[Organic calcium antagonists verapamil and ryodipine prevent an increase of free calcium in synaptosomes of the rat brain during corazol kindling]. In experiments on Wistar male rats it was shown that i.p. administration of verapamil or ryodipine (1,4-dihydropyridine) 15 min before each daily injection of pentylenetetrazol (PTZ) in a subconvulsive dose 30 mg/kg during 28 days significantly delayed the development of PTZ-induced kindling and attenuated kindled seizure reactions during 21-23 days as compared with control. One week after kindling an increase in free Ca2+ concentration in control rat brain synaptosomes by 60% was revealed; the treatment by verapamil and ryodipine prevented this increase. Nevertheless, Ca2+ antagonists studied at least under our experimental conditions inspite of a significant decrease in free Ca2+ concentration in synaptosomes would not completely prevent the development of kindling. Thus, an alteration in calcium homeostasis will not be the only mechanism of plasticity and long-term changes of neurons during kindling.


[Oxygen tension and water-soluble products of lipid peroxidation in blood of volunteers in hypobaric hyperoxia]. Oxygen tension in the arterial blood with transcutaneous method (tcPO2) and TBA-active products of venous blood plasma were measured during simulation of extravehicular activity. There was a parallel increase of tcPO2 and the level of TBA-active products upon introduction of hypobaric hyperoxia factor. Detrimental action of lipid peroxidation products on erythrocyte membranes can be one of the factors of anemia during space flight.


[Experimental atherosclerosis and its correction with Co-35]. Initial and Co-35-induced parameters of lipid metabolism and hemostasis were studied in rabbits with experimental atherosclerosis. Control atherosclerotic animals were administered cobalt chloride and placebo. The findings demonstrated initially increased levels of cholesterol, lecithin, beta-lipoproteins, lysolecithin, sphingomyelin, cephalin, saturated acids in low levels of phosphatidylserine, polyglycerophosphatide and unsaturated acids. Hemostasis was characterized by hypercoagulation. A course of Co-35 brought about positive shifts in both lipid metabolism and hemostasis. Co-35 is recommended as an effective means against atherosclerosis.


[Thymosin alpha(1)--an endogenous modulator of alpha-thrombin recognition site]. Thymosin alpha 1-inhibited fibrinogen clotting activity of alpha-thrombin, but not amidolysis of H-D-Phe-Pip-Arg-pNA. Modulation of thrombin interaction with rat peritoneal mast cells (RPMC) by suppressors of additional recognition binding site (thymosin and heparin) was studied. Thrombin-induced pHi changes of RPMC were controlled with pH-sensitive fluorescent dye, BCECF. Thrombin caused a biphasic changes in pHi: rapid cell acidification (0.02) followed by slow alkalinization (0.06 above baseline for 18 min). Thymosin suppressed thrombin-induced pHi increase above resting level. Similar changes in pHi were observed after modification of additional recognition binding site by heparin. Beta/gamma-thrombin with disrupted additional binding site was shown to induce only a decrease of pHi. It is concluded that thymosin alpha 1 is endogenous modulator of alpha-thrombin activity.


[Effects of vitamins A, E, C and P on intensity of blood coagulation in experimental animals]. In experiment on white rats it was shown that preventive 12-day administration of vitamins A, E, C, P decreases the death rate of animals with exogenous thromboplastinemia and reduces hemocoagulative changes, microcirculation disorders, destructive changes of functionally active elements of inner organs. The protective effect of the above vitamins combination in thromboplastinemia is promoted by hypoactivity of platelet aggregation, by low thromboplastic activity of erythrocytes, by limited destruction of vascular endothelium.


[Effects of pyrazidol on resistance of animals to hypobaric hypoxia]. The influence of monoamine oxidase type A inhibitor pyrazidol on rats sensitivity to hypobaric hypoxia was investigated. Preliminary pyrazidol administration shows evident protective effect under hypoxia. It increases animals survival at the altitude of 12,000 m above the sea level, prevents lungs affection and erythrocyte membrane destabilization at the altitude of 9,000 m during 3 hours. Plasma total peroxidase activity, extraerythrocyte hemoglobin concentration and free iron content were used as the indexes of erythrocyte membrane stability reflecting the organism state under stress effects.


[Metabolism of articular cartilage in the presence of interleukin-I alpha, its inhibitor and blood serum]. The study was made of the effect which interleukin receptor antagonist protein (IRAP) and bovine serum have on interleukin-1 alpha (IL1a) activity in cartilage culture of young bulls. It was established that IL1a leads to cartilage degradation as shown by an increase of sulphated glycosaminoglycans (sGAG) in culture medium and their decrease in tissue, inhibition of proteoglycan (PG) synthesis by chondrocytes. This effect of IL1a is suppressed by IRAP. In serum-free culture the cartilage tissue produced proteoglycans in much less quantities. In these conditions IL1a stimulated chondrocytes, cytokine did not respond to IRAP.


[Anomalous excretion of glycosaminoglycans in patients with syringomyelia]. Glycosaminoglycan (GAG) urine concentrations in syringomyelia patients were much higher than in healthy subjects from January to September. Maximum values of GAG excretion (twice as much as control) in affected patients were observed in spring and summer (from March to July). The results suggest that syringomyelia is accompanied by disorders in GAG connective tissue accumulation.


[Free-radical mechanism of antimicrobial action of xanthine oxidase and lactoperoxidase]. The interaction between milk xanthine oxidase (XO) and lactoperoxidase (LP) in model system and antimicrobial action of these enzymes on Escherichia coli 0-111 were studied. It was shown, that bacterial superoxide dismutase (SOD), which transforms O2-. (XO-reaction product) into H2O2 (substrate of LP), is necessary for binding of the reaction sequence: XO-->LP-->antimicrobial products. It is suggested, that these enzymes unite in the protective system in intestinal infections of newborns. Bacterial SOD in this case acts as the key factor, creating the system.


[Effects of the fraction (1-10 kDa) of the brain of a Yakut horse on kinetic parameters of Ca2+ transport system in sarcolemma vesicles of cardiomyocytes]. The effect of the fraction (1-10 kDa) obtained from the brain of cold-adapted animal (Yakut horse) on Ca2+ transport in sarcolemma vesicles of cardiomyocytes was investigated. It was shown that during insertion of Yakut horse brain fraction into incubation medium at the concentration from 10(-9) M to 3.10(-5) M at Ca2+ transport substrate concentration from 0.1 mM to 1.0 mM, the rate of Ca2+ passive penetration into vesicles slightly increased and at Ca2+ transport substrate concentration 3 mM, which is physiologic, a decrease of rate values was established for all concentrations of the fraction (1-10 kDa) of Yakut horse. While studying the kinetics of an active Ca2+ transport for all investigated concentrations of the fraction (1-10 kDa) of Yakut horse brain from 10(-9) M to 3.10(-5) M at Ca2+ concentration in incubation medium from 10(-7) to 3.10(-6) M, calcium accumulation rates by vesicles exceeded control values. So we can suppose that application of brain fraction (1-10 kDa) of genotypically cold-adapted animal, results in a decrease of intracellular Ca2+ concentration.


[Endocytosis by liver cells during stimulation of the mononuclear phagocyte system by yeast polysaccharides]. Endocytosis (phagocytosis, fluid-phase- and receptor-mediated endocytosis) by liver cells, lysosomal enzyme activities have been studied during macrophages stimulation by yeast polysaccharides. It was shown that like macrophages stimulator zymosan, yeast polysaccharides cryelan and rhodexman increased the carbon particles phagocytosis. The most effective was intravenous administration of yeast polysaccharides. Compared to rhodexman, the effect of cryelan was more prominent. Macrophages stimulation was followed by suppression of fluid-phase endocytosis by liver cells. Increased activity of cathepsin B was discovered on day 5 after macrophages stimulation (proteinase, most typical for macrophages enzymes).


[Effects of cortisol on calcium contents of lymphocytes in patients with bronchial asthma]. A fluorescent probe was used to study hydrocortisone (10 microM) action on mitogen-stimulated free cytoplasmic calcium level in lymphocytes of patients with bronchial asthma. The patients were divided into two groups according to their sensitivity to glucocorticoid therapy. Hydrocortisone-specific calcium-blocking effect was absent in hormone-resistant patients. Lymphocytes of hormone-sensitive patients responded to hydrocortisone administration by a decline of mitogen-induced calcium level.


[Effects of systemically-administered beta-casomorphin-7 on nociception in rats]. The influence of food-derived heptapeptide beta-casomorphin-7 (beta-CM-7) on pain sensibility of white rats was studied by tail flick test. As shown for doses 10 and 20 mg/kg intraperitoneally, injected beta-CM-7 induced significant analgesia; lower peptide concentration (5 mg/kg) was ineffective. As a whole, there is a significant positive correlation between the intensity of analgesia and the quantity of administered exorphine. These changes of pain sensibility were observed for one hour after injection of heptapeptide; further measurements showed no significant difference of time reaction between control and experimental groups of rats. It was found out that animals with high native level of pain sensibility (4-8 sec) made the main contribution to manifestation of analgesia.


[Effects of melatonin and epiphysectomy on electrical activity of the rat brain at different times of the day]. The pineal hormone melatonin in a dose-effect manner (0.1, 1 and 10 mg/kg) reorganized EEG spectral characteristics of rat sensorimotor cortex and hippocampus, decreasing medium (6-12 Hz) and high frequency (12-22 Hz) waves only in the evening. On the contrary, pinealectomy increased high-frequency waves only during morning hours. It is suggested that the observed changes may accompany anxiolytic and hypnotic effects of melatonin.


[Effects of diisopropylfluorophosphate, paraoxon and dichlophos on [3H] quinuclidinyl benzylate binding to the rat striatum synaptic membranes]. The binding of [3H] quinuclidinyl benzilate (QNB) to rat striatum membranes after diisopropylfluorophosphate (DFP) induced seizures was characterized. There was a 36% decrease in Kd and a 33% decrease in the number of muscarinic receptors. Paraoxon caused inhibition fo [3H] QNB binding to the striatal membranes of intact rats. It is possible that a direct action of DFP on the muscarinic receptor is not the cause of anti-cholinesterase-induced changes in [3H] QNB binding.


