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Biomedical subjects

D Robinson

Publications and source records attributed to D Robinson.

At least 217 records · Page 12Linked to original sources

Comparison between urinary diaries completed with and without intensive patient instructions.

The evaluation of the incontinent patient relies on accurate assessment of urinary symptoms. Although the 7 day urinary diary is a reproducible method of data collection, the optimal means of implementing this diary is unknown. The urinary diary is usually employed after the initial clinical pathophysiologic evaluation has been performed and the patient has received intensive instructions on the correct method of diary completion. This study aims to determine if a urinary diary provided to the patient prior to the initial clinical evaluation along with minimal instructions will provide symptom data comparable with that obtained by conventional methods. Two hundred seventy-eight women were recruited to participate in one of three clinical trials for urinary incontinence treatment. All subjects completed a diary prior to the initial clinical evaluation, the Minimal Instruction Diary, and a second diary after clinical evaluation, the Intensive Instruction Diary. The Minimal and the Intensive Instruction Diaries were compared for number of episodes of diurnal and nocturnal voluntary micturition and incontinence. Pearsons' correlation coefficients ranged from 0.67 to 0.78 for each of the urinary symptoms. Intra-subject comparison indicated a decline in reports of nocturnal voluntary micturitions from the Minimal to the Intensive Instruction Diary. No demographic or urodynamic parameters could account for the difference. The 7 day urinary diary is a reliable tool to asses urinary symptoms, which can be utilized prior to the initial clinical evaluation. Its case of use and practicality make this diary promising for use in a wider patient population.

Aged↗

Effects of estrogen and progestin replacement on the urogenital tract of the ovariectomized cynomolgus monkey.

Menopause is presumed to have a causative role in the development of female urinary incontinence. While some clinical trials have shown that estrogen can affect urinary tract function, our knowledge of the pathophysiologic changes resulting from menopause and hormone replacement therapy is poor. The cynomolgus monkey is a well-established model for study of menopause and hormone replacement therapy, particularly in the cardiovascular arena. We have utilized this animal model to determine the histologic effects of estrogen and estrogen/progestin replacement therapy in the proximal urethra and vagina. Estrogen and estrogen/progestin replacement induced an increase in the amount of vaginal but not urethral epithelium. Hormone replacement also resulted in a significant increase in the loose, vascular component of the connective tissue layer of the urethra. The cynomolgus macaque shows promise as a useful model for further study of the effects of hormone replacement on the lower urinary tract.

Animals↗

Evolution of science-based uncertainty factors in noncancer risk assessment.

The science behind the use of uncertainty factors has progressed considerably. Increased knowledge of inter- and intraspecies sensitivity, mechanisms of action, and detailed evaluation of data bases can support the use of data-derived uncertainty factors, which ultimately results in a risk assessment with greater confidence. Papers that highlight available data for each of several areas of uncertainty are discussed, indicating that choice of the appropriate factor requires scientific judgement on a case-by-case basis. Case studies from EPA and Health Canada risk values illustrate the use of data in chemical specific risk assessments to support the selection of uncertainty factors other than the default value of 10-fold. In the case studies, the types of data that have been used to support a change in the default value are explicitly reviewed, as well as why the data support a different uncertainty factor, how the uncertainty was reduced, and what assumptions have been satisfied or replaced. Incorporation of all available scientific data into the risk assessment process fosters increased research and ultimately reduces uncertainty. The results of this review support the use of data-derived uncertainty factors when appropriate scientific data are available.

Animals↗

Outcome analysis of carotid endarterectomy in Connecticut: the impact of volume and specialty.

