PubMed Health⌕ Search

Biomedical subjects

M Barkin

Publications and source records attributed to M Barkin.

At least 19 recordsLinked to original sources

New mechanisms by which secretory phospholipase A2 stimulates neutrophils to provoke the release of cytotoxic agents.

BACKGROUND: Secretory phospholipase A2 (sPLA2) is a potent proinflammatory enzyme that stimulates inflammation through the production of reactive lipids. However, enzymatic inhibitors have been disappointing in their effectiveness in halting hyperinflammation. OBJECTIVE: To determine whether sPLA2 acts directly on neutrophil plasma membrane lipids or via a nonenzymatic mechanism. DESIGN: Isolated neutrophils (PMNs) were incubated with 3 types of sPLA2, and elastase and superoxide release from PMNs was measured. Ethyleneglycotetraacetic acid was used as a selective enzymatic inhibitor. The PMNs were exposed to sPLA2 in the presence and absence of ethyleneglycotetraacetic acid and the release of elastase was measured. SETTING: Urban trauma research laboratory. PATIENTS: Normal healthy donors of PMNs. MAIN OUTCOME MEASURES: Stimulated release of superoxide and elastase. RESULTS: The sPLA2 acted directly on plasma membrane lipids to stimulate the PMN to produce superoxide and release elastase. This mechanism is blocked with enzymatic inhibition of sPLA2. The sPLA2 also provokes elastase release from PMNs independently of its enzymatic function. This mechanism is not blocked with traditional enzymatic inhibitors. CONCLUSIONS: These data indicate that the sPLA2 can act directly on PMNs to stimulate the release of inflammatory mediators via enzymatic degradation of plasma membrane lipids. In addition, sPLA2 can act as a ligand and stimulate the PMN independently of its enzymatic activity.

Animals↗

Nitric oxide attenuates platelet-activating factor priming for elastase release in human neutrophils via a cyclic guanosine monophosphate-dependent pathway.

BACKGROUND: Nitric oxide (NO) has proven benefits in treating adult respiratory distress syndrome (ARDS). The protective mechanism remains unclear, but cyclic guanosine monophosphate (cGMP)-dependent signal transduction pathways have been suggested. Our laboratory has implicated polymorphonuclear neutrophil (PMN) priming and subsequent activation in the pathogenesis of postinjury ARDS and has shown that NO inhibits superoxide anion production from activated PMNs. More recently, the pivotal role of elastase in PMN-mediated tissue injury has been emphasized. Consequently, our study hypothesis was that NO attenuates platelet-activating factor (PAF) priming for elastase release through a cGMP-dependent pathway in human PMNs. METHODS: PMNs isolated from human volunteers were preincubated with the NO donor 3-morpholinosydnonimine hydrochloride (SIN-1; 10(-6) to 10(-2) mol/L), cGMP (10(-3) mol/L), or the cell-permeable cGMP analog dibutyryl-cGMP (10(-3) mol/L) for 10 minutes. The cells were then primed with platelet-activating factor (PAF) 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (200 nmol/L), which was followed by N-formyl-methionyl-leucyl-phenylalanine (fMLP) activation (1 mumol/L). Elastase release was measured by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide (AAPV-pNA). RESULTS: NO (through SIN-1) significantly attenuated elastase release from PAF-primed PMNs in a dose-dependent manner. Cell-permeable dibutyryl-cGMP attenuated PMN elastase release similar to NO, but cGMP (not cell-permeable) had no effect. CONCLUSIONS: NO attenuates elastase release from PAF-primed PMNs through an intracellular cGMP-dependent signal transduction pathway. These findings may partially explain the beneficial effects of NO in the treatment of postinjury ARDS and add to our knowledge of the complex intracellular pathways involved in NO/PMN interactions.

Adult↗

The Canadian health care system.

Canadians have enjoyed a close and harmonious relationship with Americans for more than a century. We have learned and benefited greatly from our close association. We are pleased to share our experiences with the United States in the same spirit of mutual respect and support that has characterized our close relationship and opened our borders.

Canada↗

Prevalence of antibody to Chlamydia trachomatis in spontaneous abortion and infertility.