[Ultrastructure of donor blood lymphocytes incubated with Amanita phalloides poison]. Heparinized donor blood was investigated incubated with Amanita Phalloides poison in the dose of 0.05 and 0.5 LD100 during 1 and 3 hours. Lymphocyte structure changes showed cytoplasma and organoid membrane destabilization, cytoplasma degranulation, appearance of autolysis foci and lysed cells. This destruction became particularly marked with increasing poison dose and infusion time.


[Is aspartic acid regulator of hemopoiesis?]. The effect of aspartic acid on myelopoiesis was examined. A method of bone marrow cultivation was used in diffusion chambers in vivo. We found that injection of 1 x 10(-4) g/kg aspartic acid to intact rats during 5 days resulted in increase of cloning efficiency of granulocyte-progenitor cells by 24 per cent and growth of cluster/colony-forming unit fibroblastic. On the basis of these data we came to the conclusion that aspartic acid acts directly on hemopoietic cells and stromal system.


[Submicroscopic features of cecal cells in experimental Escherichia infection]. Ultrastructural changes of the caecum cells were studied for the period from 15 minutes to 2 weeks after inoculation using the model of experimental escherichiosis. Evolution processes in relation to different caecum cell populations were followed up submicroscopically. Ultrastructural changes observed evidence derangement of protein and water-salt cell metabolism, immune trends of experimental escherichiosis.


[Lipid metabolism in experimental virus infections]. The effect of herpes simplex virus (HSV) and influenza virus (IV) on lipid metabolism was studied. In conditions of acute herpetic infection of rabbits we detected typical dyslipidemia, characterized by increased contents of total cholesterol, beta-cholesterol and triglycerides in the absence of trustworthy differences in concentrations of alpha-cholesterol. The use of antiherpetic preparation furavir, on the background of infection, corrected lipid spectrum of the infected animals. Blood lipid disturbances in acute influenza virus infection of mice were not detected. HSV infection of cell culture of human aorta was accompanied by increased accumulation of free lipids in cells. IV infection, in the same conditions of experiment, did not change the contents of intracellular lipids. The obtained data deepen the existing notions of herpetic and influenza infections pathogenesis and may be useful in understanding etiopathogenesis of certain somatic metabolism diseases.


[Effects of alcoholic intoxication in the antenatal period on the development of male germ cells]. During 1-20 days of pregnancy rats were given 20% alcohol orally in a dose 0.4 mg/kg bw. This led to a significant increase in the nuclear volume of germ cells in male 19-day embryos. A karyological analysis of 2-month offspring germ cell generations at stage VII of seminiferous epithelium cycle revealed a reliable decrease in the number of spermatids on step 7 of development after introduction of antenatal alcohol. The increased proportion of spermatocytes with meiotic chromosomes pathological behaviour due to alcohol was determined by the proposed quantitative analysis of meiotic divisions.


[Effect of antenatal action of Thio-Tepa on spermatogenesis of mature 101/N and CBA mice]. On pregnancy day 12 101/H and CBA mice were injected intraperitoneally 2.5 mg/kg bw thiophosphamide. 3.5-month-old male offspring were sacrificed. The drug effect on the testes was evaluated by karyologic analysis of the germ cell generations on stage 7 of the seminiferous epithelium cycle. A reliable reduction in the number of spermatogonia A, preleptotene and pachytene spermatocytes and spermatids at development stage 7 was found in 101/H mice. There were interspecific differences in spermatogenesis intensity in intact animals and recovery of germ cell pool after thiophosphamide action inducing toxicity.


[Phenylalanine hydroxylase-like antibody in human chorionic villi]. An antigen similar by electrophoretic mobility to liver phenylalanine hydroxylase (PH) and cross-reacting with monoclonal antibody PH8 against liver PH was detected in extracts of soluble proteins in 6 from 23 samples of chorionic villi. An antigen with electrophoretic mobility corresponding to 40-41 kDa was detected in extracts of membrane proteins from these 23 samples by immunoblotting with monoclonal antibody PH8. Its molecular weight was similar to that of major chymotryptic peptide of human liver PH. The content of the antigen varied with samples and was less than 20 ng/mg of the extracted protein. Two-dimensional gel electrophoresis revealed only 1 spot of the antigen. The antigen did not react with monoclonal antibodies PH7 and PH9 epitopes of which were located in N-terminal fragment of liver PH. These data suggest that the antigen of membrane fraction could be a PH protein without N-terminal domain.


[Changes in nucleotide DNA structure and adhesive properties of blood leukocytes in early period after irradiation of animals]. Postirradiation changes of adhesive properties and supercoiled nucleoid DNA structure of blood leukocytes were studied in Macaca nemestrina and in rats. The dynamics of membrane changes demonstrated a temporary increase of the leukocyte adherence 24 h after nonlethal irradiation of rats, followed by a decrease of this parameter to normal levels on h 48. After lethal irradiation of both animal species the increase in adhesive leukocytes fraction was shown already on hr 3. This higher index was observed until the end of experiments (5 days). Early (on h 3-6) temporary loosing of supercoiled DNA structure was demonstrated in the total blood leukocytes of nonlethally irradiated animals, this seems to be connected with lymphocyte changes. This process was not dependent on altered adhesive properties of leukocyte membranes. The membrane changes of leukocytes preceded decondensation of supercoiled DNA after lethal irradiation of animals. Loosing of supercoiled DNA progressively increased on hour 24 and in later postirradiation period.


[Plasmid DNA transfection in fibroblasts of athymic rats]. Nontumorigenic clone FR-7 cl 13 from fibroblasts of athymic rat was obtained from stroma of human colon carcinoma xenograft propagated on nude animals. Spontaneous transformation of this cells was absent after 40 passages in vitro and treatment with pSV2neo. But cells give rise to tumors in athymic mice after transfection with pEJ. This cell clone can be recommended as cells-targets for transfection.


[Dynamics of chemiluminescence response of Syrian hamster blood neutrophils to the growth of 10 different strains of tumor cells]. The production of H2O2 by blood neutrophils of Syrian hamsters, bearing 10 different transplanted tumors was studied at different stages of tumor growth by the luminol-dependent chemiluminescence (CL) test. It was demonstrated that during the tumors growth, two types of the blood neutrophils CL reaction can be registered. The first type of reaction represents very early and significant decrease of spontaneous CL of blood neutrophils, already evident before the appearance of palpable tumor nodules in animals, bearing in vivo selected cell strains. Subsequent subcutaneous tumor appearance in the animals was followed by increased CL of neutrophils. The second type of reaction was characteristic for in vitro transformed cells never selected in vivo. In this case the increase of CL of blood neutrophils at early stages of tumor growth was followed with the decrease of this activity at the period of active tumor growth. Possible relation of this reactions to the survival and growth of different tumor cells in vivo is discussed.


[Lesions of ventricular cardiomyocytes in experimental massive pulmonary embolism]. The damage of ventricular myocardial cells during acute experimental massive pulmonary embolism (MPE) was studied by light, polarization and electron microscopy on anaesthetized dogs. In cases, when MPE was followed by heart failure, the deep ir reversible damage of myofibrils took place, and the relative volume of myofibrils decreased in both ventricles. The damage of right ventricular myocardium, which works against increased postload during MPE, may be reason of right ventricular insufficiency.


[Morphofunctional bases of the choice of nerves for reinnervation of transplanted heart]. In two series of experiments on 61 dogs it was found that from all the nerves approaching the heart, the largest are on the ascending aorta, pulmonary trunk and pericardium transilicual tuck along which they cross the left pulmonary artery on the way to the dorsal surface of this organ. These nerves are able to provide the adequate heart activity under cardiovascular system loading. It is they that should be primarily used for transplanted heart reinnervation.


[Identification of components of the extracellular matrix in trophoblastic cell columns of human placenta]. The distribution of five components of the extracellular matrix was studied in human placenta (9-12 and 39-40 weeks of gestation) by an indirect immunofluorescence method with polyclonal monospecific antibodies. In trophoblastic cell columns fibronectin, collagen types IV and V formed homogeneous deposits, whereas collagen types I and II comprised small conglomerates and scanty, discrete granules. The origin of these macromolecules was discussed.


[Morphological changes in the central nervous system of dogs with unilateral lesions of carotid arteries]. 16 dogs were subjected to either ligation or kinking of a single carotid artery and the resultant changes in the cortical hemisphere were studied. Light and electron microscopy findings indicate reversibility of the induced pathological processes both in microcirculation and in neurons proper.


[Structural-functional state of the thyroid gland after thymectomy]. The dynamics of morphologic and biochemical indices of the thyroid gland in puberal rats has been considered. The data obtained suggest that the thymus hormones deficiency in blood circulation after thymectomy affect thyroid-stimulating functions of adenopituitary and thyroliberin production in hypothalamus that results in significant depression of thyroid function, whereas the enhancement of thyroid function to 20-month follow-up has no central genesis but is rather a result of autoimmune processes activation when thymus is removed.


Anti-tobacco measures in the world: the French case. The devastating long-term effects of tobacco smoking registered in the developed world and now imminent in the developing world must be responded to on national and international levels. In France, governmental tobacco control action began in 1976. Despite the high rates of premature mortality among men and women, legislative controls that were introduced were not enforced. Over the past decade, overall smoking prevalence has remained stable, reflecting growth in women's rates which compensates declines in men's rates. Comprehensive tobacco control measures should include prohibiting tobacco advertising, real tobacco retail price increases and regulations protecting non-smokers in public places. New legislation was voted in 1991 both in France and in the European Community. These measures, reinforced by a framework of continuing public education, may be an important step towards effective health promotion.


Humoral response to Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. The effect of the human immunodeficiency virus (HIV) on mycobacterial antibody production was investigated. Using an enzyme-linked immunosorbent assay (ELISA) for detecting IgG against Mycobacterium tuberculosis PPD, it was observed that individuals at risk of HIV infection show a pattern of humoral response to the tubercle bacillus similar to that previously found in the immunocompetent population not exposed to risk factors: 6 of 12 (50.0%) tuberculosis cases had elevated levels of antibodies to PPD and 27 of 30 (90.0%) asymptomatic individuals had antibody levels within the normal range. In an HIV-seropositive group without AIDS indicator diseases, 8 of 22 (36.4%) tuberculous patients had detectable mycobacterial antibodies whereas 156 of 164 (95.1%) non-tuberculous subjects did not. Among AIDS cases, only 1 of 20 (5.0%) patients with tuberculosis and none of 53 non-tuberculous subjects showed a positive result. The study evidenced an increasing humoral unresponsiveness to PPD in the progression of HIV infection to AIDS. Thus, a serodiagnostic method for detecting tuberculosis such as the ELISA here employed noticeably decreases its utility in the latency stage of the HIV infection, and it is practically useless in clinical AIDS.


