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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 235 records · Page 13Linked to original sources
PubMed1997

ERCP and sphincterotomy in the context of laparoscopic cholecystectomy: academic and community practice patterns and results.

OBJECTIVE: To study the effect of practice setting and practitioner experience on the use and results of ERCP and sphincterotomy in the context of laparoscopic cholecystectomy. METHODS: Data were collected on 780 ERCPs performed before or after laparoscopic cholecystectomy. Biliary endoscopists at four academic centers and 33 community-based gastroenterologists of varying experience participated. RESULTS: Indications for perioperative ERCP were similar in academic centers and community practice, but academic experts performed a significantly higher proportion of postoperative procedures. Success rates were high for all participants, although the least experienced group of community-based gastroenterologists had a significantly lower rate of success with sphincterotomy. Complication rates did not vary significantly among participants. CONCLUSIONS: Experienced community-based gastroenterologists can perform ERCP and sphincterotomy in the context of laparoscopic cholecystectomy with results comparable to those of academic experts. Gastroenterologists with a life-time experience of fewer than 200 ERCPs have lower success rates for sphincterotomy than more experienced practitioners in either practice setting. ERCP performed in community or academic settings can provide safe and effective management of common bile duct stones and biliary leaks or strictures that occur after laparoscopic cholecystectomy.

Academic Medical Centers↗
PubMed1997

The Tripler Army Medical Center LEAN Program: a healthy lifestyle model for the treatment of obesity.

This paper provides an overview of the Tripler Army Medical Center LEAN Program for the treatment of obesity, hypercholesterolemia, and essential hypertension. The LEAN Program, a multi-disciplinary prevention program, emphasizes healthy Lifestyles, Exercise and Emotions, Attitudes, and Nutrition for active duty service members. The treatment model offers a medically healthy, emotionally safe, and reasonable, low-intensity exercise program to facilitate weight loss. We will discuss the philosophy behind the LEAN Program and the major components. Thereafter, we will briefly discuss the preliminary results.

Counseling↗
PubMed1997

Gowning: effects on patient satisfaction.

BACKGROUND: Given an extensive literature regarding the doctor-patient relationship, it appears curious that gowning status has received so little attention. The present study examined potential effects of gowning as opposed to not gowning patients at the point of presenting problem. Specifically, effects that gowning status might have on patients' trust in their physician, as well as overall duration of clinic visit, were investigated. METHODS: Patients (N = 1500) were randomly assigned to gown or non-gown status on arrival for clinic visit. Subsequent screening following predetermined guidelines resulted in 895 subjects participating in the study. Fifty-one percent of these patients (n = 455) fully completed the Trust in Physician Scale. Total time data from check-in to checkout, by gowning status, were kept on all patients. RESULTS: No significant effects for gowning status were found with respect to patients' trust in their physician or duration of clinic visit. There were also no significant interactions between gowning status, patient sex, physician sex, patient age, or patient education. Significant findings were demonstrated whereby younger patients and patients seeing a doctor for the first time reported less trust in their physician. CONCLUSIONS: There is not sufficient evidence, to date, to suggest that gowning status has a significant impact on the doctor-patient relationship or the duration of clinic visit.

Adult↗
PubMed1996

Assessment of submaximal exercise capacity in patients with left ventricular assist devices.

BACKGROUND: Long-term implantable left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation and may be used as long-term therapy for end-stage heart failure. After insertion of an LVAD, patients frequently become ambulatory. Sensors contained within these devices can measure the hemodynamic demands of submaximal exercise. In this study, we performed serial assessment of submaximal exercise capacity in patients with LVADs early (< 3 months), mid (3 to 6 months), and late (> 6 months) after device implantation to determine whether submaximal exercise capacity increased over time and whether this was related to improvements in the cardiac output response. Moreover, we compared the sub-maximal exercise capacities of these patients with those of normal subjects and patients with mild to severe heart failure. METHODS AND RESULTS: An encouraged 6-minute walk test with metabolic measurements was used to assess submaximal exercise capacity in 14 patients with LVADs, 20 patients with mild to moderate congestive heart failure (CHF), 14 patients with severe heart failure dependent on dobutamine (DB), and 6 normal subjects. Cardiac output measurements at rest and during exercise were obtained in the patients with devices. Distance walked was significantly greater for LVAD patients than DB patients and was similar to that for patients with mild CHF (LVAD, 1562 +/- 404; DB, 948 +/- 241; and CHF, 1358 +/- 278 ft; P < .01). Vo2 was also greater in the LVAD than DB or CHF patients (LVAD, 16.3 +/- 6.5; DB, 9.8 +/- 4.8; and CHF, 11.2 +/- 2.0 mL.kg-1.min-1; P < .05). Vo2 (23.4 +/- 7.4 mL.kg-1.min-1) and distance walked (2142 +/- 408 ft) in normal subjects was significantly greater than for all patient groups (all P < .01). Serial assessment of submaximal exercise capacity in LVAD patients demonstrated continued sustained improvement over time (early, 1261 +/- 341; mid, 1538 +/- 345; and late, 1867 +/- 265 ft; P < .05). However, peak cardiac output response was unchanged (early, 8 +/- 1.3; mid, 8.6 +/- 1.4; and late, 8.6 +/- 1.4 L/min; P = NS). CONCLUSIONS: The submaximal exercise capacity of LVAD patients is comparable to that of patients with mild CHF but significantly better than that of dobutamine-dependent patients. Hemodynamic and metabolic assessment during 6-minute walk tests demonstrates that in patients with heart failure and LVAD, cardiovascular demands are generally > 85% of maximum. A significant sustained improvement in submaximal exercise capacity occurs with chronic LVAD therapy. Lack of alteration of the cardiac output response to exercise suggests that this functional improvement results from peripheral mechanisms.

