Immunological reactivity in dermatophytosis

Patients with Trichophyton mentagrophytes and T. rubrum infections were compared in terms of cutaneous responses and in vitro lymphocyte reactivity to trichophytin and other antigens. Twelve out of fourteen T. mentagrophytes patients exhibited delayed cutaneous hypersensitivity to trichophytin. Most T. rubrum patients (thirty-seven out of forty-nine) lacked delayed reactions to trichophytin specifically, but these patients frequently manifested immediate weal reactions to this antigen. Positive lymphocyte responses correlated with the presence of delayed but not immediate cutaneous reactions. Serum from chronic T. rubrum patients failed to inhibit lymphocyte responses. Possible mechanisms for selective anergy in chronic T. rubrum patients are discussed.     

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats.KATZ, G. V., RENNER, E. R., JR., AND TERHAAR, C. J. (1986).Fundam. Appl. Toxicol. 6, 498–505. Rats were exposed byinhalation, 6 hr/day, 5 days/week, to target vapor concentrationsof 2000, 1000, or 0 ppm of methyl isoamyl ketone (MIAK) for12 exposures spanning 16 days, and 2000, 1000, 200, or 0 ppmfor 69 exposures spanning 96 days. Body weights, hematology,and serum clinical chemistry determinations were comparableto controls in both inhalation studies. Clinical signs of toxicitywere lethargy and decreased aural response (2000 ppm, 2-weekstudy; 2000 and 1000 ppm, 90-day study) and nasal and eye irritation(2000 and 1000 ppm, 90-day study). In addition, the excretionof gel-like casts in seminal fluid was seen in males exposedto 2000 and 1000 ppm in both studies. increases in absoluteand relative liver and kidney weights were observed in bothsexes following exposure to 2000 and 1000 ppm in the 2-weekand 90-day studies. Liver weight increases were exposure dependentand in the 90-day study reflected hepatocyte hypertrophy observedon microscopic examination. Microscopic kidney changes werehyalin degeneration or hyalin droplet formation in males inthe 2-week (2000 and 1000 ppm) and 90-day (2000 ppm) studies;and minor to moderate regeneration of tubular epithelium (2000and 1000 ppm) in both studies. Minor tubular epithelium regenerationwas seen in females exposed to 2000 ppm for 90 days. The toxicityof MIAK following inhalation exposure was not as extensive orsevere as that resulting from a prior study in which male ratswere dosed orally with 2000 mg/kg/day (a dose comparable to2000 ppm) for 13 weeks. The 90-day inhalation exposure no-observed-effectlevel for toxicity was 200 ppm MIAK.     

GUIDELINES FOR AUTOPSY IN HIV POSITIVE CASES

Autopsy on a patient who had died as a consequence of acquired immune deficiency syndrome (AIDS) can be of great value in understanding the disease process. A potential risk to the prosector for acquiring the HIV exists, but if adequate preventive measures are undertaken, the risk is negligible. Indeed there is no documented evidence of a pathologist or an autopsy room attendant acquiring HIV infection while performing autopsy on a patient with AIDS. The procedures to be followed in the autopsy of the patient with AIDS are discussed.KEY WORDS: Acquired immune deficiency syndrome (AIDS), Autopsy in HIV Positive, Autopsy, Hospital acquired infections     

ANEURYSMAL BONE CYST IN THE MANDIBLE (A Case Report)

Aneurysmal bone cyst is commonly seen in the long bones and vertebrae and is rare in the jaws. Its association with other lesions of the bone has been stressed by many workers. Because of its variable radiological appearance, diagnosis of the lesion is established by histopathological examination. A case of aneurysmal bone cyst occurring in the mandible is reported.KEY WORDS: Aneurysmal bone cyst, Mandible     

LEUKAEMIC INVOLVEMENT OF CENTRAL NERVOUS SYSTEM

Eighty two patients of leukaemia consisting of 25 cases of acute lymphocytic leukaemia, 38 cases of acute myeloid leukaemia, 14 cases of chronic myeloid leukaemia and 5 cases of chronic lymphocytic leukaemia were evaluated for central nervous system (CNS) involvement. Speech disorders, cranial nerve palsies, encephalopathy, ataxia, intracranial haemorrhage, peripheral neuropathy and spinal cord involvement were the main neurological findings detected in 23 (28.1%) cases. All except one were subjected to autopsy after death. Leukaemic infiltrations (36.6%) and intracranial haemorrhage (26.8%) were the prominent CNS autopsy findings. In addition, demyelination with astrocytosis (9.7%) and gliosis (2.4%) were seen. In all, 45 (54.9%) of the patients showed CNS involvement at autopsy. Thus a large number of CNS lesions were missed clinically and detected only on autopsy.KEY WORDS: Intracranial haemorrhage, Leukemia, Metastasis     

