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Biomedical subjects

H Gray

Publications and source records attributed to H Gray.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic necrosectomy as primary therapy in the management of infected pancreatic necrosis.

BACKGROUND AND STUDY AIMS: Open pancreatic necrosectomy is the standard treatment for infected pancreatic necrosis but is associated with significant morbidity, mortality, and prolonged hospital stay. Percutaneous or endoscopic necrosectomy are alternative techniques. We evaluated the use of endoscopic necrosectomy for treatment of patients with necrosis that could be accessed through the posterior wall of the stomach. PATIENTS AND METHODS: We retrospectively analyzed the indication, patient status according to acute physiology and chronic health evaluation (APACHE) 2 severity score, and success of endoscopic necrosectomy as primary treatment, in selected patients with localized infected pancreatic necrosis, who presented between May 2002 and October 2004. After the necrosis cavity had been accessed, with the assistance of endoscopic ultrasound, a large orifice was created and necrotic debris was removed using endoscopic accessories under radiological control. Follow-up was clinical and radiological. RESULTS: 13 patients (nine men, four women, mean age 53 years), 11 with positive bacteriology, underwent attempted endoscopic necrosectomy. Median APACHE 2 score on presentation was 8 (range 1-18). Four patients needed intensive therapy unit care and one other patient required (nonventilatory) high-dependency unit care only. Necrosis was successfully treated endoscopically in 12 patients, requiring a mean of 4 endoscopic interventions (range 1-10); one patient required open surgery; two underwent additional percutaneous necrosectomy and one required laparoscopic drainage. Two patients died of complications unrelated to the procedure. The 11 survivors have a median (range) follow-up of 16 (6-38) months. CONCLUSION: Endoscopic necrosectomy is a safe method for treatment of infected pancreatic necrosis. Multiple procedures are usually needed. It may be combined with other methods of surgical intervention. Larger prospective studies will more precisely define its role.

Adult↗
PubMed2002

The distribution of health planning and management responsibilities between centre and periphery: historical patterns and reform trends in four Caribbean territories.

The degree to which health planning and management functions are decentralised has been one of the key questions in developing countries from when they first gained independence. This paper's aim is to examine the question of the historical distribution of responsibilities within the health sector of four territories, Trinidad and Tobago, the Bahamas, Martinique, and Suriname, in order to identify the roles of the different levels, changes over time and recent reform trends, and to seek to explain the reasons for changes. These territories were selected deliberately, on the grounds of their different colonial backgrounds. Common features included identification over several decades of management structures and skills as key problems; proposals for regionalisation and greater hospital autonomy as desirable solutions; and in three of the four territories, recent implementation of major structural reforms. Important influences on the timing and nature of decentralisation reforms included political and economic factors, the attitudes of the public service unions and the medical profession, and external funders who were particularly important in financing reforms and supporting the development of detailed implementation plans. The bureaucratic inheritance of the two English-speaking countries provided major barriers to structural change, which they have addressed through reforms involving the creation of agencies with delegated authority.

Bahamas↗
PubMed2002

The historical development of human resources policies in the health sector of four Caribbean territories: imitated or created?

Health systems are labour intensive, dependent on a mix of professionals to provide health care in both public and private sectors. In this paper, we explore the historical development of human resources, focusing on doctors and nurses, in four Caribbean territories-the Bahamas, Martinique, Suriname and Trinidad and Tobago. All these territories have faced issues around the out-migration of doctors and nurses and tensions between public health, hospital services and private sector policies. Early policies to increase the number of nurses and doctors were costly, because they were implemented against a tide of increasing outward migration. Both push and pull factors were evident. Human resources policies focused on ways to counter pull factors-such as introducing regional medical training-but neglected push factors. These began to be addressed from the 1980s on, although tensions between public health, hospital services and private sector policies led to resistance and conflicts in attitudes to reform among health professionals. Policy responses were the product of many influences, and it is too simple to conclude they were either imported from abroad or internally generated. However, it is clear that in all four territories the medical profession played a dominant role in human resources policy development either directly or indirectly.

Bahamas↗
PubMed2001

Is physical activity protective against hip fracture in frail older people?

