Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guérin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions.     

A comparison of dementia in Alzheimer's disease and multiple sclerosis

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.     

Transdermal microconduits by microscission for drug delivery and sample acquisition

Background  

Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 μm diameter areas of human skin in vivo.     

MILITANCY TRAUMA : MAXILLOFACIAL INJURY,ANAESTHESIA AND CRITICAL CARE

Eighty four out of 2151 militancy trauma patients sustained severe maxillofacial injury from Jan 1990 to March 1993. The resuscitation, stabilisation and intensive care of these patients was based on management priorities of primary resuscitation, care of airway, management of haemodynamics, oxygenation and monitoring. Anaesthesia was administered in a situation when the airway was likely to be compromised and the patients were critically sick. Initial ventilation and oxygenation was the most difficult and could be achieved with satisfactory seal around the face mask by applying water-soaked guaze pieces around the mouth and nose to “fill-in” the defects. Tracheal intubation could be accomplished with intravenous sedation by an experienced anaesthesiologist. Dental occlusion and wiring necessiated the placement of nasotracheal tube for 48-72 hours after surgery.KEY WORDS: Trauma, Maxillofacial injury, Trauma anesthesia, Anaesthesia and critical care     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Dendritic cell based vaccination strategy: an evolving paradigm

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p?<?0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p?=?0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r?=?0.418 and p?=?0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.     

用正糖钳夹试验评估基础胰岛素类似物作用特点的研究

健康人通过体内胰岛素的分泌调节，可以保持正常的血糖水平。各种外源性胰岛素制剂在代谢过程上总是尽可能地模拟内源性胰岛素的分泌动力学。理想的外源性基础胰岛素制剂可以模拟健康人的基础胰岛素分泌，以致使用者可以恢复两餐之间和夜间正常生理情况下的血浆胰岛素水平。