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Biomedical subjects

J Pugh

Publications and source records attributed to J Pugh.

At least 19 recordsLinked to original sources
PubMed1999

Instability of the CAG repeat in immortalized fibroblast cell cultures from Huntington's disease transgenic mice.

Huntington's Disease transgenic mice were used for an exploration into the stability of a trinucleotide repeat. The brain shows heterogeneous somatic instability that increases quantitatively with age. To test somatic CAG-repeat alterations during long-term culture, DNA was extracted from transgenic tissue, primary fibroblasts, and SV40-immortalized fibroblasts at intervals of approximately 100 cell doublings. In fibroblasts derived from an adult mouse, there was an initial short truncation of the repeat, followed by an emerging population of cells showing continuous slow expansion. After 15 months in continuous culture (approximately 600 cell doublings following transformation) the major CAG peak has increased from 155 to approximately 170 triplets. This in vitro system can now be used to assay factors that affect instability.

Animals↗
PubMed1999

Racial/ethnic analysis of selected intermediate outcomes for hemodialysis patients: results from the 1997 ESRD Core Indicators Project.

Principal goals of the End-Stage Renal Disease (ESRD) Core Indicators Project are to improve the care provided to ESRD patients and to identify categorical variability in intermediate outcomes of dialysis care. The purpose of the current analysis is to extend our observations about the variability of intermediate outcomes of ESRD care among different racial and gender groups to a previously unreported group, Hispanic Americans. This group is a significant and growing minority segment of the ESRD population. A random sample of Medicare-eligible adult, in-center, hemodialysis patients was selected and stratified from an end-of-year ESRD patient census for 1996. Of the 6,858 patients in the final sample, 45% were non-Hispanic whites, 36% were non-Hispanic blacks, and 11% were Hispanic. Whites were older than blacks or Hispanics (P < 0.001). Hispanics were more likely to have diabetes mellitus as a primary diagnosis than either blacks or whites (P < 0.001). Even though they received longer hemodialysis times and were treated with high-flux hemodialyzers, blacks had significantly lower hemodialysis doses than white or Hispanic patients (P < 0.001). The intradialytic weight losses were greater for blacks (P < 0.05). The delivered hemodialysis dose was lower for blacks than for whites or Hispanics whether measured as a urea reduction ratio (URR) or as the Kt/V calculated by the second generation formula of Daugirdas (median 1. 32, 1.36, and 1.37, respectively, P < 0.001). Hispanics and whites had modestly higher hematocrits than blacks (33.2, 33.2, and 33.0%, respectively, P < 0.01). There was no significant difference among groups in the weekly prescribed epoetin alfa dose ( approximately 172 units/kg/week). A significantly greater proportion of Hispanic patients had transferrin saturations >/=20% compared with the other two groups (P < 0.001). Logistic regression modeling revealed that whites were significantly more likely to have serum albumin <3. 5(BCG)/3.2(BCP) gm/dL (OR 1.4, p < 0.01); blacks were significantly more likely to have a delivered Kt/V < 1.2 (OR 1.4, P < 0.001) and hematocrit <30%, (OR 1.2; P < 0.05) and both blacks and Hispanics were significantly more likely to have a delivered URR < 65% (OR 1.5, P < 0.001 and 1.2, P < 0.05, respectively).

Adolescent↗
PubMed1999

Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population.

BACKGROUND: Nontraumatic lower limb amputation is a serious complication of both diabetic neuropathy and peripheral vascular disease. Many people with end-stage renal disease (ESRD) suffer from advanced progression of these diseases. This study presents descriptive information on the rate of lower limb amputation among people with ESRD who are covered by the Medicare program. METHODS: Using hospital bill data for the years 1991 through 1994 from the Health Care Financing Administration's ESRD program management and medical information system (PMMIS), amputations were based on ICD9 coding. These hospitalizations were then linked back to the PMMIS enrollment database for calculation of rates. RESULTS: The rate of lower limb amputation increased during the four-year period from 4.8 per 100 person years in 1991 to 6.2 in 1994. Among persons whose renal failure was attributed to diabetic nephropathy, the rates in 1991 and 1994 were 11.8 and 13.8, respectively. The rate among diabetic persons with ESRD was 10 times as great as among the diabetic population at large. Two thirds died within two years following the first amputation. CONCLUSIONS: The ESRD population is at an extremely high risk of lower limb amputation. Coordinated programs to screen for high-risk feet and to provide regular foot care for those at high risk combined with guidelines for treatment and referral of ulceration are needed.

Adolescent↗
PubMed1998

Pioneering the 12-hour shift in Australia--implementation and limitations.

