth improved under cyclosporin. Children with nephropathic cystinosis also showed catch up growth after transplantation under cyclosporin. The long-term outcome and rehabilitation of grown-up recipients were encouraging.


Update of pediatric liver transplantation. Liver transplantation is an effective and widely accepted therapy for children with end-stage liver disease. Major indications include primary liver disease, resulting in hepatic insufficiency, or severe morbidity secondary to chronic non-progressive liver disease and metabolic diseases of the liver. Liver replacement should not be considered if there is an acceptable alternative therapy. Relative contraindications to transplantation include irreversible impairment of other organ systems, major systemic infection and diseases expected to recur after transplantation. Early referral for pre-transplant evaluation is important to confirm the proper diagnosis and determine priority for transplantation, to identify potential contraindications, and to assist in supportive care of the patient with chronic liver disease. Innovations such as reduced-sized liver grafts and most recently, living related liver transplantation have increased the donor supply of organs for small infants and significantly reduced pre-transplant mortality. In addition, living donor transplantation allows infants to benefit from transplantation before developing severe complications of end-stage liver disease and reduces the incidence of primary graft non-function and rejection. Immunosuppression following transplantation is maintained with methylprednisolone, azathioprine and cyclosporine. Acute rejection is treated with short bursts of high-dose corticosteroids and when necessary OKT3. With this approach, 90% of the episodes of rejection can be successfully controlled. Survival after transplantation has steadily improved and survival rates of 70%-90% are routine. Following transplantation, children experience rapid nutritional restoration, increased muscle strength, marked progress in gross motor development and improved general health.


Orthotopic liver transplantation in liver-based metabolic disorders. The efficacy of orthotopic liver transplantation (OLT) in the management of more common liver-based metabolic disorders associated with severe liver damage, alpha-1-antitrypsin deficiency (PIZZ), Wilson disease and tyrosinaemia has been demonstrated and indications defined. An early mortality in excess of 15% and finite resources limit its use. Phenotypic heterogeneity make the precise indication in other disorders less certain. In disorders in which endstage liver disease is less frequent such as cystic fibrosis, haemochromatosis and galacosaemia it has been a very effective therapy. It has been used with encouraging results in disorders in which the liver is structurally normal such as Crigler-Najjar type I, primary hyperoxaluria type I and primary hypercholesterolaemia. In these it should be performed before there is permanent damage to brain, kidneys or heart. OLT in the short term prevents hyperammonaemic coma in urea cycle defects and may prevent extrahepatic disease in glycogen storage disease type IV. Its limitation in reversing all metabolic effects in these and other disorders is discussed. It is ineffective in protoporphyria or Niemann Pick disease type II (Sea Blue Histiocyte syndrome) in which the transplanted liver acquires the lesions of the initial disorder and extrahepatic features progress. Early referral provides optimum circumstances to assess the benefits of OLT as compared with those of other forms of management and to achieve transplantation at the ideal time. The place of OLT in management will require constant review as metabolic disorders are better defined, new forms of therapy evolve and as techniques of liver transplantation and modes of immunosuppression improve.


Pre- and post-transplant assessment of liver function in paediatric liver transplantation. The pre-operative risk of paediatric liver transplantation candidates (n = 41) was assessed in a prospective study by means of clinical symptoms, conventional static and liver blood flow dependent dynamic liver function tests. Nine patients died during the 365-day waiting period. The data were subjected as covariates to a survival analysis in the Cox proportional hazards model. There was a significant relationship between the results of mono-ethylglycinexylidide (MEGX) formation and ICG test and the 365-day survival rate. In the stepwise analysis, none of the remaining parameters improved the predictive ability when added to the dynamic liver function test results. The assessment of post-transplantation liver function was studied in 27 patients during the first 28 postoperative-day period. In addition, liver function was studied in a cross-sectional study 1-7 years after successful liver transplantation in children with complete or partial rehabilitation. In the early postoperative period severe organ damage was indicated by both static and dynamic liver function tests. In the later course after transplantation no deterioration of liver function measured with MEGX formation was to be observed. These findings demonstrate the usefulness of dynamic liver function tests in the pre- and post-transplant assessment of liver function.


Bone marrow transplants in genetic diseases. The first paper [9] advocating the displacement use of bone marrow transplantation (DBMT) to treat a variety of genetic metabolic diseases (including thalassaemia major) was put before a European Working Party in 1978. It evolved from mainly Westminster experience which showed the need [6] for DBMT and first successfully used donors other than matched siblings [9]. The principles of using DBMT to install a donor marrow as a component factory which can last a lifetime are outlined. It is not a panacea, being applicable to only about 7% of known inborn errors. Worthwhile correction of some 50 previously disabling diseases in over 700 patients has already been achieved worldwide and for most of the survivors no further treatment is used after 1 year. Guidelines for future extension, including gene transplants, are offered. The superior results of elective DBMT (about 95%) should encourage paediatricians to aim for earlier diagnoses and evaluations for transplants.


