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Biomedical subjects

M J Kelly

Publications and source records attributed to M J Kelly.

At least 145 records · Page 8Linked to original sources

Cooling prevents ischaemic testicular damage after spermatic cord clamping in rats.

A controlled trial was conducted on four groups of seven rats to evaluate any beneficial effect of cooling to 15 degrees C on testicular ischaemia induced by clamping of the spermatic cord for 2, 4, 6 or 8 h. At operation the microscopic appearance of the testes on unclamping was a poor guide to ultimate viability, whereas by the third day macroscopic and microscopic appearances concurred. When killed on the third day, testicular histology demonstrated that increasing periods of clamping led to gross ischaemia and infarction when testes were maintained at 37 degrees C, and this was reduced greatly by testicular cooling. For each period of clamping, maintenance of spermatogenesis, expressed in terms of Johnsen's histological scores, was significant (P less than 0.01), being 2 (37 degrees C) vs 5.3 (15 degrees C) for 8-h clamping. It is proposed that testicular cooling should be used during autotransplantation of testes in humans.

Animals↗

Immunohistochemical demonstration of proGnRH and GnRH in the preoptic-basal hypothalamus of the primate.

An antiserum (ARK-1) specific to the gonadotropin-releasing hormone precursor (proGnRH) was produced by immunizing with a synthetic peptide (proGnRH 6-16; Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-Asp-Ala-Glu) which bridges the proteolytic cleavage site of proGnRH. When used in the radioimmunoassay, ARK-1 bound 25% of the iodinated 5-16 fragment at a 1:30,000 dilution with a sensitivity of 1 pg/tube. Using immunohistochemical techniques, we observed that in serial and the same sections through the preoptic-basal hypothalamus (POA-BH), the precursor molecule was primarily present in the cell soma, whereas GnRH was found in the cell soma, nerve fibers, and terminals of the same neurons. These data indicate that the processing of proGnRH to biologically active peptides (e.g., GnRH) in the rhesus macaque and the baboon POA-BH primarily occurs in the cell soma.

Animals↗

Undergraduate urology teaching: results of a pre-examination revision quiz.

A 'revision quiz' using some 20 projected photographic slides and a structured open-ended answer sheet was administered to, and marked for, 75 Final MB candidates and 7 Final FRCS candidates at Bristol. Despite only a modest exposure to specialist urological teaching, the undergraduates were judged to have achieved an acceptable level of performance in most areas except for treatment of urinary infections. The performance of the senior house officers was not better than that of the undergraduates. Nearly all candidates in both groups undermarked their own scripts compared to the marks given by their teachers, thus fuelling, perhaps needlessly, their anxieties about examinations.

Education, Medical, Undergraduate↗

Hepatobiliary scintigraphy. Increasing the accuracy of the preoperative diagnosis of acute cholecystitis.

The ability of hepatobiliary scintigraphy (HBS) to influence accurately the clinical diagnosis of acute cholecystitis was assessed prospectively in 70 consecutive patients with suspected acute cholecystitis. Before and after HBS, the referring surgeons completed a questionnaire on the probability of acute cholecystitis. Accuracy of diagnosis was assessed by clinical follow-up and chart review in all patients and by surgical and pathological evaluation in the 31 patients who underwent laparotomy. There were 27 patients with positive HBS results and 40 with negative HBS results; the results for three patients were indeterminate. None of the positive or negative HBS results were confirmed to be inaccurate. Negative results influenced diagnosis more often than did others. Results were negative in 13 patients whose assigned probability of acute cholecystitis was very high before HBS; in all 13 the assigned probability was very low after HBS, and in none of these patients was acute cholecystitis confirmed subsequently. These results support the use of hepatobiliary scintigraphy before proceeding to urgent cholecystectomy in patients with a clinical diagnosis of acute cholecystitis.

Acute Disease↗

alpha-Tocopherol as agonist in hypoxia.

In hypoxia, but not normoxia, alpha-tocopherol (vitamin E) acts as an agonist in guinea-pig isolated colon, producing dose-dependent increases in contractile activity. This effect is mimicked by agents, vitamin K1 and phytol, which contain a structural similarity to the phytol side chain of alpha-tocopherol, but is antagonized by vitamin K3 which has a structure similar to the chromane ring of vitamin E. All of the agonist responses were blocked by atropine and potentiated by physostigmine but were unaffected by hexamethonium. However, responses to acetylcholine were not antagonized by vitamin K3 and these data suggest that alpha-tocopherol, phytol, vitamins K1 and K3 may be acting on a 'hypoxia receptor' which mediates release of acetylcholine onto muscarinic receptors.

Acetylcholine↗

Effect of prostacyclin (PGI2) on water and solute transport in the human jejunum.