The purpose of this study was to define the relationship between the surgeon's operative experience and specialty and the postoperative morbidity and mortality of carotid endarterectomy. All patients undergoing carotid endarterectomy (code ICD-9CM 38.12) in Connecticut between October 1985 and September 1991 were retrospectively identified. A total of 3997 carotid endarterectomies were performed by 226 surgeons in four specialties: general, cardiac, vascular, and neurosurgery. Individual surgeon volume ranged from fewer than one per year to 27.5 per year (mean 2.9 carotid endarterectomies per year). Outcome was measured as a combined stroke and/or death percentage. The average combined stroke and/or death rate for the entire group was 4.9%. The combined stroke and/or death percentage was influenced significantly by the surgeon's annual volume. Surgeons who performed one or fewer carotid endarterectomies (43% of total surgeons) were 2.5 times more likely (p < 0.002) to have a poor postoperative outcome than those who performed 10 or more per year (9.3% of total surgeons). Overall there was a statistically significant correlation between a surgeon's annual volume and outcome, particularly for general surgeons.

Clinical Competence↗

Practice variations in treating urban minority asthmatics in Chicago.

This study explores provider adherence to national guidelines in treating Latino and African-American asthmatics. We hypothesized that there would be more variations in asthma treatment existing for minorities as a result of variation in physician's adherent to the guidelines. A 96-item survey was administered to 138 Latino and African-American asthmatics attending a hospital emergency department. Data were obtained on demography, severity, access, patient satisfaction, and patient's assessment of physician asthma management. Results were analyzed by ethnicity, gender, practice site of regular provider, and severity. Variation in physician practice was found in these variables. Asthma treatment received by Latino and African-American respondents was deficient compared to guidelines. Regression analyses showed that Latinos fared more poorly on the number of prednisone bursts taken, use of written crisis plans and dispensation of peak flow meters controlling for gender, practice site and severity. African-Americans expressed less dissatisfaction in obtaining services, while both groups expressed high degrees of satisfaction with their providers.

Adolescent↗

Efficacy of estrogen supplementation in the treatment of urinary incontinence. The Continence Program for Women Research Group.

OBJECTIVE: To assess the efficacy of cyclic postmenopausal hormone replacement in treating urinary incontinence in hypoestrogenic women. METHODS: Eighty-three hypoestrogenic women complaining of urinary incontinence were included. All patients were community-dwelling, age 45 years or older, with involuntary loss of urine occurring at least once a week and urodynamic evidence of genuine stress incontinence and/or detrusor instability. Evaluation consisted of a comprehensive clinical and urodynamic research protocol. The hypoestrogenic entry criterion was a plasma estradiol level of 30 pg/mL or less. Parabasal cells on vaginal smears were also monitored. The primary outcome was the number of incontinent episodes per week, as documented on a standardized urinary diary. Secondary outcomes were the quantity of fluid loss, voluntary diurnal and nocturnal micturition frequency, generic and condition-specific health-related quality of life measurements, and patient satisfaction. A randomized, placebo-controlled, double-blind design was used. Subjects in the treatment group were given conjugated equine estrogens (0.625 mg) and medroxyprogesterone (10 mg) cyclically for 3 months. Controls received placebo tablets. RESULTS: (All results are presented as mean +/- standard deviation.) Subjects were 67 +/- 9 years old. The menopause duration was 18 +/- 11 years. The duration of incontinence was 9 +/- 9 years. Estradiol level at baseline was 9 +/- 9 pg/mL, and the parabasal cell count was 42 +/- 44%. The number of incontinent episodes at baseline was 13 +/- 10 for the treatment group and 16 +/- 4 for controls. No significant changes occurred in the number of incontinent episodes after treatment: 10 +/- 10 for the treatment group, and 13 +/- 14 for the controls (P = .7). Also, fluid loss was not changed: 176 +/- 106 g for the treatment group and 64 +/- 88 g for the control group at baseline, and 101 +/- 150 and 51 +/- 69 g after treatment, respectively (P = .7). There were no significant differences for either diurnal or nocturnal voluntary micturition, quality of life measures, or patient's perception of improvement. CONCLUSION: Three-month cyclic hormone replacement therapy did not affect either clinical or quality of life variables of incontinent, hypoestrogenic women. Long-term effects are unlikely to be substantially different. The use of estrogen supplementation as preventive or adjuvant therapy was not evaluated in this study.

