Relation between arterial hypoxemia and plasma eicosanoids in neonates with congenital diaphragmatic hernia. Pulmonary hypertension is a major source of morbidity and mortality in infants born with congenital diaphragmatic hernia (CDH). Increased pulmonary vascular resistance leads to right-to-left shunting, which is evident as decreases in the PaO2 measured in postductal arterial blood. Thromboxane A2 (TXA2), a vasoconstrictor, and prostacyclin (prostaglandin I2, PGI2), a vasodilator, have been studied as possible mediators of pulmonary hypertension in certain conditions of the newborn, including congenital diaphragmatic hernia (CDH). The goal of our study was to determine the association of TXA2 and PGI2 levels with hypoxemia in infants born with CDH. Eleven newborn infants with severe respiratory insufficiency (birth weight 2.0-4.1 kg; gestational age 32-42 weeks) were studied 0-5 days after surgical repair of CDH. Umbilical artery samples were collected for arterial blood gas determinations and radioimmunoassay of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of TXA2 and PGI2, respectively. Postductal arterial hypoxemia (reflected by a low a-A ratio, the ratio of oxygen tension in arterial blood to that in the alveolus) was associated with increases in TXB2 (r = -0.71, P = 0.004) and 6-keto-PGF1 (r = -0.65, P = 0.017). The a-A ratio also correlated inversely with TXB2/6-keto-PGF1 alpha (r = -0.50, P = 0.01), suggesting an increased influence of the vasoconstrictor TXA2.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of splenectomy and splenic artery ligation on the portal pressure in portal hypertensive rats. Immediate, short-, and long-term effects of splenectomy and splenic artery ligation on the portal pressure were studied in animal models experimentally created by partial portal vein ligation. The portal pressure of these animals would usually elevate immediately after partial ligation of the portal vein from a normal level of 6.0 +/- 0.5 to 14.8 +/- 1.3 mm Hg (P < 0.005), which could be maintained at least for 6 months. The portal pressure measured at 2 weeks, 4 weeks, and 6 months after portal vein ligation was 14.0 +/- 2.7, 15.2 +/- 2.7, and 12.7 +/- 2.0 mm Hg, respectively (P < 0.005, as compared with the normal). When splenectomy was performed on these animals at 2 weeks after partial portal vein ligation, the pressure dropped immediately but only transiently from 14.0 +/- 2.7 to 11.0 +/- 3.0 mm Hg, and bounced back to the presplenectomy level in 20 sec. After an additional 2 weeks, the portal pressure in these splenectomized rats was usually at 15.2 +/- 4.2 mm Hg, which was indistinguishable from that of rats whose portal vein was ligated but the spleen was not removed. Six months after splenectomy, however, the portal hypertensive rats had a portal pressure of 17.1 +/- 6.4 mm Hg, which was significantly higher than that of the controls. Splenic artery ligation, on the other hand, did not result in any immediate decrease in portal pressure (14.0 +/- 2.7 mm Hg vs 14.6 +/- 1.4 mm Hg; P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement of flow through arterial stenoses by drag reducing agents. The potential of drag reducing polymers (DRP) to selectively improve blood flow through clinically significant arterial stenoses was investigated. An artificial stenosis of the left common iliac artery in dogs decreased left femoral artery pressure by 25%. High-molecular-weight polyacrylamide (PA) or polyethylene oxide (PEO) were infused at a slow constant rate while we measured left and right common iliac artery blood flows and left and right femoral artery and vein pressures. As DRP were infused, left iliac artery flow (QL) increased early and then decreased to baseline values as flow began to increase in the right iliac artery. The peak increase in QL was 24 +/- 9% for PA and 46 +/- 19% for PEO and occurred before right iliac artery flow (QR) increased. As additional polymer was infused, QR increased to a maximum of 41 +/- 12 and 131 +/- 40% with PA and PEO, respectively. Femoral artery pressures and hindlimb resistances tended to decrease in both limbs but the only significant differences occurred in the right (nonstenosed) side when QR was elevated. This study provides the first evidence that low concentrations of DRP might be capable of improving blood flow through stenotic blood vessels without altering flow in normal vessels. Although DRP might represent a new class of compounds that could be utilized in the treatment of cardiovascular diseases, the degree of variation in individual responses is a concern, the exact mechanism of action is unclear, and information on pharmacodynamics is lacking.


Effects of intracerebroventricular endothelin-1 on CNS and cerebral hypoxia/ischemia and their modification by cinnarizine. The central effects of endothelin-1 (ET-1) and their modification by the calcium entry blocker cinnarizine have been investigated using CNS and hypoxia/ischemia tests. CNS tests comprised behavior, horizontal and vertical motor activity and hot plate test. Hypoxia/ischemia tests used were hypobaric hypoxia and complete ischemia by decapitation. ET-1 was injected intracerebroventricularly (i.c.v.) in a volume of 0.01 ml at doses of 1.25, 2.5 and 5 pmol/mouse 15 min before the tests. Cinnarizine (10 mg/kg, i.p.) was administered 60 min prior to ET-1. The i.c.v. ET-1 at all the doses used decreased horizontal and vertical motor activity and produced barrel-rolling. Survival/gasping time of mice subjected to hypoxia/ischemia increased dose-dependently. ET-1 showed an antinociceptive effect. Cinnarizine attenuated the appearance of barrel-rolling, did not antagonize disturbances in motor activity and reversed the antinociceptive effect of ET-1. In hypobaric hypoxia and decapitation cinnarizine antagonized the effects of 5 pmol/mouse ET-1 and potentiated that of 1.25 pmol/mouse. The pharmacological modification of the ET-1 effects by cinnarizine strongly suggests that the CNS actions of ET-1 might be due to multiple mechanisms triggered by an increased influx of extracellular Ca2+ into the brain cells.


Effect of CDP-choline on learning and memory processes in rodents. The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP-choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels.


Modulation of memory retrieval by pre-testing vasopressin: involvement of a central cholinergic nicotinic mechanism. Lysine vasopressin (LVP, 0.003-1.0 mcg/kg, s.c.) and the central acting nicotinic cholinergic agonist nicotine (N, 1.0-30.0 mcg/kg, s.c.) enhanced, whereas the vasopressin receptor antagonist 1-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid-2-(O-methyl)tyrosine, arginine vasopressin (AAVP, 0.01-0.3 mcg/kg, s.c.) impaired retention test performance on a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 20 min before the retention test. Tests were done 48 h following training. In all cases, the effects on retention test performance were dose-dependent. Neither LVP, N nor AAVP when given prior to testing modified latencies to step-through of mice that had not received a footshock during training. These findings suggest that LVP, N and AAVP influence memory retrieval processes. The effect of LVP on memory retrieval was antagonized by the simultaneous administration of AAVP (0.01 mcg/kg, s.c.) or mecamilamine (5 mg/kg, s.c.), but not by hexamethonium (5 mg/kg, s.c.), atropine (0.5 mg/kg, s.c.) or methylatropine (0.5 mg/kq, s.c.). On the contrary, the effect of N was only prevented by mecamilamine (5 mg/kg, s.c.). These results suggest a modulatory role of vasopressin on the activity of central cholinergic nicotinic mechanisms which are critical for memory retrieval.


Inhibition of human brain and RBC acetylcholinesterase (AChE) by heptylphysostigmine (HPTL). Heptylphysostigmine (HPTL), a derivative of the AChE inhibitor physostigmine (PHY), is under investigation as a therapeutic agent in Alzheimer's disease. HPTL is active against human RBC AChE both in vitro and in vivo. Activity of HPTL against human brain has not been documented. We have developed an in vitro assay system using particulate membrane fractions which permits comparison of inhibition and recovery kinetics of human RBC (primarily globular dimer) and brain (primarily globular tetramer) membrane-bound forms. Under these conditions the HPTLIC50 is similar for the two forms. RBC AChE inhibition spontaneously reverses in 24 h, as occurs in vivo. In striking contrast, activity of inhibited brain enzyme does not recover on overnight incubation. DDVP-induced inhibition, but not HPTL inhibition, can be reversed by the oxime 2-PAM. Some recovery of HPTL inhibition, but not to the level seen with RBC AChE, occurs on addition of heat-stable fractions from serum or CSF. Brain enzyme recovers rapidly from PHY in this system. Responses of brain and RBC AChE to HPTL indicate that these forms are functionally as well as structurally distinct. Since brain inhibition apparently does not spontaneously reverse like RBC inhibition, peripheral measurements of patient responses should be assessed with caution during treatment with HPTL.


Internally standardized simultaneous assay of verapamil and N-demethyl-verapamil enantiomers in human plasma by means of high performance liquid chromatography. A high performance liquid chromatographic method with internal analog standardization for the simultaneous assay of the verapamil and N-demethyl-verapamil enantiomers in human plasma after administration of racemic verapamil is described. The method comprises extraction from alkalinized plasma into an n-hexane/2-propanol phase (95:5), separation of the optical antipodes on a chiral phase (Daicel OJ) and quantification by means of fluorescence detection. A detection limit of about 6 pmol was determined for all four enantiomers. Under routine conditions the limit of quantification (variation coefficient < 10%) was about 8 pmol for the (R)- and (S)-enantiomers. The determination method for verapamil and N-demethyl-verapamil enantiomers is not impaired by their known metabolites. The suitability of the method for clinical pharmacology studies is demonstrated with samples obtained from healthy subjects. First results of comparative kinetics studies in humans and various animal species show marked species-dependency with prevailing (R)-enantiomer levels in humans and dogs, and the opposite in rats.


Comparisons of different animal skins with human skin in drug percutaneous penetration studies. The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments.