Adult↗
PubMed1996

Competition for tetrahydrobiopterin between phenylalanine hydroxylase and nitric oxide synthase in rat liver.

Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. To test this hypothesis, we determined whether conversion of phenylalanine to tyrosine was modified by changes in NO synthase activity, and conversely whether NO synthesis was limited by the rate of phenylalanine conversion to tyrosine in rat hepatocytes and perfused livers. NO production was decreased only slightly, when flux through PAH was maximized in isolated perfused livers, and in isolated hepatocytes only when BH4 synthesis was inhibited. Increases in NO synthesis did not reduce tyrosine formation from phenylalanine. Phenylalanine markedly increased biopterin synthesis, whereas arginine had no effect. Thus, basal BH4 synthesis appears to be adequate to support iNOS activity, whereas BH4 synthesis is increased to support PAH activity.

Animals↗
PubMed1996

A new animal model of reversible acute pancreatitis.

Numerous animal models of acute pancreatitis are utilized to assess pathophysiologic events and to evaluate therapeutic options. However, none of the small animal models simulates reversible biliary pancreatitis with long-term follow-up (weeks). The present study was designed to create a reversible model of acute biliary pancreatitis in small experimental animals. Male Sprague-Dawley rats were subjected to laparotomy, and the common bile duct was dissected free at its junction to the duodenum. Experimental animals had a polypropylene tie occluder passed around the common bile duct and brought out through a separate stab wound in the abdominal wall. The duct was occluded for 24 hr; the blockage was then relieved and the tie withdrawn from the animal. Sham-operative animals had similar surgical procedures but without the occluder. Serum amylase values on Days 1 and 2 following surgery were significantly increased in the experimental group, but were not different from those of control animals on Day 3 or 4, suggesting reversibility of this biliary pancreatitis model. Likewise, serum bilirubin levels were increased in the experimental group on Days 1 and 2. Histologic analysis revealed edema, zymogen degranulation, inflammatory infiltration, vacuolization of acinar cells, and focal areas of fat and parenchymal necrosis in the experimental group. Only mild edema was observed in the sham-operative controls due to surgical manipulation. Pancreatic tissues obtained at 1 week postinduction of pancreatitis showed near total destruction of the architecture and dissolution of zymogen granules; in contrast, histology at the 3rd week showed almost normal-appearing pancreas with return of zymogen granules, suggesting recovery from the acute pancreatitis. This reproducible and reversible model of acute pancreatitis in the rat will provide for further studies in the pathogenesis of pancreatitis and its therapeutic interventions.

Acute Disease↗
PubMed1996

Isolation of the full-length murine erythropoietin receptor using a baculovirus expression system.

The full-length murine erythropoietin receptor was expressed in Spodoptera frugiperda (Sf9) cells using a recombinant baculovirus vector. Erythropoietin receptor protein production was maximal 48 hours after infection, as determined by metabolic labeling and immunoblotting; receptor protein varied in molecular mass from 62 to 76 kD. Erythropoietin receptors produced in Sf9 cells could be solubilized using CHAPS in a form capable of binding erythropoietin, and the solubilized receptor bound to immobilized Concanavalin A (Con A) and wheat germ agglutinin, as well as to immobilized recombinant human erythropoietin. Analysis of the distribution of erythropoietin receptors in Sf9 plasma membrane and cytosol fractions using lectin affinity chromatography revealed that membrane-bound receptor had a higher apparent molecular mass and contained the bulk of receptors that bound to wheat germ agglutinin. The receptor was purified by sequential affinity chromatography on Con A-Sepharose and immobilized erythropoietin. Erythropoietin receptors expressed in Sf9 cells were inserted into the plasma membrane in the correct orientation, bound 125I-erythropoietin with a single affinity (kD, 330 pmol/L), and were internalized after ligand binding. However, kD varied inversely with the number of cell surface receptors. Solubilized erythropoietin receptors in whole-cell lysates and isolated plasma membranes exhibited high-affinity binding, with kD values of 92 and 57 pmol/L, respectively. Erythropoietin bound to the surface of infected Sf9 cells could be cross-linked to two proteins with molecular masses of 90 and 65 kD using the homobifunctional cross-linker, disuccinimidyl suberate (DSS). Similar results were obtained with solubilized receptors in whole-cell lysates, and both proteins could be immunoprecipitated by an antiserum to the erythropoietin receptor carboxyl-terminal domain.