Aged↗

Resurfacing of goat articular cartilage by chondrocytes derived from bone marrow.

The feasibility of using cartilaginous implants containing bone marrow derived chondrocytes in biological resurfacing procedures for correcting defects in articular cartilage was examined in goats. The experimental protocol included bone marrow aspiration, mesenchymal cell culturing, cell proliferation, favorable conditions inducing chondrogenic differentiation, and implantation of autogeneic and allogeneic cells. Autogeneic implant transplantations proved to be the best source for regeneration and repair of defective articular surfaces with use of densitometric computed image analysis of histochemical and immunohistochemical parameters on tissue sections. Allogeneic chondrocyte enriched cultures derived from bone marrow evoke a typical immune response in the host, expressed by the formation of fibrosis and progressive joint arthrosis. In the current study, a biological resurfacing procedure is described in detail for large mammals of similar weight and size as humans. Autogeneic mesenchymal cells derived from a bone marrow aspiration are the best cell source and when embedded in hyaluronic acid based adhesive glue make an excellent cartilaginous implant. The reparative regenerated cartilaginous tissue outcome within the defects appear different than neighboring normal articular cartilage shortly after surgery. Whether in the long term the cartilaginous remodeling process will shape the cartilage such that it more closely resembles the original articular cartilage is not known.

Animals↗

Subject selection biases in clinical trials: data from a multicenter schizophrenia treatment study.

To evaluate subject selection biases in clinical trials, demographic characteristics (gender, race, and age) of subjects at different phases of evaluation for a multicenter maintenance trial in schizophrenia were examined. Six thousand twelve diagnostically appropriate subjects were screened for the study; of these, 1,320 met eligibility criteria and 528 (9% of the screened sample) entered the study. Women, blacks, and older subjects were more likely not to meet eligibility criteria; women and older subjects were more likely and blacks were less likely to refuse study participation. Overall, compared with the screened population, the sample of subjects who entered the study contained proportionately fewer women (33 vs. 43%), more blacks (48.5 vs. 41%), and fewer older subjects (mean age of the entered sample was 29.4 +/- 7.4 vs. 34.8 +/- 11.3 years for the screened population). Having identified these selection factors, a second goal was to assess the potential clinical relevance of selection biases of these magnitudes on clinical trials using models of hypothetical studies with different degrees of selection bias. These showed that selection biases would rarely change overall study outcomes to a clinically relevant degree. However, in our models, selection biases did limit the ability to make inferences about results for select small subgroups of the study population. Investigators should consider collecting data on the recruitment process to allow estimation of the effects of selection biases on the generalizability of their findings.

Acute Disease↗

Mechanical methods in refractive corneal surgery.

The past year has seen considerable advances and debate with regard to several new and some established mechanical means of refractive surgery. Lamellar in situ keratomileusis is gaining increased interest, especially for the treatment of moderate and high myopia, although considerable questions still exist with regard to its safety, predictability, and the possibility of loss of lines of best corrected visual acuity. Mini-radial keratotomy may be of benefit in reducing the risk of traumatic rupture of radial keratotomy incisions, and a refinement of the nomograms for astigmatic keratotomy in the treatment of congenital astigmatism has been proposed. Another report on the use of hexagonal keratotomy for the treatment of hyperopia again raised concerns of its predictability. A blind eye study of intrastromal corneal rings has provided some reassurance with regard to its safety but has also raised doubts over its predictability. Meanwhile, several more reports of the use of both anterior and posterior chamber phakic intraocular lenses for the treatment of myopia have been presented.

Cornea↗

The tRNA(Gln) 4336 mitochondrial DNA variant is not a high penetrance mutation which predisposes to dementia before the age of 75 years.