Pharmacokinetics of epirubicin emulsion and solution in rabbits after intrahepato-arterial and intravenous injection. The study reports pharmacokinetic findings on the disposition of a formulated emulsion of epirubicin in rabbits as compared to plain epirubicin solution after intrahepato-arterial and intravenous administration. The dose of epirubicin used was 1 mg/kg body weight. Blood samples were collected at several time points up to 6 h after administration. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUC infinity 0) is smallest after intrahepato injection of epirubicin emulsion. This, together with the highest apparent volume of distribution (Vss) suggest a possible targetting effect. Although the mean residence times are similar, intrahepato injection of emulsion apparently has the largest clearance. Difference in bioavailability in the general circulation between the 2 routes of administration also suggests a certain degree of liver first-pass metabolism of the drug. In view of these findings, further investigation and assessment are worthwhile for future application in human subjects.


[Treatment of sleeping disease caused by trypanosoma brucei gambiense with alpha-difluoromethylornithine (DFMO) in a rural hospital in Zaire]. The authors report the results of 32 patients with sleeping sickness due to Trypanosoma brucei gambiense treated with DFMO (DL-alpha-difluoromethylornithine), an inhibitor of polyamine biosynthesis. Between those patients, there were 5 new cases, 1 reinfection, and 26 cases with a primary, a secondary resistance or a relapse. 26 cases got DFMO only per os, but six others received first DFMO for two weeks by the intravenous way, followed by three weeks of DFMO per os. The secondary effects were never very severe and never prompted a definitive discontinuation of treatment. 12 cases were followed for a period of 24 months, 16 for a period between 1 and 18 months and 4 patients died during the study (3 during treatment and one 8 months afterwards), but we don't think that DFMO was the cause of death. Out of the 12 cases followed for two years, 11 were in perfect health at the end of this period (one case can be considered as a secondary resistance to DFMO, but it could have been a reinfection as well). For the 16 cases followed for a period less than two years, we found a very fast disappearance of trypanosomes from body fluids, immediately after the beginning of treatment, and a significant amelioration of clinical signs. After this study, the authors estimate that DFMO given orally provides as good results as DFMO given in a combined therapy. But the oral way seems much easier to administer and much cheaper in rural areas.(ABSTRACT TRUNCATED AT 250 WORDS)


[Angkor. The mystery of the dead city and Anopheles dirus]. The desertion of Angkor, which during more than five centuries was the center of a glorious civilization, has long been a matter of mystery and conjecture. The discovery of the vectorial capacity of the jungle mosquito Anopheles dirus, its epidemiological importance in the emergence and spread of multidrug resistance in Plasmodium falciparum malaria, the wiping out of large populations after transfer or deportation of non-immune Khmers into forest areas can now easily explain the desertion of Angkor. In 1431, Angkor Thom, the capital of the Khmer kingdom surrendered to the Thai conquerors. Soon afterwards, the young king left the city in search of a new capital. As a result of the population decrease large surfaces of rice fields were abandoned and reinvaded by the jungle, the typical biotope of Anopheles dirus. Severe epidemics of Plasmodium falciparum then occurred in the non-immune population with very high mortality decreasing again the number of workers and, thus, creating a vicious circle resulting in the progressive but complete desertion of Angkor.


[Darrier-Ferrand's dermatofibroma on the forehead. Wide cranial-cutaneous exeresis followed by scalp plastic surgery]. The authors report on a case of Darier-Ferrand's dermatofibroma on forehead. It was a very uncommon localization. They stress on the specific treatment applied: forehead cranioectomy and scalp plasty, made compulsory after several exercises and their reappearances.


[Extra-pulmonary thoracic hydatid cyst (Pneumology and radiology services of the Military Hospital of Tunis)]. The authors report, in a retrospective study 11 cases of thoracic extra-pulmonary hydatic cyst observed during 4 years of pneumopathology practice. They stress the rarity of this localization and the variability of the clinical data. Chest X-Ray was found no specific whereas, computed tomography led often to the right diagnosis and helped in some cases a puncture of the hydatic cyst.


[Envenomation by Echis Carinatus in Africa: clinical study and evolution. Indications for antivenins]. In North Cameroon, venom inoculations by Echis Carinatus are frequent and severe and thus pose a serious problem at Public Health Services. 48 bites without antivenomous serum injection have been considered in Garoua, Benoue valley North Cameroon. Without antivenomous serum light inoculations heal spontaneous by in a couple of days about 20% of the average clinical forms are evoluting insidiously to severe globulolysis. The great majority of severe inoculations lead to dreadful hemorrhagic threatening the life of patients. New borns and infants are particularly exposed, it is not advisable to inject systematically antivenomous serum. But it has to be considered as compulsory in the three following clinical situations before 11 years of age, venom inoculation often brings about fast aggravation, mainly in new borns, after 11 years and at adult age, when clinical signs are of great concern, when hemoglobinometry indicates less than 9 gr/100 ml after 48 hours of evolution in youngs and adults, but without any symptom of severity.


[Prevalence of Delta hepatitis in health workers in Dakar (Senegal)]. 708 hospital workers in University Teaching Hospital of Dakar were tested to HBs antigen; among them 128 were positive and tested to Delta antibody, by ELISA Abbott kit. Seven (7) men and one woman were positive. However, the positivity of Delta antibody is neither linked to sex, nor to age of subjects. 87% of the Delta antibody carriers were found among the trainees, and 50% of them studied in the Odonto-Stomatology Institute.


[Epidemiology of human urban schistosomiasis in Bamako in Mali (the case of the "populous" quarter of Bankoni)]. From may 1989 to january 1990, we have studied parasitologic index in snails population, stools and urines examination in children (1-15 years) in one of the greatest "spontaneous" quarter of Bamako. 584 stools samples and 563 urines were tested. 4.717 snails were captured during six months. From all these data, we conclude that in Bankoni S. haematobium is mesoendemic (36.6%) and S. mansoni hypoendemic (3.4%). B. truncatus is the most important host for urogenital schistosomiasis. The two seasonal revers (Tienkole and Bankoni) are unfavourable to B. pfeifferi's production. B. globosus and B. forskalii are not frequent in this suburban area. This investigation, shows that a selective mass treatment with praziquantel is the better public health care strategy in Bankoni quarter.


Is chronic low self-esteem the cause of eating disorders? Low self-esteem occurs commonly in patients with an eating disorder, a term which includes patients with both anorexia nervosa and bulimia nervosa. In this hypothesis it is proposed that chronic low self-esteem is a necessary prerequisite to the development of an eating disorder, and that chronic low self-esteem is the final common pathway through which the multiple aetiological factors involved in the causation of eating disorders act. Thus, eating disorders can best be viewed as a 'symptom' of chronic low self-esteem. This hypothesis is able to account for the recent increase in the incidence of eating disorders, and the increased incidence of depression in eating disordered patients. Suggestions for research to test this hypothesis are made.


Extra-pyramidal symptoms in Alzheimer's disease: a hypothesis. Recent studies have shown that compensatory processes have an important role in counteracting the neurodegenerative changes underlining Alzheimer's disease (AD), much like their well known role in Parkinson's disease (PD). In the light of these reports, we review the findings of the positive correlation existing between the appearance of extra-pyramidal symptoms and an increased rate of progression in AD patients. We propose that this correlated symptomatology arises from the wasting of globally shared compensatory resources, manifested both in an increasing inability to compensate for persisting sub-clinical nigral lesions, and in enhanced AD deterioration rate. Our hypothesis gains support from various clinical reports and by the neural modeling of synaptic changes in AD.


A localized absence of interleukin-4 triggers periodontal disease activity: a novel hypothesis. Pathogenic bacteria constitute the primary extrinsic agent in the etiology of Adult periodontitis. In addition to direct toxic effects, bacteria induce destructive immunologic and other inflammatory reactions in the host, leading to the observed pathologic alteration in the tissue. The risk to develop periodontal disease is not equal for all individuals, suggesting host factors are important in determining an individuals disease susceptibility. Regulation of immune response is important in maintaining the equilibrium between periodontal health and disease. We hypothesize that, in the case of Adult periodontitis, a localized lack of the regulatory cytokine interleukin-4 (IL-4) in the gingival tissues predisposes susceptible individuals to progress from gingivitis to periodontitis.


[Cryptococcosis caused by Cryptococcus neoformans var. Gattii. A case associated with acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire]. Since the introduction of AIDS, the biovar neoformans of Cryptococcus neoformans has replaced the biovar gattii as the predominant agent of cryptococcal meningitis in Kinshasa and in other tropical areas. That this is not an absolute rule is demonstrated by the present case of a HIV-positive patient, observed at the Kinshasa University Hospital, with cryptococcal meningitis due to the biovar gattii. Only four cases of this association have been published before. The authors conclude that both biovars are capable of infecting HIV-positive patients but that the apparent decline of the biovar gattii is related to the rarity of its natural reservoir in the urban environment, where the AIDS epidemic is concentrated.


[Duodenal tuberculosis: a case report].

[Duodenal tuberculosis: a case report]. The authors relate the case of a duodenal tuberculosis shown by a pyloro-duodenal stenosis. They emphasize the absence of specific clinical, radiological endoscopic and histological manifestations. Laparotomy is in most cases necessary. The diagnosis is therefore affirmed out of the findings of peritoneal granulations or the extemporaneous anatomo-pathological investigation of lymphatic nodules.


Metabolism of the malignant cell, in vivo, is anaerobic and significantly plays a factor in the pathway to carcinogenesis. The malignant cell, in vivo, metabolizes and respires anaerobically. For a good many years scientists have been aware of anaerobia being present in malignant growths. The prevailing opinion is that the malignant cell is able to remain viable in an anaerobic medium. This assumption is incorrect and is actually misleading. My investigative studies indicates that the malignant cell metabolizes and respires intracellularly so that the consequence of such a physiology is anaerobic and the basis for such anaerobia is a metabolic phenomenon. There is a reason for this anaerobiosis. Studies demonstrated the fact that there are present within the malignant cell and in the immediate area bacterial spores arising from one of several varieties of plant bacteria. And with an adequate circulating flow of blood, by the animal (human) host, to that particular site, provides the metabolites, enzymes, and the exchange of gases to enhance this abnormal physiopathological anaerobiosis. It is this intracellular anaerobic metabolism within an animal cell that becomes the basis for its malignant transformation.


