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Biomedical subjects

K Mealy

Publications and source records attributed to K Mealy.

At least 37 records · Page 2Linked to original sources

The role of the defunctioning ileostomy in restorative proctocolectomy.

Restorative proctocolectomy is now the treatment of choice for most patients with ulcerative colitis and familial polyposis coli. Temporary defunctioning ileostomy has been advocated during the period of anastomotic healing to prevent pelvic sepsis. However, the ileostomy itself may be a source of significant complications. To examine ileostomy function we reviewed thirty five patients (mean age 34.5 +/- 1.95 years) who underwent restorative proctocolectomy. Thirty four patients had a defunctioning ileostomy established at the time of pouch anal anastomosis. Closure of the ileostomy has been carried out in 33 patients (mean closure time 3.1 +/- 0.29 months). One patient underwent early pouch excision. Thirteen of the 35 patients developed post-operative complications (37%), two directly related to the defunctioning ileostomy. Both occurred following closure of the stoma and required laparotomy. Serious complications associated with defunctioning ileostomy as demonstrated in this study are uncommon (8.5%). Given the potentially disastrous consequences of a pouch-anal anastomotic leak we feel that the relatively low morbidity associated with a defunctioning ileostomy justifies its continued routine usage in the operation of restorative proctocolectomy.

Adenomatous Polyposis Coli↗

Radiological investigation in laparoscopic compared with conventional cholecystectomy--an early assessment.

The implications of laparoscopic cholecystectomy (LC) for radiology were assessed by comparing imaging investigations in 48 LC and 48 conventional cholecystectomy (CC) patients. In addition, we attempted to identify findings on pre-operative ultrasound (US) which predicted operative difficulties at LC. There were no per-operative or T-tube cholangiograms in the LC patients, but otherwise the pattern of investigation was similar in both groups. Forty of the 48 CC patients underwent cholangiography (per-operative cholangiography in 36, endoscopic retrograde cholangiopancreatography (ERCP) in two, and both in two) demonstrating calculi in eight (16.7%) cases. Only four LC patients had cholangiography (ERCP in all cases) demonstrating common bile duct (CBD) calculi in one (2.1%) case. Ultrasound failed to identify the gall-bladder with certainty in three of the five failed LC cases. Neither gall-bladder wall thickness, contraction nor calculus size on pre-operative US served as predictors of other per-operative difficulties. Our results indicate that there may be some patients with retained CBD calculi in the LC group. The role of pre-operative US in predicting operative difficulties needs further assessment in a prospective study.

Adult↗

The effect of insulin-induced hypoglycemia on gene expression in the hypothalamic-pituitary-adrenal axis of the rat.

This study has examined the effects of insulin-induced hypoglycemia on expression of the CRH, arginine vasopressin, and POMC genes and corresponding peptides in freely moving, unanesthetized, male Sprague-Dawley rats. Animals were infused with 150 mM NaCl for 3 days before the experimental day and were then administered insulin (4 U/kg) or saline iv. In one experiment animals were killed 0, 30, 60, or 90 min after insulin or saline, and RNA was isolated from anterior pituitary, cerebral cortex, and punches of the hypothalamic paraventricular and supraoptic nuclei. In a second experiment, animals were killed 90 min after insulin or saline treatment, and RNA was isolated from whole hypothalami. RNA was analyzed by Northern blot. Plasma glucose fell from 106 +/- 5 to 38 +/- 2 mg/dl after insulin administration and remained low for the duration of the experiment. Plasma levels of ACTH, corticosterone, and vasopressin were 10-, 6-, and 4-fold higher, respectively, in the insulin-treated vs. control animals (by analysis of variance, P less than 0.0001 in all cases), while plasma CRH was unchanged. During hypoglycemia POMC mRNA levels were 1.8-fold higher in the insulin-treated group (by analysis of variance, P less than 0.025). In contrast, paraventricular nucleus, whole hypothalamic, and parietal cortex CRH mRNA and vasopressin mRNA were unchanged. These data support previous studies which indicated that POMC gene expression is increased by hypoglycemia. However, we found no evidence for an increase in paraventricular nucleus or cerebral cortex CRH mRNA expression during hypoglycemia-associated stimulation of the hypothalamic-pituitary-adrenal axis, suggesting that another factor(s) may mediate the observed increase in POMC gene expression.

Adrenocorticotropic Hormone↗

A prospective comparison of laparoscopic versus open cholecystectomy.