PRELIMINARY STUDY OF HOW ALCOHOL CONSUMPTION DURING PREGNANCY AFFECTS IMMUNE COMPONENTS IN BREAST MILK AND BLOOD OF POSTPARTUM WOMEN

Human milk has been shown to contain numerous immune componentsthat can potentially protect the infant during the period beforeits own immune system is completely developed. Alcohol consumptionin both experimental animals and humans has been associatedwith alterations to a number of immune parameters. We have investigatedthe possibility that alcohol consumption during pregnancy alterscertain immune components in day 3 postpartum breast milk andperipheral blood of women. Our study group consisted of 10 alcoholicbeverage drinkers (moderate to heavy, most of whom smoked a1/2-1 pack of cigarettes per day), 15 non-drinking/non-smokingcontrols, and 10 non-drinking/smokers (1/2-1 pack per day) controls.The immune parameters measured in these otherwise healthy womenwere: (1) percentage and absolute number of the various subsetsof leukocytes; (2) percentage of T cells, B cells, T helperand cytotoxic/suppressors subsets, and natural killer cells;(3) levels of the cytokines IL-6, IL-8 and TNF-; (4) levelsof IgA in milk and IgG in serum. Milk from the alcohol groupcontained an elevated amount of IL-8 as compared with milk fromnon-smoker controls; however, it did not differ statisticallyfrom that of the smoker controls. Blood from the alcohol groupshowed an increased level of IL-8 when compared with that fromboth smoker and non-smoker controls. The total number of leukocytesin milk was elevated in milk from the alcohol group as comparedto both the smoker and non-smoker control groups. In the leukocytecomponent of milk, neutrophils predominate and are responsiblefor the elevation in total number of cells, as both lymphocyteand macrophage populations did not differ from those of thecontrols. For lymphocytes, B cells were also increased in bloodof the smokers as compared with the alcohol and non-smoker controls.There were no statistical differences in any of the other immuneparameters tested among the three groups. The present studyfound that alcohol consumption during pregnancy could modulatethe production of IL-8 and infiltration of certain leukocytesin milk and blood of postpartum women. Some of these alterationswere also evident in the smoker controls and thus could notbe attributed to alcohol consumption alone.     

Glutamine metabolism by the endotoxin-injured lung.

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mathematical and Biostatistical Methods for Designing and Analyzing Complex Interactions

Mathematical and Biostatistical Methods for Designing and AnalyzingComplex Chemical Interactions. CARTER, W.H., Jr., AND CARCHMAN,R.A. (1988). Fundam Appl. Toxicol 10, 590–595. In thispresentation, statistical methods for designing and analyzingexperiments evaluating a mixture of drugs/chemicals are discussed.These methods are promising in that they are not limited bythe number of interacting agents in the combination. Severalexamples are given and a discussion of the results follows.     

Development of a Testing Battery to Assess Chemical-Induced Immunotoxicity: National Toxicology Program's Guidelines for Immunotoxicity Evaluation in Mice

Development of a Testing Battery to Assess Chemical-InducedImmunotoxicity: National Toxicology Program's Guidelines forImmunotoxicity Evaluation in Mice. Luster, M. I., Munson, A.E., Thomas, P. T., Holsapple, M. P., Fenters, J. D., White,K. L., Jr., Lauer, L. D., Germolec, D. R., Rosenthal, G. J.,and Dean, J. H. (1988). Fundam. Appl. Toxicol..     

A Canine Model of Torsades de Pointes

Although quinidine has been reported to induce QT interval prolongation and torsades de pointes clinically, the only experimental model currently available for quinidine-induced torsades de pointes requires the concurrent use of ischemia, reperfusion and cardiac pacing of the isolated, perfused heart. Our purpose in this study was to determine the circumstances under which quinidine might elicit torsades de pointes consistently in the intact dog. We found that maintenance of therapeutic plasma quinidine concentrations, alone, did not induce the arrhythmia. Rather, arrhythmia induction required the additional application of aconitine, which induces early afterdepolarizations and triggered activity. When aconitine was applied to two epicardial sites in dogs having quinidine-induced QT interval prolongation greater than 10%, torsades de pointes occurred in 80% of instances. When QT prolongation was less than 10%, aconitine-induced torsades de pointes was seen in only 21% of animals. Our results suggest that in a previously healthy heart quinidine-induced QT prolongation is, itself, insufficient to induce torsades de pointes consistently, and two independent sites of ectopic activity are needed as well. The ectopic foci appear to modulate one another's impulse initiation or activation sequence, thereby giving rise to the classical "twisting of the points" associated with the arrhythmia.