Twelve-hour shift rostering offers an alternative to the traditional 8- and 10-hour shifts usually worked in Australian nursing practice. This paper outlines the implementation process involved in introducing 12-hour shifts in a Melbourne hospital intensive care unit. The process was instigated by the nursing staff. After extensive consultation with the union and hospital management, a roster pattern of two 12-hour days, followed by 12-hour night shifts then days off, was introduced. Independent researchers were engaged to evaluate the impact of the 12-hour shifts on staff well-being and work performance. Effects on staff retention, sick leave and inservice education were examined. The researchers found that well-being and work performance were minimally affected by the 12-hour shift roster, while staff retention and sick leave were unaffected. Further, the pattern of 12-hour shifts, which was democratically implemented, was preferred by the nursing staff and did not diminish their well-being and work performance.

Attitude of Health Personnel↗
PubMed1998

How patients adapt diabetes self-care recommendations in everyday life.

BACKGROUND: Our study explored behavioral factors affecting what patients with type 2 diabetes do for self-care and why they do it. The findings were used to develop clinical recommendations to improve intervention strategies. METHODS: Interviewers, using open-ended questions, explored patients' own perceptions and assessments of self-care behaviors. The fifty-one subjects were self-identified Mexican Americans who had type 2 diabetes for at least 6 months, and had no major impairment as a result of this diabetes. Texts of patient interviews were analyzed by building and refining matrixes to display and compare central themes regarding treatment strategies and their contexts. RESULTS: All patients were trying to control their diabetes, but none of them followed recommendations completely. Instead, they adapted self-care behaviors to the exigencies of everyday life. Key factors influencing patients' treatment choices were: (1) the belief in the power of modern medicine; (2) the desire to act and feel "normal"; (3) the desire to avoid physical symptoms; and (4) limited economic resources. CONCLUSIONS: As patients apply treatment recommendations in the context of their everyday lives, they continually must make many small decisions affecting self-care behavior. The specific contexts of patients' lives, including their economic, educational, and cultural circumstances, determine how the generalized principles of type 2 diabetes management are implemented. Clinical strategies must be responsive to these circumstances in order to enable patients to make appropriate decisions when adapting their self-care behaviors to their own situations.

Adult↗
PubMed1994

Evidence that hepatocyte turnover is required for rapid clearance of duck hepatitis B virus during antiviral therapy of chronically infected ducks.

Duck hepatitis B virus (DHBV) DNA synthesis in congenitally infected ducks is inhibited by 2'-deoxycarbocyclic guanosine (2'-CDG). Three months of therapy reduces the number of infected hepatocytes at least 10-fold (W.S. Mason, J. Cullen, J. Saputelli, T.-T. Wu, C. Liu, W.T. London, E. Lustbader, P. Schaffer, A.P. O'Connell, I. Fourel, C.E. Aldrich, and A.R. Jilbert, Hepatology 19:393-411, 1994). The present study was performed to determine the kinetics of disappearance of infected hepatocytes and to evaluate the role of hepatocyte turnover in this process. Essentially all hepatocytes were infected before drug therapy. Oral treatment with 2'-CDG resulted in a prompt reduction in the number of infected hepatocytes. After 2 weeks, only 30 to 50% appeared to still be infected, and less than 10% were detectably infected after 5 weeks of therapy. To assess the possible role of hepatocyte turnover in these changes, 5-bromo-2'-deoxyuridine (BUdR) was administered 8 h before liver biopsy to label host DNA in hepatocytes passing through S phase, and stained nuclei were detected in tissue sections by using an antibody reactive to BUdR. The extent of nuclear labeling after 5 weeks was the same as that before therapy (ca. 1%). However, biopsies taken after 2 weeks of therapy showed a ca. 10-fold elevation in the number of nuclei labeled with BUdR. This result suggested that a rapid clearance of infected hepatocytes by 2'-CDG was caused not just by the inhibition of viral replication but also by an acceleration of the rate of hepatocyte turnover. To test this possibility further, antiviral therapy was carried out with another strong inhibitor of DHBV DNA synthesis, 5-fluoro-2',3'-dideoxy-3'-thiacytidine (524W), which did not accelerate hepatocyte turnover in ducks. 524W administration led to a strong inhibition of virus production but to a slower rate of decline in the number of infected hepatocytes, so that ca. 50% (and perhaps more) were still infected after 3 months of therapy. In addition, histopathologic evaluation of 2'-CDG-treated ducks revealed liver injury, especially at the start of therapy. No liver damage was observed during 524W therapy. These results imply that clearance of infected hepatocytes from the liver is correlated with hepatocyte turnover. Thus, in the absence of immune clearance or other sources for the accelerated elimination of infected hepatocytes, inhibitors of virus replication would have to be administered for a long period to substantially reduce the burden of infected hepatocytes in the liver.

Animals↗
PubMed1993

Methodological approaches to disinfection of human hepatitis B virus.

