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Biomedical subjects

D Sullivan

Publications and source records attributed to D Sullivan.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of dietary L-arginine on atherosclerosis and endothelium-dependent vasodilatation in the hypercholesterolemic rabbit. Response according to treatment duration, anatomic site, and sex.

BACKGROUND: Nitric oxide (NO) may protect arteries against atherosclerosis. In the present study, we examined whether dietary L-arginine, the precursor of NO, could chronically preserve endothelium-dependent vasodilatation in vivo and/or limit atherogenesis. METHODS AND RESULTS: Rabbits were randomized according to sex to receive 2% dietary cholesterol, with or without L-arginine (2.25% solution), for 7 or 14 weeks. Hindlimb vasodilator responses to acetylcholine and nitroprusside were measured with an electromagnetic flow probe. Atherosclerosis was measured with planimetry of aortic lesions stained with Oil-Red-O. In rabbits administered L-arginine, plasma arginine levels increased to 483 +/- 30 mumol/L at 3 weeks (mean +/- SEM, P < .0001 versus control animals) but declined to 224 +/- 25 mumol/L at 7 weeks (P = .02) and to 100 +/- 23 mumol/L at 14 weeks (NS versus control animals). At 7 weeks, peak hindlimb conductance in response to acetylcholine in cholesterol-fed males was 249 +/- 49% of baseline compared with 332 +/- 9% in control animals (P = .04), but peak response in arginine-fed rabbits (314 +/- 24%) did not differ from that of control animals. At 14 weeks, peak responses to acetylcholine were equally reduced in males fed cholesterol with (266 +/- 21%, P = .02 versus control) or without (263 +/- 13%, P = .01 versus control) L-arginine. Similar impairment of endothelium-dependent vasodilatation was seen in females at 14 weeks. Vasodilator responses to nitroprusside did not differ from those of control animals in any treatment group. After 14 weeks, atherosclerosis was less in the descending aorta of arginine-fed males (16 +/- 4% surface area) than that of males fed cholesterol only (42 +/- 8%, P = .04), but no treatment benefit was seen in the ascending aorta or in females. CONCLUSIONS: Dietary L-arginine supplementation causes an early rise in plasma arginine levels, with limitation of atherosclerosis in the descending aorta and preservation of endothelium-dependent vasodilatation in resistance arteries, but this treatment effect is not sustained. Dietary L-arginine may not be of long-term benefit in the prevention of atherosclerosis in humans.

Animals↗
PubMed1996

Killer factor interference in mixed opportunistic yeast cultures.

The interaction of the killer yeast Pichia anomala UP 25F with the killer toxin-sensitive clinical isolate Candida albicans UCSC 10S and its natural toxin-resistant mutant derivative C. albicans UCSC 10R were studied under various conditions. A differential inhibition was shown to occur in vitro at pH and temperature values, which are not encountered in vivo, only by using preformed killer toxin, since antagonism due to yeast growth proved to be predominant on the killer effect. Under adverse growth conditions, the P. anomala killer yeast proved to be able to produce an anatoxin antigenically related to the active or heat inactivated killer toxin. These findings suggest that killer toxins may not function as potential virulence factors in the competition between the opportunistic killer yeast P. anomala and sensitive microorganisms for colonization in the course of natural human infections.

Antibiosis↗
PubMed1996

Persistence, replacement, and microevolution of Cryptococcus neoformans strains in recurrent meningitis in AIDS patients.

Six separate human immunodeficiency virus-positive patients with cryptococcal meningitis were each found to have been infected with a unique strain of Cryptococcus neoformans on the basis of genomic DNA finger-printing analysis with the microsatellite sequence-containing oligonucleotide probe (GGAT)4 and by random amplification of polymorphic DNA. Two patients (A and B) experienced a recurrent episode of infection. Between 12 and 16 single-colony isolates recovered from primary isolation media (> 50% of C. neoformans colonies recovered) from cerebrospinal fluid specimens were fingerprinted from both patients during each episode. The fingerprints of both isolate collections from patient B were very similar, although minor polymorphisms were evident in both sets of profiles. The fingerprints of the isolate collection from the initial episode of infection in patient A were also identical to each other, apart from minor polymorphisms, but they were clearly different from the corresponding profiles of the isolate collection from the recurrent episode, the latter of which were completely identical, apart from minor polymorphisms in a single isolate. Furthermore, prolonged storage and in vitro subculture of the isolates did not alter the fingerprint profiles. These results provided convincing evidence that patients A and B were each infected with a single C. neoformans strain during each episode of infection and that in patient B, the same strain persisted and caused both episodes, while in patient A, a different strain was responsible for each episode. The prevalence of polymorphisms in multiple single-colony isolates from both patients also suggested that C. neoformans populations may undergo microevolution.

