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Biomedical subjects

D Sullivan

Publications and source records attributed to D Sullivan.

At least 91 records · Page 5Linked to original sources
PubMed1993

Ibuprofen controlled-release formulation. A clinical trial in dental impaction pain.

This double-blind study compared a controlled-release formulation of ibuprofen 600 mg with three doses of regular ibuprofen 200 mg and three doses of codeine 30 mg. Patients who had dental impaction surgery received the controlled-release ibuprofen, codeine, or regular ibuprofen when postoperative pain reached moderate to severe intensity. At 4 and 8 hours after dose 1, patients who had initially received the controlled-release ibuprofen received a placebo, and those taking ibuprofen and codeine received their second and third doses of those drugs. All doses of study medication or placebo appeared identical for each treatment. Subjects made evaluations hourly for 12 hours in a diary. The controlled-release ibuprofen had a comparable onset to ibuprofen, a higher peak effect, and was significantly more effective than ibuprofen at hour 4; the controlled-release ibuprofen was significantly more effective than codeine for all hourly observations through hour 9. Ibuprofen was significantly better than codeine only through hour 3. The controlled-release ibuprofen had the lowest incidence of side effects and codeine the highest. The single dose of the controlled-release ibuprofen formulation appeared as efficacious as three regular doses of ibuprofen 200 mg over a 12-hour period.

Adult↗
PubMed1993

Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients.

Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.

AIDS-Related Opportunistic Infections↗
PubMed1992

Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents.

Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

Aldehyde Reductase↗
PubMed1992

Effect of thermal injury on transfer of IR22 IgA myeloma protein into bile in the rat.

We previously observed a 75-90% decrease in concentration of biliary IgA after thermal injury to rat skin. Decrease in biliary IgA might result from an alteration in supply of polymeric IgA delivered to the hepatocyte or from an alteration in hepatocyte transfer of polymeric IgA into bile. In the present study, we examined the transfer of intravenously administered 125I-IgA into bile. Purified IR22 rat IgA myeloma protein consisting of both monomeric and polymeric IgA was labelled with 125I. Sprague-Dawley rats (140-180 g) received a 20-30% body surface area scald-burn or sham treatment. The bile duct was cannulated 18-24 h later and 125I-IgA preparations were injected into the tail vein. Bile was collected under light ether anesthesia for 3 h. In rats injected with 125I-IR22 IgA myeloma protein there were no significant differences in total, TCA-precipitable, or immunoprecipitable radioactivity in bile from burn-injured or sham-treated animals. On Bio-Gel A-1.5 m gel permeation, the radioactivity in bile from sham-treated animals eluted in the region of polymeric IgA as expected; the radioactivity in the bile from burn-injured animals eluted equally in the same regions as polymeric IgA and monomeric IgA. In sham-treated rats injected with isolated polymeric IgA only, bile contained primarily polymeric IgA. In burn-injured rats injected with polymeric IgA only, bile contained a mixture of polymeric IgA and monomeric IgA. These findings suggest that hepatocyte processing of polymeric IgA is altered after thermal injury, resulting in the transformation of some polymeric IgA into its monomeric form.

Animals↗
PubMed1992

Hypercholesterolemia after chemotherapy for testis cancer.

PURPOSE: The study was designed to determine prospectively the prevalence of fasting serum lipid abnormalities in patients who were treated with cisplatin-based chemotherapy for germ cell tumors. We unexpectedly had demonstrated hypercholesterolemia in 20 of 30 nonfasting patients in a prior study of long-term toxicity of chemotherapy for germ cell tumors. The present study was designed to explore this phenomenon further. PATIENTS AND METHODS: Seventeen unselected patients with biopsy-proven germ cell tumors, who underwent cisplatin-based chemotherapy and who had no prior history of cardiac disease nor known hypercholesterolemia, were studied. In addition to the standard staging tests, blood was drawn for a pretreatment fasting lipid screen, which included cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1, B, and (a). Repeat samples were drawn 24 hours after the administration of cisplatin and at intervals of 6 to 24 months after the completion of treatment. RESULTS: Seven of 17 patients (41%) had higher than desirable levels of total serum cholesterol and low-density lipoprotein cholesterol. Two of them had normal levels before treatment, four had preexisting hypercholesterolemia that increased further, and one patient had an elevated pretreatment level that did not alter. Absolute increases in serum cholesterol were noted in 14 of 17 patients. No consistent patterns of change beyond the reference ranges were found for other serum lipids. CONCLUSIONS: We have confirmed our initial observation that serum cholesterol increases in patients who received cisplatin-containing chemotherapy regimens for germ cell tumors. Further studies will be necessary to define whether other lipid abnormalities occur and the biologic significance of these findings.

Adolescent↗
PubMed1991

The effect of danazol on pulsatile gonadotropin secretion in women with endometriosis.