A higher prevalence of Chlamydia trachomatis antibody occurred in 57.6% of women with recurrent abortion, but not in their male partners, compared to 33.7% of normal pregnant women (p less than 0.01) and 44.2% of infertile women (NS). The mean titer for the recurrent abortion group was not significantly elevated, compared to controls. Women with blocked fallopian tubes had the highest prevalence of elevated titers (p less than 0.01) and the highest mean titer (p less than 0.001). Despite multiple testing, no women or men were chlamydia culture-positive. The lack of isolation among patients with antibody could be due to cryptic infection at a site not amenable to culture or to inhibition by secretory IgA. There could also be nonspecific stimulation of chlamydial antibody caused by other infections such as mycoplasma. The presence, though at a low level, of antibody in culture-negative patients suggests chlamydia may not be directly associated with recurrent abortion but reflect previous exposure to chlamydia or an altered immune system.

Abortion, Habitual↗

Regeneration of vas deferens after vasectomy.

A total of 338 specimens obtained from 182 patients undergoing reversal of previous vasectomies have been studied. The major histologic features are sprouting of tubules and extravasation of sperm. Neo-tubules grow only from the proximal end of the divided vas and were seen in 136 specimens. Sperm were present in the neo-tubules in 61 specimens, but in the lumen of the proximal vas in 88 per cent of all patients. Extravasation of sperm had occurred from the neo-tubules in 64 specimens. In 57/154 patients operated on bilaterally at the same time, regeneration was unilateral. The conclusion from the analysis of factors responsible for this selectively proximal process is that sperm secretion was probably a major factor but was certainly not the only factor responsible.

Granuloma↗

Echinococcal disease of the kidney presenting as a renal filling defect.

We report a unique case of renal echinococcal disease. The patient presented with only a left renal pelvic filling defect without hepatic, pulmonary or other renal involvement. Management consisted of successful exploration and removal of the hydatid mass without sacrifice of renal tissue. The pathogenesis, diagnosis and treatment of echinococcal disease are reviewed.

Echinococcosis↗

Management of acute spinal cord injuries.

This report describes the results achieved in 144 patients with spinal cord injury admitted during the period 1974 to 1979 to the Acute Spinal Cord Injury Unit of Sunnybrook Medical Centre in Toronto. Several innovations have been made. These are based on a systems analysis approach to care and documentation. It includes epidemiologic studies of, and programs for, urologic and respiratory management and the use of halo devices. The unit has achieved a marked reduction in both mortality and morbidity. Patients have been transferred to the unit earlier after trauma and have been discharged earlier to rehabilitation hospitals partly because of the coordination of the acute and rehabilitation phases of care. There has been a marked reduction in the cost of care, because of fewer complications and a shorter stay in the acute hospital. The study confirms the advantages of regionalization and specialization in the field of acute spinal cord injury.

Acute Disease↗

Voiding dysfunction in institutionalized elderly men: the influence of previous prostatectomy.

Voiding problems, either retention or incontinence, affect a majority of institutionalized elderly patients. Although impaired cerebral function is the dominant cause, those patients who had undergone prior transurethral prostatectomy were more vulnerable to the development of voiding dysfunction than those who had not. Moreover, the elimination of obstruction by prostatectomy did not produce the expected shift from indwelling catheterization to condom drainage.

Aged↗

The urologic care of the spinal cord injury patient.

From 1974 to 1979, 141 acute spinal cord injury patients in the acute phase were managed by sterile, intermittent catheterization without complication. Of these patients 101 have been followed to the present. We used urodynamic criteria to determine whether these patients should be in retention on intermittent self-catheterization, or voiding with or without an appliance. When compared to a matched control group managed by indwelling catheterization in the acute phase and conventional criteria in the rehabilitation phase, 1 of 10 complications and 1 of 7 infections occurred in the study group. This analysis confirms that intermittent catheterization in the acute and rehabilitation phases, and the use of urodynamic criteria to follow lower tract management to achieve a low pressure voiding system represent major advances in the care of the urinary tract in patients with acute spinal cord injury.

Adolescent↗