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Biomedical subjects

S Sarin

Publications and source records attributed to S Sarin.

At least 19 recordsLinked to original sources

The Surgical Risk Scale as an improved tool for risk-adjusted analysis in comparative surgical audit.

BACKGROUND: Comparative surgical audit is becoming increasingly important although it is fraught with difficulties due to risk-adjusted analysis. Methods have been proposed to solve this problem and allow meaningful comparison of patient outcome. None has been described without faults, making such comparison flawed or overtly complicated. An alternative risk scoring system incorporating the Confidential Enquiry into Perioperative Deaths (CEPOD) grade, the American Society of Anesthesiologists (ASA) grade and the British United Provident Association (BUPA) operative grade was formulated and assessed. METHODS: This was a prospective audit of 4308 patients admitted under the care of three surgeons between May 1997 and October 1999, creating an initial data set of 3144 procedures with 134 deaths. Each procedure was allocated a score on the basis of the CEPOD, BUPA and ASA grade. The Surgical Risk Scale (SRS) was devised by adding together the values of the three variables, which generated a scale ranging from 3 to 14. Multivariate logistic regression analysis involving the three variables and univariate analysis of the SRS score were undertaken. Receiver-operator characteristic and calibration curves were formulated. This process was validated on another data set (2780 patients) derived from all admissions to the same surgeons between November 1999 and December 2000. RESULTS: Univariate logistic analysis of the SRS score revealed it to be significantly predictive of death (beta = 0.84, P < 0.001); it did not overpredict mortality for low-risk procedures. CONCLUSION: The SRS is easy to use, formulate and interpret, and provides an accurate prediction of death in general surgical patients across the entire risk spectrum.

England↗

Peptoids as endothelin receptor antagonists.

A series of new peptoids as endothelin receptor antagonists has been synthesized. Screening them for their ability to bind with endothelin receptors (ET(A) and ET(B)) competitively in the presence of (125I) endothelin led to the discovery of compounds as possible leads with IC50s in the low micromolar concentrations.

Endothelin Receptor Antagonists↗

Comparative audit: the trouble with POSSUM.

The Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) has been proposed for use in comparative audit between surgeons and between hospitals. To assess its feasibility, POSSUM scoring was attempted on admission in all patients under the care of two consultant surgeons over a six-month period. Scores were awarded only if all investigations necessary for POSSUM were performed; investigations unnecessary for effective treatment were not performed. 815 patient discharges were recorded over the six-month period, with 521 patients undergoing operative procedures. Of those undergoing an operation, scores could be allocated in only 155 (30%). Scoring systems such as POSSUM are procedure-based, thereby excluding those who do not undergo an operation. However, most of our operative cases were also excluded. Full POSSUM scoring will often require additional investigations. POSSUM is unlikely to be of use in the wider setting of comparative audit.

Adolescent↗

Biochemical characterization of dichlorvos-induced delayed neurotoxicity in rat.

In vitro and in vivo studies were carried out to assess the delayed neurotoxicity potential of dichlorvos. In vitro, dichlorvos caused a concentration and time-dependent decrease in the activity of neuropathy target esterase (NTE). The Ki of dichlorvos for NTE was calculated to be 1.28 x 10(3) M-1 min-1. In vitro reactivation and ageing studies revealed that dichlorvos-inhibited NTE became refractory to activation by potassium fluoride after 5 min in the ageing medium, thus indicating the formation of an aged complex between dichlorvos and NTE. In vivo also, dichlorvos (200 mg/kg body wt) given as a single subcutaneous dose inhibited NTE in brain at various intervals after exposure (24 h, 10 days, and 21 days). The delayed neurotoxicity potential of dichlorvos was finally confirmed by the rota rod test, which revealed severe motor deficit in all the exposed animals.

Animals↗

Dichlorvos induced alterations in glucose homeostasis: possible implications on the state of neuronal function in rats.