BACKGROUND: there is limited evidence of a protective effect of physical activity in preventing hip fractures among older people living in institutions and in those aged 80 or over. OBJECTIVE: to examine the relationship between physical activity and risk of hip fracture in frail older people. DESIGN: a case-control study. SETTING: Auckland, New Zealand. SUBJECTS: a random sample of individuals hospitalized with a fracture of the femoral neck (n=911) and 910 randomly selected age- and sex-matched individuals from the lists of a random sample of general practitioners. METHODS: we sought information on physical activity and other potential risk factors for hip fracture from cases and controls, using a standardized interviewer-administered questionnaire. We conducted multivariate analyses, separately for those living in private homes and residential institutions. RESULTS: increasing hours of physical activity per week protected against the risk of hip fracture among individuals living in private homes, including those who are over 80. However, among individuals living in institutions, physical activity levels were extremely low (<15% participated in >/=2 h per week) and there was limited evidence of a protective effect. CONCLUSIONS: efforts to prevent hip fractures in individuals living in care homes and institutions should focus on passive interventions which are known to be effective.

Activities of Daily Living↗
PubMed2000

Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer.

In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the genetic risk of the majority of breast cancers will require the identification and analysis of several lower penetrance genes. The estrogen-signaling pathway plays a crucial role in the pathophysiology of breast cancer; therefore, polymorphism in genes involved in this pathway is likely to influence breast cancer risk. Our detailed analysis of gene expression profiles of estrogen- and 4-OH-tamoxifen-treated ZR75-1 breast cancer cells identified members of the sulfotransferase 1A (SULT1A) phenol sulfotransferase family as downstream targets of tamoxifen. On the basis of the induction of SULT1A by 4-OH-tamoxifen and the known inherited variability in SULT1A enzymatic activity, we hypothesized that polymorphism in sulfotransferase genes might influence the risk of breast cancer. Using an RFLP that distinguishes an arginine to histidine change in exon 7 of the SULT1A1 gene, we characterized SULT1A1 genotypes in relation to breast cancer risk. An analysis of 444 breast cancer patients and 227 controls revealed no effect of SULT1A1 genotype on the risk of breast cancer (P = 0.69); however, it did appear to influence the age of onset among early-onset affected patients (P = 0.04). Moreover, individuals with the higher activity SULT1A1*1 allele were more likely to have other tumors in addition to breast cancer (P = 0.004; odds ratio, 3.02; 95% confidence interval, 1.32, 8.09). The large number of environmental mutagens and carcinogens activated by sulfotransferases and the high frequency of the SULT1A1*1 allele in human populations warrants additional studies to address the role of SULT genes in human cancer.

Adult↗
PubMed2000

A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery.

We performed a systematic survey of randomized trials to determine the effects of perioperative NSAIDs on the occurrence of heterotopic bone formation, gastrointestinal side-effects and long-term clinical outcomes after major hip surgery. 13 trials involving 4,129 individuals were identified. Overall, in 12 small trials of medium-to-high-dose regimens, there was a 57% reduction (95% confidence interval 51%-63%) in the risk of heterotopic bone formation. The results of one large trial of low-dose aspirin differed markedly (2% reduction (95% CI 12% reduction to 15% increase)). The NSAID regimens studied had no definite effect on gastrointestinal complications, and data about the effects of NSAIDs on pain and function were too few, and too incompletely reported, to draw conclusions about their effects on these outcomes. Routine prophylaxis against heterotopic bone formation with NSAIDs may be a useful adjuvant therapy for patients undergoing major hip surgery, but the overall balance of risks and benefits requires assessment in a large-scale randomized trial.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

No effect of low-dose aspirin for the prevention of heterotopic bone formation after total hip replacement: a randomized trial of 2,649 patients.

2,649 patients scheduled for elective total hip replacement were recruited to the Heterotopic Bone Formation Sub-study of the Pulmonary Embolism Prevention Trial. Heterotopic bone formation was determined by radiographic examination and associated late postoperative outcomes were assessed by telephone interview. Heterotopic bone formation was observed in 627 (31%) of 2,048 radiographic examinations. There was no detectable effect of low-dose aspirin on the risks of heterotopic bone formation (RR 0.98; 95% CI 0.85-1.12), late postoperative pain (RR 1.10; 95%CI 0.91-1.35) or late postoperative impaired function (RR 1.03; 95% CI 0.94-1.12). The balance of benefits and risks of low-dose aspirin is determined by its effects on vascular events and bleeding, since it has no major effects on heterotopic bone formation or associated clinical outcomes.

Activities of Daily Living↗
PubMed2000

A role for phosphorylation of glycogen synthase kinase-3alpha in bovine sperm motility regulation.

