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S Manek

Publications and source records attributed to S Manek.

68 records · Page 4Linked to original sources

Pathology of warm ischaemia and reperfusion injury in adipomusculocutaneous flaps.

In-vivo assessment and histological analysis after 168 hours of reperfusion were used to determine the normothermic (37 degrees C) ischaemic tolerance of adipomusculocutaneous, free flap, isotransplants in inbred AS rats. Flaps stored for up to 2 hours under normothermic conditions survived; flaps stored for 4 hours partially survived but those which had been stored for more than 6 hours became totally necrotic. Neither treatment with the iron chelator desferrioxamine (DFX) nor hypertonic citrate (HCA) flush increased the ischaemic tolerance of flaps which had been stored for 4 hours since neither diminished the amount of necrosis. Treated and untreated flaps stored for 4 hours were also assessed 0, 0.5, 24, 48, 96 and 168 hours after isotransplantation. They were compared to control flaps which had not been stored prior to reperfusion and negative control flaps which were not stored but isotransplanted without a blood supply. Oedema reached a peak at 24 hours and there was progressive increase in general severe necrosis, reaching a plateau by 48 hours. Suture line epidermalization and thickening was established by 48 hours. Among flaps stored for 4 hours, those treated with DFX had the most necrosis. Adipose tissue and striated muscle proved the least tolerant to warm ischaemic stress. These experiments suggest reperfusion injury contributes to eventual flap necrosis, but the role of free radicals has not been established. The 4-hour stored flap is a useful model to study the effects of ischaemia both in flap tissue and at the suture line.

Adipose Tissue↗

Ultrastructural changes in rat adipomusculocutaneous flaps during warm ischaemic storage and reperfusion.

Electron microscopy (EM) was used to evaluate ultrastructural changes in adipomusculocutaneous rat flaps which had been stored for 0, 2, 4, 6 and 8 hours under normothermic conditions (37 degrees C). The effects of treatment with desferrioxamine (DFX) or hypertonic citrate flush (HCA), prior to 4 hours of storage, were compared to untreated flaps which had been stored for 4 hours. Ultrastructural changes caused by 30 minutes of reperfusion, were also studied. Most ultrastructural alterations occurred between 2 and 4 hours of warm storage and there were further changes in some cells after short periods of reperfusion. DFX decreased smooth muscle damage and HCA protected adipocytes but neither of these agents preserved endothelial cells. These studies indicated that free radical-dependent and independent mechanisms were both involved in events which led to flap necrosis after periods of warm storage and reperfusion.

Adipose Tissue↗

Ebselen. Antioxidant capacity in renal preservation.

Ebselen (PZ51) was tested for its ability to inhibit oxidative membrane damage and improve outcome of rabbit kidneys rendered cold ischaemic for 72 hr. In view of the rapid metabolism of ebselen, the antioxidant capacities of its two principal metabolites were first compared with that of the parent drug in an in vitro hepatic microsomal lipid peroxidation system initiated by NADPH/Fe(3+)-ADP. The potent antioxidant activity of ebselen was confirmed but metabolite I (2-glucuronylselenobenzanilide) exhibited no antioxidant potential up to a concentration of 50 microM; metabolite II (4-hydroxy-2-methyl-selenobenzanilide) did inhibit lipid peroxidation but was about 80 times less effective than the parent compound. The storage of rabbit kidneys in hypertonic citrate solution at 0 degrees for 72 hr of cold ischaemia resulted in greatly increased susceptibility to oxidative membrane damage in both the cortex and medulla as determined by the subsequent in vitro formation of two markers of lipid peroxidation (Schiff's bases and thiobarbituric acid-reactive material). Inclusion of ebselen (50 microM) in the flush and storage solution led to a highly significant reduction in these oxidative markers in both regions of the kidney. Intracellular and interstitial oedema was noted in organs subjected to 72 hr cold ischaemia and was reduced by ebselen (50 microM in the flush/storage solution). The rate of post-ischaemic lipid peroxidation was found to correlate well with the extent of oedema in the renal medulla (r = 0.84, P less than 0.001) but no such correlation was found in the cortex. Administration of ebselen (5.5 mg/kg i.v. and 100 microM in the flush/storage solution) did not improve the long-term survival of rabbits following autotransplantation of a single kidney stored for 48 or 72 hr. No protective effect of ebselen could be demonstrated either in terms of graded physiological function or histological outcome.

