Multiple system atrophy following chronic carbon disulfide exposure

Carbon disulfide toxicity is well characterized. The principal target organ is the nervous system, although cardiovascular, reproductive, ophthalmologic, and other effects are also recognized. The neurotoxicity manifests in three ways: encephalopathy, peripheral and cranial nerve dysfunction, and movement abnormalities. This report describes a case of olivopontocerebellar atrophy, a form of multiple system atrophy, developing in an adult after over 30 years of occupational exposure to carbon disulfide. The patient presented with the insidious onset of balance problems, impotence, and irritability, without tremor, cogwheel rigidity, bradykinesia, or changes in facial expression. Over the next few years severe ataxia developed, and the clinical diagnosis was confirmed with computed tomography and magnetic resonance imaging scans. The patient experienced multiple medical complications and died approximately 9 years after diagnosis. This case is consistent with a large body of clinical and experimental literature, much of it 50 years old, showing that carbon disulfide can cause movement disorders. It also serves as a reminder that movement disorders, ranging from parkinsonism to dystonia, are associated with a variety of toxic exposures such as manganese, carbon monoxide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and medications.     

Effect of carbon disulfide on cholesterol content in rat tissue

The effect of chronic intoxication of rats with CS2 on the level of cholesterol in the body tissues was studied. Prolonged exposure to CS2 vapour results in the increased level of cholesterol in serum. It was interesting to find out whether accumulation of cholesterol occurs subsequently in the body tissues. Studies were performed on male Wistar albino rats exposed to CS2 vapour at concentration 0.8--1 mg/1 during 13 months. The level of cholesterol in the blood, aorta wall, muscles, liver and adipose tissue was estimated after 4, 10 and 13 months of intoxication. Chronic exposure of rats to CS2 vapour causes: (a) loss of body weight about 30 per cent after 10 months of intoxication; (b) increase of concentration of free and esterified cholesterol in the aorta wall about 20 and 63 per cent, whereas in the skeletal muscles about 40 and 80 per cent, after 10 and 13 months of exposure respectively; (c) no changes of the level of cholesterol in the liver. On the base of the results obtained in this study it was concluded, that prolonged exposure to CS2 contributed to accumulation of cholesterol only in some tissues. Changes we found are probably the result of quantitative shift in the redistribution of cholesterol among the tissues.     

Covalent cross-linking of erythrocyte spectrin by carbon disulfide in vivo

The effects of inflation, generic competition, market introduction of new drug entities, and recent legislation on forecasting drug expenditures are discussed. Inflation as it relates to pharmaceutical prices has been decreasing over the past couple of years. The U.S. Bureau of Labor Statistics reported a 6.9% increase in the Producer Price Index for drugs and pharmaceuticals in 1991, diminishing to a 4.5% increase for part year 1992. Pharmaceutical industry analysts predict overall annual inflation rates for pharmaceuticals in 1993-94 will range from 2% to 11%. Explanations for the recent low inflation rates and the wide variance among analysts may include the uncertainty of future government regulation on price increases and the backlog of FDA approvals for biotechnologically derived agents. To evaluate generic competition, information on patent or market exclusivity expiration can be used. The price of a generic drug may be 60-70% of the brand price at market introduction, but it usually stabilizes at approximately 50% of the list price. Predicting the market entry of new drug products is difficult and requires monitoring of (1) filing dates for new drug applications (NDAs) and (2) changes within the FDA approval process. According to an FDA report, the mean time to approval for an NDA in 1991 was 28.5 months and for a new molecular entity was 30.03 months. These figures represent little change from the previous five years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral vasoreactivity by transcranial Doppler in carbon disulfide poisoning cases in Korea

