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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 55 records · Page 3Linked to original sources
PubMed2000

Safety and efficacy of solvent/detergent-treated antihaemophilic factor with an added 80 degrees C terminal dry heat treatment in patients with haemophilia A.

Plasma-derived factor VIII concentrates remain an important resource for haemophilia A patients. To improve the safety of these preparations, various methods of viral removal and inactivation have been used that are designed to eliminate both enveloped and non-enveloped viruses. There have been rare reports that some viral inactivation processes altered the immunogenicity of some concentrates, leading to the development of factor VIII inhibitors in previously treated haemophilia A patients. This study evaluated the safety, efficacy and lack of neo-antigenicity of a highly purified factor VIII preparation which undergoes both solvent/detergent treatment and final dry heat treatment at 80 degrees C for 72 h. The study included: (i) a single blind, single-dose crossover pharmacokinetic study in 18 previously treated patients, comparing sibling lots of the unheated preparation (Koate(R)-HP) and the heat-treated preparation (Koate(R)-DVI), and (ii) an extended home treatment programme for 36 patients at two haemophilia treatment centres primarily to assess immunogenicity. Clinical parameters were assessed at regular intervals. The results confirm that Koate(R)-HP and Koate(R)-DVI are bioequivalent, and that Koate(R)-DVI is safe and efficacious for treatment of acute bleeding episodes and for surgery. Furthermore, the heat-treated preparation is not associated with the development of inhibitors in previously treated patients.

Adolescent↗
PubMed2000

Severe carbon monoxide poisoning: outcome after hyperbaric oxygen therapy.

This paper reports the outcome after carbon monoxide poisoning in 31 consecutive patients treated with mechanical ventilation and hyperbaric oxygen therapy, compared with another study of mechanically ventilated patients treated with normobaric oxygen. We found 16.1% hospital mortality and 3.8% severe short-term memory loss, compared with 30% hospital mortality and 20% incidence of serious neurological deficit after treatment with normobaric oxygen; outcome was poor in 19.4% and 44.3% of those treated with hyperbaric and normobaric oxygen, respectively (P < 0.05). Cerebral oedema caused three of five deaths despite hyperbaric therapy, occurring at 24-48 h after poisoning. Intracranial pressure monitoring and CT scan of the head before wakening should be considered in any severely poisoned patient.

Adolescent↗
PubMed2000

Should control measures be based on air measurements or biological/biological effect monitoring?

The setting of, and the review of, exposure limits takes into account toxicological, occupational hygiene and epidemiological data. The COSHH Regulations 1994 define a hierarchical approach to controlling workplace exposures with a particular emphasis on the measurement and control of airborne substances. Absorption via the lungs is considered the most important route of entry in the workplace, however, percutaneous absorption must not be overlooked. Biomarkers are used extensively in the surveillance of workers' exposure to metals and organic chemicals. In addition, Genetic polymorphism for xenobiotic metabolism has been widely studied. The selection, validation and application of any biomarker is a complicated process and requires careful consideration prior to any application.

Biomarkers↗
PubMed2000

Occupational and environmental medicine: sustainable development?

Occupational medicine is evolving to meet the needs of the 21st century. There is a need to define the remit of occupational and environmental medicine in order to facilitate the development and maintenance of requisite competencies, the establishment of educational goals for practitioners and production of a professional product for the global market place. The delivery of occupational health services will be underpinned by quality assurance systems.

Environmental Medicine↗
PubMed2000

SFE1, a constituent of the fertilization envelope in the sea urchin is made by oocytes and contains low-density lipoprotein-receptor-like repeats.