In one surgical unit, 115 patients undergoing cholecystectomy were studied to compare patient recovery, subjective and objective pain experienced and complications after laparoscopic and open cholecystectomy. The data were collected prospectively where allocation to open or laparoscopic cholecystectomy was by consecutive attendance. Laparoscopic cholecystectomy was feasible in 90% of patients presenting with symptomatic gallstones. Compared with the open operation, laparoscopic cholecystectomy was safe with less peroperative and postoperative morbidity, was more cost-effective and was associated with faster patient recovery as documented by less postoperative pain, earlier return to diet, earlier full mobilisation and discharge home. Laparoscopic cholecystectomy is superior to open cholecystectomy and should be available to all patients requiring elective cholecystectomy.

Adult↗

Tumour necrosis factor increases hepatic cell mass.

The effect of tumour necrosis factor (TNF) on hepatic cellularity was investigated in male Wistar rats maintained on total parenteral nutrition. Twenty-eight rats were infused with TNF (2 x 10(5) units TNF-alpha kg-1 24 h-1) or saline (controls) for 6 days. Wet and dry liver weights and nitrogen content were significantly increased by TNF (P less than 0.001), indicating an increase in liver mass. A further 81 rats were infused with TNF (2 or 4 x 10(5) units kg-1 24 h-1) or saline over 1, 3 and 6 days. Total liver DNA and protein content and counts of hepatocyte mitosis were determined. Liver DNA and protein increased with dose of TNF and time (P less than 0.001), suggesting that TNF increased hepatic cellularity. Histological examination demonstrated no significant inflammatory infiltrate to account for the increased cell mass. However, the number of hepatocyte mitoses increased with dose of TNF and time (P less than 0.05), indicating that the increase in liver cellularity was due to increased hepatocyte cell number. TNF-induced hepatic hyperplasia appears to be an additional feature of the integrated host response to injury and infection.

Animals↗

Splenectomy attenuates the inappropriate diuresis associated with tumor necrosis factor administration.

Tumor necrosis factor (TNF) is an important mediator of the systemic response to gram-negative sepsis and endotoxemia. We studied the renal effects of a sublethal TNF infusion in dogs (0.54 = 10(5) international units per kilogram of body weight during a six hour period). The TNF-infused dogs (n = 4) had marked polyuria and natriuresis in comparison with those in the control group (n = 12) (urine output, 35.3 +/- 4.1 versus 3.7 +/- 0.5 millimeters per kilogram per six hours p less than 0.01; sodium excretion, 2.82 +/- 0.27 versus 0.75 +/- 0.19, p less than 0.01). To evaluate the role of the spleen in this response, seven dogs that had splenectomy were infused with TNF. Splenectomy abolished both the polyuria and the natriuresis; this could not be explained by the differences in fluid balance or in hemodynamic or metabolic alterations. Treatment with ibuprofen given intravenously (12.5 milligrams per kilogram 40 minutes before and three hours after the beginning of TNF infusion) in eight dogs that did not undergo splenectomy also abolished these renal effects. Prostaglandin 2 (PGE2) concentrations in selected blood samples from the splenic vein did not increase with TNF infusion, excluding circulating PGE2 as a possible mediator of the renal effects. The results of these studies indicate that, during septic challenge or severe inflammation, the spleen participates in signaling the kidney to increase water and sodium excretion. These renal events are mediated through the cyclo-oxygenase pathway.

Analysis of Variance↗

Are the catabolic effects of tumor necrosis factor mediated by glucocorticoids?

The effect of tumor necrosis factor (TNF) on the hypothalamic-adrenal stress response was determined by infusion of TNF, 0, 2 x 10(5), and 4 x 10(5) U/kg per 24 hours, in parenterally fed male Wistar rats. Following infusions over 1 to 6 days, adrenal weight was increased with increasing dosage of TNF. Tumor necrosis factor at a dosage of 4 x 10(5) U/kg per 24 hours increased the plasma corticotropin level over the same period. In a further series of experiments the metabolic effects of TNF were compared with the effects of corticosterone, the predominant glucocorticoid in the rat. In comparison with controls, rats given corticosterone (75 mg subcutaneously) or TNF (2 x 10(5) U/kg per 24 hours) demonstrated decreased nitrogen balance and diminished carcass nitrogen content over a 6-day period. Tumor necrosis factor alone, however, induced a significant increase in liver nitrogen content and diminished jejunal mucosa DNA and protein levels in comparison with the control and corticosterone groups. Finally, adrenalectomized animals receiving basal corticosterone replacement were infused with TNF. Urinary nitrogen loss was significantly diminished in these animals compared with sham adrenalectomized controls, indicating that an intact adrenal stress response is necessary for the increased nitrogen loss following TNF infusion. Tumor necrosis factor may exert an important regulatory influence on the interorgan substrate flux that occurs during critical illness. The effects of TNF on skeletal muscle proteolysis can be simulated by adrenal glucocorticoid administration. The effects of this cytokine on visceral organs appear to be unique to TNF and cannot be reproduced by the administration of glucocorticoids alone.

