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Biomedical subjects

A Moran

Publications and source records attributed to A Moran.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nutritional screening--evaluation and implementation of a simple Nutrition Risk Score.

Development of a simple, validated Nutrition Risk Score for identification of patients at risk of undernutrition is described. The score is easy to use, applicable to all patient categories and ages, and correlated well with a validated Nutrition Risk Index (r = 0.68, p < 0.001) and clinical impression (r = 0.83, p < 0.001). Reproducible scores were obtained between dietitians (r = 0.91, p < 0.001) and between dietitians and nursing staff (r = 0.80, p < 0.001). The score was used to assess risk of undernutrition in 153 consecutive admissions to medical and surgical specialties. Patients were categorised as low (50%), moderate (24%) or high risk (26%). Evaluation of measures to prevent nutritional depletion revealed that no action was taken in 64% (23/36) of moderate risk and 30% (12/40) of high risk patients. Implementation of routine, hospital-wide nutritional screening, to identify patients in need of nutritional support, has been achieved by inclusion of the score in the standard nursing assessment process.

Journal Article↗
PubMed1995

Diagnostic value of a guaiac occult blood test and faecal alpha 1-antitrypsin.

This study evaluates the diagnostic accuracy of a faecal occult blood test and faecal alpha 1-antitrypsin in the investigation of patients with gastrointestinal symptoms or iron deficiency anaemia. One hundred and seventy nine patients with either iron deficiency anaemia (n = 67), changed bowel habit and aged > 39 years (n = 107), or a history suggestive of melaena (n = 5) provided faecal samples. After investigation, 32 patients had a diagnosis of possible gastrointestinal bleeding and 139 patients had no evidence of gastrointestinal bleeding. Eight patients had a cause of enteric protein loss in the absence of gastrointestinal bleeding and were excluded from subsequent analysis. The faecal alpha 1-antitrypsin test was diagnostically more accurate than the guaiac test in identifying probable gastrointestinal bleeding (82% and 72% respectively, p < 0.05). This faecal alpha 1-antitrypsin test was also more specific (83% and 72% respectively, p < 0.05), but was not significantly more sensitive (78% and 72% respectively). The sensitivity of these tests was insufficient to recommend their use for most patients in this study.

Adult↗
PubMed1995

Regulation of intracellular pH in J774 murine macrophage cells: H+ extrusion processes.

Mechanisms of intracellular pH (pHi) regulation were characterized in the murine macrophage cell line J774.1, using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein to measure pHi. Under nominally HCO3(-)-free conditions, resting pHi of nonadherent J774.1 cells was 7.53 +/- 0.02 (n = 86), and of adherent cells was 7.59 +/- 0.02 (n = 97). In the presence of HCO3-/CO2, pHi values were reduced to 7.41 +/- 0.02 (n = 12) and 7.40 +/- 0.01 (n = 28), respectively. Amiloride, an inhibitor of Na+/H+ exchange, did not affect resting pHi. Inhibitors of a vacuolar type H(+)-ATPase [bafilomycin A1, N-ethylmaleimide (NEM), 7-chloro-4-nitrobenz-2-oxa-1,3-diazide (NBD), and p-chloromercuriphenylsulfonic acid (pCMBS)] reduced pHi by at least 0.2 pH units. Inhibitors of other classes of H(+)-ATPases (oligomycin, azide, vanadate, and ouabain) were without effect. Inhibition of H+ efflux, measured by the change in extracellular pH of a weakly buffered cell suspension, followed the same pharmacological profile, indicating that the reduction of pHi was due to inhibition of H+ extrusion. Mechanisms of recovery from an imposed intracellular acid load were also investigated. In NaCl-Hanks' solution, pHi recovered exponentially to normal within 2 min. The initial rate of recovery was inhibited > 90% by amiloride or by replacement of extracellular Na+ concentration by N-methyl-glucamine. Inhibitors of the vacuolar H(+)-ATPase also inhibited recovery. NEM and NBD nonspecifically inhibited all recovery. Bafilomycin A1 and pCMBS did not inhibit the initial amiloride-sensitive portion of recovery, but they did inhibit a late component of recovery when pHi was above 7.0. We conclude that the Na+/H+ exchanger is primarily responsible for recovery from an acid load but does not regulate resting pHi. Conversely, a vacuolar H(+)-ATPase regulates the resting pHi of J774 cells but contributes little to recovery from acidification.