OBJECTIVE: To determine whether the effect of danazol on gonadotropin pulsatility was due to a direct effect of the drug or the suppression in the estradiol (E2) levels. DESIGN: Prospective analysis of serial blood samples at 10-minute intervals for 5 hours on days 3, 4, or 5 of the control cycle and 2 months after the start of danazol treatment. SETTING: Tertiary institutional outpatient care. PATIENTS, PARTICIPANTS: Six eugonadal women with minimal endometriosis. INTERVENTIONS: Oral administration of danazol, 200 mg three times daily. MAIN OUTCOME MEASURES: Gonadotropin mean levels, pulse frequency, and amplitude. RESULTS: The mean level of E2 was the same in the control cycle as that during danazol treatment (170 pmol/L). Danazol administration resulted in a 16% increase in the mean luteinizing hormone (LH) pulse amplitude (95% confidence interval [CI] 6% to 26%, P less than 0.01), associated with a 20% decrease in LH pulse frequency (95% CI -71% to +31%, P = 0.37). There was a nonsignificant increase in follicle-stimulating hormone (FSH) pulse amplitude (2%, 95% CI -9% to +14%, P = 0.68) and in FSH pulse frequency (27%, 95% CI -4% to +58%, P = 0.08). The 22% decrease in the mean LH level (95% CI -85% to +12%, P = 0.13) and the 20% decrease in the mean FSH level (95% CI -53% to +37%, P = 0.33) were also not significant. CONCLUSIONS: The increase in LH pulse amplitude represents a direct effect of danazol on the hypothalamic-pituitary axis.

Adult↗
PubMed1991

Tumour evolution in rats monitored by changes to serum and lipoproteins.

The biochemical, physicochemical and magnetic resonance (MR) properties of rat serum allow tumour evolution to be monitored. Serum from female Fischer rats injected with rat mammary adenocarcinoma cells contained a low-density lipoprotein (LDL)-like lipoprotein and decreased high-density lipoprotein levels compared with normal rat serum. Increases in secondary tumour burden coincided with enlarged LDL-like particles, altered MR properties and elevation of serum triglyceride. By fucosidase treating metastatic R13762 cells prior to injection, not only was metastatic capacity retarded, but serum lipoproteins were also altered. These physicochemical alterations suggest an intricate relationship between both primary and secondary tumour burdens and the serum lipoprotein profile.

Adenocarcinoma↗
PubMed1990

Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.

The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.

Adult↗
PubMed1990

Assay of apolipoproteins A-1 and B by immunoturbidimetry: detection of individuals at risk for atherosclerotic artery disease.

Recent evidence has suggested that the levels of Apolipoprotein A-1 and B in plasma are better indicators of the risk of atherosclerotic artery disease than plasma lipids. This study describes the measurement of plasma Apolipoprotein A-1 and B by immunoturbidimetry in patients with atherosclerotic artery disease and in normal controls. Apoprotein B and the ratio of Apoprotein A-1/Apoprotein B were found to be the best discriminators between the two groups.

Adult↗
PubMed1990

Determinants of pulmonary function in patients undergoing coronary bypass operations.

Pulmonary function testing was conducted consecutively in 29 healthy men (age range, 42 to 71 years) undergoing elective coronary artery bypass grafting. Lung volumes, expiratory flow rates, diffusing capacity, and blood gases were determined before operation, at discharge (8.7 +/- 1.9 days), and at 3 months postoperatively. In addition, peak expiratory flow rate was measured immediately after extubation (21.4 +/- 2.7 hours). Fifteen patients had smoked within the past year, but none had a history of pulmonary impairment. Twenty-two patients had internal mammary artery (IMA) dissection. Operation and recovery were uneventful in all cases. After extubation, peak expiratory flow rate was decreased by 65%. At discharge, lung volumes were decreased by 19% to 33% below preoperative values and expiratory flow rates were decreased by 33% to 37% below preoperative values. Some minor changes were detected at 3 months. Further analysis of these changes according to smoking history, age, preoperative weight, dissection of IMA, and aortic cross-clamp time showed that only IMA dissection affected the postextubation changes in peak expiratory flow rate (p less than 0.0001), whereas the decreases in functional residual capacity and expiratory reserve volume at discharge were affected by IMA dissection (p less than 0.05) and age (p = 0.01). Thus, median sternotomy is associated with severe but short-term pulmonary dysfunction; IMA dissection has a significant adverse effect on these changes.

Age Factors↗
PubMed1990

Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics, and urine prostaglandin production of healthy humans.

The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Cocaine and lidocaine interfere with epinephrine-induced changes in intracellular calcium concentration and glucose efflux from rat hepatocytes.

