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Biomedical subjects

G Kelly

Publications and source records attributed to G Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1999

Seasonal variation in long-day stimulation of prolactin secretion in ewes.

Whereas ewes initiate reproductive activity in response to a photoperiod signal initiated after the winter solstice of 35 long days (35 LD) followed by short days, the reproductive axis fails to respond to this signal between the autumn equinox and the winter solstice. The aim of experiment 1 was to determine whether the prolactin axis, like the reproductive axis, is unresponsive to a 35 LD photoperiod signal followed by continuous exposure to short days between the autumn equinox and the winter solstice. Whereas the 35 LD signal from September 21 (</= 6 h increase in day length) failed to influence prolactin secretion, all other long-day treatments (> 6 h increase in day length) initiated a rise in prolactin in at least 75% of ewes in each group (p < 0.05). The aim of experiment 2 was to determine whether ewes failed to secrete prolactin during a 35 LD photoperiod from September 21 because they did not recognize a 6-h increase in day length at any time of year as a stimulatory photoperiod signal or because hypothalamic/pituitary regulation of prolactin synthesis or secretion is compromised in September. The results demonstrated that while hypothalamic regulation of prolactin secretion and pituitary stores of prolactin were normal at all times of year examined, the ability of ewes to secrete prolactin in response to a long-day photoperiod signal appears to be dependent on photoperiodic history rather than the time of year of the photoperiodic challenge.

Animals↗
PubMed1999

A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients.

The effects of multiple opportunistic infection medications on stavudine pharmacokinetics were evaluated. Ten patients with CD4 counts of less than 200 cells/mm3 received stavudine (40 mg twice daily) in combination with one to three other drugs used to treat opportunistic infections. Serial blood samples for stavudine concentrations were collected after 1 week of therapy on each regimen and assayed for stavudine by using a validated high-pressure liquid chromatography method. Although the maximum concentration of drug in serum was significantly decreased when the drug was given in combination with three opportunistic infection medications, the area under the concentration-time curve did not significantly differ across various treatment regimens. Stavudine exposure was not significantly altered by multiple concomitant medications. Side effects were minor throughout the 3-month study period. The tolerability of stavudine, combined with its lack of drug interactions, makes it an attractive agent for use as part of a combination regimen.

AIDS-Related Opportunistic Infections↗
PubMed1998

Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion In vivo.

Malignant gliomas (primary brain tumors) aggressively invade the surrounding normal brain. This invasive ability is not demonstrated by brain metastases of nonglial cancers. The brain-specific, brain-enriched hyaluronan binding (BEHAB)/brevican gene, which encodes an extracellular hyaluronan-binding protein, is consistently expressed by human glioma and is not expressed by tumors of nonglial origin (Jaworski et al., 1996). BEHAB/brevican can be cleaved into an N-terminal fragment that contains a hyaluronan-binding domain (HABD) and a C-terminal fragment (Yamada et al., 1995). Here, using antisera to peptides in the predicted N-terminal and C-terminal proteolytic fragments, we demonstrate that the BEHAB/brevican protein is cleaved in invasive human and rodent gliomas. A role for this protein in glioma cell invasion was tested by transfecting a noninvasive cell line with the BEHAB/brevican gene. The noninvasive 9L glioma cell was transfected with either full-length BEHAB/brevican or the HABD and tested for invasion in in vitro and in vivo invasion assays. Although both constructs increased invasion in vitro, only the HABD increased invasion by tumors growing in vivo. Experimental intracranial tumors from full-length transfectants showed no increase in invasion over control tumors, whereas tumors from HABD transfectants showed a marked potentiation of tumor invasion, producing new tumor foci at sites distant from the main tumor mass. This work demonstrates a role for a brain-specific extracellular matrix protein in glioma invasion, opening new therapeutic avenues for a uniformly fatal disease.

Amino Acid Sequence↗
PubMed1998

A prospective evaluation of the feasibility of day-case microlaryngeal surgery.

An increasing number of surgical procedures are being performed on a day-case basis. In the UK otolaryngologists have been reluctant to introduce same day discharge in microlaryngeal surgery (MLS). The reason for this is the perceived risk to the airway from bleeding and oedema after MLS. The aim of this study was to investigate the feasibility of establishing a same day discharge service for MLS patients. One hundred consecutive patients under the care of one consultant otolaryngologist were recruited. A clinical street-fit assessment and objective measures of peak expiratory flow rate (PEFR) and oxygen saturation (SaO2) were recorded pre- and post-operatively. Results indicate that the PEFR and SaO2 did not change significantly during the course of the study. The street-fit criteria for discharge were satisfied in 80 per cent of patients following surgery. By combining the ASA score (American Society of Anaesthesiologists) with street-fitness 63 per cent of our patients were eligible for same day discharge.

Adult↗
PubMed1998

Eukaryotic RNA polymerase subunit RPB8 is a new relative of the OB family.

RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.

Amino Acid Sequence↗
PubMed1998

In vitro nerve repair--in vivo. The reconstruction of peripheral nerves by entubulation with biodegradeable glass tubes--a preliminary report.

Biodegradeable "controlled release" inorganic polymer glass tubes can be manufactured to fit the dimensions of any nerve and their rate of solubility can be adjusted to encompass the time taken for nerve regeneration. They have been used in a number of biological applications. The facial nerve was repaired in a group of five sheep by entubulation with biodegradeable glass tubes. The sheep were assessed 10 months after repair and compared with a similar sized group of normal sheep. It was found that while there was a reduction in the peak velocity of conduction in the repaired nerves and in the range of conduction velocities, the minimum conduction velocity was within normal limits. There was a diminution in all of the measured variables of nerve morphometry but in no case did this reach statistical significance. These findings are consistent with the view that regeneration of the nerves had taken place to a degree at least as effective as that seen in nerves of a similar size repaired by conventional means.

Animals↗
PubMed1998

A canine model of familial mammary gland neoplasia.

Intact female Beagles from life-span studies in the Lovelace Respiratory Research Institute colony were examined for mammary tumor incidence. The breeding colony, founded in 1963, produced five generations from 28 founder females. After proportional hazards analysis, two maternal families were shown to have markedly different phenotypes, one susceptible and one resistant to mammary neoplasia, as compared with the entire colony. When tumors were subdivided into benign and malignant based on local invasiveness, familial differences in tumor incidence were preserved for each tumor type. Fifty-seven females in the susceptible family developed 149 benign and 39 malignant tumors, and 95 females in the resistant family developed 70 benign and 20 malignant tumors. The ratio of benign to malignant tumors of about 4:1 for both families was higher than expected. Using Kaplan-Meier and log-rank analyses, the susceptible family had a 50% malignant tumor incidence by age 13.6 years, whereas the resistant family did not have a 50% incidence until 17.0 years (P = 0.0065). Because of marked censoring, Kaplan-Meier analyses could not provide an estimate of the 50% benign tumor incidence; mean incidence age was calculated instead. These estimates for benign tumors for susceptible and resistant families were 10.8 and 13.8 years (P = 0.0001), respectively. Using chi(2) tests, families had no differences in the occurrence of the types of benign (P = 0.098) or malignant (P = 0.194) tumors or in the ratio of benign to malignant tumors (P = 0.778). Immunohistochemical analysis of malignant tumors from both families did not demonstrate differences in p53 mutation rate or p185erbB-2 expression. These results suggest that 1) genetic factors produce familial differences in the age of onset of both benign and malignant mammary tumors; histologic types do not segregate by family; 2) the ratio of benign to malignant tumors is greater than formerly reported; and 3) neither p53 nor p185erbB-2 alterations are the basis for the familial predisposition.

Animals↗
PubMed1998

The use of telemedicine to treat ophthalmological emergencies in rural Australia.

A retrospective analysis was made of a cohort of patients who presented sequentially with acute ophthalmological conditions which were managed by telemedicine consultation. Twenty-four patients presented with acute problems requiring specialist ophthalmological advice to the emergency department of a remote hospital in Mt Isa, Queensland, between December 1996 and February 1997. Tele-ophthalmology consultations were carried out with three ophthalmologists working in a specialist eye clinic in Townsville, 900 km away. Patients and doctors were extremely positive about the telemedicine facility. Tele-ophthalmology was an effective means of providing acute specialist consultation in a remote emergency department. By reducing the need for acute transfers to the tertiary hospital in Townsville, significant benefits can be anticipated--both financial and in terms of convenience for the patient. Benefits for medical staff in skills acquisition and education were also evident.

Australia↗
PubMed1997

Determinants of case selection at morning report.

OBJECTIVE: To determine why residents present certain cases and not others at morning report (MR) in an institution that permits residents the free choice of cases. DESIGN/PARTICIPANTS: Prospective survey of 10 second- and third-year residents assigned to the medical service. SETTING: A 241-bed teaching hospital with 55 categorical internal medicine residents. MEASUREMENTS AND MAIN RESULTS: Over a 4-week period, there were 194 admissions to the medical service on 18 call days preceding MR. Of these admissions, 30 (15%) were presented at MR. Cases were more likely to be presented if they were considered unusual or rare in presentation or incidence (P = .001), involved significant management issues (p = .001), or were associated with remarkable imaging studies or other visual material (p = .006). Residents were more likely to present cases in which they disagreed with attending physicians on management plans (p = .005). Overall, residents rated few admissions as having notable physical examination findings (29/194) or ethical or cost issues (6/194). Of the seven most common admitting diagnoses, representing 44% of admissions, residents did not present cases involving four of these diagnoses. CONCLUSIONS: Residents presented cases at MR that they felt were unique or rare in presentation or incidence for purposes of discussing management issues. Complete resident freedom in choosing MR cases may narrow the scope of MR and exclude common diagnoses and other issues of import such as medical ethics or economics.