Adrenal Glands↗

Hilton Head revisited--cytokine explosion of the 80s takes shape for the 90s.

The Second International Workshop on Cytokines was held two years after its predecessor. The scope was extremely broad--cytokines. This attracted a large and extremely diverse group of participants (700 people and 526 abstracts), interested in many different cytokines (interleukins 1-8, tumor necrosis factors, interferons, colony-stimulating factors, platelet-derived growth factor, fibroblast growth factors and others) from the perspective mainly of research laboratories devoted to studies of diverse disciplines such as immunology, endocrinology, neurobiology, molecular biology, pharmacology and biochemistry.

Animals↗

The testicular effects of tumor necrosis factor.

Tumor necrosis factor (TNF) is a cytokine that mediates many of the metabolic responses after endotoxemia, septicemia, and tissue injury. The effect of TNF on testicular function was determined in a series of studies in which rhTNF (0, 2, and 4 X 10(5) units/kg/24 hours) was administered by continuous infusion to male Wistar rats maintained on total parenteral nutrition adequate for growing rats. Testicular weight and histology, and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined at 1, 3, and 6 days. Testicular weight decreased within 24 hours and this was associated with a fall in plasma testosterone and increased LH and FSH levels. These changes persisted for 6 days, indicating a loss of testosterone-mediated negative feedback on gonadotropin release. Histologic examination demonstrated significant damage to the germ cells in the adluminal compartment of the seminiferous epithelium; extensive exfoliation of spermatocytes and spermatids occurred at day six. However the primary spermatogonia in the basal compartment were relatively spared. Damage to the seminiferous epithelium at earlier times was noted in some tubules. The decrease in testosterone concentration and increase in gonadotropin levels suggest that TNF interferes with Leydig cell function. Germ cell damage may be a direct effect of TNF on these cells or may occur through secondary mechanisms involving Leydig or Sertoli cell dysfunction.

Animals↗

The effects of tumor necrosis factor on intestinal structure and metabolism.

Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.

Acid-Base Imbalance↗

Tumor necrosis factor induces adult respiratory distress syndrome in rats.

To evaluate the effect of tumor necrosis factor (TNF), a major mediator of sepsis, on lung structure and function, we infused 200-g male Wistar rats with TNF (0, 2 x 10(5), or 4 x 10(5) U/kg of TNF) for 24 hours. Volume-pressure measurements were determined in the excised lungs using both air and saline, which eliminated surface tension forces. Total lung wet and dry weight, nitrogen level, and DNA and protein content were measured. Lungs of the rats that received TNF accepted significantly smaller volumes of air and saline at all pressures compared with the control group. Both the lung wet and dry weights increased with TNF. Lung DNA and protein content also increased, suggesting increased cellularity in the TNF-infused lungs. Thus, the lungs of the TNF-treated rats were stiffer, with reduced compliance values, and heavier due to increased water content and increased cellularity. These data indicate that sublethal administration of TNF in this rat model induces the adult respiratory distress syndrome and increases the work potential of respiration.

Animals↗

Definitive one-stage emergency large bowel surgery.

During a 30-month period, 126 operations for emergency large bowel conditions were performed: 57 were for colonic carcinoma, 26 for acute diverticulitis, 14 for colonic ischaemia, 13 for complications of inflammatory bowel disease, and 16 for other conditions. Sixty-eight patients had peritonitis. One hundred and ten patients (87.3 per cent) underwent immediate resection. Of these, 83 (65.9 per cent of the overall group) had colonic resection with primary anastomosis but without a colostomy, 56 of which were left-sided colonic resections. Excluding 9 of the 68 patients with peritonitis, who had a total colectomy, 66 per cent also underwent resection, anastomosis and no colostomy. Total group mortality was 14.3 per cent: 12.7 per cent in the immediate resection group, 9.6 per cent in those with primary anastomosis and no colostomy, 5.2 per cent in the group with peritonitis undergoing resection and anastomosis, and 25 per cent in those having non-resectional surgery. Complications included an overall wound infection rate of 10.3 per cent and a clinical anastomotic leak rate of 7.2 per cent in those who had anastomosis without colostomy. Our results suggest that resection and primary anastomosis can be performed with acceptable morbidity and mortality in a high proportion of cases of emergency large bowel conditions, irrespective of underlying pathology, site of disease or the presence of peritonitis.