The present study was carried out to assess the effect of chronic dichlorvos exposure on various aspects of glucose homeostasis in different regions of rat brain. Dichlorvos administration caused a significant depletion in the brain glycogen content accompanied with an increase in the activity of glycogen phosphorylase. The activities of key glycolytic enzymes, hexokinase, phosphofructokinase and lactate dehydrogenase were decreased significantly following dichlorvos exposure. The decreased glycolytic flux was further reflected in terms of decreased regional glucose utilization, determined by measuring 14C-glucose influx. The altered neuronal glucose homeostasis had a significant impact on the neurobehavioural patterns of dichlorvos treated animals which was reflected in terms of severe deterioration in their memory and learning functions.

Acetylcholinesterase↗

Biochemical and behavioral deficits in adult rat following chronic dichlorvos exposure.

The present study was carried out to assess the biochemical and behavioral sequelae of chronic dichlorvos (6 mg/kg b.wt/day for 8 weeks) exposure in rats. Dichlorvos administration significantly decreased the activities of neuropathy target esterase and other carboxylesterase viz., paraoxon resistant and mipafox and paraoxon resistant esterases. The acetylcholinesterase activity was also appreciably decreased following dichlorvos exposure. The alterations in biochemical parameters were also reflected in the behavioral patterns of dichlorvos-treated animals. Dichlorvos administration caused a marked decrease in both the ambulatory and stereotypic components of spontaneous locomotor activity of rats. The muscle strength and coordination of the dichlorvos-treated animals was also significantly impaired. Besides, a marked deterioration in the memory function assessed in terms of the conditioned avoidance response was discernible at the end of the treatment schedule in the experimental animals.

Aggression↗

Alterations in lipid composition and neuronal injury in primates following chronic aluminium exposure.

The effect of chronic aluminium exposure (25 mg/kg b.wt.) was studied on the lipid composition and various membrane-bound enzymes in different regions of monkey brain. Aluminium (Al) administration caused a significant decrease in the total lipid, glycolipid, and phospholipid content of primate brain. Cholesterol levels and the phospholipid to cholesterol ratio were, however, markedly increased as a consequence of Al administration, thereby indicating a loss of membrane integrity. This was further confirmed when Al treatment was found to have a significant effect on the various membrane-bound enzymes in terms of decreased activities of Na+ K+ ATPase and acetylcholinesterase, along with a decrease in the activity of the myelin-specific enzyme, 2' 3'-cyclic nucleotide phosphohydrolase.

Aluminum↗

Patch angioplasty following carotid endarterectomy using the ipsilateral superior thyroid artery.

OBJECTIVES AND DESIGN: Synthetic and saphenous vein patches, when used in the carotid territory, are disadvantaged by complications. We tested the feasibility of using a locally harvested artery, the ipsilateral superior thyroid artery (STA), as a source of patching material following carotid endarterectomy (CEA). MATERIALS AND METHODS: Twenty-two consecutive patients (15 male) with a median age of 70 (range 53-82) years underwent CEA with an intention to use the STA for patch angioplasty. The STA was harvested via a standard carotid incision and opened longitudinally to fashion a patch. RESULTS: Of the 22 STAs harvested, only two were rejected due to small calibre. Mean harvesting time was 12 min and there were no immediate complications. Duplex scanning has not revealed restenosis (mean peak velocity = 0.78 [range 0.45-1.16] m/s) in any patient with a median follow-up of 13 (range 3-19) months. CONCLUSIONS: This technique is quick, convenient and obviates many of the disadvantages associated with conventional patches. Follow-up has shown the technique to be both efficacious and durable in the medium term.

Aged↗

Regional alterations in calcium homeostasis in the primate brain following chronic aluminium exposure.

The present study investigates the possible effects of chronic aluminium exposure on the various aspects of calcium homeostasis in the primate central nervous system. Aluminium administration caused a marked decline in the activity of Ca2+ ATPase in the monkey brain. The total calcium content was also significantly raised following aluminium exposure. Concomittant to the increase in the calcium content, the levels of lipid peroxidation were also augmented in the aluminium treated animals, thereby further accentuating the aluminium induced neuronal damage. In addition, aluminium had an inhibitory effect on the depolarization induced 45Ca2+ uptake via the voltage operated channels. The results presented herein, indicate that the toxic effects of aluminium could be mediated through modifications in the intracellular calcium homeostasis with resultant altered neuronal function.

