Regional and temporal separation of serotonergic activity mediating social stress

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.     

Successful treatment of persistent bacteremia due to vancomycin-resistant, ampicillin-resistant Enterococcus faecium

Emergence of vancomycin-resistant enterococci has become an increasing problem in many medical centers. We report a liver transplant recipient with vancomycin-resistant Enterococcus faecium bacteremia who was successfully treated using very high dose continuous infusion ampicillin/sulbactam, plus gentamicin after he remained bacteremic on high dose ampicillin and gentamicin. At our institution, 83% of E. faecium isolates from 1994 were inhibited by ampicillin/sulbactam compared to 66% for ampicillin at an MIC < or = 64 micrograms/ml. None of these strains produced beta-lactamase, suggesting sulbactam may have an unexplained beneficial effect against some enterococci. Although an MIC of < or = 8 micrograms/ml is required for ampicillin to be considered active against enterococci, much higher levels of ampicillin or ampicillin/sulbactam are safely achievable. The response of our patient and the reported in vivo data have implications for future treatment of this pathogen, and may necessitate a reevaluation of susceptibility interpretation guidelines by clinical laboratories, and therapeutic drug dosing by clinicians.     

Hantavirus pulmonary syndrome in the United States: a pathological description of a disease caused by a new agent

An outbreak of an acute respiratory disease in the southwestern United States has led to the recognition of a new hantaviral illness. This report describes a unique spectrum of antemortem and postmortem pathological findings seen in a case series of nine surviving patients and 13 who died. Clinical, laboratory, and autopsy findings were derived from a consecutive series of individuals confirmed to have hantavirus pulmonary syndrome. Laboratory studies included chemical, hematological, and bone marrow analyses as well as flow cytometric and immunohistochemical phenotyping. Autopsy tissues were examined by routine histological stains, immunohistochemical methods, and transmission electron microscopy. The lung is the primary target organ in this illness. Pulmonary abnormalities include pleural effusions, alveolar edema and fibrin, and an interstitial mononuclear cell infiltrate. Large immunoblast type cells are seen in the lungs, blood, bone marrow, lymph nodes, liver, and spleen. A tetrad of hematological findings includes left-shifted neutrophilic leukocytosis, thrombocytopenia, hemoconcentration in severe cases, and circulating immunoblasts. In contrast to previously described nephropathic hantaviral syndromes, hantavirus pulmonary syndrome is characterized by a unique constellation of pulmonary, hematological, and reticuloendothelial pathological findings. The pulmonary findings are distinguishable from fatal adult respiratory distress syndrome. The data suggest a capillary leak syndrome restricted to the pulmonary circulation. Likewise, the hematological picture is unique and may be valuable in the rapid identification of cases for further diagnostic studies.     

Cutaneous leishmaniasis associated with jungle training

In November 1977, 627 soldiers belonging primarily to the First Battalion, 82nd Airborne Division, stationed at Fort Bragg, were sent to the Canal Zone, Panama, for jungle warfare training. A medical surveillance program incorporating pre- and post-evaluations over a 6-month period with dermatologic examinations, questionnaires, and serologic tests was established. Ten cases of cutaneous leishmaniasis (1.6/100 men) were diagnosed by positive Leishmania culture. The demonstrated lack of sensitivity and specificity of the indirect fluorescent antibody test and the direct agglutination test render these serological methods useless as diagnostic screening methods in the early stages of this disease.     

Menopausal changes in body composition and energy expenditure

Adult American women as a group tend to gain weight with age, and many women report that their weight gain started around the time of their menopause. Moreover, as women age, there are changes in body composition that include losses in bone mineral and body cell mass, and increases in total body fat, visceral fat, and extracellular fluid. It appears as if these body composition changes begin or accelerate during the menopausal years. The importance of weight gain and changes in body composition are their associations with an increased risk of developing some malignancies, cardiovascular disease, osteoporosis, and several other clinical conditions. This overview describes selected studies of menopause and aging-associated weight gain, changes in body composition, and alterations of energy expenditure in women. Gaps in the present understanding of these changes are highlighted, and an emphasis is placed on new research methodologies for investigating body composition and energy expenditure in vivo. A concluding section of the report summarizes areas in need of future investigation.     

A microplate-based bioassay system for measuring porcine serum mitogenic activity

A bioassay system was developed to measure porcine serum mitogenic activity, which is an indicator of growth factor activity. A MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide++ +] cell proliferation assay was used to monitor cell growth. In comparison with electronic cell counting, this bioassay system is sensitive, economical, and semi-automatic. A non-fusing myoblast cell line, BC3H1, was used, making it possible to increase seeding density and thus improve precision. The assay was carried out in 96-well microplates with automatic reading and data processing by a computer-controlled ELISA reader. Results were highly correlated with Kotts' method. This assay system is of potential value in studying growth regulation in pigs.     

Comparison of cytotoxic action of iphosphamide and cyclophosphamide

We compared the cytotoxic effects of cyclophosphamide and iphosphamide on normal hematopoietic colony-forming units (NCFU) and L1210 leukemia colony-forming units (LCFU), using the quantitative spleen colony assay. Cyclophosphamide was more cytotoxic for NCFU than iphosphamide, but both agents had a similar cytotoxic effect on LCFU survival, whether given as a single injection or a 24-hour infusion. Although both agents were less cytotoxic for LCFU when administered in 24-hour infusions, host toxicity indicated that correspondingly larger doses of each agent could be given by infusion. The two agents also exhibited very similar cell-killing kinetics.     

Relations of left ventricular mass to fat-free and adipose body mass: the strong heart study. The Strong Heart Study Investigators

STUDY DESIGN: The effects of nucleus pulposus and various treatments to block tumor necrosis factor alpha activity were evaluated in an experimental set-up using immunohistochemistry and nerve conduction velocity recordings. OBJECTIVES: To assess the presence of tumor necrosis factor alpha in pig nucleus pulposus cells, and to see if block of tumor necrosis factor alpha also blocks the nucleus-pulposus-induced reduction of nerve root conduction velocity. SUMMARY AND BACKGROUND DATA: A meta-analysis of observed effects induced by nucleus pulposus revealed that these effects might relate to one specific cytokine-tumor necrosis factor alpha. METHODS: Series-1: Cultured nucleus pulposus cells were stained immunohistologically with a monoclonal antibody for tumor necrosis factor alpha. Series-2: Nucleus pulposus was harvested from lumbar discs and applied to the sacrococcygeal cauda equina in 13 pigs autologously. Four pigs received 100 mg of doxycycline intravenously; five pigs had a blocking monoclonal antibody to tumor necrosis factor alpha applied locally in the nucleus pulposus, and four pigs remained nontreated, forming a control group. Three days after the application, the nerve root conduction velocity was determined over the application zone by local electrical stimulation. RESULTS: Series-1: Tumor necrosis factor alpha was found to be present in the nucleus pulposus cells. Series-2: The selective antibody to tumor necrosis factor alpha limited the reduction of nerve conduction velocity, although in comparison with the control group this was not statistically significant. However, treatment with doxycycline significantly blocked the nucleus-pulposus-induced reduction of conduction velocity. CONCLUSION: For the first time, a specific substance, tumor necrosis factor alpha, has been linked to the nucleus-pulposus-induced effects of nerve roots after local application. Although the effects of this substance may be synergistic with those of other similar substances, the data of the current study may be of significant importance for the continued understanding of nucleus pulposus' biologic activity, and of possible potential use for future strategies in managing sciatica.