Adolescent↗

The true incidence of ruptured abdominal aortic aneurysms.

The number of ruptured abdominal aortic aneurysms (RAAA) was documented over an 8-year-period in a known population age group. Patient figures were collected from the operative and post-mortem registers in the Worthing Health District. The overall mean incidence of RAAA was 13.9/100,000 patient years, although the incidence was noted to increase from 9.2 to 17.5/100,000 patient years during this period. The incidence in the male population rose from 4.7/100,000 for those in the fifth decade to 184.8/100,000 for those above 80. For patients undergoing operation, the peri-operative survival was 38%, however the overall survival was 11% as 64% of patients died at home. These figures demonstrate an increasing incidence of ruptured AAA. They also add support to the need for screening of asymptomatic abdominal aortic aneurysms and elective repair if the incidence and hence mortality is to be reduced.

Aged↗

Combined effects of glutamine and epidermal growth factor on the rat intestine.

Glutamine (GLN) is an important fuel and epidermal growth factor (EGF) is a potent mitogen for intestinal mucosa cells. GLN-enriched parenteral nutrition was administered to male Wistar rats, and subcutaneous injections of EGF were given for 3, 6, and 7 days. Control animals were fed a non-GLN-containing solution. Other groups of animals received GLN or EGF alone. Mucosal samples were obtained from the jejunum, ileum, and colon for measurement of weight, DNA, protein, and mucosal thickness. Disaccharidase activity was measured in the jejunum. After 3 days, only animals that received both GLN and EGF had a significant increase in small-bowel mucosal protein and thickness relative to controls. A similar pattern was observed in the colon, where animals that received both agents had a greater mucosal thickness, DNA, and protein content than controls. At 7 days, animals that received EGF or GLN had greater nitrogen retention. In addition, animals that were treated with EGF had elevated sucrase and maltase activity compared with GLN-fed animals at this time. Animals treated with GLN and EGF tended to have increased sucrase activity relative to controls. GLN feeding was associated with increased mucosal DNA and protein contents throughout the intestine for the combined series. EGF increased mucosal DNA and protein in the small intestine but not in the colon. The effect of EGF on the protein content of the small-bowel mucosa was dose dependent. The effects of GLN and EGF on the small bowel and colonic mucosa were additive. These studies suggest that specific nutrients and hormones may be used in combination to decrease the mucosal atrophy that commonly occurs after gut disuse or disease.

Animals↗

Yersinia infection and acute abdominal pain.

In 194 patients presenting with acute abdominal pain from whom sequential serum samples were taken, the frequency of yersiniosis, established serologically, was significantly higher (23%) than in 320 control subjects (2%). Yersiniosis occurred in 31% of patients with acute appendicitis. Acute-phase serum samples only, obtained in a further 307 patients, yielded a falsely low frequency of yersiniosis (4%). Y pseudotuberculosis was five times more common than Y enterocolitica, and Y pseudotuberculosis type IV was the most common serotype, accounting for 43% of Yersinia infections. Yersinia may play a more important part in the aetiology of acute abdominal pain, and particularly acute appendicitis, than has been previously appreciated. Antibody titres to both Y enterocolitica and Y pseudotuberculosis frequently rise late in infections causing abdominal pain. Consequently analysis of acute-phase serum samples alone leads to underdiagnosis of yersiniosis.

Abdomen↗

Impaired neutrophil function during anesthesia and surgery is due to serum factors.

Neutrophil function was assessed in patients undergoing anesthesia and surgery using a chemiluminescence (CL) assay. With the anesthetic agents enflurane and nitrous oxide, peroperative CL (99.1 mV; 13.8 SEM: postinduction but prior to surgery) was significantly lower than the preoperative value (146.5 mV; 14.1 SEM) with a mean fall of 30% (P less than 0.001). CL measurements taken 24 hr postoperatively were significantly increased (193.9 mV; 16.4 SEM) over the pre- and peroperative values, showing mean increases of 32 and 96%, respectively (P less than 0.001 in both cases). The inhibitory influence on CL appeared to be due to serum factors since peroperative patients' sera inhibited control neutrophils. Significantly depressed levels of the complement component C3 and IgG detected during the peroperative period (P less than 0.05) may explain this phenomenon. Postoperatively, C3 and IgG levels returned to normal. The transient decrease in peroperative neutrophil function may be a contributory factor to the establishment of postoperative sepsis in surgical patients.

Anesthesia, Inhalation↗