Aluminum↗

Deficiency in T cell responses of human fetal lymph node cells: a lack of accessory cells.

Lymph node and spleen cells of human foetuses from the 18th to the 24th week of gestation were analysed with regard to their phenotypes and their functional capacities. Fetal mesenteric lymph nodes contain high percentages of CD45RA+ T cells and few B cells and monocytes, whereas the fetal spleen is comprised of equal numbers of T and B cells as well as monocytes/macrophages. Functional analysis of lymph node T cells revealed a lack of proliferative response to PHA or CD3 specific mAb, despite induction of expression of the activation marker CD69. Proliferation of LN cells and thymocytes was observed upon addition of exogenous IL-2. An allogeneic EBV transformed tumour cell line, known to be an effective antigen presenting cell, could induce proliferation of LN cells without exogenous IL-2 and fetal spleen cells could proliferate in response to all stimuli tested without additional IL-2. Splenic non-T cells could restore the proliferation of lymph node cells as efficiently as IL-2 or the EBV transformed B cell line. Separated B cells were more effective than plastic adherent cells on a per cell basis. Naivity of the fetal immune system is therefore not only reflected by the expression of markers representative for naive lymphocytes but can also be due to the absence of potential accessory cells in the different lymphoid organs.

Adult↗

Stripping of the long saphenous vein in the treatment of primary varicose veins.

Eighty-nine legs with long saphenous vein (LSV) reflux and saphenofemoral junction incompetence were treated by saphenofemoral ligation and multiple avulsions; patients were randomized to undergo additional stripping of the LSV from groin to upper calf (n = 43) or no additional treatment (n = 46). At a median of 21 months after surgery recurrence was evaluated by duplex ultrasonography, photoplethysmography, clinical examination and patient assessment. Fewer persisting incompetent LSVs in the calf were found (21 versus 38) and median (interquartile range) photoplethysmographic refilling times were longer (20 (13-27) versus 14 (11-21) s) when the LSV was stripped than after saphenofemoral ligation alone (both P < 0.1). More patients were completely satisfied (65 versus 37 percent and were recurrence-free (65 versus 17 per cent) when the LSV had been stripped compared with saphenofemoral ligation alone (P < 0.05 and P < 0.001 respectively). The addition of LSV stripping to saphenofemoral ligation and multiple avulsions results in a better overall outcome.

Adult↗

Plasma elastase in venous disease.

The plasma elastase level was measured as a marker of neutrophil degranulation in three groups, each of 15 patients, with uncomplicated varicose veins, lipodermatosclerosis (LDS) and venous ulceration. The values obtained were compared with those in age- and sex-matched control subjects. Significantly higher levels of elastase were found in all patient groups compared with controls: median 25.6 ng/ml for patients with uncomplicated varicose veins, 22.1 ng/ml for those with LDS, 26.0 ng/ml for those with venous ulceration. There was no difference in neutrophil count between the patient and control groups. These results provide evidence of increased neutrophil degranulation in patients with venous disease. The finding of raised elastase levels in all three patient groups shows that this was not due solely to the inflammatory process characterizing LDS and venous ulceration.

Adult↗

Duplex ultrasonography for assessment of venous valvular function of the lower limb.

Both legs of 29 patients with venous disease and those of 15 controls without venous disease were assessed by duplex ultrasonography. The duration of reverse flow after release of manual calf compression was measured in the common femoral, long saphenous, popliteal and short saphenous veins. Before undertaking the study, the reproducibility of the technique was evaluated in six subjects by repeating the examination over 3 consecutive days; the coefficient of variation of the test was 7.3 per cent. The 95 per cent confidence interval (c.i.) of the median (0.16 s) of all measurements in the normal limbs was 0.12-0.18 s. The 95 per cent c.i. for the 95th percentile of all measurements in normal limbs was 0.32-0.52 s. In limbs with clinical evidence of venous disease at least one of the sites examined was found to have reverse flow lasting longer than 0.5 s. These data suggest that the measurement of reverse flow after release of manual calf compression is a reproducible technique. While the method records some reverse flow in normal veins, its duration is unlikely to exceed 0.5 s; significant reflux is therefore defined as reverse flow exceeding 0.5 s.