The long-term goal of our work is to understand biochemical mechanisms underlying sperm motility and fertility. In a recent study we showed that tyrosine phosphorylation of a 55-kDa protein varied in direct proportion to motility. Tyrosine phosphorylation of the protein was low in immotile compared to motile epididymal sperm. Inhibition or stimulation of motility by high calcium levels or cAMP, respectively, results in a corresponding decrease or increase in tyrosine phosphorylation of the 55-kDa protein. Here we report purification and identification of this motility-associated protein. Soluble extracts from bovine caudal epididymal sperm were subjected to DEAE-cellulose, Affi-Gel blue, and cellulose phosphate chromatography. Tyrosine phosphate immunoreactive fractions contained glycogen synthase kinase-3 (GSK-3) activity, suggesting a possible correspondence between these proteins. This suggestion was verified by Western blot analyses following one-dimensional and two-dimensional gel electrophoresis of the purified protein using monoclonal and affinity-purified polyclonal antibodies against the catalytic amino-terminus and carboxy-terminus regions of GSK-3. Further confirmation of the identity of these proteins came from Western blot analysis using antibodies specific to the tyrosine phosphorylated GSK-3. Using this antibody, we also showed that GSK-3 tyrosine phosphorylation was high in motile compared to immotile sperm. Immunocytochemistry revealed that GSK-3 is present in the flagellum and the anterior portion of the sperm head. These data suggest that GSK-3, regulated by phosphorylation, could be a key element underlying motility initiation in the epididymis and regulation of mature sperm function.

Amino Acid Sequence↗
PubMed1999

Mortality after hip fracture: regional variations in New Zealand.

AIM: To determine the 35-day and one-year mortality rates following a hospital admission for hip fracture, among individuals aged 60 years or older in New Zealand. METHODS: New Zealand Health Information Service mortality data for the years 1988 to 1992 were examined to determine the case fatality rate among individuals aged 60 years or older admitted to hospital for fractures of the neck of femur (ICD-9 N-code 820). Case fatality rates assessed at 35 days and one year after admission to hospital were examined by age, gender, year of admission, place of residence, area health board region and cause of death. RESULTS: Between 1988 and 1992, the case fatality rate was 8% within 35 days of admission to hospital and 24% within one year of admission. Case fatality rates were found to be twice as high in men compared to women and four to five times higher in individuals aged 85 years and older, compared to people aged between 60 and 64 years. The only regional difference in hip fracture mortality was found in the Canterbury area health board region, which had a 30% higher rate of hip fracture mortality compared to all regions combined. The two main cited underlying causes of death after hip fracture were accidental falls (ICD E880-E888) and ischaemic heart disease (ICD 410-414). CONCLUSION: Over three-quarters of individuals aged 60 years or older who are hospitalised with a hip fracture in New Zealand survive for at least one year after admission. However, significant variations in mortality exist with age and gender. These data highlight the importance of preventive strategies for hip fracture in older people and the need to identify ways of improving post-admission care.

Age Distribution↗
PubMed1999

Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys.

Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 microg Escherichia coli heat-labile enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered over an 8 week period. All five vaccinated monkeys had a greater than two-fold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori colonization. H. pylori was eradicated from these monkeys with a course of antimicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H. pylori. Necropsy was performed 23 weeks after rechallenge and H. pylori colonization was determined by histological examination of 12 individual gastric sites. A significant reduction in colonization (p < or = 0.0001; Friedman's analysis of variance) was found in the vaccinated animals. Histopathologic examination of necropsy tissues also revealed a trend towards reduced gastritis and epithelial alterations in the vaccinated group compared to animals receiving LT alone. This study provides the first evidence for effective vaccination of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gastric inflammation.

Adjuvants, Immunologic↗
PubMed1999

Oral immunization with recombinant Helicobacter pylori urease confers long-lasting immunity against Helicobacter felis infection.

Recombinant Helicobacter pylori urease (rUre) has been shown to confer protection against challenge with Helicobacter felis in mice. The purpose of the present study was to examine duration of the immune response and long-term protective efficacy of immunization with rUre. Swiss Webster mice were orally immunized four times at weekly intervals with 100 microg rUre plus 5 microg heat-labile enterotoxin of Escherichia coli (LT) adjuvant, or with LT only. At 4, 10, 20 or 40 weeks post immunization, 25 rUre-immunized mice and control mice were challenged with H. felis and sacrificed at 2 or 10 weeks post-challenge. H. felis infection was assessed by gastric urease assay and by histology. Anti-H. pylori urease specific antibody levels were measured in serum and saliva both pre- and post-challenge. Over the 40 week time period, the infection rates in rUre-immunized mice were significantly lower than those in controls (p < 0.05) as assessed by gastric urease activity. Protection ranged from 79 100% at 2 weeks post-challenge and 63-78% at 10 weeks post-challenge. Gastric bacterial density in rUre-immunized mice was significantly lower than that of controls (p < 0.03) as determined by histologic assessment. Anti-urease antibody levels remained elevated in the serum and mucosal compartments at 39 weeks following immunization. This study shows that immunization with rUre plus LT results in long-lasting protective immunity against challenge with H. felis.