Acids↗
PubMed1995

Na+ channels in membrane vesicles from intralobular salivary ducts.

Electrical potential-driven 22Na+ fluxes were measured in membrane vesicles prepared from male and female rat submandibular intralobular ducts. A relatively temperature-independent (Q10 = 1.45 +/- 0.15), amiloride-inhibitable (mean affinity constant approximately 1 microM), rheogenic Na+ transport pathway was observed. The relative potency of amiloride analogues for inhibition of this pathway was amiloride > ethylisopropyl-amiloride > phenamil, similar to that of the "low-amiloride-affinity" Na+ channel recently observed in a number of other tissues. These results are consistent with the existence of the apical Na+ channel thought to be involved in intralobular ductal salt reabsorption. No significant difference was found in the magnitude or pharmacology of electrogenic Na+ fluxes in vesicles prepared from male and female rat intralobular ducts, suggesting that the sexual dimorphism observed in this tissue is not reflected at the level of the apical membrane Na+ channel. Amiloride-sensitive 22Na+ fluxes in intralobular ductal membranes were of the same magnitude as 22Na+ fluxes measured in similarly prepared and assayed vesicles from the toad bladder, a tissue thought to be a rich source of amiloride-sensitive Na+ channels.

Amiloride↗
PubMed1995

Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess.

Four deleterious mutations are described in the gene for HSD11B2, which encodes the type 2 isoenzyme of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD2). In seven families with one or more members affected by apparent mineralocorticoid excess, this disorder is shown to be the result of a deficiency in 11 beta HSD2. Surprisingly, the patients are all homozygous for their mutation. This results from consanguinity in two families and possibly from endogamy or a founder effect in four of the other five families. The absence of compound heterozygotes remains to be investigated.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Intracellular acidification mediates the inhibitory effect of peritoneal dialysate on peritoneal macrophages.

Commercial peritoneal dialysis solution (CDS) is known to have a detrimental effect on the capacity of peritoneal macrophages (PM phi) to kill bacteria and produce acute phase cytokines. This cytotoxic effect is largely caused by the low pH of CDS. Because the cytoplasmic pH (pHi) is an important determinant of cellular function, the effect of CDS on the pHi of PM phi from continuous ambulatory peritoneal dialysis patients was studied. The pHi of PM phi was measured fluorometrically in N-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered salt solution (HBSS) or CDS at pH values of 5.3, 6.5, and 7.0, values that represent the pH existing in dialysate during the first 30 min of dwell time. For any given pH of the experimental medium, the pHi was always more acidic in CDS than in HBSS. When PM phi were incubated with a lactate-containing HBSS, a cellular acidification was observed that was similar to that attained by exposure to CDS at the same pH. This supports the hypothesis that the decrease in pHi was due to the influx of lactic acid from the CDS into the PM phi. In order to demonstrate a causal association between the CDS-induced cellular acidification and a defect in phagocytosis and cytokine production, these functions were studied after pHi clamping by means of K+/nigericin. It was found that clamping pHi to values below 6.5 led to a markedly reduced tumor necrosis factor-alpha production and phagocytosis. However, at values of pHi > 6.5, these functions were normal. (ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗
PubMed1995

Laboratory markers of colonoscopic activity in ulcerative colitis and Crohn's colitis.