At fertilization in most animals, cortical granules of the egg or oocyte secrete their contents, whose function it is to modify the extracellular matrix. This modified matrix then participates in the block to polyspermy and protection for early embryonic development. In the sea urchin, contents of the cortical granules are secreted within 30 sec of insemination. Several of these content proteins then bind to the nascent vitelline layer of the egg and lift off the cell surface to form a stable, impervious, fertilization envelope. At least six major proteins are present in the envelope, and recently we have identified cDNA clones of two, ovoperoxidase, and SFE9. Here we report on the identification and characterization of SFE1, a constituent of the fertilization envelope of the sea urchin Strongylocentrotus purpuratus, that has revealing characteristics of how the envelope might form and what protein interaction domains might predominate. We present the largest cDNA sequence we were able to identify representing approximately two thirds of the predicted protein coding region. The C-terminal half of the cognate SFE1 protein contains two different amino acid repeat motifs: a cysteine-rich (15%) motif of 40 amino acids that is tandemly repeated 22 times and is followed by a serine/threonine-rich (38%) repeat of 63 amino acids that is tandemly repeated 3.5 times. Surprisingly, just N-terminal to the cysteine-rich repeat region is a sequence of five repeats with similarity to repeats in another cortical granule protein, SFE9, and to the motif originally identified in the receptor of low-density lipoproteins, the LDLr motif. The amino acid composition deduced from the partial SFE1 cDNA is similar also to the composition of proteoliaisin, a protein thought to tether the ovoperoxidase to the vitelline layer of the egg and thereby sequester the crosslinking activity of the ovoperoxidase to a limited population of proteins in the fertilization envelope. However, by use of monoclonal and polyclonal antibodies to SFE1 and proteoliaisin, we show here that they are distinct gene products. We also show that SFE1 is packed selectively into the cortical granules and then is crosslinked into the fertilization envelope following fertilization. In situ RNA hybridization analysis shows that the mRNA of SFE1 (9 kilobases) is present in oocytes selectively and is turned over rapidly in the oocyte following germinal vesicle breakdown. Our findings suggest that the gene encoding this major product of the egg is activated concomitantly with the other cortical granule-specific products already identified, and that a common LDLr-like motif of the fertilization envelope may reveal a structural mechanism for protein interactions in its construction.

Amino Acid Sequence↗
PubMed2000

Mechanical and histologic evaluation of Collagraft in an ovine lumbar fusion model.

The purpose of this study was to determine the effectiveness of a composite material composed of Type I bovine dermal collagen, 65% hydroxyapatite, and 35% tricalcium phosphate ceramic (Collagraft Bone Graft Matrix Strip NeuColl Incorporated, Palo Alto, CA) as a bone graft substitute for spinal fusion with and without the use of autologous bone marrow in an ovine lumbar spine model with pedicle screw fixation. Twenty-four adult sheep underwent a single level posterolateral (intertransverse process) L3-L4 lumbar fusion with one of three graft materials combined with rigid pedicle screw fixation. The three graft materials were Collagraft, Collagraft with marrow, and autogenous corticocancellous bone graft. Animals were euthanized 6 months after surgery and evaluated using dual energy x-ray absorptiometry, radiographs, histologic analysis, and mechanical testing. Dual energy xray absorptiometry between the transverse processes revealed that the mineral densities for the two Collagraft groups were significantly higher than the autogenous bone graft group. Histologic analysis confirmed that Collagraft was highly compatible and was well incorporated into the fusion mass. Both Collagraft groups had thick trabeculae and a mixture of lamellar and plexiform bone. The autogenous bone graft group had a smaller fusion complex, composed primarily of lamellar bone with thinner and fewer trabeculae. All three groups had similar mechanical properties. These results support the use of Collagraft in spinal fusion with pedicle screw fixation.

Absorptiometry, Photon↗
PubMed2000

Histologic, neurologic, and immunologic effects of methylmercury in captive great egrets.

Captive great egret (Ardea albus) nestlings were maintained as controls or were dosed with methylmercury chloride at low (0.5), and high doses (5 mg/kg, wet weight) in fish. Low dosed birds were given methylmercury at concentrations comparable to current exposure of wild birds in the Everglades (Florida, USA). When compared with controls, low dosed birds had lower packed cell volumes, dingy feathers, increased lymphocytic cuffing in a skin test, increased bone marrow cellularity, decreased bursal wall thickness, decreased thymic lobule size, fewer lymphoid aggregates in lung, increased perivascular edema in lung, and decreased phagocytized carbon in lung. High dosed birds became severely ataxic and had severe hematologic, neurologic, and histologic changes. The most severe lesions were in immune and nervous system tissues. By comparing responses in captive and wild birds, we found that sublethal effects of mercury were detected at lower levels in captive than in wild birds, probably due to the reduced sources of variation characteristic of the highly controlled laboratory study. Conversely, thresholds for more severe changes (death, disease) occurred at lower concentrations in wild birds than in captive birds, probably because wild birds were exposed to multiple stressors. Thus caution should be used in applying lowest observed effect levels between captive and wild studies.

Analysis of Variance↗
PubMed2000

Prioritising referrals to a community mental health team.

