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Biomedical subjects

H Clark

Publications and source records attributed to H Clark.

At least 19 recordsLinked to original sources

Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family.

The SWI2/SNF2 gene family has been implicated in a wide variety of processes, involving regulation of DNA structure and chromatin configuration, mitotic chromosome segregation, and DNA repair. Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a site in the myosin light chain 1/3 enhancer. The protein has single-stranded DNA-dependent ATPase activity, includes seven helicase motifs, and a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spliced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor lines and in Li-Fraumeni fibroblast cultures, suggesting that it is aberrantly regulated in malignant cells. The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product.

Adenosine Triphosphatases

A semi-solid drug delivery system for epidermal growth factor in corneal epithelial wound healing.

PURPOSE: To examine the effects of EGF, delivered from a semi-solid drug delivery system, on corneal epithelial wound healing following anterior keratectomy wound creation in the eyes of New Zealand white rabbits. METHODS: A semi-solid drug delivery system based on a Carbopol gel was developed. Following creation of a 7.5 mm circular anterior keratectomy wound, 50 microL of either a placebo gel or an EGF-containing gel, was instilled in the inferior fornix. The gel remained in the eye for 8 hours, at which time it was removed. Anaesthesia was maintained for the entire 8-hour period. Wound healing was evaluated by quantitative morphometry. We evaluated 0.04, 0.1, 0.2, 0.4, and 1% EGF concentrations in the gel. Tear EGF concentrations and histology of the healing corneas were also examined. RESULTS: The enhancement factor (ratio of the healing rate with the EGF gel and control gel) was 1.13 +/- 0.12, 1.40 +/- 0.14, 1.29 +/- 0.12, 1.80 +/- 0.22, and 1.09 +/- 0.12 for the gels containing 0.04, 0.1, 0.2, 0.4, and 1% EGF by mass, respectively. The increases in the rate of wound healing were significant with the 0.1, 0.2 and 0.4% gel formulations. Histologically, the 0.4% gels resulted in cellular hyperplasia after 5 days of healing. Differences between the placebo gel-treated and EGF-containing gel-treated eyes were evaluated at both 2 and 5 days. The concentration of EGF in the tears during the treatment period was approximately constant for both the 1% and 0.04% gels. The average tear concentration during the instillation period was 2.87 +/- 0.36 micrograms/mL and 200.61 ng/mL +/- 116.10 for the 1% and 0.04% gels respectively. CONCLUSIONS: Treatment with EGF in a Carbopol gel carrier for a period of 8 hours results in significant wound healing enhancement (p < 0.05). The optimum EGF loading in the gel was determined to be 0.4%. A slow release gel may be an effective way to deliver EGF to the corneal surface.

Animals

Femorotibial bypass: the learning curve.

Femorotibial bypass is still infrequently performed in many district hospitals, because it is time consuming and the risk of failure is high, especially during the learning curve. This article reviews the results of a single consultant surgeon and his team after starting femorotibial bypass de novo in a district general hospital. During the period 1987 to 1992, 85 femorotibial grafts were performed in 76 patients for ulceration and gangrene (57), rest pain (19) and severe claudication (9). Sixty-six were autogenous vein, 15 were PTFE with distal vein cuff, two were composites and two were umbilical vein. Overall, 22 grafts (26%) failed within the first 30 days (two were salvaged) and 21 amputations were required (five despite patent grafts). There were three early deaths (mortality 3.9%). At the end of 1993, 39 limbs had been amputated and 24 patients had died (eight with amputations). Twenty-three (44% of survivors) were alive with patent grafts. These disappointing early results were due to an initial technical learning curve, after which increased confidence may have led to reconstructing some patients with inadequate distal arteries. A more selective approach is now used. Limb salvage can be achieved in a worthwhile proportion of these patients and 3-year primary patency rates are similar to those of teaching hospitals in this country.

Aged

A postal survey evaluation of prostatectomy.

BACKGROUND: The aims of this study were to determine the prevalence of urinary symptoms after prostatectomy, and the relationship between pre- and post-operative symptoms. METHODS: A retrospective postal survey was carried out, on an unselected series of patients in Leicestershire, one to two years after transurethral resection. Four hundred and sixty-five men received a questionnaire, and of these 78 per cent responded. RESULTS: The operation relieved 92 per cent of all preoperative urge-incontinence, but 3 per cent of those who were continent beforehand developed urge-incontinence. Urgency and hesitancy also responded well. Nocturia, frequency and dribbling were the least responsive. There was a general tendency for symptoms to persist rather than develop post-operatively. CONCLUSIONS: Prostatectomy is an effective intervention, particularly for cases with urge-incontinence, urgency, incontinence or hesitancy. These results are consistent with those of other, prospective, studies. Postal surveys may provide a cheap and effective method of evaluating local prostatectomy services.

Aged

Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes?

Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness.

Biopsy

Psychological determinants of health and performance: the tangled web of desirable and undesirable characteristics.

Correlations were determined for male (n = 225) and female (n = 242) college students between sets of undesirable personality traits (anxiety, stress reactivity, anger, and alienation) and desirable personality traits (instrumentality, achievement strivings, and optimism measured by the Scheier-Carver [1987] Life Orientation Test), and a series of outcome variables related to health (self-reported health complaints and health maintenance behaviors and beliefs) and academic performance (academic expectations and actual grade point average). Significant correlations were found between many of the personality variables and the outcome variables. However, partial correlations revealed different relationships for the various criteria. With other variables held constant, health complaints were related to several undesirable characteristics, whereas health maintenance behaviors and beliefs were related to several desirable attributes. Only achievement strivings made an independent contribution in both sexes to the 2 measures of academic performance. The theoretical and methodological wisdom of using measures of multiple personality constructs and outcome variables is discussed.

Achievement

Medical research.

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New Zealand

Medical management decisions in nursing home patients. Principles and policy recommendations.

The ethical principles of medical decision making are inherently the same for nursing home residents, who represent an increasingly large segment of the population, as they are for other adult patients. In practice, however, a number of considerations require specialized application of these principles in nursing homes. Notably, a large proportion of nursing home patients are at high risk for morbid and mortal events yet are incapable of expressing medical management preferences due to dementia and confusion. Policies and procedures regarding medical decisions for nursing home patients are needed. We present and discuss a policy for patient care in nursing homes based on recommendations of a national biomedical ethics committee. This policy, which may be adapted for use in specific institutions, explicitly discusses the principles of care and their application in nursing homes. It also encourages prospective decision making and provides advance care directives for patients making and provides advance care directives for patients and their decision-making surrogates to do so.

Decision Making, Organizational

Imipramine poisoning in a child: lack of efficacy of resin hemoperfusion.

A three-year-old boy ingested up to 1,500 mg of the tricyclic antidepressant imipramine (Tofranil). He entered our facility within two hours of discovery, and multiple resuscitative efforts, which proved unsuccessful, followed. Resin hemoperfusion was used in an effort to remove imipramine from the systemic circulation. Serum concentrations of imipramine and its major metabolite desipramine were determined from serum drawn before, during, and after hemoperfusion. Serum concentrations of imipramine and desipramine did not change appreciably. No improvement in the clinical condition was noted during the hemoperfusion period, which was due in part to the fact that our patient was clinically brain dead upon arrival in our intensive care unit. Our subsequent literature review documents that this case represents the first reported use of hemoperfusion in a pediatric tricyclic antidepressant ingestion, hemoperfusion removes an insignificant portion of the total amount of tricyclic antidepressant ingested, and some pediatric literature misleadingly suggests that hemoperfusion may be useful in such patients. Physicians treating tricyclic antidepressant ingestion cases should avoid using hemoperfusion; standard supportive care remains the essential management response.

Child, Preschool

Humoral immune response to herpes simplex virus type 2 glycoproteins in patients receiving a glycoprotein subunit vaccine.

Serial serum specimens from 22 herpes simplex virus (HSV)-seronegative recipients of an HSV type 2 (HSV-2) glycoprotein subunit vaccine were analyzed by radioimmunoprecipitation and polyacrylamide gel electrophoresis for the development of antibodies to HSV-2 gB, gD, and g80, a complex of gC and gE. Volunteers received 50 (n = 12) or 100 micrograms (n = 10) of vaccine at days 0, 28, and 140; sera were drawn weekly for 8 weeks and again at days 140, 147, and 365. Among seronegative volunteers, antibody to gB was detected 2 weeks after the first dose, while antibodies to g80 and gD were detected after the second dose (day 35). Antibodies to nonglycosylated HSV-specific proteins were not detected. A dose-response effect between recipients of 50- and 100-micrograms doses was observed in the proportion of vaccine recipients seroconverting to g80 and in the proportion of recipients retaining antibodies to both gD and g80 over time. Diminishing complement-independent neutralizing antibody titers occurred after the second dose and were associated with loss or reduction of detectable antibody to gD. Volunteers who were seropositive for HSV-1-specific antibody (n = 11) were also enrolled in the trial and received 50-micrograms doses of vaccine. Vaccination resulted in conversion to HSV-2 complement-independent neutralizing antibody specificity or indeterminant specificity in 10 of 11 volunteers. These shifts were accompanied by changes in the radioimmunoprecipitation and polyacrylamide gel electrophoresis profile. These changes, which were apparent by 14 days after the first vaccine dose, included de novo appearance or increased levels of antibody to g80 and increased levels of antibody to gD and gB. These studies document the immunogenicity of solubilized glycoproteins gB, gD, gC, and, possibly, gE in humans.

Antibodies, Viral