Search PubMed⌕ Search

Biomedical subjects

S Jenkins

Publications and source records attributed to S Jenkins.

At least 37 records · Page 2Linked to original sources
PubMed2000

Internet use amongst New Zealand general practitioners.

AIMS: To assess how extensively New Zealand doctors are using medical information on the Internet, and to examine how the new technology is affecting their practice of medicine. METHODS: All general practitioners (GPs) known to be working in Otago and Southland were asked to complete a postal questionnaire regarding their use of the Internet and their impressions of patient use of online medical resources. RESULTS: Of 259 questionnaires mailed out, 168 (65%) were returned by GPs currently in practice. Of those, 114 (68%) said they used the Internet at least monthly. A total of 71% of GPs had patients who indicated they had sought medical information from the Internet. Nearly half of respondents expressed concerns that the Internet could have unwelcome effects on the doctor-patient relationship. CONCLUSIONS: Internet use among New Zealand doctors and patients is widespread, and is likely to have significant impact on medical practice now and in the future. While the potential benefits of the new technology are numerous, the Internet may become a source of conflict between doctors and patients.

Data Collection↗
PubMed2000

Manual hyperinflation--effects on respiratory parameters.

BACKGROUND AND PURPOSE: Manual hyperinflation (MH) of the lungs is commonly used by physiotherapists in the treatment of intubated mechanically ventilated patients with the aim of increasing alveolar oxygenation, reversing atelectasis or mobilizing pulmonary secretions. However, the efficacy of MH, used in isolation, has not been clearly established. METHOD: This randomized, controlled trial investigated the effects of MH on lung compliance (CL), the arterial oxygen to fraction of inspired oxygen ratio (PaO2:FIO2) and the alveolar-arterial oxygen tension difference (A-a)PO2 in 100 medically stable, mechanically ventilated subjects who had undergone coronary artery surgery (CAS). Post-CAS subjects were used for this study as they constitute a large, homogeneous and accessible group. Subjects were randomized to either a control group (non-MH group) or to a treatment group (MH group) which received MH within four hours of surgery. RESULTS: After four minutes of MH there were significant improvements in CL, PaO2:FIO2 and (A-a)PO2 with values remaining above baseline measures at 60 min post-intervention. The mean improvement in CL was 6 ml/cmH2O (approximately 15%), 56 mmHg for PaO2:FIO2 (approximately 17%) and 29 mmHg for (A-a)PO2 (approximately 17%) immediately post-intervention. No significant changes in mean CL, PaO2:FIO2 or (A-a)PO2 were seen in the non-MH group. CONCLUSIONS: MH performed in the stable ventilated patient significantly increased CL and PaO2:FIO2 and decreased (A-a)PO2, but the clinical significance of this improvement is unclear. Further investigations are required to validate the findings of this study as well as to determine the therapeutic value of MH on patient outcome.

Adult↗
PubMed2000

Differential role for competitive reverse transcriptase-polymerase chain reaction and intracellular cytokine staining as diagnostic tools for the assessment of intragraft cytokine profiles in rejecting and nonrejecting heart allografts.

The early and reliable diagnosis of allograft rejection is a difficult task and the assessment of cytokine expression in the grafts can be a helpful parameter. We have compared competitive reverse transcriptase-polymerase chain reaction (RT-PCR) with intracellular cytokine staining by flow cytometry as tools to measure cytokine expression in rejecting and nonrejecting murine cardiac allografts. Both techniques gave comparable results for cytokine expression in rejecting allografts and syngeneic controls. Grafts from mice pretreated with anti-CD4 antibody and donor-specific blood transfusion showed a marked reduction in cytokine expression, as assessed by competitive RT-PCR, even though a cellular infiltrate was present in the graft. In contrast, the cytokine production measured by intracellular cytokine staining of the isolated graft-infiltrating cells was high and exceeded even that of the rejecting allografts. We conclude that intracellular cytokine staining of graft-infiltrating leukocytes by flow cytometry does not necessarily reflect accurately the cytokine milieu in the graft. This technique might therefore have a limited clinical application in contrast to competitive RT-PCR for the differentiation between graft acceptance and graft rejection.

Animals↗
PubMed2000

Effects of a selective 5-HT(1B/1D) receptor agonist on spinal and trigeminal reflexes in the anaesthetized rabbit.