This study was undertaken to assess a multiple-marker RT-PCR and Southern blot assay for detection of metastases in frozen sections of sentinel lymph nodes from breast cancer patients. Sentinel lymphadenectomy was performed in 41 AJCC (American Joint Committee on Cancer) stage I-IIIA breast cancer patients and 57 sentinel nodes (SNs) were excised. The SN, which is the first node in the lymphatic basin to receive metastases from the primary tumor, was identified using isosulfan blue dye. Hematoxylin and eosin (H&E), immuno-histochemistry (IHC) and RT-PCR were performed on adjacent sections of the SN. Six consecutive 12-microm frozen sections of each SN were obtained for the RT-PCR assay to determine expression of mRNA tumor markers C-Met, beta1 --> 4GalNAc-T and P97. Metastatic breast cancer was detected by H&E in 10 of 57 (18%) SNs and by IHC in an additional 7 (12%). Only 1 of 17 (6%) SNs with metastases did not express any of the 3 tumor mRNA markers. C-Met, beta1 --> 4GalNAc-T and P97 tumor mRNA markers were expressed in 31 (78%), 21 (53%) and 25 (63%) of 40 SNs without metastases, respectively. At least 2 mRNA tumor markers were expressed in 25/40 (63%) histo-pathologically tumor-free SNs, whereas all 3 mRNA tumor markers were expressed in 17/40 (43%) SNs. Expression of all 3 mRNA tumor markers in a SN was significantly higher in patients with a family history of breast cancer (p = 0.05), prior history of breast cancer (p < 0.05), infiltrating lobular carcinoma (p = 0.06), estrogen receptor-negative (p = 0.04) tumor or a higher Bloom Richardson score (p = 0.04). The multiple-marker RT-PCR and Southern blot assay improves the detection of occult metastases in the SN when compared to conventional H&E and IHC analysis. Expression of all 3 tumor mRNA markers in the SN correlated with poor prognostic clinico-pathologic factors compared to expression of 0 to 2 markers.     

Updating of hygiene standards for carbon disulfide based on health risk assessment

OBJECTIVES: Clinicians are more and more frequently studying fetal blood flow velocity curves recorded by Doppler ultrasound in vital organs such as the placenta and fetal brain to evaluate fetal well-being. We have therefore developed a mathematical model of the utero-placental and fetal circulations which could be used for teaching and for a better understanding of regulatory mechanisms. METHODS: The model is based on two basic elements-an arterial segment and a bifurcation-and we have reproduced the major arteries of the feto-maternal circulation combining these basic elements. The mathematical model of the system is based on the Navier-Stokes equations. The peripheral areas such as the brain, kidneys and placenta are modeled by a simple Windkessel model and the model computes instantaneous flow and pressure at any point in the fetal arterial tree and the uterine arteries. RESULTS: We have compared the computed instantaneous flow curves and pressure with in vivo data and our results agree with the findings in physiological situations and in gravidic hypertension. CONCLUSIONS: Our model provides new interesting insights into fetal hemodynamics such as a better understanding of the mismatch impedance phenomena and is a promising model for the study of blood redistribution mechanisms in hypoxic situations.     

Effects of carbon disulfide and FLA-63 on operant behavior in pigeons

Carbon disulfide (CS2) and FLA-63 [bis(4-methyl-1-homopiperazinylthiocarbonyl)disulfide] were studied in pigeons working on a differential-reinforcement-of low-rates or a multiple fixed-interval fixed-ratio schedule of food reinforcement. Response rate on both schedules decreased after 8-hour exposures to CS2 (2 mg/1) of administration of FLA-63 (40 and 80 mg/kg). The effects of two successive 8-hour exposures to CS2 were cumulative and ten successive 4-hour exposures produced changes in differential-reinforcement-of-low-rates performance resembling those following acute exposure. Fixed-interval performance was disrupted by exposures to CS2 and doses of FLA-63 that left fixed-ratio performance intact.     

Release of carbon disulfide is a contributing mechanism in the axonopathy produced by N,N-diethyldithiocarbamate