Animals↗
PubMed1996

High-dose melphalan followed by autograft employing non-cryopreserved peripheral blood progenitor cells in children.

High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) enables dose escalation in the treatment of childhood malignancies. Here we report our experience of using peripheral blood progenitor cells (PBPC) to restore haematopoiesis in five children using a simple cell mobilising regime and non-cryopreservation of the harvests. Cells were mobilised using cyclophosphamide and granulocyte colony stimulating factor. Each patient underwent only two leukaphereses, the product being stored before use at 4 degrees C. Successful autologous PBPC transplantation was achieved with melphalan conditioning chemotherapy and re-infusion of the total progenitor cell product. No colony stimulating factors were administered after transplantation. The median numbers of mononuclear cells collected per patient was 10.0 x 10(8)/kg (range 8.13-19.44) and CFU-GM 57.6 x 10(4)/kg (range 10.4-178.85). All patients subsequently engrafted with the median number of days to a neutrophil count > 0.5 x 10(9)/l being 11 (range 10-16), and to a platelet count > 50 x 10(9)/l being 14 (range 12-31). The median number of in-patient days was only 20 (range 19-30). The median demand for blood was 2 units (range 1-2), and platelets 4 units (range 2-28). Usage of systemic antimicrobials and intravenous feeding was also low. Using this simple strategy, collection and transplantation of autologous progenitor cells can be a straightforward procedure in children. It is possible that this could enable dose escalation in some poor prognosis paediatric tumours.

Adolescent↗
PubMed1996

Lessons from combination therapy in Veterans Affairs Studies. Department of Veterans Affairs Cooperative Study Group on antihypertensive agents.

A subset of 102 patients of an original cohort of 1292 with stage 1 to 2 hypertension was characterized by having failed to achieve goal blood pressure (< 90 mm Hg diastolic) after treatment with two single antihypertensive drugs. These patients were given a combination of the two drugs on which they had failed to achieve blood pressure goal when they were administered as single-drug therapy. The drugs were hydrochlorothiazide, atenolol, captopril, diltiazem-SR, clonidine, and prazosin. We examined the responses in each of the drug combination categories by the order that the drugs were administered, by estimated total response rates for the combinations, and by age and race. The order of drug administration did have an effect for some of the drug pairs. This was of two types: 1) different results for each member of the pair, but the same combination result; and 2) different end result of the combination. An example of the first type is that prazosin had only a 6% response rate in patients who had failed on diltiazem, while diltiazem had a 22% response rate in patients who had failed on prazosin. Nevertheless, the combinations yielded the same total responses (86% and 84%) regardless of order. An example of the second type is that captopril-diltiazem was less effective in total response than diltiazem-captopril (88% v 97%). Differences were seen in the response to combinations in the race and age groups. There were ordering differences of type similar to those described above. We conclude that combination drug therapy is highly effective even when the individual components have failed and that some differences in response by order of drug administration may occur.

Antihypertensive Agents↗
PubMed1996

Age-related changes in O-deethylase and aldrin epoxidase activity in mouse skin and liver microsomes.

The metabolism of three model substrates for the cytochrome P450 dependent mono-oxygenase enzyme system (P450-MMO) was studied in microsomes isolated from skin and liver of young adult and senescent C57B1/6J mice. The substrates chosen were aldrin (AE), 7-ethoxycoumarin (EOC), and 7-ethoxyresorufin (EOR). Both EOC and EOR activities were lower in senescent skin. By contrast, no-age related changes were seen in senescent liver. AE was similar in young and old, in both tissues. We suggest that some important age-related differences in cutaneous xenobiotic metabolism do occur, but that these are not mirrored by hepatic differences, and are substrate specific. Previous work from these laboratories would also suggest significant species differences.

Aging↗
PubMed1996

Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure.