BACKGROUND: Previous studies have not identified a convenient laboratory marker of colonoscopic activity in Crohn's colitis or ulcerative colitis. METHODS: Twenty-eight patients with either ulcerative colitis or Crohn's colitis undergoing colonoscopy by the same observed had laboratory measurements of serum albumin, orosomucoid, C-reactive protein, plasma viscosity, haemoglobin, leucocyte and platelet counts, and faecal alpha-1-antitrypsin from single non-lyophilized samples. Multiple linear regression was performed using each laboratory variable as the dependent variable and the lengths of each grade of endoscopic activity as the explanatory variables. RESULTS: Multiple regression analysis using all the endoscopic grades of acute activity showed significant correlations with faecal alpha-1-antitrypsin (p < 0.001), serum albumin (p < 0.001), C-reactive protein (p = 0.02), and plasma viscosity (p = 0.03). CONCLUSIONS: The highest multiple correlation coefficients were obtained with faecal alpha-1-antitrypsin (r = 0.82) and serum albumin (r = 0.80), and these measurements can be recommended as convenient markers of endoscopic activity in these diseases.

Adult↗
PubMed1995

Localized stage non-Hodgkin's lymphoma of the testis: a retrospective study of 16 cases.

The present report concerns a retrospective study of 16 patients with localized intermediate- or high-grade non-Hodgkin's lymphoma of the testis treated in one institution from 1973 to 1990. Ann Arbor stage of disease was IE in 11 and IIE in 5 cases. All except one patient underwent initial inguinal orchidectomy, 11 were disease free after surgery and 12 received inverted Y radiation therapy. All patients achieved a complete remission (CR). Relapse occurred in 8 of 9 patients who did not receive initial chemotherapy, but in only 3 of 7 patients initially treated with chemotherapy including anthracyclins. In 3 cases relapse was confined to the CNS, while diffuse relapse in 8 others included 4 cases of CNS involvement. Eight patients are now alive in CR (5 in first CR, 1 in second CR and 2 in third CR) with a median follow-up of 68.5 months (range 54-101). Chemotherapy thus emerges as the initial treatment of preference for localized testicular lymphoma. Therapy should be preceded by a thorough assessment of the stage of disease and due to the high frequency of CNS relapse, CNS prophylaxis should be considered for all patients.

Adult↗
PubMed1994

Characterization of regulatory volume decrease in the THP-1 and HL-60 human myelocytic cell lines.

Exposure to hypotonic stress produces a transient increase in cell volume followed by a regulatory volume decrease (RVD) in both THP-1 and HL-60 cells. In contrast, cells exposed to hypotonic stress in a high K/low Na Hanks' solution not only failed to volume regulate, but displayed a secondary swelling. Thus, while an outward K gradient was required for RVD, the secondary swelling indicated that hypotonic stress increased permeability in the absence of a negative membrane potential. The K channel blocker quinine (1-4 mM) blocked RVD in both cell types. Gramicidin's ability to overcome the quinine block of RVD indicated that RVD is mediated by a quinine-sensitive cation transport mechanism that is independent of the swelling-induced anion transport mechanism. Barium (1-4 mM), another K channel blocker, slowed the rate of RVD, while 4-aminopyridine, charybdotoxin, tetraethylammonium chloride, tetrabutylammonium chloride, and gadolinium had no effect on RVD. Furthermore, RVD was not mediated by calcium-activated conductances, since it occurred normally in Ca-free medium, in medium containing cadmium, and in BAPTA-loaded cells. Gramicidin produced little or no volume change in isotonic medium, suggesting that basal C1 permeability of both THP-1 and HL-60 cells is low. However, swelling induced an anion efflux pathway that is permeable to both chloride and bromide, but is impermeable to methanesulfonate and glutamate. The anion channel blocker 3,5-diiodosalicylic acid (DISA) antagonized RVD in both cell types. In conclusion, RVD in THP-1 and HL-60 cells is mediated by independent anion and cation transport mechanisms that involve both a DISA-sensitive anion pathway and a quinine-inhibitable K efflux pathway, neither of which requires increases in intracellular calcium to be activated.

