Biomedical subjects
J Kelly
Publications and source records attributed to J Kelly.
Quality assurance of physiological saline used for blood grouping.
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Hospital design. How flexible are nucleus hospitals?
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Alpha-gliadin antibodies in childhood coeliac disease.
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Medical architecture. Dismantling an old institution.
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Nursing care study. Blessing in disguise.
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DRGs: how are they stacking up?
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Reduced bile output with chronic enteral and parenteral infusion of amino acids, glucose, and fat emulsion in rabbits.
To assess the effect of chronic administration of amino acids, glucose, and fat on hepatic excretory function, bile flow and bile salt secretion were directly measured in adult rabbits alimented either intravenously or intragastrically. Five groups of animals were studied after 9-11 days on different nutritional regimes: the first, controls, received 154 mM NaCl intravenously and rabbit chow ad libitum; the second, 2.5% amino acid-10% glucose-10% fat emulsion intravenously; the third, the same nutrients intragastrically; the fourth, reduced intake of rabbit chow to match the weight change in the intragastrically fed animals; the fifth was allowed rabbit chow ad libitum and then received the nutrient solutions intragastrically only during bile collection. Bile was collected directly at laparotomy from the common bile duct during three 1-h periods: a basal period when no exogenous bile salt was infused, then with the addition of 1, and finally 2 mumol/min/kg of glycodeoxycholic acid, the main bile acid of rabbits. During the 3-h experiment either saline (control) or the nutrient solution was administered by the respective route. Chronic administration of the nutrient solutions, whether intravenously or intragastrically, significantly (p less than 0.05) reduced bile flow and bile salt secretion compared with controls and the rabbits on a reduced chow intake. The chronic intravenous route had a more pronounced cholestatic effect than the intragastric route. Acute intragastric nutrient infusion had no effect. The decreased bile output in the chronic groups resulted from a reduction in both bile salt secretion and bile salt-independent flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Evolution of a "right to health care".
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Naproxen disposition in patients with alcoholic cirrhosis.
Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.
Adrenoceptor function and ageing.
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Naproxen pharmacokinetics in the elderly.
While naproxen pharmacokinetics appear to be altered in the presence of both diminished renal and hepatic function, the degree to which naproxen disposition might be influenced in the elderly by concurrent alteration in these functions is not obvious. Total plasma clearance/bioavailability (CL/F) of naproxen after a single 375 mg oral dose was found to be less in a group of 10 healthy men between 66 and 81 years of age than in 10 healthy men between 22 and 39 years (0.318 +/- 0.078, 0.416 +/- 0.061 l/h). At steady state (375 mg, 12 hourly), however, CL/F was statistically indistinguishable between the two groups. The fraction of naproxen unbound to plasma protein was doubled in elderly subjects, both at peak and trough drug concentrations. The lowered protein binding tended to obscure a 50% decrement in the intrinsic clearance of naproxen in the elderly as estimated by unbound clearance/bioavailability (213 +/- 64, 396 +/- 155 l/h). As a result, mean steady-state plasma concentrations of naproxen were indistinguishable between the elderly and young (64.2 +/- 8.5, 58.2 +/- 8.1 mg/l) but the elderly generated twice the mean steady-state unbound plasma drug concentration (0.157 +/- 0.039, 0.0859 +/- 0.0212 mg/l). Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group. If a similar perturbation with age occurs in benoxaprofen protein binding as was observed with naproxen, benoxaprofen intrinsic clearance in the elderly might be only one quarter of that in younger individuals; a factor which may contribute to the toxicity of this drug in the elderly.
Smoking in pregnancy: effects on mother and fetus.
The maternal and fetal effects of smoking tobacco or non-tobacco cigarettes were studied in 75 pregnant patients and compared with a matched control group of 22 pregnant patients who did not smoke. The increase in maternal heart rate, maternal mean arterial pressure and fetal heart rate, and decrease in fetal heart rate 'baseline variability' and in fetal movements, were shown to be due primarily to the nicotine content of the cigarette.
Role of gastrin and cholecystokinin in the ontogenic development of the gastrointestinal tract.
The role of gastrin and cholecystokinin (CCK) in postnatal development of the small intestine was examined in infant rabbits. Experimental animals received daily intraperitoneal injections of pentagastrin, 500 micrograms/kg, or CCK-octapeptide, 40 micrograms/kg, starting on day 3 of life. The animals were sacrificed at age 17-18 days. Weight and histologic sections of pancreas, stomach, duodenum, proximal jejunum, and ileum were obtained and mucosal lactase and sucrase activities determined in the intestinal segments. No differences were seen in any of the parameters assessed in pentagastrin-treated animals compared to saline-injected littermate controls. Body weight, weight and morphology of pancreas, stomach and intestinal segments, and enzyme activities did not differ significantly. Na+ transport in proximal jejunum under short-circuited conditions was not altered by pentagastrin. CCK-octapeptide also had no effect on weight or morphology of pancreas, stomach, and duodenum, but did lead to a significant increase in weight of proximal jejunum and ileum. Mucosal enzyme activities and morphometric measurements of villus height and mucosal thickness, however, did not differ significantly between CCK-octapeptide-treated animals and saline-injected littermate controls. The increase in weight of jejunal and ileal segments was reflected by an increase in thickness of the muscle layer. The findings indicate that neither gastrin nor CCK plays a role in the ontogenic development of the small intestine.
Pseudocyesis.
While reports of pseudocyesis have been declining, this is still an important condition for physicians to recognize. Symptoms of pregnancy, abdominal distention, galactorrhea, amenorrhea and depression are common findings. Follow-up and counseling are necessary to assure that the patient accepts not being pregnant and the mental health is restored.
Alpha gliadin antibody levels: a serological test for coeliac disease.
The diagnostic value in coeliac disease of circulating antibodies to casein, crude gliadin, and alpha gliadin was assessed using an adaption of the enzyme linked immunosorbent assay system. alpha Gliadin was the only antigen which consistently separated 26 patients with untreated coeliac disease from 26 normal controls and 13 patients with chronic inflammatory bowel disease. The mean assay index for the 26 patients was 3.1 (SD 1.2) compared with 1.05 (0.5) for the normal controls and 1.1 (0.6) for patients with chronic inflammatory bowel disease. The alpha gliadin antibody levels of six patients with coeliac disease who had maintained a gluten free diet for at least two years were not significantly higher than normal (1.0 (0.4)). The validity of the test was determined in 90 consecutive patients who were being investigated for the presence of coeliac disease. Levels of alpha gliadin antibody were raised in 36 out of 44 patients found to have histologically proved coeliac disease and in six out of 46 subjects whose jejunal mucosa was normal. Serial alpha gliadin concentrations were measured in 12 patients with coeliac disease who had repeat jejunal biopsies performed six months after starting a gluten free diet. The levels of antibody fell in seven of the eight patients whose jejunal mucosa improved on maintaining the diet. They remained raised in four patients who did not adhere to the diet and whose mucosa did not improve. Although a test measuring alpha gliadin antibodies is unlikely to replace jejunal biopsy in the diagnosis of coeliac disease it may be useful in screening for the disease among outpatients.
Acute dermal toxicity of tetrachlorophenols in the rat.
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