The genetic factors that predispose to Alzheimer's disease (AD) are heterogeneous. Two recent reports have suggested that a mitochondrial DNA mutation within the tRNAGln gene, located at position 4336, may be a risk factor for AD, as it was found in 10/256 (3.9%) cases with AD confirmed by necropsy. Although low prevalences of this mutation were detected in non-demented subjects in both of these studies, the controls were not carefully matched with the AD cases. We have investigated the frequency of this mutation in two community based elderly cohorts in Cambridgeshire, who have participated in longitudinal studies of cognitive function. The 4336 mitochondrial mutation was detected in 8/ 443 people examined. These people were found to be non-demented at ages 74, 81, 84, 86, 89, 90, 91, and 102 years, in contrast to the previously described cases whose onset of dementia occurred between 60 and 76 years (mean 68). Accordingly, we believe that this mitochondrial variant is not a high penetrance mutation which predisposes to dementia before the age of 76 years.

Age of Onset↗

X inactivation analysis in a female with hypomelanosis of Ito associated with a balanced X;17 translocation: evidence for functional disomy of Xp.

X inactivation analysis was performed on normal and hypopigmented skin samples obtained from a female with hypomelanosis of Ito associated with a balanced whole arm X;17 translocation. Severe skewing of X inactivation resulting in inactivity of the intact X was found in blood and cultures of both types of skin, but analysis of DNA prepared directly from hypopigmented skin showed significant inactivation of the translocated X, inconsistent with the usual mechanism of phenotypic expression in X;autosome translocations. In addition, dual colour FISH analysis using centromere specific probes for chromosomes X and 17 showed that the breakpoints on both chromosomes lie within the alphoid arrays, making interruption of a locus on either chromosome unlikely. While partial variable monosomy of loci on chromosome 17p cannot be excluded as contributing to the phenotype in this patient, it is argued that the major likely factor is partial functional disomy of sequences on Xp in cell lineages that have failed to inactivate the intact X chromosome.

Adult↗

Trends in pharmacotherapy of Schizoaffective and bipolar affective disorders: a 5-year naturalistic study.

OBJECTIVE: The authors' goal was to determine if the actual treatment of schizoaffective and bipolar affective disorders had changed in light of recent clinical drug trials that have suggested that valproate and carbamazepine may be equivalent in efficacy to lithium. METHOD: Medication utilization rates for each 6-month period from July 1, 1989, to June 30, 1994, were compiled from the clinical database of the Palo Alto Veterans Affairs Medical Center. RESULTS: The use of valproate and valproate plus lithium was negligible in 1989. by 1994, these medication regimens accounted for 25% of the standard antimanic treatments used for bipolar affective disorder and 38% of the treatments used for schizoaffective disorder. Regimens of carbamazepine and carbamazepine plus lithium dropped from 24% of antimanic treatments in 1989 to 18% in 1994. From 1989 to 1994, there was a decline in the rate of lithium monotherapy for treatment of bipolar affective disorder (from 84% to 43%) and schizoaffective disorder (from 100% to 53%). CONCLUSIONS: In the past 5 years, valproate monotherapy has increased as a percentage of total antimanic pharmacotherapies, while lithium monotherapy has declined.

Bipolar Disorder↗

The effects of cigarette smoking and alcohol consumption on blood lipids: a dose-related study on men.

The separate and joint effects of cigarette smoking and alcohol consumption on serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides were investigated in 46 750 men attending the BUPA Health Screening Centre in London during the period 1983-1987, after allowing for differences in age, body mass index and exercise level. Drinking alcohol was found to raise both total cholesterol and HDL-C concentrations, in such a way that HDL-C as a percentage of total cholesterol increased with increasing alcohol consumption. LDL-C concentrations increased with increasing alcohol consumption in non-smokers, but decreased in those smoking over 10 cigarettes per day. Drinking had no significant effect on triglycerides except at high levels of consumption. Smoking raised total cholesterol, LDL-C and triglycerides, but lowered HDL-C concentrations. In particular, smoking even small amounts could negate any protective benefit in HDL-C concentrations gained from moderate consumption of alcohol. Assuming a desirable lipid profile to consist of low total cholesterol, LDL-C and triglycerides and a high HDL-C value, this is best achieved for men by being a non-smoking moderate drinker.