The effects of the 5-HT(1B/1D) receptor agonist L-741,604 on a trigeminally-mediated (jaw depressor) reflex and a spinally-mediated (flexion withdrawal) reflex have been compared between spinalized and intact, anaesthetized rabbits. L-741,604 depressed the jaw depressor reflex dose-dependently in all animals, to a median of 5% (inter-quartile range, IQR, 3 - 28%, n=18) of pre-drug levels after a cumulative dose of 3.1 micromol kg(-1) i.v. This effect was reversed by the 5-HT(1B/1D) antagonist GR 127,935 (1 - 2 micromol kg(-1) i.v.). The flexion withdrawal reflex was depressed by L-741, 604 in non-spinalized animals, to a median of 22% (IQR 10 - 36%, n=10) of pre-drug levels after the highest dose, an action that was reversed by GR 127,935. In spinalized rabbits, L-741,604 up to 0.3 micromol kg(-1) i.v. cumulative increased the flexion reflex to a median of 189% (IQR 169 - 198%, n=8) of pre-drug controls. With higher doses the reflex decreased, so that after 3.1 micromol kg(-1) it was 75% (IQR 55 - 96%) of pre-drug levels. Subsequent GR 127,935 increased reflexes to a median of 180% (IQR 136 - 219%) of controls. L-741,604 increased arterial blood pressure and decreased heart rate in both preparations, effects that were reversed by GR 127,935. Thus, when the spinal cord was intact L-741,604 inhibited spinal and trigeminal reflexes in the same way. Although spinalization enabled a non-5-HT(1B/1D)-mediated excitatory effect of L-741,604 on spinal reflexes, there was a clear inhibitory effect of the drug at high doses. These data suggest that L-741,604 inhibits spinal reflexes by increasing descending inhibition and by a direct action in the cord. The same processes could apply to inhibition of trigeminally-mediated events.

Animals↗
PubMed2000

Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.

OBJECTIVE: To assess the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Inc) in the prevention of migraine. BACKGROUND: Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. Botulinum toxin type A injections often reduce the pain associated with conditions such as cervical dystonia, achalasia, rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study of botulinum toxin type A suggested benefits for patients with migraine. DESIGN AND METHODS: This was a double-blind, vehicle-controlled study of 123 subjects with a history of two to eight moderate-to-severe migraine attacks per month, with or without aura. Participants were randomized to receive single administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into multiple sites of pericranial muscles at the same visit. During a 1-month baseline period and for 3 months following injection, subjects kept daily diaries in which they recorded migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. RESULTS: Compared with vehicle treatment, subjects in the 25-U botulinum toxin type A treatment group showed significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A groups were significantly better than the vehicle group on subject global assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U treatment group exhibiting a significantly higher rate of treatment-related adverse events than vehicle. CONCLUSIONS: Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.

Adolescent↗
PubMed2000

Divergent and composite gonadotropin-releasing hormone-responsive elements in the rat luteinizing hormone subunit genes.

GnRH pulses regulate gonadotropin subunit gene transcription in a frequency-dependent, subunit-specific manner. The alpha-subunit gene is stimulated by constant GnRH and by rapid to intermediate pulse frequencies, while stimulation of LHbeta subunit gene transcription requires intermediate frequency pulses. We have defined the GnRH-responsive elements of the rat LH subunit gene promoters by deletion/mutation analysis and transfection studies in rat pituitary cells and two clonal gonadotrope cell lines. The alpha-subunit gene GnRH-responsive region lies between -411 and -375 bp. The region contains two Ets-domain protein binding sites, and mutating either site obliterates the response. DNA protein binding studies demonstrate the two sites are not equivalent, and that Ets-1 does not mediate this response. Studies of the LHbeta promoter reveal a major GnRH-responsive region between -456 and -342 bp. Within this region, two Sp1 binding sites contribute to the GnRH response, and the 3'Sp1 site is also critical for basal expression. The 5'Sp1 site partially overlaps a CArG box, and mutating the CArG element specifically eliminates the response to pulsatile GnRH. DNA containing this mutation cannot form intermediate mobility complexes with nuclear proteins, but retains Sp1 binding. Mutation of the 3'Sp1 site and either the 5'Sp1 or CArG element partially restores GnRH stimulation, suggesting a downstream element contributes to the full GnRH response. These studies demonstrate that unique composite elements and transcription factors are responsible for GnRH stimulation of the LH subunit genes and may contribute to their differential responses to GnRH pulses.

Animals↗
PubMed1999

CONTINUUM-Activity Index: managing admission inappropriate stays in a community hospital.