Anions↗
PubMed1994

Insulin-mediated and glucose-mediated glucose uptake following hemipancreatectomy in healthy human donors.

Healthy humans undergoing hemipancreatectomy for the purpose of donation to a family member with IDDM have previously been demonstrated to maintain serum glucose values equal to matched control subjects during short-term glucose infusion despite significant decrements in glucose- and arginine-induced insulin secretion. In order to determine whether humans compensate for hemipancreatectomy by increasing insulin- or glucose-mediated glucose uptake, we measured glucose turnover and insulin sensitivity by three protocols. Insulin-mediated glucose uptake was measured during sequential infusions of insulin at rates of 0.25, 1.0, and 10.0 mU.kg-1.min-1 in 12 donor subjects and 12 matched control subjects maintained at euglycaemia. Both groups displayed similar increases in rates of glucose disappearance and similar decreases in rates of hepatic glucose production. Glucose-mediated uptake was calculated as the difference between the rates of glucose disappearance measured during a hyperglycaemic clamp performed at identical rates of insulin infusion and was also found to be similar in both donor subjects and control subjects. Both groups also had indistinguishable measures of insulin sensitivity and glucose effectiveness as determined by the minimal model technique. Therefore, donor subjects appear to compensate for diminished insulin secretion following hemipancreatectomy by an unidentified mechanism since neither insulin- nor glucose-mediated glucose uptake are increased.

Adult↗
PubMed1994

Enteric alpha-1-antitrypsin loss and comparison with Okokit II and Haemoccult for the detection of colorectal cancer.

Faecal samples from patients with symptomatic colorectal cancer (n = 19) and from control subjects (n = 54) were analysed for alpha-1-antitrypsin (A1AT) and compared with Haemoccult and Okokit II. A1AT was also measured in paired samples of normal colonic mucosa and cancer tissue (n = 16) and in media from four human colorectal cell lines (COLO 320 DM, SW620, HT29, LS 174T). Faecal A1AT concentrations were greater than controls (P < 0.0001) and detected 12 (63%) patients with cancer compared to 10 (53%) by Okokit II and 7 (37%) by Haemoccult (P > 0.05). A1AT concentrations from colonic mucosa (median, range: 0.46, 0.17-0.79 mg/g wet wt) were greater (P = 0.01) than cancer tissue (0.29, 0.13-0.74 mg/g wt wt). Adjusting for albumin, A1AT concentrations from mucosa (12.0, 3.8-32.2 mg/g albumin) remained greater (P = 0.003) than for cancer tissue (5.9, 2.4-21.4 mg/g albumin). A1AT was not detected in any of the cell-line media. The most likely mechanisms for increased faecal A1AT concentrations, apart from increased blood loss, are increased cell turnover or leakage from epithelial tight junctions. The use of faecal A1AT measurement for the detection of colorectal cancer deserves further assessment.

Aged↗
PubMed1994

Dual bezafibrate-simvastatin therapy for combined hyperlipidaemia.

Statins and fibrates are both effective in the treatment of hyperlipidaemias but are not recommended in combination because episodes of rhabdomyolysis have followed combined lovastatin-gemfibrozil therapy. We assessed treatment with dual bezafibrate-simvastatin therapy in routine clinical practice. In 22 patients, total cholesterol, LDL-cholesterol and triglycerides fell by 20.1% (P < 0.0001), 35.1% (P < 0.001) and 31% (P < 0.05) respectively, and HDL-cholesterol rose by 18.4% (P < 0.05) on combination therapy. The reduction in cholesterol followed the introduction of simvastatin, while the decrease in triglycerides followed treatment with bezafibrate. No patient developed myopathy. We conclude that dual simvastatin-bezafibrate therapy is well tolerated and may reduce triglyceride concentrations, but offers no advantage in cholesterol reduction over treatment with simvastatin alone.