Case Management↗
PubMed1997

Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients.

The pharmacokinetics of thalidomide in nine human immunodeficiency virus-infected patients were studied. Single doses of thalidomide were well absorbed, with mean peak concentrations (+/- standard deviations) of 1.17 +/- 0.21 and 3.47 +/- 1.14 microg/ml in the 100- and 300-mg dosing groups, respectively, and the mean elimination half-life was approximately 6 h. Adverse effects were mild, with drowsiness being reported for seven of nine patients.

Adult↗
PubMed1997

Alterations in the K-ras and p53 genes in rat lung tumors.

Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. Only two agents, TNM and plutonium, led to mutation frequencies of > 10%. In both cases, the transition mutations formed could have been derived from deamination of cytosine. The identification of non-ras transforming genes in rat lung tumors induced by mutagenic and nonmutagenic exposures such as NNK and beryllium would help define some of the mechanisms underlying cancer induction by different types of DNA damage. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarcinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 to 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors.

Animals↗
PubMed1996

Peer education: a strategy for improving health education in disadvantaged areas in Belfast.

The paper reports on the initial phase of an evaluation of a multi-agency project designed to deliver social and health education to 16-18-year-old trainees attending four community workshops in North and West Belfast. A survey of the first year of the project was carried out using quantitative and qualitative methodologies which included a questionnaire survey of those trainees attending the programme and structured interviews with a representative sample of trainees. The first stage of the research involved a baseline measure (time 0) which provided valuable insights into the behaviours, attitudes and values of the trainees regarding a range of health issues, including smoking and alcohol behaviours, and substance abuse. Some changes in behaviour, during the first year of the project, were noted, such as reported reductions in substance abuse and increased awareness of sources of advice relating to health issues.

Adolescent↗
PubMed1996

Inhibition of immunoreactive tumor necrosis factor-alpha by a chimeric antibody in patients infected with human immunodeficiency virus type 1.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to stimulate human immunodeficiency virus type 1 (HIV-1) replication, has been implicated in the pathogenesis of HIV-1 infection. Inhibition of TNF-alpha by a chimeric humanized monoclonal antibody, cA2, was investigated in 6 HIV-1-infected patients with CD4 cell counts < 200/mm3. Two consecutive infusions of 10 mg/kg 14 days apart were well tolerated, and a prolonged serum half-life for cA2 (mean, 257 +/- 70 h) was demonstrated. Serum immunoreactive TNF-alpha concentrations fell from a mean prestudy value of 6.4 pg/mL (range, 4.2-7.9) to 1.1 pg/mL (range, 0.5-2.2) 24 h after the first infusion and returned to baseline within 7-14 days. A similar response was seen after the second infusion. No consistent changes in CD4 cell counts or plasma HIV RNA levels were observed over 42 days. Future studies evaluating the therapeutic utility of long-term TNF-alpha suppression using anti-TNF-alpha antibodies are feasible and warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1996

State of the science. HIV vaccine development.

Developing a vaccine able to prevent HIV infection would be a great benefit to the world. Vaccines have contributed to substantially reduced morbidity and mortality from several important infectious diseases. However, HIV has some characteristics that distinguish it from many other viruses and make vaccine development challenging. This article discusses scientific strategies, obstacles, and progress to date towards the development of a preventive HIV vaccine.

AIDS Vaccines↗
PubMed1996

Hybrid total hip arthroplasty: a 7- to 11-year followup.

A consecutive series of 125 hybrid total hip arthroplasties were performed in 120 patients by a single surgeon and were observed for an average of 8.6 years (range, 7-11 years). There were 38 men and 82 women with an average age of 71 years (range, 25-87 years) at the time of surgery. The diagnoses included primary and secondary osteoarthritis in 112 patients, osteonecrosis in 5 patients, and rheumatoid arthritis in 3 patients. All acetabular components were modular and had a Ti shell fixed with an average of 3 screws. The cemented femoral component was either Precoat or Precoat Plus with a 28-mm modular CoCr femoral head. The patients were prospectively observed clinically using the Harris hip score and radiographically using the Hip Society methods. Of the 125 total hip arthroplasties, 123 were followed for the entire observation period. The average preoperative Harris Hip Score was 37 (range, 15-55) and at the latest followup was 92 (range, 65-100). One acetabular component was revised for recurrent dislocations 3 years after surgery, and 1 stem was revised for mechanical loosening and 1 stem was radiographically loose. There was no evidence of cup migration of more than 1 mm. There were no radiolucencies around any of the screws. Two sockets had polyethylene wear of 2 mm. Localized pelvic osteolysis was noted in 5 hips (4%). The results of this study suggested that hybrid total hip replacement is an excellent procedure for reconstruction of the arthritic hip with minimal evidence of polyethylene wear and pelvic osteolysis.

Adult↗