Adult↗

Differing embryotoxic effects of senecionine and senecionine-N-oxide on the chick embryo.

The embryotoxic properties of pyrrolizidine alkaloids senecionine (water insoluble) and senecionine-N-oxide (water soluble) were examined using the CHEST method (Chick Embryotoxicity Screening Test). The beginning of the embryotoxicity range for senecionine was found to be between 3-30 micrograms; senecionine-N-oxide, on the other hand, showed no effect even with 100 micrograms dose. On the basis of the theoretical calculation, it can be expected that senecionine embryotoxicity for mammals ranges between 10-100 mg/kg maternal body weight, overlapping in this way the known adult toxicity range. The rat LD50 of most alkaloids known to be significant for human health are in the range of 34-300 mg/kg.

Animals↗

Long-term outcome of patients presenting with acute complications of diverticular disease.

The immediate management of acute diverticular disease is well defined but the risk of further complications and the long-term course of the disease, after conservative or surgical treatment, is not clearly documented. Over an 8-year period, a total of 164 patients (male/female = 69/95, median age 68 years) presented with acute complications of diverticular disease and were prospectively followed up for a median of 48 months. Medical treatment of acute diverticulitis was effective in 85% of 86 patients, with a mortality of 1.3% and a recurrence rate of 2% per patient year follow-up. All 37 patients presenting with bleeding responded to conservative management without mortality and a readmission rate, with further bleeding, of 5% per patient year. Patients who required colonic resection (n = 52), either as a single or staged procedure, had a mortality of 12% but with no further admissions with complications of diverticular disease. The low risk of readmission with recurrent disease after successful conservative treatment of the acute complications of diverticular disease does not justify elective operation in this group of patients.

Acute Disease↗

When do vascular surgeons prescribe antiplatelet therapy? Current attitudes.

A large number of studies have addressed the efficacy of antiplatelet agents in the prevention of primary and secondary atherosclerotic events. We have undertaken to review the literature and conclude that there is good evidence for the routine prescription of antiplatelet therapy in the prevention of secondary atherosclerotic events in patients with unstable angina, myocardial infarction, transient ischaemic attacks and post-arterial reconstruction. The evidence for any benefit in the prevention of vascular graft occlusion is less clear cut. We therefore conducted a postal survey of Vascular Surgeons in Britain and Ireland, receiving 112 responses to 134 questionnaires. Forty-seven percent of surgeons used antiplatelet therapy following any vascular procedure that they undertook. The rest were more selective in their use of these drugs, reserving them for specific vascular reconstruction, e.g. with synthetic grafts. Five percent of surgeons used anti-platelet aggregating prophylaxis only in patients following transluminal balloon angioplasty. In view of extensive evidence of reduction in long-term vascular mortality and non-fatal vascular events by the use of these drugs in patients who have had a primary vascular event, we would suggest that there is a strong argument for the routine use of anti-platelet drugs in patients presenting with arterial disease to a Vascular Surgeon, regardless of vascular reconstruction, angioplasty or type of graft used.

Angioplasty, Balloon↗

Does venous function deteriorate in patients waiting for varicose vein surgery?

We have looked at the deterioration in the condition of the lower limbs in a group of 36 patients who were waiting for a median time of 20 months for varicose vein surgery, using clinical examination, colour Duplex scanning and photoplethysmograph (95% refilling times). We found a significant deterioration in this group of patients, with four limbs initially unaffected developing reflux on Duplex scanning, of which three had clinical varicose veins (all four were offered surgery), and of the initial 56 involved limbs, 10 further sources of reflux were found (18%), necessitating alteration of the initial planned surgical procedure. No patient developed deep venous insufficiency or ulceration while on the waiting list, although there was one new case of lipodermatosclerosis. However, had surgery been undertaken after the first assessment, 14 patients (25%) would potentially have required further surgery, although accepting this as justification for allowing patients to wait takes no account of patients suffering or quality of life while waiting for operation.

Adult↗