Three commercial disinfectants (two quaternary formulations and one phenolic) were tested against human hepatitis B virus (HHBV). The treated virus was assayed for infectivity by the chimpanzee assay and for morphological alteration by the Morphological Alteration and Disintegration Test. The same agents were tested against duck hepatitis B virus in a duck hepatocyte infectivity assay. It is apparent that human and duck hepatitis viruses were relatively susceptible to disinfection, becoming noninfectious after < or = 10 min of contact with the disinfectant. The Morphological Alteration and Disintegration Test accurately predicted activity in the two infectivity tests. The anti-human hepatitis B virus effect of the low-level quaternary ammonium germicides is a novel finding and suggest that members of the family Hepadnaviridae are relatively susceptible to chemical agents.

Animals↗
PubMed1992

Total serum cholesterol levels in Asians living in New York City: results of a self-referred cholesterol screening.

Asians historically have low total cholesterol levels and low incidence of coronary heart disease. In performing a coronary heart disease and total cholesterol screening in New York City's Chinatown, we obtained data supportive of previous studies, which focused on Japanese populations and described the influence of environment on total cholesterol. In the present study, Chinese living in Chinatown have higher levels of total cholesterol than would be expected from studies of Chinese living in Shanghai. For every age group examined, Asian-born Chinese living in Chinatown had higher total cholesterol levels than both urban and rural Chinese in Shanghai. In subjects less than or equal to 30 years of age, urban males in Shanghai had cholesterol levels of 160 +/- 34 mg/dL, compared with 206 +/- 38 mg/dL for Asian-born males in Chinatown. For females in the same age category, cholesterol levels were 162 +/- 35 mg/dL vs 224 +/- 45 mg/dL, respectively. Applying National Cholesterol Education Panel (NCEP) guidelines, the distribution of desirable, borderline-high, and high blood cholesterol levels for the Chinese in Chinatown (41%, 35%, and 23%, respectively) were similar to a group of Caucasians screened (42%, 32%, and 26%) and the group recently used to determine the prevalence of high blood cholesterol in American adults (43%, 30%, and 27%). Studies are needed to stratify the risk of coronary heart disease in other groups that traditionally have a low incidence of coronary heart disease, but which now have adopted Western lifestyles.

Adult↗
PubMed1990

Synthesis of hepadnavirus particles that contain replication-defective duck hepatitis B virus genomes in cultured HuH7 cells.

To evaluate the possibility of producing transducible replication-defective hepadnaviruses, cloned mutant duck hepatitis B virus genomes were tested both for virus antigen production and viral DNA synthesis following transfection into the human hepatoma cell line HuH7. Deletion of a cis-acting 12-nucleotide sequence implicated in viral DNA synthesis, direct repeat 1 (DR1), resulted in the loss of ability to synthesize both mature viral DNA and infectious virus. The delta DR1 mutant, however, produced envelope and core antigens and was shown to provide trans-acting functions required for the assembly of infection-competent particles. Thus, mutants with mutations in viral genes could be rescued as DNA-containing viral particles after cotransfection with delta DR1. The efficiency of rescue was influenced by the site of mutation. A mutant DNA encoding truncated core and envelope proteins not only was poorly rescued but also was able to suppress the production from a wild-type DNA of infectious virus.

Animals↗
PubMed1990

Deterioration of trapeziometacarpal arthritis due to trigger thumb: a biomechanical evaluation.

Patients with trigger thumb and trapeziometacarpal joint arthritis accompanied by swan-neck deformity of their first rays find that their arthritic pain becomes worse whenever their thumbs "catch." Six hands with adduction contracture and arthritis of the trapeziometacarpal joint are studied biomechanically and demonstrate significantly excessive shear forces (p less than 0.01) around their trapeziometacarpal joint relative to six normal hands. Increased pain with deformity suggests aggressive treatment of trigger thumb in cases such as these.

Aged↗
PubMed1989

Cortical pelvic strains with varying size hemiarthroplasty in vitro.

Four human pelves were dissected of soft tissues and instrumented with rosette strain gages. The pelves were left intact (not separated at the pubic symphysis or sacroiliac joints) although each of the eight hemipelves was tested separately. The pelves were loaded to simulate single leg stance with use of a wire mesh cemented to the wing of the ilium, representing the abductor muscles. Loading was carried out with the intact hip joint and 1 mm undersized, correct sized, and 1 mm oversized hemiarthroplasty. The correct sized component produced a strain pattern closet to normal. The oversized component was associated with an increase in strain at the medial acetabular dome.

Acetabulum↗
PubMed1989

Normal pelvic strain pattern in vitro.

Four cadaver pelves were dissected of soft tissue and each of the eight hemipelves instrumented with ten rosette strain gauges. Static loading was conducted to simulate single leg stance, and applied through the intact hip joint. The medial portion of the pelvis was under tension directed vertically and the lateral ilium was in compression. This strain pattern is consistent with bending applied to the ilium from the action of the abductor and joint reaction forces.

Biomechanical Phenomena↗