Adult↗

The effects of cigarette smoking and alcohol consumption on serum liver enzyme activities: a dose-related study in men.

The separate and joint effects of cigarette smoking and alcohol consumption on serum activities of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were investigated in 46,775 men attending the BUPA Health Screening Centre in London during the period 1983-1987, after allowing for differences in age, body mass index and exercise level. As expected, all showed a significant positive correlation with alcohol consumption. Cigarette smoking produced a significant increase in GGT activity in all drinking categories bar teetotallers, particularly for those smoking more than 20 cigarettes per day. There were no changes of clinical significance in AST or ALT activities with smoking. We postulate that the combined effects of alcohol and smoking on GGT activity are a result of induction of the enzyme by both alcohol and nicotine. Smoking as well as drinking habits should be taken into account when assessing the significance of an individual's enzyme activities.

Adult↗

Establishing a community network for recruitment of African Americans into a clinical trial. The African-American antiplatelet stroke Prevention Study (AAASPS) experience.

A major aspect of a clinical trial is the ability to successfully recruit patients. There is a paucity of information concerning the nuances of recruiting study patients, especially those from minority communities. As minorities generally have been underrepresented in the health-care system, they may be less likely to participate in clinical trials or other studies. Thus, a strategy is needed to overcome this potential shortfall. One of our solutions has been the development of a community network to help disseminate information about our program. We believe that a key aspect has been the involvement of community members during pre-trial planning, community awareness programs, and our Community Advisory Panel. We also believe that it may be a major error to bring a health-care initiative unannounced into a targeted community without extensive pre-program planning in cooperation with that community. As our community awareness scheme suggests (Figure), there are many possible avenues to heighten awareness about a health-care program. While the church remains an important institution for religious and cultural activities in the African-American community, we have found that the news, television, and radio media also can be a powerful source for spreading awareness. Thus, we recommend creating awareness about an initiative through a "grassroots" approach of church and community organizations, along with a global approach through news, television, and radio media. As part of the awareness promotion campaign, it must be emphasized that the study is safe and provides benefits to enrollees. The success of health programs is largely dependent on community acceptance, which must be established in the pre-program planning stages of the initiative. This concept of obtaining community approval and acceptance prior to program initiation is not a new one, nor does it exclusively apply to the African-American community. Community leaders and members need to have a vested interest in such a program and a sense of empowerment. Through this type of communication, patient enrollment and community satisfaction can be substantial. Such success can serve as a springboard for other targeted health-care studies or programs in high-risk communities.

Black or African American↗

The delta pH-driven, ATP-independent protein translocation mechanism in the chloroplast thylakoid membrane. Kinetics and energetics.

Previous studies have shown that proteins are transported across the chloroplast thylakoid membrane by two very different mechanisms, one of which requires stromal factors and ATP, whereas the other mechanism is ATP independent but completely reliant on the thylakoidal delta pH. We have examined the role of the delta pH in the latter mechanism by simultaneously monitoring the magnitude of delta pH (by 9-aminoacridine fluorescence quenching) and the rate of import of the 23-kDa photosystem II protein into isolated pea thylakoids. We show that protein import can take place, at low but significant rates, at very low values of delta pH (in the region of 1.2-1.4), and that plots of the rate of protein import against proton concentration gradient are probably hyperbolic in nature. There is no evidence for a threshold level of delta pH which is required to drive translocation of the 23-kDa protein. Addition of uncouplers midway during import incubations results in a rapid and complete inhibition of translocation, showing that the continuous presence of the delta pH is required for translocation to take place. During import into intact chloroplasts, the intermediate-size 23-kDa protein substrate for the thylakoidal protein transport machinery is found only in the stromal fraction at all values of delta pH, suggesting that the initial interaction with the machinery is relatively weak, reversible and delta pH-independent. We therefore propose that the delta pH is required for both the initiation and completion of translocation; these roles are in marked contrast to the roles of protonmotive force in mitochondrial and sec-dependent bacterial protein transport.

Adenosine Triphosphate↗