BACKGROUND: Current national policies encourage prioritisation of people with severe mental illness (SMI) as well as the development of a primary care-led National Health Service. Where resources for mental health are limited, there is a potential conflict between the needs of people with SMI and the much more common depressive and anxiety disorders that form the bulk of the mental health workload in primary care. AIM: To describe the re-organisation of a community mental health team in order to prioritise people with SMI. METHOD: The number and type of referrals received in the 12 months before and after re-organisation were compared, and general practitioners' (GP) views on the changes sought. RESULTS: There was a significant reduction in GP referrals of patients with less severe disorders in the second year. In both years the proportion of patients with a possible psychotic diagnosis or risk of self-harm was much higher among referrals from within the psychiatry department (92% of referrals) than among GP referrals (20% of referrals). Using data from a postal survey, 46% of referring GPs reported a significant improvement in the service provided to patients with SMI, but 34% reported a deterioration in services for other patient groups. GPs were more likely to be satisfied with the service for people with SMI than with the service for other patient groups. CONCLUSIONS: Improvements in the service provided for those with SMI can be achieved, but this may be at the expense of services for other patient groups. Primary care groups will need to consider this potential conflict in setting priorities for mental health.

Community Mental Health Services↗
PubMed2000

The role of positron emission tomography in selecting patients with metastatic cancer for adrenalectomy.

Metastases to the adrenal glands usually signal disseminated disease. However, isolated metastases do occur that may be curable with adrenalectomy. Functional imaging with positron emission tomography (PET) can differentiate benign from malignant pathology and isolated from disseminated metastases. The purpose of this study was to determine whether PET scanning can influence the outcome of adrenalectomy for metastatic disease. We conducted a retrospective review of eight patients undergoing adrenalectomy for presumed isolated metastatic disease from 1985 through 1997. The patients included six women and two men with an average age of 58 (range, 36-74). Their primary tumors were six lung carcinomas, one renal cell carcinoma, and one colon carcinoma. The adrenal masses were located on the right in six patients, on the left in one, and bilaterally in one. Before operation, all patients were evaluated by chest and abdominal CT. Four patients were also evaluated by PET scan. Six right, one left, and one bilateral adrenalectomies were performed. Associated organ resections included two right partial nephrectomies and one right total nephrectomy, one left partial nephrectomy, two distal pancreatectomies, one splenectomy, and two partial hepatic resections. All eight patients survived operation. There were no major perioperative complications, but one patient required readmission for congestive heart failure. Three of the four patients who did not have PET scanning died from 4 to 48 months after operation with disseminated disease from lung, colon, and renal carcinoma respectively. The remaining patient who did not have PET scanning is alive and well 11 years later. Two of the four patients who had PET scans showing isolated disease are alive at 28 and 43 months after operation, whereas the other two died of disseminated disease at 29 and 36 months after operation. We conclude that 1) adrenalectomy can provide survival benefit in patients with isolated metastases, and 2) PET scanning is useful in confirming isolated metastatic disease and selecting patients for adrenalectomy.

Adrenal Gland Neoplasms↗
PubMed2000

Identification of multiple cis-acting elements mediating the induction of prostaglandin G/H synthase-2 by phorbol ester in murine osteoblastic cells.

The tumor promoter phorbol 13-myristate 12-acetate (PMA), the best characterized protein kinase C agonist, frequently regulates gene expression via activation of Fos/Jun (AP-1) complexes. PMA rapidly and transiently induces prostaglandin G/H synthase-2 (PGHS-2) expression in murine osteoblastic MC3T3-E1 cells, but no functional AP-1 binding motifs in the 5'-flanking region have been identified. In MC3T3-E1 cells transfected with -371/+70 bp of the PGHS-2 gene fused to a luciferase reporter gene (Pluc), PMA stimulates luciferase activity up to eightfold. Computer analysis of the sequence of the PGHS-2 promoter region identified three potential AP-1 elements in the -371/+70 bp region, and deletion analysis suggested that the sequence 5'-aGAGTCA-3' at -69/-63 bp was most likely to mediate stimulation by PMA. Mutation of the putative AP-1 sequence reduces the ability of PMA to stimulate Pluc activity by 65%. On electrophoretic mobility shift analysis (EMSA), PMA induces binding to a PGHS-2 probe spanning this sequence, binding is blocked by an unlabeled AP-1 canonical sequence, and antibodies specific for c-Jun and c-Fos inhibit binding. Mutation of this AP-1 site also causes a small (22%) but significant reduction in the serum stimulation of Pluc activity in transiently transfected MC3T3-E1 cells. On EMSA, serum induces binding to a PGHS-2 probe spanning the AP-1 site, binding is blocked by an unlabeled AP-1 canonical sequence, and antibodies specific for c-Jun and c-Fos inhibit binding. Joint mutation of this AP-1 site and the nearby CRE site at -56/-52 bp, previously shown to mediate serum, v-src and PDGF induction of PGHS-2 in NIH-3T3 cells, blocks both PMA and serum induction of Pluc activity in MC3T3-E1 cells. Hence, the AP-1 and CRE binding sites are jointly but differentially involved in both the PMA and serum stimulation of PGHS-2 promoter activity.