Adult↗
PubMed1994

Percutaneous endoscopic gastrostomy in a general hospital: prospective evaluation of indications, outcome, and randomised comparison of two tube designs.

The indications for percutaneous endoscopic gastrostomy (PEG) and patient outcome, were examined prospectively in the setting of a general hospital. In the course of 26 months, 76 patients underwent PEG (median age 62 years (range 18-99)) and were followed up for 6887 patient days. The median (range) duration of PEG feeding was 93 (3-785) days. The procedure was carried out for neurological indications in 76% of cases (stroke 51%) and 53% of patients were severely malnourished (body mass index < 17 kg/m2) at the time of referral. In 12 (16%) patients swallowing recovered and the PEG was removed after a median (range) of 55 days (20-150). Three (4%) deaths were related to PEG (one oesophageal perforation, one haemorrhage, and one aspiration pneumonia). One patient developed peritonism and ileus, which resolved with conservative treatment. Minor complications included local sepsis 3%, tube blockage 12%, and tube connector leak 5%. During seven days of observation, demands on nursing time for routine care of the PEG were the same as for nasogastric tube feeding, median (range) 21 (4-42) v 16 (4-40) min/day respectively, but in about half the latter cases the tube had to be replaced at least once. Over 15 months, 29 patients were randomised to receive a 1.9 mm inner, 2.9 mm (9F) outer diameter Fresenius and 27 a 3.0 mm inner, 4.0 mm (12F) outer diameter Bower polyurethane tube and were followed for 2920 and 2388 patient days respectively. There was no difference in the insertion time (median (range) 20 (10-45) v 24 (10-45) min respectively) or number of patients with complications (three v eight patients NS), although there were more minor mechanical problems (three v 12, p < 0.01) with the 12F tube. The internal anchoring device of the 12F tube allowed its non-endoscopic removal, a method applicable too 16% of cases. No tubes were removed because of blockage.

Adolescent↗
PubMed1994

Cyclooxygenase inhibitors suppress inhibitory effect of PGE2 on Na-K-ATPase in MDCK cells.

In a previous work, we showed that picomolar concentrations of prostaglandin E2 (PGE2) inhibit Na-K-ATPase activity and ouabain binding in a clone of Madin-Darby canine kidney (MDCK) cells. In the present study, we demonstrate that the inhibitory effects of PGE2 on Na-K-ATPase activity, ouabain-sensitive Rb+ uptake, and ouabain binding in MDCK cells were diminished by treatment of the cells with nonsteroidal anti-inflammatory drugs. These results suggested that products of arachidonic acid synthesized through the cyclooxygenase pathway are involved in the inhibitory mechanism of PGE2. Treatment of the cells with arachidonic acid resulted in inhibition of ouabain binding, and the inhibition was eliminated by cyclooxygenase inhibitors. These observations further support the involvement of cyclooxygenase products in the PGE2-induced inhibitory process. Finally, we demonstrated that dopamine inhibits Rb+ influx and ouabain binding in MDCK cells similarly to PGE2. Cyclooxygenase inhibitors suppressed the inhibition of ouabain binding by dopamine, thus also suggesting the involvement of cyclooxygenase products in the inhibitory effect of dopamine.

Animals↗
PubMed1994

Insulin sensitivity in cystic fibrosis.