In vitro, in vivo, and intracellular chemotherapeutic activity of B746, a clofazimine analogue against Mycobacterium avium complex. B746, an analogue of clofazimine, was compared with the parent compound for its activity against Mycobacterium avium complex (MAC), using several methods. All the studies using simulated in vivo conditions, and those with macrophages from healthy mice or from those treated with these drugs, revealed B746 to be similar to clofazimine. When used alone against experimental MAC infections in beige mice, B746 required an optimal dose of 20 mg/kg. At that dose it proved to be inferior to clofazimine, given at the same dose, but was slightly superior to streptomycin given intramuscularly at 150 mg/kg. On the other hand, in combination with other drugs, it proved to be inferior when given along with either clofazimine or streptomycin. Addition of B746 did not improve the chemotherapeutic efficacy of streptomycin-clofazimine combination in the treatment of established MAC infections of beige mice.


HIV-related tuberculosis in England and Wales. Numbers of tuberculosis notifications in England and Wales increased by 8% from 1987 to 1989. An analysis of notifications by age and sex has been undertaken to determine whether this increase has been due to an increase in young male adults, as has occurred in the USA, implying that HIV is largely responsible for the increase in notifications. Though notifications increased by 9.5% in younger males between 1987 and 1989 they also increased by over 10% amongst most age groups of females, and elderly males. These findings would suggest that there are a number of factors causing a rise in tuberculosis notifications, and that HIV is not yet directly implicated in England and Wales.


Cohort study of HIV-positive and HIV-negative tuberculosis, Nairobi, Kenya: comparison of bacteriological results. We have set up a cohort of human immunodeficiency virus (HIV) positive and negative patients with tuberculosis in order to address the problems associated with HIV-related tuberculosis. We present here the results of sputum smear microscopy, culture, mycobacterial identification tests and drug susceptibility assays from specimens taken at presentation. In this selected population of largely pulmonary tuberculosis cases, HIV infection is not associated with significant differences in sputum smear positivity rate, culture positivity rate or initial drug resistance. No atypical mycobacteria were found. Direct sputum smear examination remains specific for the diagnosis of tuberculosis in Kenya in spite of the presence of HIV. HIV infection was not associated with an increase in the proportion of pulmonary cases still culture-positive at 6 months. However a significant increase in the proportion of cases still culture-positive at 6 months was seen in those with initially resistant strains and also in those treated with standard regimen (streptomycin, thiacetazone and isoniazid for 1 month followed by thiacetazone and isoniazid for 11 months, 1STH/11TH) rather than a short-course, rifampicin-containing regimen (rifampicin, pyrazinamide and isoniazid for 2 months, together with streptomycin for the first month and followed by 6 months of thiacetazone and isoniazid, SHRZ/6TH).


Heaf status 12 years after infant BCG immunization. Uncertainty exists over the long-term influence of Heaf status and immunity of infant BCG immunization. BCG is offered to all Leeds Asian infants with uptake estimated at 86%. We have examined the effect of this immunization policy on the Heaf status of all 12- to 13-year-old children tested in the city in 1988. 6363 children (431 Asians) were eligible for Heaf testing of whom 5379 (366 Asians) were tested. 90 (25%) Asians and 4596 (92%) non-Asians had a Heaf grade 0-1 with no definite previous BCG and were, using current UK Department of Health recommendations, eligible for BCG immunization. With an annual incidence of tuberculosis in Asian children in Leeds of only 6 per 100,000 it is probable that most of the 75% of Asian children who did not require immunization had persisting immunity from their infant BCG rather than as a result of primary infection. We conclude that infant BCG immunization is effective at providing appropriate immunity, avoiding repeat BCG, in most children at age 12 years.


Tuberculous infection in a rural population of south India: 23-year trend. A survey was conducted in Bangalore district of south India between February 1984 and January 1986 to study the tuberculosis infection rate. The data from this survey, along with the information derived from the earlier ones in the same area conducted between 1961-1968, have been used in the report to study the trend of tuberculosis. Tuberculin test results in 0- to 14-year-old unvaccinated children from each survey were distributed, and based on the antimode, infected persons were identified. The standardized prevalence rates in population from the surveys were converted into risk rates by using the TSRU methodology and compared. The average annual risk of infection of 1.1% observed in 1961 declined to 0.61% in 1985, representing a decline of approximately 37% in nearly 23 years. This amounted to an average decline of 3.2% per annum over the period. The trend probably represented a natural dynamics. Whether organized intervention played some role could not be commented upon. Similar studies in other parts of the country are recommended in order to have information on the trend in the country as a whole.


Drug resistance of Mycobacterium tuberculosis in Korea. Drug resistance of Mycobacterium tuberculosis has been investigated with isolates from patients screened from a sample population of the nationwide tuberculosis prevalence surveys or from routine cultures. The results showed a close inverse relationship between the prevalence of drug resistance and the efficiency of the past or current National Tuberculosis Control Program (NTP) treatment regimens. Individual drug resistance also showed a close relationship with the extent of use of the relevant drugs. Drug resistance was found in 38.0% of M. tuberculosis isolates from patients in the 1965 survey and remained unchanged until it increased to 48.0% in 1980. The resistance prevalence, however, dropped to 25.3% in the 1990 survey. Such a decrease coincided fairly well with a continuous increase of the treatment efficiency (from 60% in 1984 to 77% in 1989) in the 1980s. Initial drug resistance (IR) also showed a similar trend, namely 26.2% in 1965, 23.9% in 1970, 20.1% in 1975, 30.6% in 1980, 17.4% in 1985 and 15.0% in 1990. A higher prevalence of IR was observed among urban patients than rural patients and among young as opposed to old patients.


Analysis of case-finding process of tuberculosis in Korea. A total of 630 pulmonary tuberculosis patients newly registered with the health centres in the Republic of Korea were interviewed to determine their process of case-finding. One-quarter of the cases had a previous history of tuberculosis. About 70% of these retreatment cases had been treated for less than 1 year, indicating the importance of more thorough follow-through during treatment. Almost all of the cases had at least one standard symptom, with fatigue being most frequent, followed by cough and sputum. On developing the illness, about 40% of the cases were motivated to seek medical help after seeking advice from people other than family members such as friends or health workers. Half of the patients first went to the health centre, and one-third to a private clinic. The average time between the onset of symptoms and the initial medical consultation was 1.8 months (patient's delay). This delay is longer in the rural areas; besides location no other patient characteristics had any correlation with patient's delay. Nearly 80% of all cases were diagnosed as tuberculous within the first 2 weeks. Health centres diagnosed cases faster than private clinics and thus had a shorter doctor's delay. Mean total delay (patient's delay plus doctor's delay) was 2 months, with 80% of this being patient's delay.


Liver transplantation: an unheralded probable risk for tuberculosis. We present a patient who underwent orthotopic liver transplantation and died of previously undiagnosed pulmonary tuberculosis (TB). TB is known to complicate liver transplantation in rare circumstances. Liver transplantation is an unheralded risk factor for development of TB because of possible activation of latent infection or primary TB in immunosuppressed hosts. A tuberculin skin test should always be performed preoperatively. Preventive treatment with isoniazid is indicated when immunosuppressive therapy is started in patients with high TB risk. Radiographic signs of previous granulomatous disease may be important when tuberculin skin test is negative, unknown or anergy is present. TB is preventable--with a high degree of suspicion where TB is endemic and proactive programs, most TB cases in transplant recipients can be avoided.


Tuberculous pyomyositis in a renal transplant recipient. Infections are a major cause of morbidity and mortality in renal transplant recipients. Although these patients are susceptible to many types of infection, soft tissue infections are rare. We report a case of tuberculous pyomyositis involving the left erector spinae muscle but with no other manifestations of tuberculosis. The diagnosis was suspected from the CT scan appearance and confirmed by microscopy and culture of the pus. Surgical incision and drainage, together with antituberculosis therapy, cured the infection. The relevant literature is briefly reviewed.


[Factors associated with levels of physical activity at work and during leisure time]. Factors associated with levels of physical activity at work and during leisure time were analyzed among 577 subjects who had been selected as population controls for a case-control study by random selection from telephone directories. The intensity of physical activity at work was inversely associated with body mass index, the proportion of professionals & managers, consumption of western style breakfast, coffee, butter/margarine, and whisky; and positively associated with rice intake. Frequency of physical activities during leisure time was positively associated with consumption of vegetables, fruits, mushrooms, milk, cheese and coffee, and moderation in eating; and inversely associated with rice intake and the prevalence of gastrointestinal symptoms and medication. The association of physical activity with these factors should be considered in studying its relationship to disease risk.


[Lifestyle differentials by occupational group]. Mortality and morbidity differ by occupational group. To clarify factors which account for these variations, lifestyle and other health habits were analyzed according to a subject's main occupation for 12,130 men and 12,759 women. Intake of Western-style foods and fruits and vegetables increased and those of Japanese-style foods and instant foods decreased in the following occupational order; (1) professionals & managers, (2) clerical, (3) sales, (4) service & transportation and (5) agricultural, forestry, fisheries, mining & production process workers. The prevalence of cigarette smoking by subjects themselves and by their parents were higher in service workers than in the other workers for both men and women. Clerical workers, professionals and managers participated more frequently in stomach cancer screening tests than the other workers, and women in these occupational groups had higher prevalences of early menarche and late first childbirth. These differences in characteristics of occupational groups may contribute to the inequalities in health.