[Cure of an enormous eventration by abdominoplasty. Technical note. A case report]. The secondary eventrations after delivery are the prime cause of women's eventrations. These eventrations are enormous in Africa because the post-partum women do not make active movements to develop again the abdominal strap. In Europa or North America the treatment would make use of prosthetic materials but in Africa the climatic and working conditions do not take the utilization of such method. The authors purpose a cure allied aponevroplasty according to JUDD technique with abdominoplasty. The result is satisfactory and durable.


[Bacteremia caused by non-typhoid Salmonellas during an infection by the human immunodeficiency virus (HIV) in the African adult]. Infection caused by non-typhous Salmonellae during the course of HIV infection is known since 1983. The authors report on 103 bacteremiae of this type found in one year. Diagnosis has been based on hemocultures. 86 patients out of 103 were HIV+. All of them were febrile. 67 suffered from digestive disorders, 33 with diarrhoea. Splenomegalia was noted in 16 cases and consciousness troubles in 13 cases. At the admission, 8 complications were observed. Other infections were associated in 86 cases particularly in HIV+ patients evolutive tuberculosis (38 cases), candidosis of oropharynx (32 cases), neuromeningeal crytococcosis (13 cases), pneumocystosis (3 cases), Kaposi's sarcoma was discovered in 3 cases. The salmonellae isolated were in the 54 cases where characterization was made: Salmonella typhi murium in 44 cases and Salmonella enteridis in 10 cases. Classical cure (chloramphénicol) was effective in 85% of the treated patients. 28 positive hemocultures out of 103 isolated non-typhous Salmonellae were sampled later than the 72th hour after admission. This fact poses the problem of nosocomial infections in hospital departments in Black Africa, where HIV+ patients represent 52% of the admissions. Non-typhous Salmonellae would be part of the definition of African AIDS concerning patients with HIV test positive.


Risk factors for coronary heart disease: synthesis of a new hypothesis through adaptation. A risk factor is a characteristic which is associated with a greater than average probability of developing coronary disease. Raised serum cholesterol and hypertension are two such factors. Intervention studies conducted to confirm the risk factor hypothesis have shown that reduction of serum cholesterol and essential hypertension may be associated with a small decreased CHD incidence, however there were almost as many deaths due to coronary disease in the intervention groups as in the control groups. These findings suggest that our approach to risk factor intervention may be a misguided attempt which needs modification. It is possible that the major risk factors develop in an attempt of our body to adapt to environmental factors such as increased intake of salt, saturated fat and cholesterol, physical inactivity, increased intake of calories and obesity and stress. Smoking may be the result of social changes. Since the body has to modify its metabolic mechanism depending upon the factor to which it adapts, development of hyperlipidemia and hypertension may be protective mechanisms of the body which it has developed while fighting against environmental factors. Reduction of major risk factors by drug therapy may mean that we are trying to prevent the body, fighting environmental factors. Thus our approach to control of the major risk factors should be to treat the causative environmental factors or alter the lifestyle.(ABSTRACT TRUNCATED AT 250 WORDS)


Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis.


Cytokines play a central role in the pathogenesis of systemic lupus erythematosus. Excessive production of pathogenic autoantibodies is one of the hallmarks of systemic lupus erythematosus (SLE). The mechanisms that underlie this excessive production are still unclear. Although there is considerable evidence to suggest that both T cells and B cells play an important role in the etiology of SLE, convincing abnormalities at the T cell receptor or immunoglobulin gene loci have not been demonstrated. In this regard, because cytokines play such a pivotal role in the inflammatory response, a defect in the immunoregulation of B cells by cytokines should be considered as possible contender in disease etiology. The hypothesis that is proposed here is that multiple defects mediated by cytokines are present in individuals with lupus and that both cytokine production and the response of B cells to cytokines may be defective. These abnormalities could then be a central factor in the etiology of systemic lupus erythematosus.


Evidence for Randall's plaques to be the origin of primary renal stones. Lithofibrin, a non-protein organic component of renal calculi was found in renal papillas with the aid of stereo microscopy under UV illumination. Scanning electron microscopy revealed fibers of which one had a clump containing calcium on the top. The findings support the theory of Randall, that the origin of primary renal calculi is to be found in the kidney, not in the urine.


The detachment cascade during metastasis. The cause of detachment of tumour cells during metastasis is still one of the most intriguing questions of tumour propagation. A hypothesis is suggested herein for lysis of extracellular matrix that could ultimately lead to the detachment and spreading of malignant cells. According to this theory a certain optimal estrogen level initiates a series of enzymatic activations that culminate in detachment and spreading of tumour cells.


Helicobacter (aka Campylobacter) pylori as the major causal factor in chronic hypochlorhydria. Helicobacter (formerly known as Campylobacter) pylori, a recently discovered gastrointestinal bacterial pathogen, has been shown to be etiologic for Type B or antral gastritis, and usually has chronic active pathological changes associated with its presence. Acute Helicobacter infection in most cases induces reduced stomach acid secretion which usually returns to normal levels of secretion after a few months. Yet Helicobacter gastritis has never been known to spontaneously remit after it has been established, and there is evidence suggesting that it often progresses to cause atrophic changes in the gastric mucosa. Since chronic gastritis has been shown in past studies to lead to chronic persistent hypochlorhydria from atrophic damage to secretory tissue, and Helicobacter has been shown to cause most chronic gastritis, the reasonable conclusion is that Helicobacter infection is etiologic for most chronic persistent hypochlorhydria. The apparent exception of the hyperchlorhydria in duodenal ulcer disease associated with Helicobacter infection is explained. The possible clinical relevance of hypochlorhydria will be the subject of a subsequent paper.


The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. In a previous paper evidence was presented to show that Helicobacter-induced chronic gastritis is the probable cause of most chronic hypochlorhydria. In this article evidence is presented for the clinical relevance of reduced stomach acid secretion. Reduced mineral absorption is fairly well documented and has sound theoretical support from basic chemistry. Impaired digestion of protein has been suggested by a few studies. Small intestinal bacterial overgrowth in hypochlorhydria probably leads to putrefactive breakdown of the metobolically useful products of protein digestion, thereby reducing their availability for certain essential pathways. The possible lowering of tryptophan, tyrosine, and phenylalanine in the blood may be a precipitating factor in depression in hypochlorhydric patients. In reduced or absent stomach acid secretion a constellation of gastrointestinal symptoms has been consistently observed and reported by clinicians in the past, and treatment of the hypochlorhydria with hydrochloric acid or its substitutes has often been observed to be effective in reducing these symptoms.


Therapeutic gain with hyperfractionation in prophylactic cranial irradiation of children with acute lymphoblastic leukemia. IQ deterioration after prophylactic cranial irradiation is a dreaded complication for children with acute lymphoblastic leukemia. Alternate treatment schemes are needed that achieve comparable tumor control, but avoid such long-term complication. To this end, a hyperfractionated treatment scheme is proposed. Using two different radiobiological models, we analyze the doses required to achieve equivalent disease control while reducing the severity of late sequelae. Analysis based on the linear-quadratic and surviving fractions models clearly indicates a therapeutic gain with hyperfractionation.


Evaluation of suppression of growth hormone levels following a 75g oral glucose tolerance test. Growth hormone (GH) levels were measured after a 75g oral glucose load (OGTT) in normal adults, patients with impaired glucose tolerance (IGT), insulin-dependent diabetes mellitus (IDDM) and acromegaly. Nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L, the 95% confidence interval being 0.4-4.4 mIU/L. In IGT and IDDM subjects basal fasting GH levels were not significantly different from normal and did not alter during OGTT. The high fasting GH level measured in one each of the IGT and IDDM patients was suppressible at 1-hour after glucose intake. In contrast, acromegalic patients had elevated fasting GH levels (11.8-178 mIU/L) although in 3 patients, the levels were mildly elevated and overlapped with normal. OGTT failed or only partially suppressed GH secretion in all acromegalics. Therefore, elevated fasting GH levels are not diagnostic and OGTT is required for accurate diagnosis and assessment of treatment of acromegalic patients.


Breakpoint cluster region (BCR) gene rearrangement studies in chronic myeloid and acute lymphoblastic leukemias. Deoxyribonucleic acid (DNA) of twenty chronic myeloid leukemia (CML) and thirty acute lymphoblastic leukemia (ALL) patients were analysed by Southern hybridization. The DNA was digested with BglII and hybridized with a 4.5-kilobase (kb) ph1/bcr-3 DNA probe. All the 20 CML patients showed gene rearrangement within a 5.8-kb segment (the major breakpoint cluster region, M-bcr) of the breakpoint cluster region (bcr) gene of chromosome 22, indicating the presence of the Philadelphia chromosome. M-bcr rearrangement at the bcr gene of chromosome twenty-two was not detected in all the thirty ALL patients (nine adults and twenty-one children) and two normal controls.


The clinical significance of the branching pattern of the facial nerve in Malaysian subjects. Fine dissection was carried out in 79 facial halves from formalin fixed Malaysian adult cadavers of various races, to trace the extracranial part of the facial nerve and its peripheral branches. The facial nerve trunk, after leaving the stylomastoid foramen was located at a depth of 1 to 2 cm from the skin in the vagino-mastoid angle. It bifurcates at the posterior border of the ramus of the mandible and in 3.8% trifurcation was found. Mean distance of bifurcation from the angle of the mandible was 28.06 mm and 81.0% were within the range of 21 to 35 mm. The branching patterns were classified into six types, and the frequency of occurrence was type I 11.39%, type II 15.9%, type III 34.18%, type IV 18.98%, type V 7.59% and type VI 12.67%. Type I, a classical text book pattern was found to be one of the least common patterns. There is no significant difference in percentage of each type between the present study and that of Koreans, though some differences with Caucasians were noted in three uncommon types. The frontal branch could be outlined between the two diverging lines from the earlobe to the lateral ends of the eyebrow and the highest frontal crease. Posterior to the facial artery, the mandibular branch was seen passing below the inferior border of the mandible in 20%; anterior to the artery, this nerve divides into one to four branches. In almost all the cases, branches to the mentalis and the depressor labii inferioris muscles and infrequently branches to the depressor angular oris were seen below the inferior border of the mandible.(ABSTRACT TRUNCATED AT 250 WORDS)


A report of the first 20 cases using a simple external fixator. The results of treatment using a locally-designed external fixator in 20 patients are presented. Open fractures were the main indications for external fixation. Pin tract infection occurred in 8 patients. Only 2 patients had unstable fixation which required removal of the device. One third of patients developed malunion exceeding 15 degrees and two thirds had joint stiffness after conversion to plaster cast. This external fixator is adequate in the treatment of most open fractures of the tibia. However, improved techniques of pin insertion and cast application upon removal of the external fixator may help to reduce the incidence of pin tract infections and malunion.