Cystic fibrosis (CF) patients demonstrate a spectrum of pancreatic beta-cell abnormalities. Those with no exocrine insufficiency (NEXO) have normal insulin secretion. Exocrine-insufficient CF patients with overt diabetes (EXO-IT) have impaired insulin secretion and fasting hyperglycemia. Exocrine-insufficient patients without diabetes (EXO) have impaired insulin secretion but maintain normoglycemia. We postulated that EXO individuals compensate for insulin deficiency by increasing insulin sensitivity and investigated glucose utilization in CF. To examine hepatic and peripheral insulin sensitivity, euglycemic-hyperinsulinemic clamp studies were performed by using the hot GINF isotope dilution technique. Insulin was sequentially infused at 0.25, 1.0, and 10.0 mU.kg-1.min-1. Glucose-mediated glucose uptake (GMGU) was assessed on another day with hyperglycemic clamp studies, during which insulin and somatostatin were infused to hold insulin-mediated glucose uptake constant between the two clamp studies. Skeletal muscle GLUT4 levels were assessed in EXO and control patients with Western blotting. Three patterns of peripheral and hepatic insulin sensitivity were seen that were related to the degree of pancreatic beta-cell dysfunction. NEXO individuals had normal peripheral and hepatic insulin sensitivity. EXO individuals had enhanced peripheral insulin sensitivity that was not associated with a change in skeletal muscle glucose transporter abundance compared with control patients; paradoxically, EXO subjects demonstrated hepatic insulin resistance. EXO-IT had peripheral and hepatic insulin resistance. GMGU was diminished in both EXO and EXO-IT subjects. The unique combination of increased hepatic glucose production and increased peripheral glucose utilization seen in EXO may be a metabolic adaptation to increased peripheral energy needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Value of faecal alpha-1-antitrypsin, haemoglobin and a chemical occult blood test in the detection of gastrointestinal disease.

Specimens from hospital out-patients and in-patients sent for faecal occult blood tests were also analysed for faecal alpha-1-antitrypsin and faecal haemoglobin. 453 stool specimens from 222 patients were analysed. The clinicians were only aware of the faecal occult blood test results, and diagnoses were made using conventional clinical and investigative criteria. Gastrointestinal bleeding or putative sites of bleeding were diagnosed in 98 patients, whereas in 81 patients putative sites of bleeding were not found or other cause of anaemia diagnosed. In 41 patients there was insufficient information to reach a definitive diagnosis. Comparison of the 3 faecal tests using these grouping methods showed that faecal alpha-1-antitrypsin performed best, with an accuracy of 89%, specificity of 90% and sensitivity of 88%, all significantly better (P < 0.001) than the faecal occult blood test (68%, 60% and 73%, respectively). There was no significant difference between the performance of the faecal occult blood and faecal haemoglobin tests. Faecal alpha-1-antitrypsin measurement may be a useful investigation in situations where a faecal occult blood test would normally be requested.

Adolescent↗
PubMed1993

Deficient glucose phosphorylation as a possible common denominator and its relation to abnormal leucocyte function, in glycogen storage disease 1b patients.

Patients with glycogen storage disease (GSD) 1b suffer from recurrent bacterial infections related to neutropenia and impairment of neutrophil functions. One of these functions is the oxidative burst activity which is initiated by NADPH oxidase and depends on the availability of glucose. This activity was markedly reduced in the patient's intact neutrophils when either N-formyl-methionyl-leucyl-phenylalanine (fMLP), or phorbol myristate acetate were used as stimulants. In disrupted GSD 1b polymorphonuclear leucocytes (PMNs), in the presence of exogenous NADPH, this activity was within the normal range. Degranulation, which is calcium dependent but glucose independent, was not significantly different in neutrophils from the patients as compared to controls. Resting cytosolic calcium concentration was indistinguishable from controls. Activation with 10(-7) M fMLP, in the presence or absence of glucose, triggered a prompt and rapid elevation of cytosolic calcium both in the control and the patients' cells. We have previously shown that hexose monophosphate (HMP) shunt activity and glycolytic rate were found to be lower by 70% in intact PMN cells of the patients compared with controls. These activities were normal in disrupted neutrophils. The uptake of the non-metabolized glucose analogues 2-deoxyglucose (2-DOG) and 3-O-Methylglucose (3-OMG) into PMN of GSD 1b patients was studied. 2-DOG is phosphorylated within the cells, thus its uptake rate reflects hexose transport at low concentrations, as long as phosphorylation is not rate limiting. Under those conditions (5 microM 2-DOG) transport was found to be similar to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