[Health problems treated by primary care physician]. For the purpose of clarifying functions expected of primary care physicians (PC physicians) in Japan, a study of the types and frequencies of health problems seen in primary care clinics located in three areas, together with consultation/referral rates of the patients to other institutes. The study was conducted using ICHPPC-2 (Japan version) which had been compiled by WONCA as a classification of diseases. In order to obtain much more generalized characteristics of the primary care, clinics located in the city, suburban district and remote places in the mountains were studied. The results were as follows: 1) The health problems treated by the clinics in each of the three areas were respectively: 162 types/7,207 items/4 months: 303 types/17,519 items/2 years: and 280 types/61,916 items/2 years. 2) The consultation/referral rates were under 2%. 3) PC physicians treated over 98% of the health problems encountered. This was found by the investigation, which had been intended to disclose a range of so-called COMMON DISEASES treated by PC physicians themselves, based on a relation between the referral rates and the types of health problems. The above findings suggested that the COMMON DISEASES should include at least 95% of the health problems which had been treated by the PC physicians. This corresponded to approximately 100 types of diseases.


[Suicide deaths among psychiatric patients--a study based on vital statistics]. Utilizing data from the Vital Statistics in 1987 of the Ministry of Health and Welfare, a study was performed to estimate suicide mortality rates among psychiatric in and out-patients. Mental disorder was recorded as being present on 1,755 certifications of suicide deaths (984 men and 771 women). Suicide rate per 100,000 person-years in psychiatric in-patients was 167.3 for males, 116.0 for females. Compared with the general population, this represented an age-standardized mortality ratio (SMR) of 4.5 for males and 5.3 for females. For out-patients the suicide rate was 135.7 for males and 103.7 for females, and the SMR was 4.6 and 5.9 respectively. Considering that the possibility of omission of mental disorders in a death certificate is greater for an out-patient than that for an in-patient, it is concluded that the suicide rate of psychiatric out-patients is greater than that of in-patients.


[Practical use of mortality statistics and mass examination results by health workers in the local authority of the community]. In Kochi prefecture, the prefectural health service bureau tabulates both mortality statistics and mass examination results for each community and the tabulated report is sent annually to public health services staff in each local authority. While recognizing its limitations, methods of how to use the annual report are demonstrated. For example comparison of the mortality statistics and the mass examination results of the male population of A town, which is administered by Susaki Health Center, to that of the combined male population of all the towns administered by the health center shows that although the mortality rate for cerebrovascular disease for the A town-male population had been much higher than that of the combined male population in the early 1980's, the difference disappeared in the late 1980's. On the other hand, prevalence of systolic hypertension in the A town-male population continued to be higher than that for the combined male population in the late 1980's. Therefore hypertension prevention programs appears to still have significance in the A town-male population. Certain weaknesses exist in this annual report. In the comparison of mass examination results among different populations, the presence of selection bias of those receiving examinations should be considered. Standardization of mass examination procedures and quality controls of the examinations should also be considered. To get health workers to utilize the annual report further, the reported items should be improved. Particularly useful would be tabulation by residential subdivision and occupation.


[A study on personal information system using movable media for effective welfare services]. A data system which enables utilization of individual patient data by public health nurses, physicians and home helpers, is required both for the continuous and comprehensive monitoring of the various needs of the aged receiving care services at home in the local district and for facilitating welfare services. Therefore, an experimental and comprehensive system for public health, medical services and welfare was put into practice for district public health services for the aging society. The results of this trial system shows that this system is useful indeed for the welfare services, though it also has several problems.


Evaluation of acidic heteropolysaccharide structures in Rhizobium leguminosarum biovars altered in nodulation genes and host range. 1H-NMR spectroscopy showed that the extracellular heterpolysaccharides (EPS) from derivatives of Rhizobium leguminosarum bv. trifolii ANU843 altered in pSym nod composition or function (transposon insertions, deletion of pSym, induction by flavone, and introduction of cloned pSym nod regions from ANU843 and R. l. bv. viciae 248 on recombinant plasmids into the pSym-cured background of ANU843) differed only in 3-hydroxybutyrate stoichiometry per octaglycosyl unit. This change in EPS was likely to be an indirect effect of altered growth during expression of pSym nod genes in the presence of the flavone. No modifications were found in EPS made by R. l. bv. phaseoli 8002 when its resident pSym was deleted or replaced with pSym from R. l. bv. viciae 248, or with a derivative of this pSym lacking the host-specific nodulation genes nodFELMNTO. Thus, although certain O-acyl noncarbohydrate substitutions in EPS are affected by pSym nod genes (including the ones that determine host range) in certain backgrounds of R. leguminosarum, this change does not occur universally among all strains of R. leguminosarum. We conclude that the structure of the acidic EPS does not control host-specific nodulation of white clover, hairy vetch, and beans for the strains of R. leguminosarum tested here.


Current treatment of obesity: a behavioral medicine perspective. Obesity is a complex biopsychosocial phenomenon. It has a profound effect on patients' physical and psychological health. Due to the complexity of the problem and the recidivism following treatment, it is recommended that obese patients receive in-depth interdisciplinary evaluation to match them appropriately to comprehensive treatment. Participation in an interdisciplinary comprehensive active weight loss treatment program followed by participation in a professionally led biweekly behavioral maintenance program that included social influence and aerobic exercise has generated maintenance of 83% of initial weight loss at an 18-month follow up. This comprehensive multi-disciplinary treatment approach, best offered in a behavioral medicine center setting, represents state-of-the-art treatment at this time and can result in long-term medical and psychological benefits for the obese patient.


A new multigene family inducible by tobacco mosaic virus or salicylic acid in tobacco. A previously undescribed cDNA family was isolated from tobacco challenged with tobacco mosaic virus (TMV). A cDNA library was constructed with mRNA from upper leaves of Xanthi nc tobacco plants that had been inoculated with TMV on the lower leaves 11 days previously. The library was screened differentially with radiolabeled cDNA synthesized with mRNA from upper, uninoculated leaves of either TMV-inoculated or mock-inoculated tobacco plants. The new cDNA family, designated SAR8.2, had at least five expressed members, one or more of which were inducible by TMV inoculation and by salicylic acid treatment. The cDNAs encoded small, highly basic proteins containing N-terminal hydrophobic signal peptides and highly conserved cysteine-rich C-terminal domains. One of the SAR8.2 family members contained a direct repeat of the C-terminal domain in tandem. Hybridization of SAR8.2 cDNA to tobacco genomic DNAs indicated a gene family of 10-12 members.


Sequence and expression of a wheat gene that encodes a novel protein associated with pathogen defense. Wheat (Triticum aestivum) exhibits local acquired resistance to the powdery mildew pathogen Erysiphe graminis f. sp. tritici. The resistant state can be induced by a preinoculation with the nonhost pathogen E. g.f. sp. hordei, the barley powdery mildew, and is accompanied by the activation of putative defense genes. Here, we report the sequence of a pathogen-induced gene, WIR1a, and a corresponding cDNA, WIR1, that encode novel defense-related proteins of 88 and 85 amino acids, respectively. Analysis of the primary structure of these proteins predicts them to be integral membrane proteins with extracytoplasmic C-terminal domains rich in proline and glycine, through which the proteins possibly interact with the cell wall.


Expression of a modified Dutch elm disease toxin in Escherichia coli. The fungal toxin associated with Dutch elm disease, cerato-ulmin, has been produced in the bacterium Escherichia coli by the assembly of oligonucleotides according to the unpublished amino acid sequence of the toxin. This toxin was produced at approximately 80 micrograms/L of cell culture as a fusion to glutathione S-transferase. We synthesized the toxin as a fusion protein to improve purification and stability. Recombinant cerato-ulmin was analyzed by immunoblot analysis and then separated from its fusion partner by thrombin. We incorporated this molecule into an appropriate medium to test the activity of the toxin on the growth of American elm callus cultures.


Broad-spectrum photoprotection: the roles of tinted auto windows, sunscreens and browning agents in the diagnosis and treatment of photosensitivity. Since window glass absorbs sunlight below 320 nm, it provides a means of assessing sensitivity to longer wavelengths, i.e. UVA and visible radiation. Positive responses to the query of whether symptoms develop in the auto with the windows up must now be interpreted with regard to the possible presence of tinted plastic film on side and rear windows. These films block nearly all UVA radiation, as does the plastic interleaf of windshields. Thus, occupants of an auto equipped with plastic film receive photoprotection from UVB radiation and well into the UVA region. We define three classes of topical sunscreens: (1) conventional UVB screens, (2) broad-spectrum preparations containing a UVB screen and a UVA absorber and (3) browning agents such as dihydroxyacetone (DHA) that produce a skin coloration that absorbs in the low end of the visible region, with overlap into long-wavelength UVA. By considering responses of photosensitive persons in autos with tinted or untinted windows, coupled with efficacy of appropriate sunscreens, we produced an algorithm defining three photosensitivity subsets. Persons sensitive to long-wavelength UVA and/or visible radiation will benefit from tinted auto windows. In particular, patients with lupus erythematosus (LE) have actively promoted legislation allowing tinted windows. Support for their position is documented by recent reports of induction of lesions in LE patients by exposure to UVA and visible radiation. The brown color produced by DHA is a useful adjunct to the screening action of broad-spectrum sunscreens. Development of a durable color overnight allows application of the DHA preparation in the evening, thus eliminating possible interference with sunscreen use during the day.


Clinical controversy on the effect of topical ciclosporin: what is the target site? In recent years attempts have been made to treat T-cell-mediated skin diseases with topical therapeutics. Based on clinical data on the local treatment of recalcitrant erosive lichen planus (LP) with ciclosporin (CS) we discuss in vitro and in vivo studies on percutaneous absorption of CS, drug localization and drug metabolism in the skin as well as clinical data. Clinically relevant immunosuppressive activity depends not only on drug distribution in the target organ skin. The inhibition of T cell response is also dependent upon T cell subsets involved and the activation stage of the T cell. There are different proportions in T cell subpopulations during different evolutional stages of LP. Thus responsiveness to therapy with this drug may depend on the disease activity. Furthermore lymphocyte migration throughout various organs in the body including skin depend on a variety of molecular and cellular interactions. Whether local CS is sufficient to inhibit these interactions or to inactivate already activated T cells remains unclear. Assuming that the T lymphocyte is the target site for CS, local therapy reaches only a small fraction of the T cell population. This may be insufficient, and a systemic inhibition of helper/inducer T lymphocyte function is needed for successful therapy. With CS and with other drugs it seems that percutaneous absorption is not the only key to variable clinical responses to topical therapy.