The ADV-G isolate of Aleutian mink disease parvovirus (ADV) replicates permissively in Crandell feline kidney (CRFK) cells but is nonpathogenic for mink, whereas the highly pathogenic ADV-Utah isolate is nonviable in CRFK cells. To assign control of host range in CRFK cells and pathogenicity to specific regions of the ADV genome, we constructed a full-length molecular clone chimeric between ADV-G and ADV-Utah. If either the map unit (MU) 54-65 (clone G/U-5) or MU 65-88 (clone G/U-7) sections were ADV-Utah, viability in CRFK cells was abolished, thus indicating that in vitro host range was controlled by two independent determinants: A in the MU 54-65 segment and B in the MU 65-88 segment. Determinant B could be divided into two subregions, B1 (MU 65-69) and B2 (MU 73-88), neither of which alone could inhibit replication in CRFK cells, an observation suggesting that expression of the B determinant required interaction between noncontiguous sequences. Adult mink of Aleutian genotype inoculated with G/U-8 or G/U-10 developed viremia, antiviral antibody, and histopathological changes characteristic of progressive Aleutian disease. The capsid sequences of G/U-8 and G/U-10 differed from ADV-G at five and four amino acid residues, respectively. Our results suggested that the host range and pathogenicity of ADV are regulated by sequences in the capsid protein gene.     

Chronic carbon monoxide poisoning: from smoking to accidental poisoning

The authors describe a case of furosemide possibly inhibiting the hypoprothrombinemic effect of warfarin. The initiation of furosemide dosing in a patient receiving a stable dose of warfarin was associated with an 28% decrease in the international normalized ration (INR). Using normal volunteers, two previous controlled studies of an interaction between warfarin and chlorthalidone, and between warfarin and spironolactone, assert that volume depletion produced by forced diuresis results in the inhibition of warfarin's hypoprothrombinemia. Consistent with this hypothesis, the authors found that their patient's hematocrit (believed to reflect hydration status) correlated with the INR: r2 = 0.78, p < 0.05. This case provides further evidence suggesting that acute diuresis can decrease the hypoprothrombinemic effect of warfarin.     

Early infantile epileptic encephalopathy and glycine encephalopathy

INTRODUCTION: Early infantile epileptic encephalopathy (EIEE) with suppression burst activity in EEG (Ohtahara syndrome) is a rare type of epileptic encephalopathy in infancy and represents the earliest type of age-related symptomatic generalized epilepsy. The main etiologic factors associated to EIEE are cerebral dysgenesia and metabolopathies, principally nonketotic hyperglycinemia. CLINICAL CASE: We report a neonate with EIEE secondary to glycine encephalopathy, diagnosed by increased of LCR/plasma glycine index.     

Hepatic encephalopathy

The syndrome of hepatic encephalopathy has mystified physicians since the time of Hippocrates, and it continues to do so. It is difficult to succinctly define, diagnose with certainty, or attempt to explore its pathogenesis. The literature on this topic is confusing and often contradictory. Nevertheless, very effective empirical therapy has been devised for this syndrome. We discuss selected aspects of diagnosis, pathogenesis, clinical manifestations, and treatment of hepatic encephalopathy. Emphasis is placed on the three-pronged clinical strategy to manage hepatic encephalopathy that encompasses both diagnostic and treatment measures. The burgeoning area of subclinical hepatic encephalopathy is discussed in more detail than in most reviews of this topic. We also propose a new term for the field-acute liver failure-associated hepatic encephalopathy (ALFA-HE)-to replace the unsatisfactory older term, fulminant hepatic failure.     

HIV-related encephalopathy

The questionnaire data of 860 patients with bronchial asthma (BA) and the 7-year catamnestic investigation depth were analysed. According to clinical effect achieved the extracorporal methods of the patients with BA treatment were ranked in such a manner: splenosorption, immunosorption to DNA, which contains the sorpents, the conventional method of hemosorption (HS), using the SKN sorpent, plasmapheresis and the ultra-violet irradiation of blood (UVIB). The applicational efficacy of HS using KAU and "Gemosfer" sorpents is significantly lesser than such of SKN sorpents. UVIB do not effects late follow-up results of the hormonally-dependent patients treatment.     

Cat-scratch encephalopathy

We present a case of cat-scratch disease in a 9-year-old girl, complicated by encephalopathy and seizures. Bartonella (formerly Rochalimaea) henselae is the causative agent in cat-scratch disease; methods now available for detection of this pleomorphic, gram-negative bacterium, including polymerase chain reaction amplification and indirect fluorescence antibody testing, may lead to changes in standard criteria used to verify a diagnosis of cat-scratch disease.