Oral pefloxacin in the treatment of CAPD peritonitis. Continuous ambulatory peritoneal dialysis (CAPD), a widely used replacement therapy for end stage renal failure, is frequently complicated by bacterial peritonitis. The infecting organisms are mainly staphylococci and gram negative aerobes. Pefloxacin is a fluorinated quinolone with good in-vitro activity against these pathogens. The objective of this open non comparative study is to determine the effectiveness and safety of oral pefloxacin mesylate as a single first line antimicrobial treatment of CAPD peritonitis. 28 episodes of CAPD peritonitis were treated with a stat dose of pefloxacin 800 mg. followed by 400 mg. 12 hourly for about 15-18 days. A pefloxacin sensitive organism was isolated in 17 episodes. 11 episodes were culture negative. Treatment results showed a cure in seventeen (60.7%), no treatment response in seven (25%), and relapses in four (14.2%). Side effects encountered were not serious except for one incident of a generalized seizure. We conclude that oral pefloxacin is convenient, safe and effective enough as a single first line antimicrobial treatment for CAPD peritonitis.


Malignant lymphoma of nasal septum--a case report. Malignant lymphoma of nasal septum is uncommon. It presents a problem in diagnosis to both otorhinolaryngologist and pathologist. This case report is about one such patient in whom the local disease has been controlled with the treatment of radiotherapy alone. However it is suggested that combined treatment of radiotherapy and cytotoxic therapy might improve the survival rate.


A survey of breast feeding practices in infants seen in general practice. This is a study of infant feeding practices of 126 mothers. Seventy-seven mothers or 61.1% practised breast feeding. The typical breast feeding mother was more likely to be a Malay, with lower family income and residing in the rural area. The educational status of the mother was not an important factor in influencing her to breast feed. Health education on breast feeding should be intensified in schools to reinforce the implementation of the Malaysian Code of Ethics for Infant Formula Products.


Thalassaemia and haemoglobinopathies in Brunei Darussalam. One thousand consecutive Brunei Darussalam patients referred with low Hb, and/or low MCV and MCH (Hb < 12.5g/dl, MCV < 76fl, MCH < 27pg) were studied in the laboratory for underlying haemoglobinopathies. 30.0% of such patients were proved to have either beta-thalassaemia trait, beta-thalassaemia major, Hb AE, Hb EE, Hb E beta-thalassaemia or Hb H disease. In some, the haemoglobin abnormality was not identified precisely. Alpha-thalassaemia was suspected in an additional 4.3% of cases but confirmation study by globin-chain synthesis was not available. Beta-thalassaemia trait which was the predominant disorder was equally distributed among the three major race groups of Brunei Darussalam. Hb E was found exclusive among the Malay population. Hb H disease appeared as more common among the Chinese or the Malays (p > 0.05). This study reveals that thalassaemia and haemoglobinopathies are prevalent in Brunei Darussalam.


Design of a novel system for the construction of vectors for Agrobacterium-mediated plant transformation. The loxP-Cre site-specific recombination system of phage P1 was used to develop a novel strategy to construct cointegrate vectors for Agrobacterium-mediated plant transformation. A pTi disarmed helper plasmid (pAL1166) was constructed by replacing the oncogenic T-DNA by a loxP sequence and a spectinomycin resistance marker in the octopine-type pTiB6 plasmid. The cre gene was cloned into an unstable incP plasmid. A third plasmid, which did not replicate in Agrobacterium and contained another loxP sequence together with a kanamycin resistance marker, was used to test the system. Electroporation of this third plasmid into an Agrobacterium strain harbouring both pAL1166 and the Cre-encoding plasmid resulted in kanamycin-resistant cells containing a cointegrate between pAL1166 and the incoming plasmid. Cointegration occurred by Cre-mediated recombination at the loxP sites, and the cointegrate was stabilized in the Agrobacterium cells by the loss of the Cre-encoding plasmid shortly after the recombination event had taken place.


A dominant selectable marker that is meiotically stable in Neurospora crassa: the amdS gene of Aspergillus nidulans. When Neurospora crassa is transformed using a Neurospora gene as the selectable marker, the vegetatively stable transformants obtained cannot be used successfully in a cross because the selectable marker will be inactivated by the process of RIP (repeat-induced point mutation). Introduction of the acetamidase-encoding gene amdS of Aspergillus nidulans into N. crassa by transformation yielded transformants that would grow in minimal medium containing acetamide as a sole nitrogen source. In mitotically stable transformants containing a single copy of the amdS gene, the capacity to utilize acetamide as a sole nitrogen source was maintained in the progeny of a sexual cross. Therefore, the A. nidulans amdS gene is an appropriate dominant selectable marker for use in transformation analyses with N. crassa in which sexual crosses will be subsequently performed.


Nucleotide sequence analysis and comparison of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida. The complete nucleotide sequences of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida were determined; the DNA sequences of the lexA genes from these bacteria were 86%, 76%, 61% and 59% similar, respectively, to the Escherichia coli K12 gene. The predicted amino acid sequences of the S. typhimurium, E. carotovora and P. putida LexA proteins are 202 residues long whereas that of P. aeruginosa is 204. Two putative LexA repressor binding sites were localized upstream of each of the heterologous genes, the distance between them being 5 bp in S. typhimurium and E. carotovora, as in the lexA gene of E. coli, and 3 bp in P. putida and P. aeruginosa. The first lexA site present in the lexA operator of all five bacteria is very well conserved. However, the second lexA box is considerably more variable. The Ala-84--Gly-85 bond, at which the LexA repressor of E. coli is cleaved during the induction of the SOS response, is also found in the LexA proteins of S. typhimurium and E. carotovora. Likewise, the amino acids Ser-119 and Lys-156 are present in all of these three LexA repressors. These residues also exist in the LexA proteins of P. putida and P. aeruginosa, but they are displaced by 4 and 6 residues, respectively. Furthermore, the structure and sequence of the DNA-binding domain of the LexA repressor of E. coli are highly conserved in the S. typhimurium, E. carotovora, P. aeruginosa and P. putida LexA proteins.


Cloning, nucleotide sequence and characterization of the gene encoding the Erwinia chrysanthemi B374 PrtA metalloprotease: a third metalloprotease secreted via a C-terminal secretion signal. Erwinia chrysanthemi, a phytopathogenic enterobacterium, secretes three proteases (PrtA, PrtB and PrtC) into the extracellular medium. The gene encoding the 50 kDa protease, prtA, was subcloned from a recombinant cosmid carrying a fragment of the E. chrysanthemi B374 chromosome. prtA was shown to be located immediately 3' to the structural genes for the other two extracellular proteases. The amino acid sequence of PrtA, as predicted from the prtA nucleotide sequence, showed a high level of homology with a family of metalloproteases that are all secreted via a signal peptide-independent pathway, including PrtB and PrtC of E. chrysanthemi B374, PrtC of E. chrysanthemi EC16, PrtSM of Serratia marcescens and AprA of Pseudomonas aeruginosa. PrtA secretion requires the E. chrysanthemi protease secretion factors PrtD, PrtE and PrtF. The secretion signal of PrtA is near to the carboxy-terminal end of the protein, as was previously shown to be the case for PrtB and PrtSM and for Escherichia coli alpha-hemolysin. The C-termini of these four proteins do not show extensive primary sequence homology, but PrtA, PrtB and PrtSM each have a potential amphipathic alpha-helix located close to the C-terminus.


STE50, a novel gene required for activation of conjugation at an early step in mating in Saccharomyces cerevisiae. A new gene, STE50, which plays an essential role in cell differentiation in Saccharomyces cerevisiae was detected and analysed. STE50 expression is not cell type-specific and its expression in MATa and MAT alpha cells is unaffected by pheromones. When present on a high copy number plasmid, STE50 causes supersensitivity to alpha-pheromone, and increases the level of alpha-pheromone-induced transcription of FUS1 in haploid a cells. Mutants bearing either of the two gene disruptions, ste50-1 or ste50-2, are sterile and have a modulated sensitivity to alpha-pheromone. The overexpression of STE4 (G beta) in wild-type cells elicits a constitutive growth arrest signal, however this phenotype is suppressed by a C-terminal truncation mutation in STE50 (ste50-2). In contrast, the constitutive activation of the pheromone response pathway caused by disruption of GPA1 (G alpha) is not suppressed in ste50-2 mutants. The ste50-2 mutation partially suppresses the desensitisation defect of the sst2-1 mutation, and the resulting ste50-2 sst2-1 mutants restore fertility. Our results indicate that the ste50-2 mutant may have a defect in adaptation (hyperadaptation), and suggest a possible interaction of STE50-2 with the G alpha subunit of the G protein.


The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. We measured the relative steady-state levels of the mRNA transcribed from the Saccharomyces cerevisiae REV3 gene in cells at different stages of the mitotic and meiotic cycles, and after UV irradiation. This gene is thought to encode a DNA polymerase concerned only with a specific recovery function, the replication on mutagen-damaged templates that produces damaged-induced mutations. In keeping with this proposed function, the REV3 gene showed no evidence of the periodic transcription at the G1/S boundary of the mitotic and meiotic cycle that occurs with genes encoding replication enzymes. However, levels of REV3 mRNA were much increased in late meiotic cells, like those of transcripts of some other DNA repair-related genes. Steady-state levels of REV3 transcript were increased only slightly in response to UV irradiation.