Generation of terminal complement complexes in psoriatic lesional skin. The complement system is thought to play an important role in the recruitment of neutrophils within the epidermis. In the present study we examined whether or not complement activation in psoriatic lesional skin results in the deposition of terminal complement complexes within the epidermis by measuring levels of SC5b-9 in the plasma and horny tissues of psoriatic patients. The levels of SC5b-9 in psoriatic plasma were significantly higher than those of controls or those of patients with atopic dermatitis. However, when the levels of SC5b-9 in the psoriatic plasma were compared before and after successful treatment of psoriasis, a significant reduction was observed after treatment. Studies of total protein extracts from lesional skin showed that, while no SC5b-9 was detected in the noninflammatory horny tissues, there were high levels of SC5b-9 in lesional horny tissues of psoriasis. By immunofluorescence using a monoclonal antibody to the C5b-9 neoantigen, deposition of C5b-9 was observed only in the stratum corneum of psoriatic skin. Thus the results of the present study suggests that in psoriatic lesional skin, the complement system is activated and that this complement activation proceeds all the way to the terminal step, generating membrane attack complex.


Light exposure of the lower leg as a pathogenetic factor in the occurrence of malignant melanoma. Of the 1,198 women and men studied in Mainz from 1966 to 1987 there was an approximately fivefold increase in the incidence of melanoma. Among the men melanomas on the trunk (59.9%) predominated, whereas among the women melanomas on the extremities (40.0%) were more common, especially on the lower leg (26.3%). Comparing the decades 1966-1976 and 1977-1987 there was a significant decrease in melanomas affecting women's lower legs (1966-1976: 33%,; 1977-1987: 24.2%). Fashion-dependent sun exposure of this body area might offer an explanation. It could be demonstrated that common stocking materials do not sufficiently protect against UV radiation (average permeability for UV light about 55%), therefore an intense sun exposure of the lower leg in the fifties and sixties (nylon stockings and knee-long skirts) and a less intense sun exposure in the seventies (skirts of all lengths and trousers) can be assumed. The difference in the incidence of women's melanomas on the lower leg in our two subgroups correlates indeed with the fashion-dependent insolation 10-20 years before tumour diagnosis.


Lack of effect after local treatment with a new ciclosporin formulation in recalcitrant erosive oral lichen planus. We treated 7 patients with recalcitrant enoral lichen planus (Lp) with a new hydrophilic ciclosporin (CS) formulation during 8 weeks. The preparation with proven in vivo percutaneous absorption was designed for topical use and contained 100 mg CS/g formulation. The patients applied a cumulative daily dose of about 126 mg CS. We did not see the previously reported clinically impressive response with our CS formulation. No CS was detected in the blood of our patients. We conclude that percutaneous absorption of CS is not the key event to the clinical responses. Clinical benefit after CS in enoral Lp seems rather to the clinical responses. Clinical benefit after CS in enoral Lp seems rather to be related to a systemic effect of the drug.


Renal impairment probably induced by etretinate. A 83-year-old patient had been treated for pityriasis rubra pilaris with 70 mg etretinate daily. He developed acute renal impairment, with creatinine levels reaching 73 mg/l on day 7. After discontinuation of etretinate, all biological changes were reversible. Although renal impairment is not considered as retinoid side effect, the chronology of renal changes is very suggestive of etretinate responsibility.


Apudoma and subcorneal pustular dermatosis (Sneddon-Wilkinson disease). The subcorneal pustular dermatosis (SPD) is a rare dermatosis. IgA monoclonal gammapathy is the most frequently associated disease with the SPD. We report a case of SPD in a patient with metastatic apudoma, an association not previously described. The rare nature of both diseases suggests that this association is not fortuitous.


Eosinophilic pustular folliculitis starting initially only with palmoplantar pustular lesions. Report of a case and review of the literature. We report a 23-year-old Japanese male with eosinophilic pustular folliculitis (EPF) that had started with palmoplantar rash. Only when follicular pustules appeared on the bilateral cheek 31 months later, we revised our initial diagnosis of pustulosis palmaris et plantaris (PPP) to EPF, and all the skin eruptions cleared mostly with indomethacin. A review of the Japanese literature for the past 20 years disclosed that in 207 cases of EPF so far reported, palmoplantar pustular lesion was noted in 38 (18%). Among them, in 16 cases (8%) the skin lesions started first from the palmoplantar region with the average period of 26 months until the appearance of other eruptions of EPF. None of them was diagnosed as EPF when skin lesions were localized only to the palmoplantar region. When we find pustules on the palmoplantar region, we should suspect the possibility of early lesions of EPF as well as PPP. Histopathologic demonstration of multilocular pustules located in the upper epidermis containing numerous eosinophils in the palmoplantar pustular lesions, together with the dramatic therapeutic response to indomethacin greatly favor the diagnosis of EPF.


Acute follicular graft-versus-host disease. We documented by clinical, histopathologic and immunohistochemical analysis a case of acute follicular graft-versus-host disease (GVHD), in which an erythematous-to-violaceous follicular papular eruption constituted the major clinical pattern of cutaneous involvement. Although acute follicular GVHD is rare, it is important to recognize it as an early skin manifestation of acute cutaneous GVHD allowing prompt therapy.


Atrichia and papular lesions: report of a case. We report a case of atrichia with papular lesions in a 4-year-old girl. The scalp was completely hairless since birth, except for dark, shiny, coarse hair on the frontoparietal region. Eyelashes and eyebrows were sparse. Numerous papular lesions developed on the hairless scalp, cheeks and neck during the second year of life. Teeth and sweating function were normal. The family history was negative. Histologic examination of a papular lesion showed the presence of a keratin-filled cyst in contact with the overlying epidermis. The pathology of the bald scalp showed the presence of tubular epithelial structures devoid of hair bulbs extending from the epidermis to the deep dermis and the superficial hypodermis. Sebaceous and outer root sheath differentiation was evident in most of the tubular structures that also frequently contained small ducts surrounded by two or three layers of flat epithelial cells. The superficial dermis contained horny cysts, similar to those present on the cheeks.


Dermatofibrosarcoma protuberans: ultrastructural investigation. The ultrastructural aspects of nucleus and cytoplasm of tumor cells and the interstitial material of dermatofibrosarcoma protuberans are described in detail, especially the very peculiar labyrinthic nucleus. Opinions about its development are reviewed; some, such as melanocytic, neural, histiocytic and smooth muscle proliferation, might be discarded. The myofibroblast appears as the most probable stem cell.


Sneddon's syndrome: generalized livedo reticularis and cerebrovascular disease. Importance of hemostatic screening. We report two cases of Sneddon's syndrome. Both cases had widespread livedo reticularis with repeated cerebrovascular accidents without persistent neurological deficit. In one case, hemostatic examination revealed an imbalance of plasminogen activator-inhibitor values, possibly related to the thrombogenic propensity of the syndrome. Treatment with acetylsalicylic acid led to normalization of hemostatic parameters and resulted in a symptom-free period of more than 10 months. The importance of hemostatic screening in patients with Sneddon's syndrome is discussed.


Neonatal treatment of giant naevi.

Neonatal treatment of giant naevi. A technique of curettage of giant congenital naevi in newborns was proposed by Moss in 1987. We used this technique in 6 children during the last 2 years. The long-term aesthetic results appear to be better than those observed after other methods of treatment. Light microscopy of the pigmented skin confirmed the presence of the majority of naevus cells in the upper dermis. For 3 patients, cultures of the curetted cells showed a melanocyte behaviour similar to that seen in malignant melanoma. These observations are limited to in vitro cultures and are not representative of the in vivo evolution as biopsies of the remaining naevus cells at 3 months of age did not show any malignant characteristics.


A case of Omenn-like immunodeficiency syndrome. We report the case of a child with a variant of the Omenn immunodeficiency syndrome. He presented with erythroderma, lymphadenopathy, hepatosplenomegaly, failure to thrive, and recurrent purulent infections. The immunological studies showed marked disturbances in the subpopulations and functions of T lymphocytes, which suggests a defect in T cell differentiation as the cause of the disease.


Lung cancer with skin metastases.

Lung cancer with skin metastases. Skin metastases in the fingertips were the first-presenting symptom of a still occult, giant-cell bronchial carcinoma. We report the presentation, diagnosis and clinical course.


Acitretin as cancer chemoprophylaxis in a renal transplant recipient. The use of acitretin in a renal transplant recipient who had been treated for several premalignant and malignant skin lesions is the subject of this case report. During the treatment period no new dysplastic lesions developed.


Transient acanthosis-nigricans-like dermatosis in re-epithelializing lesions of pemphigus foliaceus. A patient is described who developed hyperkeratotic, hyperpigmented plaques, similar to acanthosis nigricans in re-epithelializing erosions of pemphigus foliaceus. The lesions regressed completely after a few months. This phenomenon can be attributed to a Köbner phenomenon after epidermal damage or can be a result of systemic corticosteroid therapy.


Intraepidermal neutrophilic IgA dermatosis: pemphigus-like IgA deposits. A case of intraepidermal neutrophilic IgA dermatosis with intercellular IgA deposit in the upper epidermis is reported. Indirect immunofluorescence was negative but immunoelectrophoresis showed a slight increase of IgA. The chemotactic activity of neutrophils was normal. Colchicine controlled the lesions.


Oral cyclosporin and alopecia areata.

Oral cyclosporin and alopecia areata. A 30-year-old woman with severe alopecia areata of the scalp was treated with oral cyclosporin for 3 months. Clinical, histological and immunohistochemical assessments failed to reveal any improvement.


Genital squamous-cell carcinoma after PUVA therapy. Among our patients treated with very high doses of PUVA (more than 1,500 J/cm2) for recalcitrant disseminated psoriasis, three developed squamous-cell carcinoma of the genitalia. The tumors were located on the scrotum in all patients; one of them displayed three times running a carcinoma of the dorsal aspect of the penis. All these genital tumors arose more than 2 years after PUVA cessation, in patients with previous arsenic and tar treatment.


Erosive adenomatosis of the nipple.

Erosive adenomatosis of the nipple. Two cases and histological observations of erosive adenomatosis of the nipple are presented in detail, and the literature on the subject is reviewed. Erosive adenomatosis is a rare but clearly delineated pathology of the nipple and seems to be essentially benign. Careful clinical and histological examinations with complete investigation of the breast are required for the diagnosis. Nonmutilating curative surgery can be performed.


