Search PubMed⌕ Search

Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 73 records · Page 4Linked to original sources

Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents.

BACKGROUND: Cardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6+/-7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin. CONCLUSIONS: Antihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined.

Aged↗

Sulfation of minoxidil by multiple human cytosolic sulfotransferases.

Minoxidil is an antihypertensive agent and hair growth promoter that is metabolized by sulfation to the active compound, minoxidil sulfate. Thermostable phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST). Information about human ST activities toward minoxidil would be useful in developing the capacity to predict individual responses to minoxidil based on tissue levels of STs. Therefore, human STs were studied from platelet homogenates, partially purified platelets, scalp skin high speed supernatants and COS-1 cell cDNA expressed preparations using a radiochemical enzymatic assay with minoxidil as the substrate. Studies showed the presence of TS PST, TL (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical properties and correlation studies suggested that in addition to TS PST, the TL PST activity, another ST activity or both were involved in the reaction. Partially purified human platelet TL PST tested with minoxidil and dopamine showed identical thermal stabilities and similar responses to the inhibitors 2,6-dichloro-4-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST toward minoxidil, several biochemical properties of the enzyme expressed from a human liver cDNA clone were investigated. When assayed with minoxidil and dopamine, thermal stabilities of the expressed enzyme were identical and IC50 values for the inhibitors DCNP and NaCl were similar. It was also demonstrated that cDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotransferase contributed to the sulfation of minoxidil. The results confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST activity represents a combination of ST activities. The data indicate that multiple ST activities should be taken into account in attempts to predict the regulation of minoxidil sulfation and individual responses to minoxidil.

Animals↗

Visual acuity and visual field impairment in Usher syndrome.

OBJECTIVE: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. METHODS: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. RESULTS: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9). CONCLUSIONS: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.

Adult↗

Toward a new urban health model: moving beyond the safety net to save the safety net--resetting priorities for healthy communities.

Parkland Health and Hospital System has been successful by every measure of comparison among its peer institutions, yet it recognizes the imperative of adapting to changes in the regulatory, legislative, and market environments. Given its mandate and a desire to preserve its multiple missions and its partnerships with a highly rated medical school, the playing field for achieving robust survival is very uneven. This article describes the evolution of one of the best "sick care systems" in the United States into an integrated, excellent health care system for the 21st century. The problems faced by the safety net in many urban areas of this country are similar. Many problems are structural in nature and will, therefore, require structural solutions at the local, state, and national levels. Parkland will continue and will be needed for many years as the tertiary and quaternary center of a comprehensive service network made up also of a series of outreach Community Oriented Primary Care clinics and special populations projects. In addition, we hope to help create a community-oriented managed-care plan that encompasses the desire to work with both denominator and numerator populations in a real partnership with many other stake-holders.

Academic Medical Centers↗

Managed health care and resident education.

OBJECTIVE: We wished to determine the impact of managed health care on resident education in obstetrics and gynecology. STUDY DESIGN: A multiquestion survey was mailed to program directors of the 267 obstetrics-gynecology resident training programs in the United States. The questions ascertained departmental philosophy regarding the role of obstetrician-gynecologists as primary care versus specialist physicians, the extent of involvement with managed health care companies, educational curriculum content, the effect of managed care on patient volume, faculty time available for resident teaching, and the effect of managed care on resident education. RESULTS: Completed surveys were received from 210 (79%) program directors. One hundred twenty-six (63%) program directors responded that obstetrician-gynecologists should be primary care physicians for women, and 120 (60%) believed that the role of subspecialists will be reduced in the near future. In 1996, 177 (94%) programs had managed care contracts; many (57%) had >20 contracts. All programs participate with other specialties to teach primary care to their residents. One hundred twelve (59%) programs have had a decrease in patient volume, prompting 90 (45%) programs to increase their number of teaching sites. Of concern, 54 (26%) program directors noted that managed care companies discourage but do not restrict resident participation in the care and treatment of managed care patients, and 41 (20%) programs had some restrictions placed on such resident involvement. Budgetary constraints have decreased resources to 97 (47%) programs and threaten the time available for faculty teaching. CONCLUSIONS: Managed health care is having an effect on many resident teaching programs. Program directors are integrating managed care concepts into the educational curriculum and are negotiating with managed care organizations to involve residents in the care and treatment of managed care patients.