Regulatory elements for expression of the alkA gene in response to alkylating agents. Expression of the alkA gene in Escherichia coli is controlled by Ada protein, which binds to a specific region of the alkA promoter and enhances further binding of RNA polymerase holoenzyme to the complex. To determine the sequence recognized by the Ada protein, we introduced various base substitutions into the promoter region of alkA and examined their effects on expression of the gene, both in vivo and in vitro. Base changes within the sequence AAAGCAAA, located between positions -41 and -34 from the transcription initiation site, greatly decreased the frequencies of initiation of transcription. In footprinting experiments, the region containing this sequence was protected by the Ada protein and base changes within this sequence led to failure of binding of Ada protein to the promoter. It is likely that the Ada protein recognizes the AAAGCAAA sequence in the alkA promoter and binds to the region containing the sequence, thereby allowing ready access of RNA polymerase to the promoter. There are considerable differences between the mechanisms of action of Ada protein on the promoters of alkA and ada, even though the expression of both genes is positively regulated by Ada protein.


The nad4L gene is encoded between exon c of nad5 and orf25 in the Arabidopsis mitochondrial genome. In the Arabidopsis thaliana mitochondrial genome the gene coding for subunit 4L of NADH dehydrogenase (nad4L) is located between exon c of the nad5 open reading frame and orf25. The physical proximity of these genes further supports the trans-splicing model for assembly of the nad5 mRNA. Some transcripts comprise the nad4L open reading frame cotranscribed with nad5 exon c and orf25, while other mRNAs contain only nad4L and orf25. Both open reading frames for nad4L and orf25 are edited in several positions with different frequencies.


Organization and nature of fortimicin A (astromicin) biosynthetic genes studied using a cosmid library of Micromonospora olivasterospora DNA. The cloning of five DNA segments carrying at least seven genes (fms1, fms3, fms4, fms5, fms7, fms11, and fms12) that participate in fortimicin A (astromicin) biosynthesis was described previously. These DNA fragments were used to screen a cosmid library of genomic DNA in order to examine if these biosynthetic genes are clustered in Micromonospora olivasterospora. One cosmid clone (pGLM990) was obtained, which hybridized to all the probes. Complementation analysis, using mutants blocked at various steps and chimeric plasmids subcloned from pGLM990, showed that three additional genes (fms8, fms10, and fms13) are present in pGLM990. A gene conferring self-resistance to the antibiotic, which was independently cloned in Streptomyces lividans, using the plasmid vector pIJ702 was also found to be linked to the cluster of biosynthetic genes. Thus, at least ten biosynthetic genes and a self-defense gene are clustered in a chromosomal region of about 27 kb in M. olivasterospora. Interestingly, the fms8 gene which participates in the dehydroxylation step of fortimicin A biosynthesis was found to have homology with a neomycin resistance gene nmrA from the neomycin-producing Micromonospora sp. MK50. Studies using a cell-free extract of the fms8 mutant and its parent strain showed that the enzyme encoded by fms8 phosphorylates a biosynthetic precursor, fortimicin KK1, in the presence of ATP. Thus the dehydroxylation reaction is suggested to occur via the phosphorylation of the target hydroxyl group. DNA regions homologous to fms genes were found in Micromonospora sp. SF-2098 and Dactylosporangium matsuzakiense, both producers of fortimicin group antibiotics.


N-formimidoyl fortimicin A synthase, a unique oxidase involved in fortimicin A biosynthesis: purification, characterization and gene cloning. Micromonospora olivasterospora, a fortimicin A (FTM A, astromicin) producer, was found to carry an enzyme that converts FTM A to N-formimidoyl FTM A (FI-FTM A). This enzyme (FI-FTMase) was purified to homogeneity and shown to be a flavin adenine dinucleotide (FAD) enzyme. Tracer experiments proved that the formimidoyl group was derived from C-2 of glycine via oxidation of the amino acid in the presence of FTM A and oxygen. The gene encoding this enzyme, fms 14, was cloned using a 26-mer oligonucleotide probe, designed according to the N-terminal amino acid sequence of purified FI-FTMase, from a cosmid clone pGLM990, which has been shown to contain a cluster of FTM A biosynthetic genes. The nucleotide sequence, and biochemical and genetic analysis revealed that FI-FTMase is composed of four identical subunits of mol. wt. 52,000, and contains at least one FAD per subunit. DNA regions homologous to fms14 were found in two other producers of the fortimicin group of antibiotics, Dactylosporangium matsuzakiense ATCC31570 and Micromonospora sp. SF-2098.


Intramolecular homologous recombination in Bacillus subtilis 168. Plasmid resolution from a phage::plasmid chimera was used to measure directly intramolecular recombination in Bacillus subtilis. The system is based on a sigma-replicating plasmid (pC194) cloned into a dispensable region of the lytic bacteriophage SPP1. The plasmid, which confers chloramphenicol resistance, is resolved when SPP1::pC194 phages infect B. subtilis cells, provided the chimera carries a functional, intact copy of the plasmid repH gene. Intramolecular homologous recombination was independent of the RecA and RecL-RecR functions, but dependent on RecF, RecB, RecG, RecP, RecH and AddAB functions. These results are consistent with the hypothesis that B. subtilis has multiple pathways for genetic recombination and allow us to tentatively place the recB and recG genes into a new epistatic group epsilon.


Downstream activating sequence within the coding region of a yeast gene: specific binding in vitro of RAP1 protein. Using a gel retardation assay, a protein factor that specifically interacts with a 33 bp intragenic sequence of the highly expressed and glucose-inducible SRP1 gene of Saccharomyces cerevisiae has been detected. This binding site is located in a transcribed region and within the open reading frame (positions +710 to +743 relative to the first base of the initiation codon). A mutant strain carrying a deletion of this binding site showed a dramatic decrease in steady-state levels of SRP1 transcripts. This decline is not the result of a decrease in mRNA stability, since expression of hybrid genes in which the SRP1 promoter was replaced by the heterologous CYC1 promoter was not affected by the binding site deletion. These findings suggest that the 33 bp sequence contains a cis-acting downstream activating element which is involved in the transcriptional activation of the SRP1 promoter. Sequence comparisons showed similarities between a site located within the 33 bp sequence and the high-affinity consensus binding site of the RAP1/GRF1 (also named TUF) factor and methylation interference experiments confirmed that this site was involved in the protein-DNA interaction. Both the results of competition experiments with upstream activating sequences of ribosomal protein genes (UASrpg), which are targets for RAP1 binding, and determination of the apparent molecular weight of the affinity-purified DNA-binding protein indicated that RAP1 factor recognized the SRP1 33 bp element. The 33 bp sequence was found to be unable to provide UAS activity when placed upstream of the TATA box and transcription start site.


Cloning and DNA sequence analysis of the mercury resistance genes of Streptomyces lividans. A broad-spectrum mercury resistance locus (mer) from a spontaneous chloramphenicol-sensitive (Cms), arginine auxotrophic (Arg-) mutant of Streptomyces lividans 1326 was isolated on a 6 kb DNA fragment by shotgun cloning into the mercury-sensitive derivative S. lividans TK64 using the vector pIJ702. The mer genes form part of a very large amplifiable DNA sequence present in S. lividans 1326. This element was amplified to about 20 copies per chromosome in the Cms Arg- mutant and was missing from strains like S. lividans TK64, cured for the plasmid SLP3. DNA sequence analysis of a 5 kb region encompassing the whole region required for broad-spectrum mercury resistance revealed six open reading frames (ORFs) transcribed in opposite directions from a common intercistronic region. The protein sequences predicted from the two ORFs transcribed in one direction showed a high degree of similarity to mercuric reductase and organomercurial lyase from other gram-negative and gram-positive sources. Few, if any, similarities were found between the predicted polypeptide sequences of the other four ORFs and other known proteins.


Differential repair and recombination of psoralen damaged plasmid DNA in Saccharomyces cerevisiae. Psoralen photoreaction with DNA produces interstrand crosslinks, which require the activity of excision and recombinational pathways for repair. Yeast replicating plasmids, carrying the HIS3, TRP1, and URA3 genes, were photoreacted with psoralen in vitro and transfected into Saccharomyces cerevisiae cells. Repair was assayed as the relative transformation efficiency. A recombination-deficient rad52 strain was the least efficient in the repair of psoralen-damaged plasmids; excision repair-deficient rad1 and rad3 strains had repair efficiencies intermediate between those of rad52 and RAD cells. The level of repair also depended on the conditions of transformant selection; repair was more efficient in medium lacking tryptophan than in medium from which either histidine or uracil was omitted. The plasmid repair differential between these selective media was greatest in rad1 cells, and depended on RAD52. Plasmid-chromosome recombination was stimulated by psoralen damage, and required RAD52 function. Chromosome to plasmid gene conversion was seen most frequently at the HIS3 locus. In RAD and rad3 cells, the majority of the conversions were associated with plasmid integration, while in rad1 cells most were non-crossover events. Plasmid to chromosome gene conversion was observed most frequently at the TRP1 locus, and was accompanied by plasmid loss.


NADPH: protochlorophyllide oxidoreductases in white pine (Pinus strobus) and loblolly pine (P. taeda). Evidence for light and developmental regulation of expression and conservation in gene organization and protein structure between angiosperms and gymnosperms. NADPH: protochlorophyllide oxidoreductase (pchlide reductase, EC 1.6.99.1) catalyzes the light-dependent reduction of protochlorophyllide in higher plants. Cloned cDNAs encoding two distinct pchlide reductases were isolated from a lambda gt11 library constructed from poly(A)+ RNA prepared from the cotyledons of dark-grown white pine (Pinus strobus) seedlings and a nuclear gene (lpcr) analogous to one of these cDNAs has been characterized from loblolly pine (P. taeda). The pine gene encodes an approximately 43 kDa precursor polypeptide consisting of a 334-amino acid mature protein and a 66-amino acid transit peptide. The deduced primary structures for the pine proteins are highly homologous to those reported from monocots and dicots. The coding portion of the pine lpcr gene is interrupted by four introns. The placement of these introns within the pine lpcr gene is identical to that observed in pea (Pisum sativum), suggesting conservation in gene organization between dicot and gymnosperm species. Western blot analysis using polyclonal antiserum against oat pchlide reductase detected in extracts of dark-grown pine cotyledons a single immunoreactive protein, which declined in abundance during a 48 h period of illumination with white light. Cotyledons of dark-grown seedlings were also found to accumulate high levels of pchlide reductase mRNA; however, little or no change in the steady-state levels of mRNA encoding pchlide reductase was observed in these tissues following illumination. Stem tissue of dark-grown seedlings did not contain significant levels of pchlide reductase mRNA, whereas stems of light-grown plants of the same age accumulated substantial amounts of the message. These results suggest that light and the developmental age of the tissue affect regulation of lpcr expression in pine.