Abstract. NGNG dimethyl-L-arginine (asymmetric dimethyl-L-arginine; ADMA) and NGNG dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis. ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of patients with renal failure. However the precise concentration of ADMA and SDMA in renal patients is still controversial. This study was performed to measure plasma ADMA and SDMA concentrations by two different HPLC techniques in nine healthy controls and 10 uraemic subjects, and to investigate the effects of haemodialysis. In controls, the mean (+/-SEM) plasma concentrations of ADMA and SDMA were 0.36 +/- 0.09 and 0.39 +/- 0.05 mumol/l respectively, yielding an ADMA/SDMA ratio of 1.2 +/- 0.17. In uraemic patients, the plasma concentrations of ADMA and SDMA were 0.9 +/- 0.08 mumol/l (P < 0.001 compared to controls) and 3.4 +/- 0.3 mumol/l (P < 0.001 compared to controls) with an ADMA/SDMA ratio of 0.27 +/- 0.015 (P < 0.001). In the course of one 4 h haemodialysis session, ADMA concentrations decreased from 0.99 +/- 0.13 to 0.77 +/- 0.3 mumol/l and SDMA concentrations from 3.38 +/- 0.44 to 2.27 +/- 0.21 mumol/l. The plasma ADMA/creatinine ratio tended to increase from 1.26 +/- 0.20 x 10(-3) to 2.01 +/- 0.41 x 10(-3). It is concluded that there is a modest (3-fold) but definite increase in plasma ADMA concentration in uraemic patients compared to controls. SDMA accumulates to a greater degree (8-fold increase) and more closely parallels creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not accounted for by greater renal or dialysis clearance of ADMA, and, even though alternative explanations are not excluded, greater metabolism of ADMA than SDMA is the most likely explanation. Although small in magnitude, the increase in ADMA concentration might by biologically significant.

Adult↗
PubMed1996

Intracellular glutathione in the peripheral blood cells of HIV-infected patients: failure to show a deficiency.

OBJECTIVE: To determine whether HIV-infected patients have a deficiency of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) and erythrocytes. DESIGN: Initial experiments determining the stability of intracellular GSH preceded the measurement of GSH levels in 33 HIV-positive patients and 40 control subjects within 1 h of isolation of their blood cells. In addition, the susceptibility of erythrocytes to dapsone hydroxylamine-induced methaemoglobinaemia was evaluated. METHODS: GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically. RESULTS: GSH levels remained stable for only 1 h after cell isolation, thereafter showing a decrease of 20 and 60% at 4 and 24H, respectively, There was no difference in the GSH levels in PBMC and erythrocytes of the HIV-positive patients compared with controls. The GSH levels were not related to the disease stage or to CD4+ cell counts. There was no difference in GSH levels in PBMC taken from trimethoprim-sulphamethoxazole-hypersensitive and non-hypersensitive patients. Methaemoglobinaemia on exposure of erythrocytes to dapsone hydroxylamine was concentration-dependent, but there was no significant difference between patients and controls. CONCLUSION: In contrast to previous studies, no deficiency of intracellular GSH in the PBMC and erythrocytes of HIV-infected patients was found. The discrepancy between studies may be methodological reflecting the instability of GSH, which requires prompt sample analysis.

Adult↗
PubMed1996

Incidence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-positive Haemophilus influenzae in clinical isolates from patients with otitis media.

BACKGROUND: The prevalence of penicillin-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae in otitis media infections is increasing; emergence of these pathogens has complicated treatment. OBJECTIVES: To evaluate the incidence of penicillin resistance and the in vitro activity of amoxicillin/clavulanate, cefaclor, loracarbef, cefixime, trimethoprim/sulfamethoxazole, azithromycin and clarithromycin in S. pneumoniae isolates. The in vitro activity of azithromycin, clarithromycin and cefaclor was also evaluated in beta-lactamase-positive and -negative isolates of H. influenzae. METHODS: Bacterial isolates of S. pneumoniae and H. influenzae were obtained by tympanocentesis and subsequent culture of middle ear effusion from children with acute otitis media enrolled in a multicenter trial. Susceptibility to test agents was assessed by disk diffusion and broth dilution techniques with criteria established by the National Committee for Clinical Laboratory Standards. RESULTS: Nineteen (31%) of the 61 S. pneumoniae isolates were resistant to penicillin. A significantly lower percentage of the S. pneumoniae isolates were resistant to azithromycin (16%) and clarithromycin (11%) than to penicillin, amoxicillin/ clavulanate, cefaclor, loracarbef or cefixime (31% in all cases). Azithromycin was also more active than cefaclor and significantly more active than clarithromycin against the 55 H. influenzae isolates. CONCLUSIONS: The susceptibility of resistant and nonresistant strains of S. pneumoniae to azithromycin and clarithromycin and of isolates of H. influenzae to azithromycin, coupled with penetration of azithromycin into the middle ear, may provide a significant advantage in the treatment of otitis media.

Anti-Bacterial Agents↗