3T3 Cells↗
PubMed2000

Helicobacter pylori and the learning disabled.

Those with a learning disability previously cared for in institutions have now been discharged into smaller community homes. This has meant that an increased burden has been placed on general practitioners (GPs) to evaluate and treat those who have symptoms that may be difficult to interpret. This report presents the prevalence of Helicobacter pylori in those still awaiting discharge and discusses the possible symptoms that GPs may encounter.

Adolescent↗
PubMed1999

Integration of microfabricated devices to capillary electrophoresis-electrospray mass spectrometry using a low dead volume connection: application to rapid analyses of proteolytic digests.

This report describes the development of a compact and versatile, micromachined chip device enabling the efficient coupling of capillary electrophoresis to electrospray mass spectrometry (CE-ESMS). On-chip separation provides a convenient means of achieving rapid sample cleanup and resolution of multicomponent samples (typically 2-5 min) prior to mass spectral analysis. A low dead volume connection facilitating the coupling of microfabricated devices to CE-ESMS was evaluated using two different interfaces. The first configuration used disposable nanoelectrospray emitters directly coupled to the chip device via this low dead volume junction, thereby providing rapid separation of complex protein digests. The performance of this interface was compared with that of more traditional configurations using a sheath flow CE-ESMS arrangement where a fused-silica capillary of varying length enabled further temporal resolution of the multicomponent samples. The sensitivity and analytical characteristics of these interfaces were investigated in both negative and positive ion modes using standard peptide mixtures. The separation performance for synthetic peptides using a chip coated with amine reagent ranged from 26,000 to 58,000 theoretical plates for a sheath flow CE-ESMS interface comprising a 15-cm CE column. Replicate injections of a dilution series of peptide standards provided detection limits of 45-400 nM without the use of on-line preconcentration devices. The reproducibility of migration time ranged from 0.9 to 1.5% RSD whereas RSDs of 5-10% were observed on peak areas. The application of these devices for the analysis of protein digests was further evaluated using on-line tandem mass spectrometry.

Amino Acid Sequence↗
PubMed1999

beta Blockade after myocardial infarction: systematic review and meta regression analysis.

OBJECTIVES: To assess the effectiveness of beta blockers in short term treatment for acute myocardial infarction and in longer term secondary prevention; to examine predictive factors that may influence outcome and therefore choice of drug; and to examine the clinical importance of the results in the light of current treatment. DESIGN: Systematic review of randomised controlled trials. SETTING: Randomised controlled trials. SUBJECTS: Patients with acute or past myocardial infarction. INTERVENTION: beta Blockers compared with control. MAIN OUTCOME MEASURES: All cause mortality and non-fatal reinfarction. RESULTS: Overall, 5477 of 54 234 patients (10.1%) randomised to beta blockers or control died. We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%), but only a 4% reduction in the odds of death in short term trials (-8% to 15%). Meta regression in long term trials did not identify a significant reduction in effectiveness in drugs with cardioselectivity but did identify a near significant trend towards decreased benefit in drugs with intrinsic sympathomimetic activity. Most evidence is available for propranolol, timolol, and metoprolol. In long term trials, the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments for patients with acute or past myocardial infarction. CONCLUSIONS: beta Blockers are effective in long term secondary prevention after myocardial infarction, but they are underused in such cases and lead to avoidable mortality and morbidity.

Adrenergic beta-Antagonists↗
PubMed1999

Trends in hospital efficiency among metropolitan markets.

This study evaluates trends in efficiency among American hospital markets. A total of 6010 hospitals were identified for use in the analysis from the American Hospital Association's Annual Surveys for 1989 and 1993. Using data envelopment analysis (DEA), a longitudinal study of hospital efficiency was conducted on all 314 metropolitan markets in the United States. Results suggest that large hospital markets generally demonstrated higher inefficiency. The major inefficiencies exist in the availability of hospital services, the number of operating beds, the utilization of hospital staffing and operating expenses. Consequently, the large hospital market had a significant excess of health manpower that resulted in inefficiency that amounted to approximately $23 billion. From a policy perspective, this study has shed some light on the need to establish more specific policies to address inefficiency in the health care industry.

American Hospital Association↗