Thallium-201 myocardial imaging in patients with coronary artery disease: comparison of intravenous adenosine and oral dipyridamole. To compare thallium-201 (201Tl) myocardial perfusion imaging following intravenous adenosine and oral dipyridamole. Open-label, randomized, comparison. Outpatient, university-affiliated clinic. Fifteen patients with angiographically documented coronary artery disease. Planar 201Tl myocardial perfusion imaging following both intravenous adenosine 140 micrograms/kg/min for six minutes and oral dipyridamole suspension 300 mg. A comparison between adenosine and dipyridamole was made in the following areas: concordance in interpretation of 201Tl scintigrams, cardiac and noncardiac 201Tl uptake and clearance, hemodynamic and electrocardiographic changes, and adverse effects. The scintigraphic studies showed perfusion defects in 13 patients (87 percent) after dipyridamole and in 15 patients (100 percent) after adenosine. 201Tl uptake and clearance were quantitated in nine myocardial segments and in four extracardiac segments in each patient. 201Tl uptake was not significantly different between adenosine and dipyridamole studies in most cardiac regions. Extracardiac 201Tl uptake was significantly less in the liver and splanchnic regions following adenosine compared with dipyridamole. 201Tl clearance was not significantly different following adenosine and dipyridamole except in the anterolateral region in the anterior view. Hemodynamic changes following administration of intravenous adenosine and oral dipyridamole were not significantly different. Adverse effects were more common with adenosine than with dipyridamole. Adverse effects with adenosine were transient; however, adverse effects with dipyridamole were prolonged and required reversal with aminophylline in 2 patients. No patients required termination of the adenosine infusion or administration of aminophylline. These preliminary data suggest that adenosine 201Tl imaging may be a useful alternative to dipyridamole 201Tl imaging. Although adenosine produces more frequent adverse effects, they are generally better tolerated than those associated with dipyridamole.


Mathematical examination of dual individualization principles. (III): Development of a scoring system for pneumonia staging and quantitation of response to antibiotics: results in cefmenoxime-treated patients. In order to quantitatively express the important, time-related aspects of response to antimicrobial therapy in patients with pneumonia, we required validated measures of the time course of events during the infection. To quantitate the changes in clinical status in relation to changes in cultures, we developed a scoring system to be used for patient assessment during therapy. Retrospective data collection, prospective analysis of factors. Intensive care unit, Millard Fillmore Hospital. Twenty-eight patients with nosocomial pneumonia. Clinical parameters were assessed daily for the duration of antimicrobial therapy. Using linear regression, the rate of clinical change in each patient treated was quantified. Eradication of the pathogen was determined by serial cultures of the infection site. Seventeen of the patients demonstrated eradication of the organism, and 11 demonstrated persistence of the pathogen (7 were considered colonization). The system described the patients at baseline in that the mean baseline scores were similar in both groups of patients (p = 0.79). Patients in whom the pathogen was eradicated showed a rate of clinical improvement significantly different from those who had persistence of the organism (p = 0.04). In patients demonstrating eradication, the time to eradication inversely correlated with the rate of clinical improvement (p < 0.05). Of the ten parameters descriptive of the disease, those most sensitive to change after eradication of bacteria were body temperature, bacterial Gram stain, white blood cell Gram stain, and volume of sputum. In this set of pneumonia patients, the scoring system effectively quantified both baseline and time-related changes in clinical status. The system distinguished between the clinical course of the patient with organism eradication versus organism persistence. A shorter time to eradication was associated with a better clinical response. Prospective study of the system will determine its sensitivity.


Prolonged recurrence of pentamidine-induced torsades de pointes. To report a case of recurrent pentamidine-induced torsades de pointes (TdP) and to review previously reported cases in the literature. Medical records of the subject patient, case reports, and relevant studies identified by MEDLINE. Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. A 43-year-old woman with AIDS experienced pentamidine-induced TdP. TdP and other cardiac arrhythmias recurred repeatedly for 13 days after pentamidine therapy was discontinued and in the presence of normal magnesium and potassium serum concentrations. Infusions of magnesium, lidocaine, and isoproterenol were used to treat the arrhythmias. The exact mechanism of pentamidine-induced TdP has not been clearly established. It is postulated, however, that the similarity of pentamidine's structure to procainamide may contribute to its proarrhythmic effects. The tissue-binding capacity of pentamidine may result in a prolongation of its effects. No distinctive characteristic appears to predispose people to the development of cardiac arrhythmias. Laboratory values that should be monitored include serum magnesium, potassium, and creatinine. The corrected QT interval also should be monitored. Recurrent arrhythmias may be seen for many days after intravenous administration of pentamidine has been discontinued. Clinicians should consider this phenomenon as they decide how to monitor patients who have received this drug.


Possible severe thrombocytopenia associated with a single dose of plicamycin. To report a case of possible severe thrombocytopenia associated with administration of a single dose of plicamycin. A 73-year-old man with prostate cancer was admitted to the hospital with hypercalcemia (total serum calcium concentration 4.02 mmol/L) and a low baseline platelet count (152 x 10(9)/L). Because of his symptomatic hypercalcemia, he was treated with NaCl 0.9%, furosemide, oral inorganic phosphate, and a single dose of plicamycin (15 micrograms/kg). Five days after plicamycin administration his platelet count decreased to 52 x 10(9)/L, and continued to decrease further even after the transfusion of four units of platelets to a nadir of 7 x 10(9)/L (hospital day 20). A second transfusion produced a small increase in his platelet count. The patient's clinical status continued to deteriorate, however, and he subsequently died. Plicamycin and other drugs that may induce thrombocytopenia are reviewed. The time course between plicamycin administration and the development of thrombocytopenia in our patient is assessed. Other contributing factors such as a low baseline platelet count and advanced age are also addressed. It is likely that the severe thrombocytopenia experienced by our patient was caused by a single dose of plicamycin. Adjusting the dosage for a patient's renal function as well as close monitoring of the platelet count are necessary when administering this drug. We report this case to remind clinicians of the potential for the development of severe thrombocytopenia following administration of a single dose of plicamycin.


Verapamil overdose: case report and review of the literature. To report the presentation and controversies regarding therapy of an 18-year-old man following a life-threatening ingestion of verapamil. An 18-year-old man ingested large quantities of dipyridamole, trimethoprim/sulfamethoxazole, amoxicillin, and verapamil. He presented to an outlying hospital and was initially conscious. Soon thereafter, the patient had a seizure; he required intubation, developed cardiac conduction abnormalities, and became hypotensive. The patient required pharmacologic pressors and a pacemaker for transfer to our institution. At our institution, vigorous fluid resuscitation, cardiac pacing, and careful attention to acid/base and electrolyte management provided the basis of therapy. The patient recovered without deficit and was discharged from the intensive care unit five days later. Current controversies regarding the management of verapamil overdose are reviewed. Removal of the drug by gastric lavage is a mainstay of therapy. Administration of syrup of ipecac is contraindicated. Although specific recommendations for calcium dosing in the overdose situation have not been rigorously studied, maintenance of a normal serum ionized calcium concentration is suggested. An exogenous catecholamine, rather than dopamine, may be the drug of choice for treating hypotension. Cardiopulmonary bypass provides a method for drug removal in cases of severe toxicity; however, this invasive method requires further study. Management of fluid/electrolyte, acid/base, and ventilation abnormalities is required to treat large ingestions of verapamil. Treatment guidelines for critical care clinicians are provided.


Fixed drug eruption of the scrotum due to methylphenidate. To report two cases of fixed drug eruption induced by methylphenidate. Two children with attention deficit disorder treated with methylphenidate as a simple drug developed fixed drug eruption of the scrotum. Drug discontinuation was followed by a complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration-inhibiting factor (MIF) assay with methylphenidate was positive. The pathogenesis of fixed drug eruption and the role of MIF assay in the diagnosis of adverse drug reaction is discussed. Fixed drug rash induced by methylphenidate is a possible but rare phenomenon.


Toxicity potential of oral lidocaine in a patient receiving mexiletine. To report a case of toxicity from orally administered lidocaine in a patient with cardiomyopathy receiving concurrent mexiletine therapy. Case reports, review articles, and studies identified by search of the MEDLINE database and Current Contents. All reports of toxicity from orally administered lidocaine were reviewed. Lidocaine, a local anesthetic, is widely used to treat cardiac arrhythmias. Toxicity with the parenteral form occurs frequently. In contrast, there are few reports of toxicity with oral lidocaine, most of them occurring in children receiving large doses relative to body weight. We report a case of intoxication in an adult with severe cardiomyopathy and concurrent mexiletine therapy who received only two doses of oral lidocaine. Although it is rarely reported in adults, clinicians must be alert to the possibility of toxicity from orally administered lidocaine. This is most likely to occur in patients with conditions known to reduce lidocaine clearance, when higher-than-usual doses are administered, or when concurrent therapy with oral lidocaine analogs may be present.


Taurine: an essential amino acid to prevent cholestasis in neonates? To review the evidence that taurine can prevent cholestasis in neonates. MEDLINE and EMBASE searches were conducted to identify both animal and human data regarding taurine's role in bile acid conjugation and liver disease (key terms: taurine, children less than two years old). Emphasis was placed on human data supplemented by relevant animal data. Taurine appears to more effectively conjugate bile acids than glycine, and the end-products of conjugation are more soluble. Taurine deficiency may increase glyco-conjugates of bile acids and result in cholestasis. Although the cause of neonatal cholestasis probably is multifactorial, there are data indicating that adequate taurine may prevent cholestasis in neonates. Taurine should be considered an essential amino acid for neonates and should be included in total parenteral nutrition solutions for these patients.


Transdermal fentanyl.