AIDS-Related Opportunistic Infections↗
PubMed1995

Insulin resistance is associated with abnormal dephosphorylation of a synthetic phosphopeptide corresponding to the major autophosphorylation sites of the insulin receptor.

Insulin resistance in the ob/ob mouse model is associated with a reduction in insulin-induced protein-tyrosine phosphorylation in tissues such as liver. To ascertain whether this decrease in phosphorylation may be due to increased phosphatase activity, protein-tyrosine phosphatase (PTPase) activity was determined in particulate and soluble fractions from livers of 5- to 23-week-old ob/ob mice and age-matched lean littermates. PTPase activity was measured using a synthetic phosphopeptide, TRDIY(P)ETDY(P)Y(P)RK, as the substrate, corresponding to residues 1142 to 1153 of the insulin receptor and containing the major autophosphorylation sites of the regulatory domain. The ob/ob mice were hyperinsulinemic across all age groups, but only the youngest mice (aged 5 to 7 weeks) were hyperglycemic. Most PTPase activity was present in the liver particulate fraction and was 19% to 114% greater in ob/ob mice as compared with controls. PTPase activity in the liver soluble fraction was 26% less than control values in the youngest ob/ob mice (5 to 7 weeks), but increased with age and was 41% and 131% above control values at 21 to 23 and 25 to 27 weeks of age, respectively. Oral administration of the PTPase inhibitor sodium orthovanadate (0.6 mg/mL in drinking water for 2 weeks) to young ob/ob mice caused a significant reduction in the elevated particulate PTPase activity, with concomitant decreases in plasma insulin and plasma glucose. Assessment of PTPase activity with a monophosphate form of the same synthetic peptide, TRDIY(P)ETDYYRK, showed lower PTPase activities as compared with the triphosphate form and no significant differences between ob/ob and control preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

An epidemiological study of Candida species infection in cancer patients using genetic fingerprinting and morphotyping.

During a six-week period a cluster of four cases of Candida fungaemia occurred in a mixed haematology/oncology unit of a large Dublin teaching hospital. A study was conducted to determine whether the cluster of cases was caused by a particular strain. Nine patients were studied; five who were colonized with Candida spp. and four who developed Candida fungaemia. Twenty-two clinical isolates of Candida spp. were collected and identified. Three of the patients with fungaemia yielded Candida albicans from blood cultures and C. tropicalis was isolated from the fourth patient. C. albicans isolates were serotyped, morphotyped and analysed by DNA fingerprinting of total cellular DNA using the cloned C. albicans-specific, mid-repeat sequence element 27A as a molecular probe. All C. albicans isolates were of serotype A. Eight distinguishable types were identified by both morphotyping and DNA typing from 19 C. albicans isolates recovered from seven individual patients, although there were several discrepancies. Of three patients from whom two or more isolates of C. albicans were recovered on separate occasions, two yielded recurrent isolates with different morphotype codes. However, in both cases, the recurrent isolates from individual patients yielded indistinguishable, or closely related, DNA fingerprint profiles. Both morphotyping and DNA fingerprint analysis readily distinguished the three blood culture isolates of C. albicans. We conclude that the Candida spp. infections in the unit were not due to cross-infection and were probably related to the patients' indigenous flora.

Candida↗
PubMed1995

Managing pharmaceutical sales activities in an academic anesthesiology department.

To contain costs, departments of anesthesiology must control the use of new, expensive drugs. Conflicts with pharmaceutical companies can arise when they promote drug sales. Pharmaceutical company sales represent anesthesiology department expenses. Anesthesiologists hold diverse opinions on this clash of interests, on the proper roles of pharmaceutical sales representatives in anesthesiology departments, and on the ethics of accepting industry gifts. Our department has managed pharmaceutical sales activities by encouraging discussion of the ethics and legal limits of industry gifts, by banning sales representatives from bringing food into the department, and by adopting The American Medical Association Guidelines on Gifts.

Academic Medical Centers↗
PubMed1994

Benchmarking: finding ways to improve.