Curriculum↗

Sustaining the development of primary care in academic medicine. Working Group on Sustaining the Development of Academic Primary Care. Association of American Medical Colleges.

This article is the report of the Working Group on Sustaining the Development of Academic Primary Care, one of the six subgroups of the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) sponsored by the Association of American Medical Colleges (AAMC). To begin, the group draws a distinction between primary care and generalism. Primary care is a core domain of health care and, in the context of emerging integrated systems, will increasingly be a multidisciplinary shared function. Non-subspecialized physicians, or "generalists," are a key element in the provision of primary care, but do not act alone. Core competencies for primary care are central to the education of all physicians. Therefore, irrespective of workforce goals for generalist physicians, primary care should have a strong, central position in the medical school so that graduates can receive a sound general medical education and can be prepared for any specialty and for lifelong learning in an evolving health care system. For primary care to achieve that position, medical schools must integrate primary care into their missions, strategic plans, operation, organization, academic administrative structures, curriculum development, faculty development (both school- and community-based), resource development, alliances with appropriate clinical services networks, financial policy, and evaluation and educational monitoring systems. The group briefly describes the elements of those changes and also proposes ways that the AAMC and medical school leaders could promote the central role of primary care in medical schools.

Curriculum↗

Potential autocrine and paracrine mechanisms of recovery from mechanical injury of renal tubular epithelial cells.

The present studies were done to clarify potential pathways of the nephrogenic repair process. Media removed from mechanically injured vascular smooth muscle cells and LLC-PK1 renal tubular epithelial cells significantly stimulated [3H]thymidine uptake and cell number in quiescent LLC-PK1 cells, demonstrating the existence of potential autocrine and paracrine pathways of nephrogenic repair. The effect of mechanical injury resulting in release of one or more growth factors into culture media was also found in the opossum kidney OK renal tubular cell line. The nonspecific peptide growth factor antagonist suramin inhibited the effect of media from injured LLC-PK1 cells to stimulate [3H]thymidine uptake in quiescent LLC-PK1 cells. Exposure of quiescent LLC-PK1 cells to six growth factors, including acidic and basic fibroblastic growth factors (aFGF and bFGF), platelet-derived growth factors AA and BB (PDGF-AA and PDGF-BB), endothelin-2, and hepatocyte growth factor, reproduced the biological responses seen when quiescent LLC-PK1 cells were exposed to media from injured cells. Immunoblotting and enzyme-linked immunosorbent assay experiments demonstrated the presence of aFGF, bFGF, and PDGF-BB but not other candidate growth factors in the media from injured LLC-PK1 cells. A neutralizing antibody directed against bFGF attenuated the effect of media from injured cells to stimulate [3H]thymidine uptake in serum-starved LLC-PK1 cells. These results demonstrate that mechanical injury to renal tubular epithelial cells results in release of aFGF, bFGF, and PDGF-BB into the media and suggests that bFGF may be involved in an autocrine fashion to promote recovery from injury.

Animals↗

Inflammatory large bowel disease in immunodeficient rats naturally and experimentally infected with Helicobacter bilis.

Proliferative and ulcerative typhlitis, colitis, and proctitis were found incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within the crypts of the large intestine, modified Steiner's silver stain revealed spiral organisms that were identified by culture, polymerase chain reaction, and sequencing to be Helicobacter bilis. The large bowel disease was reproduced in H. bilis-free male athymic nude rats that were injected intraperitoneally with a culture of H. bilis from the affected colony. The organism was isolated from the feces and cecum of the experimentally infected rats. H. bilis should be considered a potential pathogen in immunocompromised rats. The infection in immunocompromised rats may serve as an animal model for inflammatory large bowel disease.

Animals↗

Retinoic acid regulation of renal tubular epithelial and vascular smooth muscle cell function.