Adjuvants, Immunologic↗
PubMed1999

Residential status and risk of hip fracture.

OBJECTIVE: to examine the association between residential status and risk of hip fracture in older people. DESIGN: population-based case-control study. SETTING: Auckland, New Zealand. SUBJECTS: a random sample of all individuals > or = 60 years, hospitalized with a fracture of the proximal femur between July 1991 and February 1994. Controls were age and gender frequency-matched to the cases, randomly selected from a random sample of general practitioners. MAIN OUTCOME MEASURES: radiographically-confirmed fracture of the proximal femur. Fractures sustained as a result of major trauma, such as in a motor vehicle crash, and those associated with pre-existing pathological conditions were excluded. RESULTS: individuals living in institutions were almost four times more likely to sustain a hip fracture [age- and gender-adjusted odds ratio (OR)=3.8; 95% confidence interval (CI): 3.0-4.8] than those living in private homes. After adjustment for potential confounding factors, the risk of hip fracture associated with living in an institution remained significantly increased (P< 0.0001), although the magnitude of the risk was somewhat diminished (OR=2.2; 95% (CI: 1.5-3.5). CONCLUSIONS: living in an institution is associated with an increased risk of hip fracture in older people. Specific factors that place these individuals at increased risk need to be identified, in order to develop intervention strategies.

Aged↗
PubMed1998

Selective inhibition by kringle 5 of human plasminogen on endothelial cell migration, an important process in angiogenesis.

Angiogenesis is a multi-step process that includes endothelial cell proliferation, migration, basement membrane degradation, and new lumen organization. Angiostatin, an internal fragment of plasminogen comprising the first four triple disulfide-linked kringle structures, is one of the most potent endogenous angiogenesis inhibitors described to date. The kringle 5 domain of plasminogen, which shares high sequence homology with the four kringles of angiostatin, was previously shown to antagonize endothelial cell growth. We now describe that the recombinant kringle 5 of human plasminogen inhibits endothelial cell migration with an IC50 (concentration for half maximal inhibition) of approximately 500 nM. We demonstrate that the lysine-binding sites of kringle 5 may not be involved in its anti-migratory activities. The anti-migratory activity of kringle 5 is similar to that of angiostatin. Kringle 5 also shows selective inhibition on endothelial cells as opposed to other cell types. Relative to its native form, reduced kringle 5 displays a significant increase in anti-migratory activity, implying that the kringle conformation may shield kringle 5 from effectively interacting with endothelial cells. This report thus constitutes the first demonstration that kringle 5 of plasminogen is a selective inhibitor for endothelial cell migration.

Amino Acid Sequence↗
PubMed1998

Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis.

Angiogenesis is a complex process that involves endothelial cell proliferation, migration, basement membrane degradation, and neovessel organization. Angiostatin, consisting of four homologous triple-disulfide bridged kringle domains, has previously been shown to exhibit profound inhibition of endothelial cell proliferation in vitro and angiogenesis in vivo. It was also demonstrated that angiostatin could suppress the growth of a variety of tumors via the blocking of angiogenesis. The primary aim of our study was to characterize the kringle domains of angiostatin for their inhibitory activities of endothelial cell migration in order to elucidate their contributions to the anti-angiogenic function of angiostatin. In this report, we demonstrate for the first time that the kringles of angiostatin play different roles in inhibiting endothelial cell migration, a crucial process in angiogenesis. Kringle 4, which has only marginal anti-proliferative activity, is among the most potent fragments in inhibiting endothelial cell migration (IC50 of approximately 500 nM). In contrast, kringle 1-3, which is equivalent to angiostatin in inhibiting endothelial cell proliferation, manifests only a modest anti-migratory effect. The combination of kringle 1-3 and kringle 4 results in an anti-migratory activity comparable to that of angiostatin. When kringle 1 is removed from kringle 1-3, the resulting kringle 2-3 becomes more potent than kringle 1-3. This implies that kringle 1, although virtually ineffective in inhibiting endothelial cell migration, may influence the conformation of kringle 1-3 to alter its anti-migratory activity. We also show that disruption of the kringle structure by reducing/alkylating agents markedly attenuates the anti-migratory activity of angiostatin, demonstrating the significance of kringle conformation in maintaining the anti-angiogenic activity of angiostatin. Our data suggest that different kringle domains may contribute to the overall anti-angiogenic function of angiostatin by their distinct anti-migratory activities.

Adrenal Glands↗