Chemotherapy versus bone marrow transplantation in childhood acute lymphoblastic leukaemia. BFM Study Group. Twenty-five years ago over 90% of children with acute lymphoblastic leukaemia (ALL) died of this disease. Dramatic improvement has been achieved since then by employing risk-adapted, aggressive polychemotherapy protocols. More than 90% of children with ALL treated according to, for example BFM-protocols, have nowadays cure rates in the range of 70%-80%. However, 10% of patients do not initially respond adequately to standard induction chemotherapy. They are characterized by distinct chromosomal abnormalities such as translocation (9; 22) or combinations of early treatment failure and other risk factors as cytogenetic abnormalities, lineage-specific surface markers or tumour load at diagnosis. In this group of patients in first complete remission and certainly in the vast majority of relapsed patients, allogeneic bone marrow transplantation (BMT) has evolved as an alternative approach allowing further intensification of myeloablation and the introduction of an additional antileukaemic alloreactivity. Nevertheless, the decision for a marrow transplant in children has to be made very carefully because of a significant increase in treatment related mortality and BMT-specific risks like acute and chronic graft-versus-host disease with a critical iatrogenic chronic morbidity. This is even more evident, if mismatched or unrelated transplants are being considered. The indications for one or the other treatment modality according to the current BFM strategy are discussed.


Heart-lung transplantation for cystic fibrosis. Heart-lung transplantation for cystic fibrosis has become an established form of treatment over the last few years. This paper considers the assessment and preparation of patients, the surgical procedure, immunosuppression, post-operative care and the results of surgery. The best survival rates to 1 year are 70%-80% with possibly a less favourable survival for younger patients. Major problems include shortage of donor organs, post-operative management of patients with multisystem disease and obliterative bronchiolitis. The majority of patients, however, do well with a greatly improved quality of life and the medium-term results are encouraging.


Heart transplantation in children: mid-term results and quality of life. From 1987 to 1991, heart transplantation was undertaken in 49 infants and children with either end-stage cardiomyopathies (28 patients) or severe congenital heart disease (21 patients including 16 having already been surgically but unsuccessfully treated). Their age ranged from 13 days to 15 years (mean = 4.5 +/- 4.2 years; median = 2.5 years). There were 12 early and 7 late deaths (overall mortality = 38%), mainly due to graft dysfunction, acute or chronic rejection, and infectious complications, mostly viral. Optimal criteria in selecting both donors and recipients are crucial to reduce early mortality and should never be transgressed despite the critical shortage of organs. The actuarial probability of survival was 64% at 1 year and 57% at 5 years. Our 30 mid-term survivors (62%) were submitted to a close follow up programme which includes endomyocardial biopsies, even in the very young, since non invasive criteria failed to mark every rejection episode. Maintenance therapy was always steroid-free to start with (cyclosporin+azathioprine) but in almost one half of our oldest survivors, it failed to avoid rejection and we had to add low-dose oral steroids for at least several months. Epstein-Barr virus related lymphoproliferations occurred in four patients, two of whom died and two recovered with specific therapy. Renal function was closely monitored: tubular and interstitial lesions were found on renal biopsies and were associated with moderate functional changes. The quality of life of the children who survived heart transplantation was considered as near normal in a little more than one half of the cases but many issues (late coronary disease, drug toxicity, long-term compliance to follow up and therapy) remain significant concerns for the future.


Thoracic organ transplantation in the paediatric age group. The Hannover experience. Growing experience in terms of immunosuppression, recipient and donor selection as well as organ preservation has established thoracic organ transplantation as a therapeutic option for many children with end-stage cardiopulmonary diseases. While dilated cardiomyopathy and isolated myocardial failure represent the main indications for cardiac transplantation, replacement of the lungs or heart and lungs is necessitated in cystic fibrosis, primary and secondary pulmonary hypertension as well as some types of complex congenital heart defects involving the pulmonary arteries. We have performed a total of 20 heart, 4 heart-lung, 2 single lung and 1 double lung transplantation in the paediatric group up to 17 years of age. While with respect to the limited experience worldwide, early mortality after lung and heart-lung transplantation is still high (50%), long-term results in isolated cardiac transplantation using triple drug immunosuppression are excellent (79% survival after 6 years) without major impairment of renal function, arterial blood pressure, growth development and physical rehabilitation as well as social reintegration. Freedom from graft atherosclerosis of the allografted heart is documented over a 5 year follow up, while no data are available on the incidence of obliterative bronchiolitis after lung transplantation in the paediatric group. Despite only limited evidence of long-term dysfunction, diagnosis and prevention of chronic rejection should be given utmost attention to allow for a normal life span in this younger age group.


Age and the immune response in pediatric renal transplantation. Because renal transplant outcome is poorer in young children when compared with older children or adults, it is reasonable to question whether immune reactivity relative to renal allograft rejection differs between young children and adults. While this hypothesis is far from established, preliminary data suggest that young children may represent an immunologically-defined subgroup distinct from adults and perhaps at high risk for renal allograft rejection. From a histocompatibility standpoint, infants may show some subtle differences in HLA typing results when compared with older children or adults. Children may also be at higher risk than adults for rejection when the transplant is performed in the presence of a historically positive, currently-negative lymphocytotoxicity crossmatch. Several non-specific tests of cellular immunity have been used to characterize the strong immunologic responder, i.e. the person who has an increase tendency to vigorously reject a renal allograft. Children in general and young children in particular may fall into this group. Children 5 years old and younger have significantly increased numbers of CD2+, CD3+, and CD4+ T lymphocytes when compared with older children. Young children also have higher than expected functional indices of cellular immune function. Taken together, these data suggest that children, and particularly young children, may have a heightened immunologic responsiveness, which may in turn represent an increased propensity for allograft rejection. Appropriate modification in immunosuppression may be indicated to optimize renal transplant outcome.