Vitamin A and its derivatives have been postulated to play an important role in renal tubulogenesis and compensatory hypertrophy. This study examined the effects of two carboxylic derivatives of vitamin A on Lewis lung carcinoma-porcine kidney-1 (LLC-PK1) renal tubular epithelial cell mito- and motogenesis and cell size. It was found that all-trans and 13-cis retinoic acids exerted modest, dose-dependent effects to stimulate incorporation of 3H-thymidine into acid-precipitable material of LLC-PK1 cells. The effects of all-trans retinoic acid to promote 3H-thymidine uptake in LLC-PK1 cells modestly enhanced that seen with acidic fibroblastic growth factor. Similar findings of these two retinoic acid derivatives to promote 3H-thymidine uptake and to enhance 3H-thymidine uptake stimulated by another growth factor (platelet-derived growth factor BB) were also observed in cultured bovine aortic smooth muscle cells. Both retinoic acids promoted healing of denuded areas made within confluent monolayers of serum-starved LLC-PK1 cells. All-trans retinoic acid also stimulated recovery of mechanically denuded areas within bovine aortic smooth muscle monolayers. Neither all-trans nor 13-cis retinoic acids s affected cell size as assessed by forward light scatter with flow cytometry, suggesting lack of effect to induce hypertrophy. These results demonstrate that two carboxylic acid derivatives of vitamin A are capable of stimulation of basal and growth factor-induced incorporation of 3H-thymidine uptake into acid-precipitable material and healing of denuded areas in disparate cell types. These findings are compatible with a role for vitamin A and its analogues in the tissue repair process.

Animals↗

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors.

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.

Adult↗

The effect of propranolol versus placebo on resident surgical performance.

PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.

Adrenergic beta-Antagonists↗

5-year outcome of surgical resection and watchful waiting for men with moderately symptomatic benign prostatic hyperplasia: a Department of Veterans Affairs cooperative study.

PURPOSE: We determine outcomes after 5 years of followup for men who were randomized to receive transurethral resection or watchful waiting for moderate symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 556 patients were evaluated up to 60 months after randomization providing 966 patient-years of followup for transurethral prostatic resection and 990 for watchful waiting. Patients randomized to watchful waiting were evaluated according to whether they remained on treatment or crossed over to surgery. Outcomes included treatment failure, a genitourinary symptom score, peak flow rate, post-void residual urine volume and the degree of bother from genitourinary symptoms. RESULTS: All outcomes were significantly better for transurethral prostatic resection than for watchful waiting. Treatment failure rates were 10% for transurethral prostatic resection versus 21% for watchful waiting (p = 0.0004). The crossover rate at 5 years was 36% and was positively associated with the degree of bother. Men with low pretreatment peak flow rates who were randomized to transurethral prostatic resection had 85% greater improvement in peak flow rate than comparable men who were randomized to watchful waiting and eventually crossed over to resection. However, after crossover, bother from genitourinary symptoms was similar to that of the resection group. CONCLUSIONS: For men with moderate symptoms of benign prostatic hyperplasia transurethral prostatic resection has more favorable outcomes up to 5 years of followup compared to watchful waiting. While many men do well on watchful waiting, those who undergo transurethral prostatic resection after a trial of watchful waiting have less improvement in measures of bladder function than men randomized to resection, although there is no difference in serious adverse outcomes or bother from genitourinary symptoms.

Follow-Up Studies↗

Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure, 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean, -42.9; 95% confidence limits, -65.5, -20.2 g), captopril (mean, -38.7; 95% confidence limits, -61.0, -16.4 g), and atenolol (mean, -28.1; 95% confidence limits, -50.9, -5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. CONCLUSIONS: Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.

Adrenergic alpha-Antagonists↗

Case-control study of an outbreak of clinical disease attributable to Salmonella menhaden infection in eight dairy herds.

OBJECTIVE: To identify risk factors associated with Salmonella menhaden associated disease in adult dairy cows during an outbreak in California. DESIGN: Case-control study. SAMPLE POPULATION: 8 case dairies that had > or = 1 adult animal that had clinical signs of salmonellosis and from which S menhaden was isolated and 22 control dairies, 16 of which were matched on the basis of herd size and county and 6 of which were matched on the basis of herd size, county, and breed (Jersey). PROCEDURE: A questionnaire was developed and reviewed with the herdsman or owner of each dairy. Primary areas of concern were herd management, disease characteristics, and feed-related information. RESULTS: Use of 1 particular feed mill and feeding animal fat were significant risk factors for clinical disease attributable to S menhaden infection. CLINICAL IMPLICATIONS: Feed should not be overlooked as a potential source of Salmonella organisms in dairy herds.

Animal Feed↗