Transdermal fentanyl. To review the use of transdermal fentanyl for the treatment of moderate to severe chronic pain. The article provides background on the pharmacology and pharmacokinetics of the drug, as well as the properties of the transdermal system. In addition, clinical trials, adverse effects, and therapeutic considerations and recommendations are presented. Clinical trials, review articles, and reference texts. Comparative clinical trials involving the use of transdermal fentanyl on postoperative and chronic pain patients. Data from clinical human trials published in the English language were reviewed. Trials were assessed by sample size, opioid dosage regimen, and therapeutic outcome. Transdermal fentanyl was found to be effective in the control of chronic and postoperative pain. In one trial the overall patient satisfaction with pain control was 79 percent for the transdermal fentanyl group and 44 percent for the placebo group. In another trial, the amount of additional parenteral morphine was significantly lower for the group receiving transdermal fentanyl than for the placebo group (49.9 +/- 4.9 vs. 77.0 +/- 6.3 mg, respectively, p < 0.01). The most common adverse effects recorded were nausea (45-85 percent), pruritus (14-60 percent), and sedation (40-59 percent). The cost of analgesic therapy with this delivery system is higher than that of parenteral opioid analgesia, but less than patient-controlled analgesia. The transdermal fentanyl formulation offers some minor advantages over other forms of conventional pain management. Results of early clinical trials are promising, but more studies are needed to evaluate its long-term effectiveness and adverse effects. Specifically, comparisons with standard parenteral and patient-controlled opioid analgesia in chronic malignant and nonmalignant pain are necessary for adequate evaluation of transdermal fentanyl.


Continuous ambulatory peritoneal dialysis: a review of its mechanics, advantages, complications, and areas of controversy. The primary objective of this article is to review the mechanics, advantages, complications, pharmacokinetics, and future trends of continuous ambulatory peritoneal dialysis (CAPD) as they pertain to pharmacotherapy. Pertinent articles were obtained from an English-language literature search using MEDLINE (1980-1991), Index Medicus (1987-1990), and bibliographic reviews of review articles. Indexing terms included peritoneal dialysis, pharmacokinetics, peritonitis, vancomycin, and fluoroquinolones. All clinical studies comparing organism recovery methods and treatment of peritonitis have methodologic limitations (e.g., comparison of disparate patient groups, different definitions of peritonitis, lack of follow-up, lack of control for sterile cultures) that may affect the reported results. CAPD is an alternative to hemodialysis for the treatment of endstage renal disease and has many complications, leading to significant morbidity. This indicates that CAPD is not appropriate for all patients. Using blood-culturing techniques to culture for dialysate is most productive, but also the most costly. There are few data to indicate exactly the drugs, doses, and durations of choice for peritonitis. Both intraperitoneal and oral administration appear to be appropriate.


Contribution of the human kidney to the metabolic clearance of drugs. To demonstrate that the human kidney is capable not only of filtering and secreting drugs and their metabolites, but also of carrying out conjugation reactions such as acyl glucuronidation, N-glucuronidation, and glycination. Plasma concentrations and renal excretion rates of drugs are measured and renal clearance is calculated in a series of selected pharmacokinetic studies in healthy human volunteers (some studies were conducted in the authors' laboratory and others were reported in the literature). BACKGROUND THEORY: It is generally agreed that the liver plays the dominant role in drug metabolism, and that the function of the kidneys is limited to excretion of parent drug and metabolites. This can be easily understood when a metabolite is present in both plasma and urine. When the metabolite is present in urine but is not measurable in plasma, then the possibility exists that the metabolite is formed by the kidneys. "Simple" excretion by the kidneys is demonstrated for sulfatroxazole/sulfamethoxazole. Ether glucuronides of codeine are formed in the liver, and the resulting glucuronide is excreted by the kidneys. Possible formation of N1- and N2-glucuronides by the kidneys is demonstrated for sulfadimethoxine, sulfametomidine, and sulfaphenazole. Acyl glucuronidation of probenecid and nalidixic acid is carried out by the kidneys. The acyl glucuronidation of probenecid shows a capacity-limited formation/excretion rate of 46 mg/h, which is subject dependent. During this process, the acyl glucuronidation of co-administered nalidixic acid is reduced from 53 to 16 percent compared with that of nalidixic acid alone. Probenecid and its acyl glucuronidation do not inhibit the ether glucuronidation of codeine in the liver, but only interfere with the active tubular secretion process. The acyl glucuronidation of the nonsteroidal antiinflammatory drug naproxen and its metabolite, O-desmethylnaproxen, may be carried out by the liver and kidneys. Glycination of benzoic acid and salicylic acid is carried out in both the liver and kidneys. It is difficult to recognize renal drug metabolism in the intact human body (in vivo); the glucuronides or conjugates must be measured via direct HPLC analysis. In cases where the metabolite is present in high concentrations in urine but not in blood, there may be an indication that the kidneys are responsible for the formation of the metabolite. Impaired kidney function not only affects renal excretion but may also affect renal metabolism.


Haemophilus influenzae type B conjugate vaccines. To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines. Pertinent literature was identified via a MEDLINE search. Additionally, references cited in published articles were used as data sources. Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed. Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years. The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age. The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine. They stimulate an immune response that is distinctly different from that elicited by the original vaccine. Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease. The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae.


Intravenous-to-oral stepdown program: four years of experience in a large teaching hospital. To assess the impact of an intravenous-to-oral (iv-po) stepdown program on the relative use of oral and parenteral dosage forms of select antimicrobials. A retrospective review of drug utilization records before and after a trial comparing metronidazole and clindamycin prescribing trends from a 12-month baseline period to a four-year follow-up period. One thousand-bed Canadian tertiary care referral teaching center. An authorized iv-po stepdown program was developed to promote the oral route of drug administration. Reminders of iv-po stepdown were produced for metronidazole and clindamycin and these notes were sent to nursing units with the parenteral dosage form. The notes then were attached to the front of the health record to serve as a reminder to prescribers that an equally effective, well-tolerated, and less-expensive oral dosage form was available for use. A 44 percent relative increase in the use of oral metronidazole and a 79 percent relative increase in the use of oral clindamycin occurred. When acquisition and delivery costs were considered, cumulative cost savings from 1988 to 1991 resulted for metronidazole ($31,920) and clindamycin ($53,880). This intervention represents a simple yet effective method of promoting a process of stepdown from parenteral to oral antibiotic therapy.


Current treatment recommendations for leishmaniasis. To review the epidemiology, clinical presentation, risk factors for transmission, and pathogenesis of leishmaniasis, as well as current treatment options for this disease. DATA SOURCES/DATA SELECTION: We reviewed unclassified medical-threat briefing material, subject-matter reviews, and case reports from the world's infectious disease literature. We concentrated on literature pertaining to the pathogenesis and management of leishmaniasis indigenous to Southwest Asia. Data from subject reviews published in the English language were evaluated. Case reports and clinical trials provided supplemental data on evolving theories and management options. The clinical presentation of leishmaniasis is highly variable. Management relies heavily upon the use of parenteral antimonial drugs. Although these agents are effective in most cases, toxicity and the emergence of resistance limit the usefulness of standard therapies. Alternative treatment modalities include heat, surgical curettage, ketoconazole, metronidazole, pentamidine, rifampin, amphotericin B, aminoglycosides, allopurinol, and immunotherapy. Although the number of reported cases of leishmaniasis in the US has generally been low, there is a possibility that more cases may be reported in the future because of the large number of military personnel returning to this country from endemic areas. Medical personnel, particularly those working in governmental institutions, should be familiar with the pathogenesis of this unusual infection as well as potential treatment options.


Lipoprotein(a) levels in the nephrotic syndrome. We investigated serum lipoprotein(a) [Lp(a)] levels in 20 patients with the nephrotic syndrome. Lp(a) levels in the nephrotic syndrome patients were significantly higher than those in a control group (30.4 +/- 22.5 vs 10.4 +/- 17.7 mg/dl). Overall, the serum Lp(a) and lipid levels showed no relationship, but on an individual basis the serum Lp(a) level varied with the serum levels of total cholesterol and low density lipoprotein cholesterol in the nephrotic syndrome patients. Our findings suggest that a decrease in serum albumin led to increased hepatic Lp(a) synthesis. It is well known that thrombotic disease supervenes on hypercoagulability in the nephrotic syndrome, so the determination of Lp(a) levels in these patients may provide information which is useful for preventing thrombotic complications.


Clinical application of the polymerase chain reaction for a rapid diagnosis of Mycobacterium tuberculosis infection. A gene amplification method of Mycobacterium tuberculosis DNA by the polymerase chain reaction (PCR) has been devised. A primer pair used in this study is 5'GTTGCCGTGGCGG TATCGG3' and 5'GCGACATTACGGGGCAGGTGG3', which brackets a 152-base region encoding the 65KD antigen, and a specific probe is 5'TTTGGGGTCATCTTTGGAGCG3'. The procedure could be completed within 2 days. The specificity and the sensitivity of the PCR for M. tuberculosis complex in identifying M. tuberculosis complex did not conflict with the conventional methods at all. Using this method, we could diagnose three cases of the disease, which had been very difficult to diagnose by the conventional methods, by detecting the DNA from the blood, liver biopsy specimen, lung aspirate, and pleural effusion.


Amyotrophic lateral sclerosis associated with the syndrome of inappropriate secretion of antidiuretic hormone. A 71-year-old female with amyotrophic lateral sclerosis (ALS) developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during respiratory failure due to atrophy of the respiratory muscles. Serum sodium concentration fell to 116 mEq/l and then returned to the normal range after water restriction and respiratory care. This is considered to be the first case report of ALS associated with SIADH.


Polysplenia syndrome with various visceral anomalies in an adult: embryological and clinical considerations. A 26-year-old female with polysplenia syndrome is reported. She had numerous visceral anomalies including polysplenia, a short pancreas, a preduodenal portal vein, malrotation of the bowel, azygos continuation of the inferior vena cava, bilateral hyparterial bronchi and symmetrical liver lobation. Embryological and clinical considerations of polysplenia syndrome are described.


Familial spinal xanthomatosis with sitosterolemia. A family with multiple spinal xanthomas and sitosterolemia is described. A 48-year-old woman presented with paraplegia due to multiple intradural extramedullary tumors. The patient also showed marked tendon xanthomas and analysis of sterol composition in both plasma and the xanthoma established the diagnosis of the rare inherited metabolic disease, sitosterolemia and xanthomatosis. Two other siblings in the family presented with marked tendon xanthomas and coronary atherosclerosis, but did not show any neurological signs or symptoms. Magnetic resonance imaging (MRI) study revealed multiple intradural extramedullary tumors in spinal canals of the proband and her sister, but not in the other affected sibling (brother). This is the first report of familial occurrence of multiple extramedullary spinal tumors due to the inherited metabolic abnormality.