Animals↗

Experimental pathology of intravenous polyurethane cannulae containing disinfectant.

Cannula tubing (1.6 mm external, 1 mm internal diameter) manufactured from medical grade polyurethane containing 2%, 2,4,4'-tri-chloro-2'-hydroxydiphenylether ('Irgasan', Ciba-Geigy) was found to have no effect other than that seen with control ('Irgasan'-free) tubing in the following test systems: (i) haemolysis, (ii) endothelial cell cultures, (iii) paravertebral muscle of rabbits, (iv) jugular vein of rabbits, (v) cannulation of baboons and (vi) clotting times of human platelet-rich plasma. However, the results from (iv) showed a significant amount of damage from both inpregnated and control cannulae and (v) showed that all detectable 'Irgasan' had been eluted from the portions of tubing retained within the animal before the end of the experiment, more rapidly than predicted from in-vitro studies. The rate of elution of 'Irgasan' in vivo needs to be further investigated, and consideration should be given to developing a plastic-disinfectant combination with a slower rate of loss of disinfectant.

Animals↗

The terminal branch of posterior interosseous nerve: a useful donor for digital nerve grafting.

The anatomical relationships of the terminal branch of posterior interosseous nerve have been studied in 57 cadaver and amputation specimens. Removal of the nerve leaves the patient with no apparent sensory deficit. In all dissections the nerve was present and its location was constant. The mean obtainable length was 3.7 cm (range 2.7-5.1 cm) and its cross-sectional area made the nerve suitable for grafting of digital nerves.

Fingers↗

Ultrastructural changes and lipid peroxidation in rat adipomusculocutaneous flap isotransplants after normothermic storage and reperfusion.

Parallel in vivo, histological, and ultrastructural studies were carried out and markers of lipid peroxidation (Schiff's bases [SB] and thiobarbituric-acid-reactive material [TBAR]) were measured in rat adipomusculocutaneous flap isotransplants that had been stored for 0, 2, 4, 6, and 8 hr under normothermic (37 degrees C) conditions and reperfused for specific periods. Flaps stored for 4 hr and treated with intravenous desferrioxamine (DFX) or hypertonic citrate flush (HCA) were also evaluated. In vivo assessment was made after 7 days of reperfusion. Flaps stored for 4 hr eventually exhibited partial necrosis in vivo, and neither DFX or HCA flush increased the area of surviving skin. Electron microscopy revealed extensive storage damage in epidermal, follicle, fat, and smooth muscle cells and in endothelium. HCA significantly preserved fat cells (P = 0.0035) and DFX diminished smooth muscle damage. Reperfusion injury was seen in endothelial cells in the form of swelling that was not prevented by HCA or DFX. Ultrastructural alterations correlated with changes in susceptibility to lipid peroxidation in fat but not in skin. The results of these parallel studies indicate that both free radical-dependent and independent mechanisms operate in ischemia and reperfusion injury in flap tissue and that fat has a greater predisposition to free radical damage than skin.

Adipose Tissue↗

Molecular, immunological, and biological characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile.

A cytotoxigenic Clostridium difficile strain that fails to produce toxin A but causes hemorrhage and bloody fluid accumulation in ligated ileal loops of rabbits and hemorrhage and diarrhea in hamsters is described. The lack of reaction of DNA from this strain in hybridization studies with a toxin A gene-specific 4.5-kb probe and polymerase chain reaction studies with six toxin A-specific primers indicate the absence of the toxin A gene. The cytotoxin produced by this strain was not responsible for the enterotoxic or hemorrhagic activity and shared characteristics with toxin B, i.e., its cytotoxicity was neutralized by antibodies to toxigenic strains of C. difficile and Clostridium sordellii. Polymerase chain reaction studies with toxin B-specific primers showed that the DNA from this strain produced a 690-bp product in addition to the expected 591-bp product.