BACKGROUND: This article provides health care organizations with a benchmarking methodology to use in comparing practices and processes to identify and actualize opportunities for improvement. The 15-step model can be used to guide internal and external benchmarking activities in a variety of health care settings. EXAMPLES: Two internal benchmarking case studies are illustrated: (1) one hospital used the Baxter model to evaluate its laparoscopic cholecystectomy services, and (2) another prepared for expansion of cardiac catheterization services. CONCLUSIONS: Two key factors of a successful benchmarking initiative are highlighted: management commitment and involvement, and the need to understand internal practices and processes before benchmarking.

Cholecystectomy, Laparoscopic↗
PubMed1994

Use of DNA fingerprinting and biotyping methods to study a Candida albicans outbreak in a neonatal intensive care unit.

During a 15-day period, 7 premature infants hospitalized in a neonatal intensive care unit presented with sepsis caused by Candida albicans. The local environment and hands of all 54 persons involved in the intensive care unit were examined for the presence of this organism. Five techniques were used in the analysis of the isolates recovered from blood cultures of the children, the hands of personnel and 10 control isolates. The methods used were serotype determination, genetic fingerprinting, morphotyping, resistotyping and killer yeast typing. Morphotyping and genetic fingerprinting proved to be the most discriminatory techniques, and only combined analysis of the results obtained with these various methods allowed the source of the outbreak to be identified. An isolate from the hands of a healthy staff member and isolates from infected children all belonged to the same strain.

Adult↗
PubMed1994

Cholesterol and non-cardiovascular disease: basic science.

Cholesterol metabolism is of fundamental biological importance. This review examines the role of cholesterol metabolism in relation to non-cardiovascular disease (non-CVD). Particular attention is paid to the question of whether or not low levels of cholesterol may have harmful effects on cell function or lead to pathological processes. Many in vitro phenomena have been demonstrated at levels of cholesterol which are very low in comparison to physiological conditions. Nevertheless, low cholesterol is more favourable than high cholesterol for most aspects of cell function. There is no evidence that any catastrophic cellular response or pathological process occurs due to exposure of organisms to low cholesterol. On the other hand, the inflammatory process is a powerful and consistent cause of decreased cholesterol levels. This, together with other confounding factors, appears to explain a major component of the association between low cholesterol levels and non-CVD.

Cell Division↗
PubMed1994

In situ hybridization and the polymerase chain reaction (PCR) in the analysis of biopsies and exfoliative cytology specimens for definitive diagnosis of oral hairy leukoplakia (OHL).

The definitive diagnosis of oral hairy leukoplakia (OHL) demands that Epstein-Barr virus (EBV) is demonstrated in the lesional tissue, since the histopathological features on conventional light microscopy are not pathognomonic. We have investigated the possible use of polymerase chain reaction (PCR) technology in reaching a definitive diagnosis of this lesion by its application to ten biopsy specimens with definitive diagnoses of OHL determined by in situ hybridization. EBV DNA was demonstrated by PCR in all ten OHL biopsy specimens analysed, and none of ten control specimens. Furthermore, we have investigated the role of PCR in analysis of exfoliative cytology samples collected from the lateral border of the tongue by a minimally-invasive scraping technique. EBV DNA was not only detected in all OHL lesional scrapings but also in more than one-third of healthy controls, due to viral presence in saliva at the time of sampling. In this application, the highly sensitive PCR technique has low specificity and cannot be recommended.

Adolescent↗
PubMed1994

Work-site cholesterol screening and dietary intervention: the Staff Healthy Heart Project. Steering Committee.

OBJECTIVES: The Staff Healthy Heart Project was established to run a work-site cholesterol screening project and a randomized controlled trial of dietary interventions. METHODS: Screening was offered to all staff at six Australian hospitals. Participants with blood cholesterol of 5.2 mmol/L (200 mg/dL) or above were randomly allocated to receive screening only (control group), a self-help package, or a nutrition course. Participants were seen 3 and 6 months after intervention to measure blood cholesterol and dietary changes. RESULTS: Eighty percent of available staff (n = 2638) were screened. Of those eligible, 67% (n = 683) entered the trial. Follow-up measures of blood cholesterol and dietary intake were obtained for 63% and 38% of trial participants, respectively. A reduction in reported dietary fat was found for all groups, but there were no significant differences between groups. Reported dietary fiber rose by 0.6 g/MJ/day for those in the nutrition course. There were no changes in total blood or high-density lipoprotein cholesterol. CONCLUSIONS: Cholesterol reduction was not demonstrated, but this result is difficult to interpret given the poor ongoing participation rates. Strategies to improve ongoing participation in work-site projects are needed to achieve adequate assessment of dietary interventions used in cholesterol screening.

Adolescent↗
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↗