Comparative studies on the postantifungal effect produced by the synergistic interaction of flucytosine and amphotericin B on Candida albicans. A turbidometric method was used to measure Candida albicans yeast cell growth and to quantitate the postantifungal effect (PAFE) after exposure to various concentrations of flucytosine and amphotericin B, alone and in combination, for 2 hr at 30 degrees C. The drug concentrations used in the PAFE assays were determined by initial MIC and FIC (fractional inhibitory concentration) evaluations. The PAFE was calculated by the difference in time (hr) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. A synergistic PAFE was evidenced with combinations of the two drugs at concentrations below their individual MICs. Combinations of flucytosine (0.012 to 0.049 micrograms ml-1) and amphotericin B (0.195 to 0.39 micrograms ml-1) produced PAFEs ranging from 6.3 to 21.8 hr. These PAFEs persisted from 0.3 to 14.7 hr longer than those achieved when each of the two agents was assayed separately.


Isolation of dermatophytes from clinically normal sites in patients with tinea cruris. Sixty patients clinically suspected of tinea cruris were studied by collecting skin scrapings from the site of their lesions and six clinically normal sites including the thighs, scrotum, crural clefts, natal cleft and the web between their 4th and 5th toes. Dermatophytes were detected in scrapings in 46 (77%) and by culture in 36 (60%) patients from lesions. Trichophyton rubrum was isolated from 32 and Epidermophyton floccosum from 4 patients. Dermatophytes were also isolated with maximum isolation from the scrotum, crural clefts and the natal cleft in that order. Thus, when tinea cruris is treated with topical antifungal agents they should be applied also to the potential carriage sites to prevent recurrence.


Extensive dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patient with AIDS. Retrospective studies have shown the occurrence of episodes of deep or superficial fungal infections in 58 to 81% of HIV/AIDS patients as a result of impairment of cell immunity. We describe a case of disseminated cutaneous dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patients with AIDS. Diagnostic and therapeutic problems in relation to this unusual presentation are emphasized as well as the importance of an early mycologic diagnosis to prescribe antifungal therapy.


Antifungal activity of allylamines on Epidermophyton floccosum: scanning electron microscopy study. The action of allylamine antifungal agents on Epidermophyton floccosum was studied using scanning electron microscopy. After 7 days of culture on Sabouraud dextrose agar, Epidermophyton floccosum samples were brought in contact with concentrations of 0.2 and 2 micrograms ml-1 and 0.01 and 0.1 micrograms ml-1 of naftifine and terbinafine, respectively. Lesions observed after 24 h, 3 and 7 days of contact were mainly on the structure and rigidity of the mycelial and macroconidial wall. They were characterized by hyphal ballooning and twisting and by apical bulbous bulges. Deterioration of macroconidia was characterized by wall exfoliation. The intensity of the deterioration depended on the dose and only slightly on the length of time that the sample and the antifungal drug were in contact.


Tremorgenic mycotoxins produced by strains of Penicillium spp. isolated from toxic Poa huecu parodi. Seventeen strains of Penicillium spp. have been isolated from Poa huecu Parodi from the Zapala zone, exhibiting toxicity to sheet. The following strains have been identified: P. crustosum, cyclopium, notatum, palitans, puberulum, verrucosum, viridicatum and Penicillium spp. The toxigenic capacity of the strains was studied after growing them under suitable conditions. Toxins produced were analysed by thin layer chromatography (TLC). Penitrem A (PA) and Penitrem B (PB) neurotoxins were identified and quantitated in twelve strains; verruculogen (VERR) and fumitremorgen B (FTB) being present in one of them. The effect of these mycotoxins was studied in mice. Neurological symptoms characteristic of the intoxication by tremorgenic toxins and similar to those observed in sheep suffering from 'huecu's disease' were observed. The possible role of these toxins as causative agents of 'huecu's disease' is discussed.


Cytotoxicity of Fusarium species mycotoxins and culture filtrates of Fusarium species isolated from the medicinal plant Tribulus terrestris to mammalian cells. Ayurvedic medicine, which uses decoctions made of medicinal plants, is used to cure diseases in many Asian countries including Sri Lanka. Although proper storage facilities for medicinal plants are unavailable in Sri Lanka, neither the potential for growth of toxigenic fungi nor their ability to produce mycotoxins in stored medicinal plants has been investigated. We isolated three Fusarium species, F. culmorum, F. acuminatum and F. graminearum from the medicinal plant Tribulus terrestris. Culture extracts of the 3 Fusarium spp. were cytotoxic to mammalian cell lines BHK-21 and HEP-2. Three toxic metabolites produced by Fusarium spp; T-2 toxin, zearalenone, and diacetoxyscirpenol were also cytotoxic to the mammalian cell lines. The 3 Fusarium spp. grown on rice media produced zearalenone. Plant material destined for medicinal use should be stored under suitable conditions to prevent growth of naturally occurring toxigenic fungi prior to its use.


An interview with Bernadine P. Healy. Interview by Carmella A. Bocchino. In April 1991, Dr. Bernadine P. Healy was appointed director of the National Institutes of Health--the largest biomedical research organization in the world. In assuming this position, Dr. Healy became the nation's premier woman in science and broadened the opportunities for women in an arena traditionally dominated by men. She has aggressively tackled the research agenda for NIH and assured the inclusion of women's health issues. Using her leadership, Dr. Healy has redefined the director's role, broadened women's visibility in science, and defended the extensive Women's Health Initiative and the Administration's stand on fetal tissue research.


The impact of leadership upon productivity. Shifting from management to leadership behaviors increases productivity. Five specific behaviors, but particularly the ability to be an excellent role-model, are vital in enhancing and supporting productivity.


Cost reductions Part 2: an organizational culture perspective. Part One of this series described how an Operations Improvement process, computer simulation, and a focus on the dollars per patient day or unit of service ($PPD) can enhance a hospital's cost-reduction efforts. Part Two will address the organizational culture issues that can hamper or support nursing's cost-reduction efforts.


Economic awareness of registered nurses employed in hospitals. The basic knowledge and beliefs of RNs in three hospitals in the midwest are described. Nurses lack basic knowledge of how economics affect their practice, yet desire to learn more about economic issues related to nursing practice and health care.


[Reciprocal inhibition of human motor neurons at different firing rates]. Reciprocal inhibition (RI) has been studied for its effect on repetitive firing of single motoneurons in the extensor carpi ulnaris and soleus muscles of healthy subjects. The peristimulus time histograms (PSTHs) were plotted for different mean firing frequency of motoneurons. Changes in the interspike interval duration were analyzed. It was shown that the "effectiveness" of reciprocal volleys (as it was previously shown for other types of inhibition) depended on the firing rate of a motoneurons. It was found out that RI duration derived from the PSTH, duration of the "effective part" of the interspike interval, rate of the interspike interval lengthening depended on the motoneuron firing frequency. It was also found that the inhibitory effect of the motoneuron firing was pronounced mostly at its low-frequency range. The dependence of "effectiveness" of an inhibitory volley on the moment of its arrival within the interspike interval was analyzed as well.


Ethical concerns regarding cardiac retransplantation. Health care professionals face many ethical dilemmas regarding cardiac transplantation and retransplantation. A thorough understanding of ethical theories and careful examination of each case encourages decisions reflective of the values of the health care team.


[Vascular and autonomic disorders of the spinal cord in dystopia of the spinal motor segment]. Microcirculation disorders may cause functional deviation in gray matter cells of the spinal cord. One of the setting moments of the disorders is the subluxation of a vertebra as a result of the disturbance in carrying ability of the spinal disc in case of spinal osteochondrosis. In this position the soft tissues of the spinal motional well innervated segment are stretched, which induces irritation in the segmental part of the spinal cord including vegetative nervous structures. Subluxation of a vertebra causes changes in the structures and in the microcirculation vessels which grow simultaneously and this permits supposing their interrelation.


[Cytophotometric and electrophysiologic analysis of the role of the celiac plexus in maintaining temperature homeostasis in cold stress in rats]. The role of the celiac plexus in maintaining temperature homeostasis in rats during cold stress was studied histochemically, ultrastructurally, and electrophysiologically. Inhibition on efferent impulses in preganglionic (splanchnic) nerves and facilitation in postganglionic (superior mesenteric) nerves during a short-term cold exposure leading to slight hypothermia were found. In cold-exposed animals after the celiac plexus decentralization, the neurons showed an increase in the fluorescence intensity and activity of energy metabolism enzymes, hyperplasia of fine structures responsible for protein synthesis and energy supply of cells. It is suggested that during cold stress when efferent impulse flow in preganglionic nerves markedly decreases, the celiac plexus becomes a regulatory centre for autonomic functions involved in the maintenance of temperature homeostasis.


[Evaluation of the cat brain activation using ECoG on the cat striate cortex]. The striate cortex electrocorticogram has been analyzed in 12 cats in following states: at rest with the eyes closed and with the eyes opened; after light electrical stimulation of ears; somnolence; eye opening after somnolence+; barbituric sleep. The behaviour of cats was controlled and the state of emotional excitability was determined. Spectral and periodometric analysis of ECoG has revealed state-dependent differences of cats in power spectra from 2 frequency ranges (2.8-5.0 Hz and 13.8-20.8 Hz). It is suggested that the ratio of ECoG power spectra in these frequency ranges can be used to evaluate the brain activation of cats.