Prostacyclin is an arachidonic acid metabolite, synthesised throughout the gastrointestinal tract, which has different effects on water and electrolyte transport across a variety of mammalian gastrointestinal epithelia. Using a perfusion technique in the human jejunum of 11 healthy subjects in vivo, the effect of intravenous prostacyclin, 4 ng/kg/min, on jejunal water and solute transport from a glucose electrolyte solution was investigated. In the prostacyclin group (n = 5), prostacyclin was infused intravenously from 70-150 minutes, and buffer administered iv from 0-70 and 150-210 minutes. In the buffer group (n = 6), iv buffer was administered from 0-210 minutes. In the prostacyclin group, net jejunal absorption of water was inhibited from 90-120 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), of sodium was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), and of chloride was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.005), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01). Prostacyclin had no effect on net movement of glucose, potassium or bicarbonate. These results are consistent with a role for prostacyclin in the endogenous humoral regulation of water and electrolyte transport in the human jejunum.

Adult↗

Luteinizing hormone-releasing hormone neuronal system during the estrous cycle of the female rat: effects of surgically induced persistent estrus.

The effects of discrete lesions of the suprachiasmatic and medial preoptic nucleus on luteinizing hormone-releasing hormone (LHRH) neurons of the female rat were examined. The lesions disrupted the estrous cycle and prevented the preovulatory surge of luteinizing hormone and prolactin. Two to three months following the lesions, control and lesioned animals were perfused, the brains were sectioned, and the tissue processed for LHRH immunocytochemistry using the peroxidase antiperoxidase method and a high-titer, conformational antiserum to LHRH. Faintly stained LHRH cells were observed in the preoptic area and the basal hypothalamus at all stages of the estrous cycle. The number of immunoreactive cell bodies varied from a high of 583 cells on proestrus, to a low of 35 cells on estrus (mean +/- SEM = 323 +/- 59; n = 11). In contrast, the constant estrous animals with lesions showed increased intensity and number of LHRH neurons rostral, lateral and caudal to the lesion. The total number of cells ranged from 625 to 954 cells per animal (mean +/- SEM = 784 +/- 44; n = 8; p less than 0.001 vs. controls). Moreover, all lesioned animals exhibited intense fiber stain in the median eminence region. In conclusion, these data support the hypothesis that persistent estrus is caused by destruction of neurons which directly or indirectly control LHRH neurons.

Animals↗

Acetate and citrate stimulate water and sodium absorption in the human jejunum.

Using a standard perfusion technique, the organic anions acetate (50 mmol/l) and citrate (5 mmol/l) have been shown to stimulate absorption of water and sodium from the human jejunum. These observations may support further the rationale for including acetate or citrate in oral rehydration solutions for the treatment of acute diarrhoeal disease in humans.

Acetates↗

Combined electrophysiological, immunocytochemical and peptide release measurements in the hypothalamic slice.

Sagittal hypothalamic slices were prepared from cycling female guinea pigs and incubated for 10-12 h during which time intracellular recordings were made from 274 arcuate and cell-poor zone (ARC-CPZ) neurons. Many of the cells exhibited spontaneous activity and a small percentage could be driven antidromically via median eminence stimulation and orthodromically via stria terminalis stimulation. During the long-term recording, the effluent medium was collected in 30 of the experiments and radioimmunoassayed using a high-titer, conformational antisera for the peptide luteinizing hormone-releasing hormone (LH-RH). The findings revealed that LH-RH is released in detectable amounts from slices prepared from a single hypothalamus, that the amount of LH-RH released is dependent on the stage of the cycle, and that it can be stimulated by known secretagogues like prostaglandin E2. Following the electrophysiological experiments, the slices were fixed and processed for immunocytochemistry using a specific antisera (EL-14) for LH-RH. LH-RH neurons were stained throughout the ARC-CPZ area with intense fiber staining in the median eminence. These findings demonstrate that the hypothalamic slice preparation can be utilized for combined electrophysiological, immunocytochemical and peptide release measurements.

Animals↗

Radionuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle.

Ventricular contraction was evaluated in 18 patients studied at a mean of 2.6 years after Fontan repair. The diagnosis was tricuspid atresia in 9 patients and single ventricle in 9. Gated first-pass and gated equilibrium radionuclide ventriculography were performed at rest and during exercise. Abnormally low ventricular ejection fraction (EF) at rest was present in 8 of 18 patients by the gated equilibrium technique and 6 of 13 technically adequate gated first-pass studies. An abnormal response to exercise (failure of EF to increase less than or equal to 5% from rest to maximal exercise) was found in 10 of 16 patients by the gated equilibrium technique and in 8 of 12 by the gated first-pass technique. Only 2 patients by each radionuclide technique had both normal EF at rest and normal exercise response. Thus, this study confirms the frequent presence of abnormalities in ventricular contraction after the Fontan procedure at rest or during exercise or both despite absence of symptoms. Both EF response and the hemodynamic response during exercise were more abnormal in the presence of an atriopulmonary than an atrioventricular connection.

Adolescent↗

Assessment of hemodynamic significance of isolated stenoses of the left anterior descending coronary artery using thallium-201 myocardial scintigraphy.