Recurrent hemoptysis due to aortobronchopulmonary fistula of false aortic aneurysm associated with repair of rupture of the sinus of Valsalva. A 54-year-old man presented with recurrent hemoptysis of one year duration. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a saccular aneurysm of the ascending aorta. The aneurysm was intraoperatively found to have formed on the superior surface of the site of aortotomy suture placed during previous repair of rupture of the sinus of Valsalva and to have a fistulous communication to the lung. CT and MRI were very useful in the diagnosis of the aneurysm as the cause of hemoptysis.


Food-dependent exercise-induced anaphylaxis. A 58-year-old farmer was admitted to our hospital because of repeated episodes of anaphylaxis. He had experienced 12 episodes of anaphylactic shock over the previous 17 years. These attacks included three episodes of bee sting. In general, the episodes occurred during farm work (exercise) and within two hours of eating cake in the afternoon. Because an immediate skin reaction to wheat flour was highly positive, a diagnosis of wheat allergy was considered. These findings suggested that his illness was consistent with food-dependent exercise-induced anaphylaxis.


Disseminated carcinomatosis of bone marrow from submucosal carcinoma in adenoma of the rectum. A 62-year-old man was admitted because of paresis of the legs and a bleeding tendency. He was diagnosed as metastatic bone cancer with disseminated intravascular coagulation (DIC). In spite of treatment, his general condition progressively deteriorated and he died of respiratory failure 13 days later. Autopsy revealed a carcinoma in adenoma in the rectum. Although the depth of cancer invasion was confined to the submucosal layer, disseminated carcinomatosis of the bone marrow and tumor emboli in blood vessels of the lung were present.


Wegener's granulomatosis with papillary adenocarcinoma of the thyroid. A 59-year-old woman was admitted with scleritis, sinusitis, skin eruptions, nodular lesions of both lung fields in chest X-ray films and renal failure. Skin biopsy and elevation of the titer of anti-neutrophil cytoplasmic antibody confirmed Wegener's granulomatosis. A right nodular goiter was palpated and a diagnosis of thyroid cancer was made based on aspiration cytology. Although combined therapy with cyclophosphamide and corticosteroid was started and the Wegener's granulomatosis improved and disappeared except for the renal lesion, the renal failure worsened and she died. Apparently only 2 cases of Wegener's granulomatosis complicated with carcinoma as in this case have been reported.


Malignant hyperthermia caused by intravenous lidocaine for ventricular arrhythmia. We encountered a case of malignant hyperthermia caused by intravenous lidocaine which had been administered as treatment for a ventricular arrhythmia. The patient, a 72-year-old male, was admitted with chronic renal failure and aortic valvular stenosis. His chronic renal failure progressed, and congestive heart failure developed, and ventricular arrhythmias occurred frequently. For the treatment of these arrhythmias, lidocaine was injected and continuous infusion was started. Despite initial improvement in symptoms and laboratory data following hemofiltration, refractory ventricular tachycardia occurred. The patient was treated with large doses of lidocaine. His body temperature rose to a maximum of 41.7 degrees C, and generalized muscular twitching was observed before he lost consciousness. Serum and urinary myoglobin levels became elevated. This abnormally high fever was relieved only by dantrolene sodium. After we made a diagnosis of malignant hyperthermia and stopped the lidocaine infusion, the high fever resolved quickly. It is important to note that malignant hyperthermia can be caused by lidocaine and amide-linked local anesthetics.


Endotracheobronchial lidocaine concentrations during flexible fiberoptic bronchoscopy (FFB). Lidocaine concentrations in 49 endotracheobronchial aspirates ranged from 12,580 to 23 micrograms/ml. The aspirates taken from the larger airway contained higher concentrations of lidocaine than those obtained from the smaller airway. Of the aspirates collected before 10 minutes after the final lidocaine administration, the lidocaine concentration of 7 (24.1%) of 29 specimens was greater than 3,000 micrograms/ml, however, in the aspirates collected after 10 minutes, only 1 (5%) of 20 specimens showed a concentration greater than 3,000 micrograms/ml. Using the dilution technique method (DTM) of lidocaine in the fiberscope (FS) suction channel, gradual injection of a 2 ml saline solution into the suction channel and removal of the saline solution in the suction channel were performed immediately with a suction machine; the statistically significant differences (p < 0.001) between lidocaine concentrations in the specimens before and after the DTM procedure were determined.


Lymphocyte subsets in muscle biopsies of human T-lymphotropic virus type I carriers with polymyositis. Recent epidemiologic studies have shown that human T-lymphotropic virus type I (HTLV-I) is associated with polymyositis. To clarify the histological features of HTLV-I positive polymyositis, we studied muscle tissue from two groups of patients with polymyositis, those seropositive for HTLV-I (5 patients) and those seronegative (5 patients). We examined the lymphocyte subsets in muscle biopsies using monoclonal antibodies. In the endomysium, a variable number of T-lymphocytes and macrophages and a smaller proportion of B-lymphocytes were found in both groups. In both HTLV-I positive and negative patients a variable number of T-lymphocytes and macrophages, with a smaller number of B-lymphocytes, were found in the perimysium. As a whole, the T-lymphocytes were predominantly of the helper/inducer phenotype in both groups. We failed to find any specific phenotype distribution among T-cells infiltrating the muscle of HTLV-I carriers with polymyositis.


Resistance to ketosis in moderately obese patients: influence of fatty liver. To elucidate whether the presence of fatty liver influences ketogenesis in obesity, the metabolic and hormonal changes in basal and low-dose epinephrine (EPI)-stimulated states were studied in 12 obese patients (OB) with normal glucose tolerance, consisting of 6 without fatty liver (OBN) and 6 with fatty liver (OBF). In the basal state, the total ketone body (TKB) concentration and the TKB to free fatty acid (FFA) ratio were significantly (p < 0.01) lower in the OBF than in the OBN group, despite elevated, but comparable, FFA levels in both groups. The basal FFA level and the TKB/FFA ratio correlated with the degree of fatty liver (p < 0.05-0.01). EPI infusion resulted in accelerated lipolysis and diminished FFA-induced ketogenesis, similar to the findings of the basal data. These results suggest that fatty liver per se is related to diminished FFA-induced ketogenesis, leading to resistance to ketosis in obesity.


Incidence of anti-mouse IgG in normal subjects and patients with autoimmune thyroid disease. Serum antibodies to mouse IgG occasionally interfere with two-site immunometric assays in which mouse monoclonal antibodies are used. We examined the titers of antibodies to mouse IgG in serum samples from normal subjects and patients with autoimmune thyroid disease (AITD) using an enzyme-linked immunosorbent assay. Anti-mouse IgG antibodies were positive in 7/119 patients with Graves' disease (5.9%) and 3/60 patients with Hashimoto's thyroiditis (5.0%). One of the 15 patients with a thyroid neoplasm (6.7%) also had antibodies to mouse IgG, as did 5/60 healthy subjects (8.3%). These antibodies were either of the IgG or IgM class. There was no significant difference in the incidence of positive anti-mouse IgG antibody between normal subjects and patients with AITD. It is important to note this high incidence of antibodies to mouse IgG due to the potential of interference with immunometric assays employing mouse monoclonal antibodies.


Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm. Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.


Distribution of Alu and L1 repeats in human YAC recombinants. Evidence is accumulating that the two major families of interspersed repeated human DNA sequences, Alu and L1, are not randomly distributed. However, only limited information is available on their relative long-range distribution. We have analyzed a set of randomly selected, human Chromosome (Chr) 11-specific YAC recombinants constituting a total length of about 2 Mbp for the local and global distribution of Alu and L1 repeats: the data show a strong asymmetry in the distribution of these two repeat classes and give weight, at the long-range molecular level, to previous studies indicating their partition in the human genome; they also suggest a strong tendency for L1 repeats to cluster, with a higher proportion of full-length elements than expected.


The AXB and BXA set of recombinant inbred mouse strains. The recombinant inbred (RI) set of strains, AXB and BXA, derived from C57BL/6J and A/J, originally constructed and maintained at the University of California/San Diego, have been imported into The Jackson Laboratory and are now in the 29th to 59th generation of brother-sister matings. Genetic quality control testing with 45 proviral and 11 biochemical markers previously typed in this RI set indicated that five strains had been genetically contaminated sometime in the past, so these strains have been discarded. The correct and complete strain distribution patterns for 56 genetic markers are reported for the remaining RI strain set, which consists of 31 living strains and 8 extinct strains for which DNA is available. Two additional strains, AXB 12 and BXA 17, are living and may be added to the set pending further tests of genetic purity. The progenitors of this RI set differ in susceptibility to 27 infectious diseases as well as atherosclerosis, obesity, diabetes, cancer, cleft palate, and hydrocephalus. Thus, the AXB and BXA set of RI strains will be useful in the genetic analysis of several complex diseases.


The murine leukemia inhibition factor gene (Lif) is located on proximal chromosome 11, not chromosome 13. Lif, the murine gene encoding leukemia inhibition factor (LIF), has been previously localized to proximal Chromosome (Chr) 11. Hilda, the murine gene encoding "human interleukin in DA cells" (HILDA) has been localized to Chr 13. Since these two growth factors are identical, the proposal for two different structural loci is intriguing. To address this issue, blot hybridization methods have been used to establish the position of the structural gene sequence unambiguously. DNAs from somatic cell hybrids, recombinant inbred mice, and backcross mice have been probed with a sequence that encodes LIF/HILDA. The results support the assignment of this sequence to proximal Chr 11. These studies also establish a synteny group, including Lif and Tcn-2, the structural gene for transcobalamin 2, that is conserved between man and mouse.


Assignment of three rat integrin genes to chromosome 19 (ITGB1), chromosome 3 (ITGA4), and chromosome 7 (ITGA5). By means of somatic cell hybrids segregating rat chromosomes, we determined the chromosome localization of three rat beta 1 family integrin genes. ITGB1 was assigned to Chromosome (Chr) 19, ITGA4 to Chr 3, and ITGA5 to Chr 7. These chromosome assignments reveal or confirm homology between two pairs of rat and human chromosomes (rat Chr 3-human Chr 2; rat Chr 7-human Chr 12).