Creating a healing environment: the nurse manager's challenge. Environments can create positive attitudes or they can induce negative feelings. The nurse manager's responsibility is to understand how different environmental designs can reduce patient and staff anxiety and stress. The patient care unit should support staff and patients and provide a caring, healing environment. Chapman makes the important point to "Do everything you can think of to take better care of your employees so that your employees in turn will take better care of patients" (1990, p. 19). Happy, cared-for staff will take excellent care of patients and create a healing environment.


[Effect of exogenous acetylcholine on potassium currents of motor nerve endings in the frog]. Mechanisms of the exogenic acetylcholine (ACh) effect on ionic currents of nerve endings (NE) were investigated by extracellular recording of NE at the cutaneous pectoris muscle of frog. It was found that ACh in concentrations 0.1-0.6 mmol/l increased the third phase of the nerve ending response, while in concentrations 0.7-2.0 mmol/l-decreased it. Tubocurarine and atropine did not alter the ACh effect. It has been also revealed that growth of the third phase of NE response, induced by ACh, occurs in the presence of calcium channel blockers and disappears under the influence of 4-aminopyridine and tetraethylammonium. In calcium-free solution or when the calcium current is blocked the suppressive effect of ACh disappears. The mechanisms of exogenic and endogenic ACh effects on the potential-sensitive and calcium-activated potassium NE currents are discussed.


[Strychnine-induced changes of the membrane and postsynaptic potentials in neocortical neurons]. Intracellular responses of neurons of the suprasylvian gyrus to the intracortical stimulation (ICS) before and after superficial application of strychnine were investigated in experiments on immobilized and unanaesthetized cats. The normal cortex neurons reacted to ICS by monosynaptic EPSPs followed by IPSPs. Strychnine application triggered the epileptiform activity and appearance in neurons of paroxysmal depolarization shifts of the membrane potential (MP) which were replaced by hyperpolarization potentials. An increase and summation of the latter elicited the MP enlargement and either reduction or suppression of background spike activity. Intracellular injections of EGTA blocking the membrane calcium-dependent potassium conductivity (gK(Ca)) have eliminated the hyperpolarization potentials. Development of epileptiform activity was accompanied by depression of IPSPs and increase of the monosynaptic EPSPs. The contribution of gK(Ca) and of postsynaptic inhibition to the epileptogenesis is discussed.


[Neurophysiologic changes and bound calcium dynamics during the elaboration of associative learning in Helix lucorum]. Neurophysiological effects and dynamics of bound calcium (Ca-b) in command neurons of defense behavior (LP11 and RP11) during food aversion conditioning were studied in snail Helix lucorum. It was found that during associative learning both conditioned reaction and nonspecific facilitation of sensory responses were determined in neurons. The nonspecific facilitation of sensory responses was similar to that found during sensitization development in neurons. However, conditioned response appeared 30 min later than long-term sensitization development. Specific dynamics of the Ca-b level in neurons was obtained after three and more conditioning. The dynamics of the Ca-b level correlated with neurophysiological effects and differed from those measured during sensitization development. It is suggested that molecular mechanisms underlying associative learning and sensitization are different in a command neuron of defense behavior in the snail.


[Role of structures of the ventrolateral medulla oblongata in the regulation of cardiovascular activity]. The review presents information on morphology, afferent and efferent connections of the ventrolateral medulla, mediator characteristics of neurons within the rostral and caudal parts of the ventrolateral division of the medulla, functional organization of the structures involved in the cardiovascular control.


[The intra-carotid amobarbital test--indications--procedure--results]. In presurgical assessment of epilepsy, the intracarotid amobarbital procedure (IAP) is used for the detection of functional asymmetries of the cerebral hemispheres with respect to cognitive functions. The IAP permits a precise and reliable determination of patterns of language dominance, although analysis of the lateralization of specific memory functions is constrained by methodological problems. In addition, the IAP yields information on the lateralization of other cognitive functions such as attention, consciousness, and emotion. It may also serve as a means of delineating the primary epileptic focus. Furthermore, the IAP may also be helpful in the assessment of non-epileptic patients prior to elective operations in brain regions relevant to cognition.


[Cystic abnormalities of the brain: stereotaxic diagnosis and therapy]. We present the stereotactic treatment and evaluation of 33 patients with congenital cysts of the brain (6 cavum septi pellucidi/cavum vergae cysts, 5 suprasellar cysts, 3 intraventricular cysts, 4 cysts of the interhemispheric fissure, 4 cysts of the cerebral convexity, 5 supracollicular cysts, 3 cysts in the cisterna ambiens, 2 temporomedial cysts and 1 cyst in the pontomesencephalic junction). The patients were seen during an 8-year period (1984-1992) and had a mean follow-up time of 27 months. In 23 patients with cysts in or near the cerebral midline or at the cerebral convexity, a stereotactic ventriculocystostomy resulted in clinical improvement with diminished cyst size. Another 8 patients with relatively small cysts profited from stereotactic aspiration of the cyst contents. Three complications (bleeding, aseptic meningitis, catheter infection) remained without sequelae. The stereotactic procedure is the treatment of choice for these lesions because of the low operative risk, its minimal invasiveness and the possibility of distinguishing primary congenital cysts from other pseudocystic lesions. In well-chosen cases the carefully planned stereotactic internal derivation of the cysts in the ventricular system led to a long-lasting beneficial effect. Open craniotomy or shunting procedures can be avoided for most cases of congenital intracranial cysts.


[Prospective follow-up of neuropsychological deficits after cervicocephalic acceleration trauma]. 30 patients with acute cervico-cephalic syndrome following whiplash injury (neck and head pain, vegetative symptoms and subjective complaints of impaired mental functions) without neurological deficits were investigated in a prospective follow-up of 3 months with neuropsychological examination in the acute phase (x = 5.7 days) and again 6 and 12 weeks after the accident. Attention, concentration, cognition and verbal and visual memory functions were quantified by neuropsychological tests, and changes over the observation period were analysed. In the acute phase all neuropsychological functions were below the individual's normal level. Deficits in attention and concentration recovered within the first 6 weeks. Further recovery within the following 6 weeks were observed in visual memory, imagination and analytic capacity. The capability of verbal memory and abstraction, cognitive selectivity and information processing speed was impaired for a longer time and first recovered after 12 weeks. In conclusion, intraindividual neuropsychological deficits following whiplash injury can be quantified and monitored to show the time course of recovery. Thus in clinical and forensic practice the diagnosis of a pseudoneurasthenic or even "neurotic" syndrome in acute whiplash injury should be made with caution.


[The status of afebrile infantile convulsions within the epilepsy spectrum--a follow-up of 55 patients]. In an earlier study we observed 411 patients with cerebral convulsions, 118 of whom had the first convulsion during the 1 year of life. Among these 118 children we found 76 with afebrile convulsions. In this study we present the development and outcome in 55 patients with afebrile convulsions in the 1 year of life which could be observed for some years, most of them up to the present. In 25 infants the fits started in the newborn period, and in 30 infants after the 1 month; they were divided into groups with and without risk factors in the history. Benign neonatal convulsions were found in about one-third of children, with a good prognosis. These convulsions are divided into a dominantly inherited but rarely observed form and idiopathic benign neonatal convulsions. In contrast, among the newborns with risk factors in the history we found only half with a positive development. The results in the 30 infants with convulsions after the 1 month were similar with respect to risk factors in the history of risks. The 15 infants without risks had a good prognosis. Only 3 patients had oligoepilepsy. However, in the 15 patients with risks only 3 developed normally, 6 had no fits, but were neurologically or mentally handicapped, and 7 had fits and disability. We believe that afebrile convulsions without risk factors after the 1 month could be considered a late manifestation of benign newborn convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)


[Computerized tomography markers of morphologically confirmed hemorrhagic brain infarct]. Radiological differentiation between hemorrhagic infarction and intracerebral hemorrhage is important for patient management. To ascertain CT features of hemorrhagic infarction, we studied the findings in 19 cases with autopsy-proven hemorrhagic infarction. Most cases had multiple, mainly cortically located, small hyperdensities. However, some presented with a single hyperdensity, deeply located, that could be mistaken for primary intracerebral hematoma. Hemorrhagic infarctions usually present as multiple, small hyperdensities within a hypodense area compatible with an arterial territory. The shape can be round, slitlike, curvilinear, or spotted. Most often the hyperdensities are located cortically; however, some larger, deeply located hyperdensities may falsely suggest primary intracerebral hematoma. Some guidelines for a more reliable radiological separation between hemorrhagic infarctions and intracerebral hematomas are suggested.


[Repeated treatment of subtotal vertebrobasilar stenosis with tissue plasminogen activator (tPA)]. We report on the successful repeated treatment of a patient with rapidly progressive severe brain-stem stroke by application of I.V. tissue plasminogen activator (tPA). This treatment twice led to a prompt remission of severe brain-stem symptoms, although a permanent therapeutic success could not be achieved. Unfortunately, the patient died a few days later from pneumonia and sepsis. Necropsy revealed bilateral partial brain-stem infarctions and a subtotal stenosis of the vertebrobasilar junction with superimposed fresh thrombus. The clinically dramatic response to tPA indicates that this type of treatment is potentially successful in high-grade subtotal basal cerebral artery stenosis with progressive stroke symptoms. In particular, application of tPA should be considered if stroke progression cannot stopped by therapeutic heprinization. A prospective randomized oligocentric study is advocated.


[Transcranial Doppler contrast study--an ideal method for detection of paradoxical cerebral embolism?]. Cerebral paradoxical embolizations can easily be detected by transcranial Doppler investigations using intravenous echo contrast medium. In some cases of TIA or stroke without vascular or cardiac disease, this method will reveal a right-to-left vascular shunting (e.g. by a patent foramen ovale). However, demonstrating a leakage through the atrial septum does not necessarily reveal the source of an embolus or the cause of the stroke. Thus the question of prolonged antithrombotic therapy must be decided in each individual case.