This study tests the hypothesis that the results of stress thallium-201 myocardial perfusion scans (TI-201) are related to the mean transstenotic pressure gradient of coronary stenoses independent of the percent luminal diameter narrowing seen at angiography. The 22 study patients (20 men, 2 women, mean age 47 years, range 30 to 62) had no previous myocardial infarction. Each underwent a symptom-limited, erect bicycle TI-201 test off antianginal therapy, shortly before percutaneous transluminal coronary angioplasty for isolated left anterior descending coronary artery stenosis. The percent narrowing, mean gradient at percutaneous transluminal coronary angioplasty and presence of a visually apparent TI-201 defect were independently evaluated and results compared. All 4 patients with 90% or greater diameter narrowing had positive TI-201 responses, and the mean gradient was 72 +/- 11 mm Hg. Among the 18 patients with less than 90% diameter narrowing, the mean gradient was higher (p less than 0.001) in the 11 with a positive TI-201 (63 +/- 15 mm Hg) than in the 7 with a negative TI-201 (33 +/- 20 mm Hg), but their percent narrowing did not differ significantly (72 +/- 14% vs 66 +/- 19%). Multiple regression analysis showed that the presence of a TI-201 defect was a strong (p = 0.003) and percent narrowing (p = 0.048) a weak independent predictor for gradient. When the mean gradient was normalized for the prestenotic pressure, both percent narrowing (p = 0.003) and TI-201 defects (p = 0.006) were significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Localization of exercise-induced myocardial ischemia with single view and biplanar radionuclide ventriculography: validation in single vessel coronary disease.

The ability of single view and biplanar radionuclide ventriculography (RVG) to determine the location of myocardial ischemia during maximal graded supine bicycle exercise was assessed in 50 patients with chest pain, no prior myocardial infarction, and a single coronary stenosis of greater than or equal to 50% luminal diameter narrowing at coronary angiography. A biplane collimator was used so that both right anterior oblique (RAO) gated first-pass and left anterior oblique (LAO) equilibrium RVG could be performed at rest and exercise. Results were compared with those obtained using 4-view 201Tl myocardial scintigraphy in the same patients. Regional wall motion abnormalities (WMA) and 201Tl perfusion defects were detected and assigned to individual coronary vessels by agreement between at least two of three independent observers, who read all studies blinded along with those from control subjects with chest pain but no angiographically significant coronary artery disease. When scintigraphic abnormalities were detected, both biplanar RVG (36/39 = 92%) and 201Tl (25/25 = 100%) were more frequently correct in predicting the stenosed vessel than single view LAO RVG (24/32 = 75%) (P less than 0.05). At RVG only inferior WMA, in the RAO view, predicted right coronary stenosis. Only posterolateral WMA, in the LAO view, predicted left circumflex stenosis. Thus biplanar, but not single view, LAO exercise RVG is a reasonable alternative to exercise 201Tl for localizing exercise-induced ischemic abnormalities to individual coronary stenoses.

Adult↗

Value of combined assessment of global and segmental ventricular contraction with right anterior oblique ECG-gated first-pass and left anterior oblique equilibrium radionuclide ventriculography.

A semi-automated, variable-region-of-interest method of analysis was used to measure both global and segmental left ventricular (LV) and global right ventricular (RV) contraction with ECG-gated first-pass and equilibrium radionuclide ventriculography. Normal values were defined in 20 healthy volunteers, and in 24 symptomatic patients, the results were compared with right anterior oblique (RAO) contrast left ventriculography. The global LV ejection fraction (LVEF) obtained by equilibrium imaging in the left anterior oblique (LAO) projection correlated closely with the results obtained by the gated first-pass method in the RAO projection (r = 0.95) and those obtained with contrast left ventriculography (r = 0.94); furthermore, the interobserver variability was small (r = 0.985). The normal values for LVEF obtained using radionuclide techniques and contrast ventriculography did not differ, but with the equilibrium radionuclide method, the RV ejection fraction (RVEF) values were underestimated in comparison to those obtained by the RAO gated first-pass technique. In five patients with localised inferior segmental akinesis at contrast angiography, the RAO first-pass cine display demonstrated a corresponding wall-motion abnormality in all cases, but LAO equilibrium cine displays did so in only one out of five patients. For segmental quantitation of LV contraction, a computer programme defined the ventricular edge, divided the RAO LV images into five segments and determined both the segmental area contraction (SAC) and the counts-based segmental ejection fraction (SEF). Radionuclide SAC measurements correlated very strongly with SEF measurements (r = 0.94-0.99). Both radionuclide SAC and radionuclide SEF correlated well with contrast angiographic SAC, except in the inferobasal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nufenoxole, a new antidiarrhoeal agent, inhibits fluid secretion in the human jejunum.

Nufenoxole is an orally active antidiarrhoeal agent which binds to opioid receptors in the brain and myenteric plexus of the intestine. A perfusion technique has been used to investigate the effect of nufenoxole (1 mg/kg intrajejunally) on water and solute transport stimulated by the secretagogue, dioctyl sodium sulphosuccinate, in the human jejunum in vivo. Nufenoxole reversed the direction of jejunal transport of salt and water from net secretion to net absorption. These changes in water and electrolyte transport were inhibited by intravenous naloxone, the opioid antagonist. Nufenoxole possesses potent antisecretory properties, which are mediated via opioid receptors and may contribute to its antidiarrhoeal action in man.

Adult↗