Animals↗

The pathology of rat lung isografts following 48 or 72-hour cold storage and subsequent reperfusion in vivo for up to 1 month.

Using a left lung orthotopic isograft model in adult male AS strain rats, the pathology of lungs which were stored for 48 or 72 hours using a simple organ flush technique followed by low temperature (0 degrees C) immersion has been investigated. Lungs were examined after cold storage alone and after storage followed by either brief (up to 1 hour) or extended (30 days) reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca(2+)-channel blocker) or prostacyclin (PGI2 which has both anti-platelet and vasodilator actions). Controls included fresh non-flushed lungs and fresh HCA-flushed lungs which were transplanted immediately after harvest. After prolonged (48 or 72-hour) cold ischaemia alone the only clear change in lung morphology was of nuclear swelling. Early reperfusion changes included: (i) oedema (interstitial and alveolar); (ii) vascular congestion; and (iii) intra-alveolar haemorrhage. Features (i) and (ii) were diffuse whilst haemorrhage was patchy. Lungs which remained in vivo for up to 30 days showed focal scarring and chronic inflammation with numerous macrophages containing haemosiderin; the extent of the changes observed in individual grafts tended to mirror the gross macroscopic outcome. Attempts to improve the cold ischaemic tolerance with added agents (verapamil and prostacyclin PGI2) failed to produce a clear advantage.

Animals↗

Reperfusion injury in rat adipomusculocutaneous flaps: an ultrastructural and microangiographic study.

Electron microscopy (EM), microangiography (MA) and histological studies were carried out to demonstrate the vascular basis of ischaemic and reperfusion injury in rat adipomusculocutaneous free flaps which had been stored under normothermic conditions (37 degrees C) for specific periods of time. MA revealed that areas destined to die reperfused for at least 6 h in this model. EM showed progressive endothelial damage as a result of both storage and reperfusion. The use of the iron chelator desferrioxamine (DFX) did not benefit the endothelium or improve salvage of ischaemic flaps.

Adipose Tissue↗

Persistence of divergent views of hospital staff in detecting and managing hypertension.

A questionnaire concerning views of hospital clinical staff was completed by 408 out of 542 staff (75%), comprising 214 medical staff of all clinical specialties, 106 first year clinical medical students, and 88 third year student nurses. On average 386 of 407 (95%) thought that blood pressure should be measured routinely in all inpatients but only 294 of 404 (73%) thought that this was appropriate for outpatients. Although 251 of 390 (64%) were taught to use the muffling of sounds (phase IV) as the diastolic blood pressure, only 219 of 406 (54%) actually used this phase alone. There were appreciable differences between the grades of staff in this respect, a small majority of most grades using phase IV. Roughly half (50 out of 102) of the medical student respondents were taught to use phase IV, but only 38 of 106 (36%) were actually using this phase. While only three out of 16 general practitioners were using phase IV diastolic blood pressure alone, the figure was 66 out of 88 (75%) for student nurses. The level of diastolic blood pressure at which clinicians would begin to treat a 50 year old asymptomatic man ranged from 90 to 121 mm Hg. When these figures were corrected to phase V values, assuming a 5 mm Hg difference between phases IV and V, the range was 85 to 116 mm Hg. Despite the general agreement among physicians interested in hypertension that the disappearance of sounds (phase V) should be used to denote diastolic blood pressure there is still considerable divergence of opinion among hospital medical staff.

Attitude of Health Personnel↗

The oblique rat groin flap.

Neovascularisation from the bed can result in the partial survival of failing rat groin flaps. This can interfere with the interpretation of pharmacological augmentation and ischaemia experiments. We describe the development of a modified rat groin flap which utilises the inguinal fat pad to diminish the effects of the bed on the skin component of the flap. The behaviour of this model is compared to that of standard rat groin flaps and flaps which have had polythene sheeting placed under them.

Adipose Tissue↗