The mechanism of cocaine-induced hepatotoxicity is not clearly understood. Recent studies show that fluctuations in intracellular Ca2+ ([Ca2+]i) and/or cyclic-AMP ([cAMP]) concentration play a major role in hormone action, and sustained elevations in [Ca2+]i may be involved in the initiation of hepatocellular damage. To evaluate the possible involvement of intracellular Ca2+ and/or cAMP, we investigated effects of cocaine and lidocaine on basal, epinephrine and dibutyryl cyclic-AMP (DBcAMP)-induced changes in [Ca2+]i and glucose efflux from isolated rat hepatocytes. [Ca2+]i was monitored continuously using a Ca2(+)-selective fluorescence indicator, Quin-2, and was calculated after correcting for autofluorescence. Neither cocaine nor lidocaine (0.1-5 mmol/l) affected basal [Ca2+]i, yet both agents decreased epinephrine (10 mumol/l) and DBcAMP (100 mumol/l)-induced increases in [Ca2+]i in a dose-dependent fashion. Half-maximal inhibition occurred at 0.75 mmol/l cocaine and 1.7 mmol/l lidocaine. Cocaine and lidocaine also decreased epinephrine and DBcAMP-induced glucose efflux. The dose-dependent effect on epinephrine-induced glucose efflux was similar to that of both anesthetics on epinephrine-induced increases in [Ca2+]i. However, 5 mmol/l cocaine or lidocaine decreased DBcAMP-induced glucose efflux by less than 50%, and [Ca2+]i by more than 80%. Taken together, these results indicate that cocaine and lidocaine decrease the ability of epinephrine to stimulate glucose efflux by interfering with the Ca2(+)-mediated, and not the cAMP-mediated intracellular pathway. It is therefore speculated that alterations in metabolic endocrine regulation may contribute to cocaine's hepatotoxic effect.

Animals↗
PubMed1990

Hepatic fibrosis with the use of methotrexate for juvenile rheumatoid arthritis.

Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. One complication of MTX is hepatotoxicity. Although liver function tests may be abnormal with its use, in this setting they do not correlate well with the development of hepatic fibrosis. Periodic liver biopsy is required to monitor for the hepatotoxic changes secondary to MTX. We describe and discuss the case of a 17-year-old woman who developed evidence of hepatic fibrosis after 3 years of MTX therapy.

Adolescent↗
PubMed1989

Efficacy of prophylactic antibiotics in vascular surgery: an arterial wall microbiologic and pharmacokinetic perspective.

This prospective study examined microbiologic features of arterial tissue and pharmacokinetics and bioactivity of cefamandole and cefazolin in patients undergoing elective primary prosthetic aortoiliofemoral/infrainguinal reconstruction. Double-blind, randomized, perioperative prophylaxis (1 gm intravenously every 6 hours for nine doses) with cefamandole or cefazolin was administered to 47 patients. Specimens of blood serum, subcutaneous fat, thrombus, atheroma, and arterial wall were obtained for culture and minimal inhibitory concentration and drug level analysis by high-pressure liquid chromatography. The serum half-life (hr +/- SEM) was 1.43 +/- 0.36 for cefamandole and 2.22 +/- 0.40 for cefazolin. Over the first 2 hours of surgery and for all time intervals combined, the serum concentration of cefazolin was significantly higher (p less than 0.025) than cefamandole. Irrespective of sampling time, the tissue concentration of cefazolin was significantly greater (p less than 0.005) than cefamandole. Positive arterial tissue cultures were obtained in 12 of 29 patients (41.4%) from 23 of 116 (19.8%) arterial tissue specimens. Coagulase-negative Staphylococcus was the predominant isolate, 64 of 93 (68.8%). Twenty-five of the 51 coagulase-negative staphylocci tested (49%) were slime-producers. During surgery, the arterial tissue concentration of cefamandole fell below the geometric mean minimal inhibitory concentration against all organisms combined, and against S. aureus (with the highest minimal inhibitory concentration of the prevalent isolates), significantly more often than the concentration of cefazolin. The data show that a significant number of primary elective aortoiliofemoral/infrainguinal reconstructions are associated with positive arterial tissue cultures, which represent a potential source of graft infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1989

Effect of thermal injury in the rat on transfer of IgA protein into bile.

Severe thermal injury is associated with bacterial sepsis; the intestine is considered a likely source of invasive organisms. Because IgA antibody in bile accounts for much of the specific immune defense of the upper intestinal tract in the rat, the effect of thermal injury on the quantity of IgA protein in bile was examined. Sprague-Dawley rats received a 20% to 30% body surface area burn under anesthesia. Eighteen hours later the common bile duct was cannulated and bile was collected for three hours. Total IgA protein in bile decreased 90% after thermal injury. The bile volume, the concentration of bile protein, and free secretory component did not change significantly. Although blood flow to the liver 18 hours after thermal injury was not changed, there was a significant reduction in total IgA concentration in the circulation; both monomeric (m-IgA) and polymeric IgA (p-IgA) were decreased. This finding may explain, in part, the reduced concentration of IgA protein in bile. Although not examined in this study, decreased local hepatic synthesis and/or transport of p-IgA across the hepatocyte may also contribute to the reduced IgA levels in bile.

Animals↗