The CONTINUUM-Activity Index was used as a concurrent tool to measure intensity of services delivered in an Acute Care Community Hospital. Applying these specific daily measures identified patients who did not meet admission-appropriateness criteria on the first day of care or did not meet those criteria on two days subsequent to admission. These patients had a high probability that their entire stay would be inappropriate. Action was then taken to move the care process forward, resulting in a significant reduction in inappropriate hospital days.

Bed Occupancy↗
PubMed1999

Effect of unilateral breathing exercises on regional lung ventilation.

We investigated the effect of a unilateral thoracic expansion exercise (TEE), a breathing manoeuvre used by physiotherapists, on regional lung ventilation. Nine trained physiotherapists aged 22-37 years completed the study. Technegas lung ventilation scans were used to determine the effect of a right unilateral TEE performed when sitting. This was compared with a maximal deep breath. Total radioactivity in each lung was determined. Each lung was sectioned into three equal zones (upper, middle and lower) and the ratio of radioactivity for each of the corresponding lung zones calculated. Ventilation was preferentially distributed to the right lung in all participants during both breathing manoeuvres. The mean (+/- S.E.M.) radioactivity ratios (right/left lung) were greater during a unilateral TEE (1.17 +/- 0.02) than during a deep breath (1.07 +/- 0.01). Seven participants achieved significantly greater ventilation to the right middle (1.15 +/- 0.03, P = 0.02) and lower zones (1.34 +/- 0.03, P = 0.02) during a unilateral TEE than to the corresponding zones on the left; this was evident soon after the initiation of the breath. The findings of this study show that relative regional ventilation to the ipsilateral lung can be increased during a unilateral TEE in trained individuals.

Adult↗
PubMed1999

Multicenter study of in vitro susceptibility of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from 1990 to 1996.

Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most beta-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within the B. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilis group species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the beta-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.

Anti-Bacterial Agents↗
PubMed1998

The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo.

5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1Dbeta and 5-HT1Dalpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6, 7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

Animals↗
PubMed1998

Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.

This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.

Double-Blind Method↗
PubMed1998

Insulin-like growth factors in human breast cancer.

IGF1 and IGF2 are circulating peptide hormones and locally-acting growth factors with both paracrine and autocrine functions. IGF1 and IGF2 signal through a common tyrosine kinase receptor, the insulin-like growth factor 1 receptor (IGF1R), and have mitogenic, cell survival, and insulin-like actions that are essential for embryogenesis, post-natal growth physiology, and breast development. The activities of IGF1 and 2 are tightly-regulated by a network of binding proteins and targeted degradation mechanisms. This complex regulatory system is disrupted in breast cancer, leading to excess IGF1R signaling. Evidence for this statement includes: a) breast cancers are infiltrated with IGF2 expressing stromal cells; b) mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) is mutated in breast cancer, leading to loss of IGF2 degradation; c) IGF1R is overexpressed by malignant breast epithelial cells, and in some cases IGF1R is amplified; and d) complex changes in IGF binding protein expression occur during breast cancer progression which most likely also affect IGF1 and 2 signaling. The clinical importance of these epigenetic and genetic changes has recently been stressed by the finding that IGF1R signaling alters the apoptotic response of breast cancer cells to genotoxic stress and, in addition, IGF1R activation sensitizes cells to estrogen by inducing phosphorylation of the estrogen receptor. As a consequence of these findings, we propose that IGF analysis of breast cancer samples should shift from prognostic studies to an evaluation of IGF ligands, receptors, and binding proteins as resistance/sensitivity markers for radiation, chemotherapy, and endocrine therapy.

Apoptosis↗
PubMed1998

Fetal growth in the baboon during the second half of pregnancy.

The normal growth profile of critical fetal organs through the last third of gestation has not been documented in detail in human fetuses or the fetus of any nonhuman primate species. Recent epidemiological studies in human pregnancy suggest that fetal growth plays a major role in the programming of life-long health by modifying cardiovascular, pancreatic, brain, and liver growth. The present study aimed to produce a detailed database of individual organ growth in the fetal baboon in late gestation. Fetal organ weights were obtained from 43 baboon fetuses between 121 and 177 days of gestation. Various organs (brain, heart, kidney, femur, intestines, and spinal cord) showed no sign of slowed growth in late gestation while growth of others (lung, liver, stomach, and bladder) accelerated in late gestation. The fetal adrenal and thymus showed a decrease in growth rate over the final 20 and 10 days of gestation respectively. These observations provide a database that will permit analysis of factors responsible for regulation of normal and altered fetal organ development in this important experimental species.

Adrenal Glands↗