[Multiple meningiomas in different compartments of the cerebrospinal axis]. Multiple meningeomas in the absence of Recklinghausen's disease are rare and usually occur in a single compartment of the neuroaxis. Multiple meningeomas in different neuroaxial compartments are an even rarer condition, only a few cases having been reported. We describe four cases, each with two meningeomas in different compartments of the neuroaxis. Their peculiarity consists in the fact that the different tumours developed at different times and locations in the supratentorial and spinal regions. The radiological and operative findings are described. The possibility of dissemination via the cerebrospinal fluid or blood or of a multifocal origin or genetic predisposition is discussed.


Simultaneous pancreas and kidney transplantation: a feasible procedure in selected patients. We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem.


Lowering of plasma glucose concentration in septic cancer-bearing patients: metabolic significance. Previous work has indicated that 40-50% of glucose intake is oxidized in normal humans with protein-sparing effect. In contrast, the catabolic stressed patient is hyperglycaemic with decreased glucose oxidation and protein wasting. This study evaluated whether the plasma glucose concentration alone would be a reliable indicator of efficient glucose utilization and protein sparing in the critically ill septic cancer patients receiving glucose infusions. Glucose turnover, glucose concentration, nitrogen excretion, oxygen consumption, and glucose oxidation were measured in 8 septic cancer-bearing patients during a glucose infusion of 4.0 mg/kg/min followed by the infusion of insulin with the same glucose load. During glucose infusion without insulin the glucose concentration was 11.8 +/- 1.4 mmol/l, glucose oxidation 10 +/- 5% of glucose tissue uptake, and nitrogen excretion 9.0 +/- 1.3 mg/kg/h. During the euglycaemic clamp the glucose concentration was 3.8 +/- 0.2 mmol/l, glucose oxidation increased to 45 +/- 6% of glucose tissue uptake (p < 0.001), and nitrogen excretion dropped to 6.8 +/- 1.2 mg/kg/h (p < 0.001). The glucose concentration was greater than 10 mmol/l in 4 patients and between 6.9 and 9.3 mmol/l in 4 patients after glucose infusion alone. Despite this difference in initial glucose concentration, normalization of plasma glucose to less than 5 mmol/l with insulin resulted in the same decrease in nitrogen excretion and improvement in glucose oxidation. We conclude that, independent of the initial glucose concentration, maintenance of euglycaemia with insulin appears to be a good indicator of efficient glucose utilization and protein sparing in septic cancer-bearing patients receiving glucose as the primary mode of nutritional support.


Peritoneal tuberculosis in two young immigrants with fever of unknown origin. Two patients with long-standing fever and weight loss underwent extensive diagnostic procedures before peritoneal tuberculosis was diagnosed by explorative laparatomy. By that time they had developed signs of intestinal obstruction. Both recovered after treatment, but one developed serious neurological complications, which could not be explained. Peritoneal tuberculosis is a manifestation of tuberculosis that is often difficult to diagnose. It should be borne in mind when diagnosing patients with fever of unknown origin, especially if they are originally from countries with a high prevalence of tuberculosis.


Kikuchi's lymphadenitis: report of a Yersinia enterocolitica-associated case and an overview of aetiology and clinical outcome. Kikuchi's lymphadenitis (KL; histiocytic necrotizing lymphadenitis without granulocytic infiltration) is a generally benign, febrile disorder of unknown aetiology with distinct histological features. To date, a minority of cases reported have been associated with infectious agents. A typical pathological case of KL is described where involvement of Yersinia enterocolitica was shown by an indirect immunofluorescent assay applied to lymphatic tissue. The case is discussed with emphasis on recent insight into the course and aetiology of KL.


Growth hormone: secretion and administration in catabolic adult patients, with emphasis on the critically ill patient. Critical illness, surgery and hypocaloric feeding are accompanied by a high rate of total body nitrogen loss. Loss of body protein, occurring despite adequate nutrition, results in increased incidence of infection, poor wound healing, skeletal muscle weakness and increased mortality. Growth hormone (GH) administration together with nutritional support attenuates protein catabolism. This review focuses on normal GH physiology and the administration of GH in adult catabolic patients.


Some skeletal dimensions of males with isolated gonadotrophin deficiency. This is a retrospective study of stature and bone age before and during androgen substitution for hypogonadotrophic hypogonadism in 25 males. Before androgen treatment, stature tends to be low for chronological age but normal for bone age. Treatment results in normal final height. Growth in length of metacarpal bone II (MC II), measured on hand radiographs, mimics growth in height. From measurements of total bone width of MC II and combined cortical thickness of MC II, the cortical area (indicating bone mass) and the relative cortical area (indicating bone density) were calculated. Bone mass was well within the limits of a published control series, both before and during androgen treatment. Bone density, however, was, without exception, below the P50 for controls prior to androgen treatment, and increased only slightly during treatment. It is concluded that prepuberal deficiency of androgen, possibly in early infancy, causes a permanent defect in bone density which is only marginally corrected by later androgen treatment.


Infection with Dengue virus.

Infection with Dengue virus. We report a male Caucasian, with a Dengue virus infection imported from Thailand to The Netherlands. General characteristics of the disease are presented and the supposed pathogenetic mechanisms of the disease are discussed.


Dialysis associated mucormycosis and desferrioxamine treatment: a case report with review of the role of oxygen radicals. A hemodialysis patient with pulmonary and cerebral mucormycosis is reported. Recently the occurrence of this infection in dialysis patients has been associated with desferrioxamine (DFO) treatment. A causal relation seems likely, but has not been proved. Several pathogenetic mechanisms are discussed, in particular the influence of DFO on host neutrophil defenses through a decreased oxygen radical production.


Mineralocorticoid excess due to precursors only in a patient with adrenal cortical carcinoma. A patient with carcinoma of the adrenal cortex presented with mineralocorticoid excess due to hypersecretion of deoxycorticosterone, which is exceedingly rare. Backache was the only symptom and an unexplained hypokalaemia was the only sign. Because of the abnormal synthesis of steroid precursors in these tumours a urinary steroid profile may be helpful as a diagnostic tool in such cases.


Alternative stress methods for the diagnosis of coronary artery disease. Bicycle exercise and treadmill exercise are the commonest devices used in the evaluation of coronary artery disease. However, not all patients are capable of performing a maximal exercise test due to orthopaedic, vascular or pulmonary disease, poor physical condition and motivation. Alternative tests as a reliable substitute for the more conventional methods have been proposed, such as right atrial pacing, arm ergometry, handgrip test, cold pressure test, and inotropic stimulation. In particular, pharmacological stress testing with dipyridamole (and recently with adenosine and dobutamine) in combination with radionuclide techniques has gained much interest. This review will consider the usefulness and role of alternative stress testing to provoke myocardial ischaemia, with emphasis on pharmacological stress testing in conjunction with thallium-201 myocardial perfusion scintigraphy.


Arachnoid cysts of the middle cranial fossa. In 18 cases of temporal arachnoid cysts the etiology, clinical and radiographic findings, surgical treatment, and outcome are reviewed. Cysts of the middle cranial fossa are susceptible to trauma, which may cause bleeding either into the cyst or into the subdural space. CT or MRI scans are diagnostic in arachnoid cysts. In cases of intracranial mass lesion with displacement of the midline structures and increasing ICP, osteoplastic craniotomy is performed and the medial wall of the cyst is resected down to the tentorial notch, with opening into the basal cisterns. There were no operative or postoperative complications in 18 consecutive cases. However, one boy required a cystoperitoneal shunt 3 months later as a result of hydrocephalus following subdural hematoma and two other patients were also subsequently shunted. Asymptomatic arachnoid cysts are discussed with the respect to brain function and potential risks.


[Autonomic nervous system disorders in 230 cases of basilar impression and Arnold-Chiari deformity]. Within the period of 1971 to 1989 we operated on 230 cases of craniocervical malformations characterised by 189 cases of basilar impression associated with Arnold-chiari malformation, 28 cases of isolated basilar impression and 13 cases of Arnold-Chiari malformation. Autonomic disturbance was observed in 136 (59.1%) cases: sexual disorders like reduced potency and impotency were observed in 86 (60.9%) out of 141 male patients, urinary symptoms in 39 (17%) patients; and other autonomic features like dyspnea, anhidrosis, hyperhidrosis, Claude Bernard-Horner syndrome and constipation in 41 (17.8%) patients.


Basilar impression and Arnold-Chiari malformation. Surgical findings in 209 cases. The surgical findings observed in a series of 209 consecutive patients with craniovertebral anomaly are presented. The high prevalence of basilar impression in the Northeast of Brazil is noteworthy. There were 28 (13.3%) patients with basilar impression alone, 10 (4.7%) cases of pure Arnold-Chiari malformation and in 171 (81.8%) cases the basilar impression was associated with Arnold-Chiari malformation. This study reflects our surgical experience of the pathology in a 17-year period (1971-1987). It reflects also the peculiarities of neurosurgical practice in an undeveloped region of this Country. The literature is extensively reviewed.


[Initial experiences with a new cerebrospinal fluid collection system]. Due to clinical requirements and to improve the handling of CSF drainage set we developed a new concept, consisting of an arrangement of constructions, which are already available. Besides other advantages, the set provides an ICP monitoring, a pump device and a protection of the air filter of the collecting tank for safer transport. Opening the system for the performance of diagnostic or therapeutic manoeuvres can therefore be avoided. This new equipment has been tested in 28 patients having a ventricular or lumbar CSF drainage with good results and has been quickly accepted by the medical staff. The construction is described in detail.


Supratentorial arachnoidal cyst with intracystic and subdural haematoma. A case of a arachnoidal cyst with intracystic bleeding and subdural haematoma is reported. The association of an arachnoidal cyst in the middle cranial fossa with a subdural haematoma or intracystic bleeding is emphasised. The diagnosis of such lesions, the nature of the pathology and therapy are discussed.