Biomedical subjects
Publications and source records attributed to R J Anderson.
Vigilance for signs of decreasing renal function--especially rising creatinine and dwindling urine output--will permit prompt preventive action. When renal shutdown does occur, the physician first must determine whether it is prerenal, intrarenal, or postrenal in origin and then institute specific restorative interventions to minimize the degree of failure and associated morbidity.
In a 10-year, multicenter, double-blind clinical trial, comparisons of the clinical behavior of crown and fixed partial denture restorations were made between a gold alloy and four less costly alternative alloys. The endpoints of interest were (1) the development of unacceptable ratings on any of 11 individual prosthodontic criteria and an overall rating, (2) the removal of the restoration, and (3) an event combining unacceptable overall rating and restoration removal. Each of 630 patients had two restorations completed, one from gold-palladium alloy and the other from one of four alternative alloys. The patients were enrolled during a period of 3 1/2 years, with some patients followed up as long as 10 years after restoration. Analysis of the endpoints showed that one of the alternative alloys was significantly poorer than the other materials for certain criteria.
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The present studies examine the effect of transforming growth factor-beta 1 (TGF-beta 1) on signal transduction pathways in two cultured renal epithelial cell lines. TGF-beta 1 promotes basal and agonist-stimulated adenylate cyclase activity in LLC-PK1 but not MDCK cell membranes. TGF-beta 1 stimulation of LLC-PK1 membrane adenylate cyclase activity occurs quickly and can be attenuated by pertussis toxin pretreatment. Both TGF-beta 1 and adenosine 3',5'-cyclic monophosphate (cAMP) exert comparable effects on [3H]thymidine uptake in LLC-PK1 cells, suggesting that TGF-beta 1 regulation of adenylate cyclase activity potentially plays a role in mediating biological responses to TGF-beta 1. The activities of protein kinase C and phospholipase A are not affected by TGF-beta 1 in either LLC-PK1 or MDCK cells. Both TGF-beta 1 and epidermal growth factor (EGF) increase expression and induce the appearance of new forms of the cAMP response element binding protein (CREB) in LLC-PK1 cells. These effects of TGF-beta 1 and EGF on CREB appear to be specific since neither TGF-beta 1 nor EGF alters expression of an activating transcription factor in LLC-PK1 cells. The effect of TGF-beta 1 and EGF to alter expression of CREB does not affect CREB binding to its regulatory element in LLC-PK1 cell lysates. These results suggest that some of the biological effects of TGF-beta 1 may be attributed to stimulation of adenylate cyclase activity and cAMP formation as well as to enhanced expression and/or modification of the CREB transcription factor in LLC-PK1 cells.
For three California dairy herds with bulk tank SCC < 200,000/ml, twice daily milking, and no mastitis vaccine, 254 quarters with mild clinical mastitis were randomly assigned to three groups. Group A (n = 74) was treated with 62.5 mg of intramammary amoxicillin every 12 h for three milkings. Group C (n = 75) was treated with 200 mg of intramammary cephapirin every 12 h for two milkings. Group O (n = 105) was treated with 100 units of intramuscular oxytocin every 12 h for two or three milkings. Aseptic pretreatment quarter samples revealed 94 (37%) coliforms, 65 (26%) environmental streptococci, 34 (13%) other bacteria, and 61 (24%) with no isolate on bovine blood agar plates. Contagious pathogens were not isolated. Clinical cure (return of quarter and milk to normal) and bacterial cure (absence of primary pathogen isolated pretreatment) were assessed at milking 8 and d 20 after initial treatment. No difference existed in clinical (67.6, 67.7, or 66.7%) or bacterial (43.9, 55.0 or 49.1%) cure rate among groups. Clinical cure rates did not differ when quarters were grouped by etiology, but clinical cure rates for quarters with pathogens other than streptococci or coliforms were lower in group O.
Caring for the whole patient requires as much understanding and commitment from managers as it does from physicians and nurses.
Familial neuroendocrine tumors are reviewed. The most dramatic advances have been the application of molecular genetic techniques to define the etiologies and develop predictive testing for patients with multiple endocrine neoplasia type 1 and type 2 syndromes. All three neoplastic lesions involved in multiple endocrine neoplasia type 1 (parathyroid, pituitary, and pancreatic islet) have shown loss of heterozygosity at chromosome 11. By contrast, the most consistent occurrence of loss of heterozygosity in tumors from multiple endocrine neoplasia type 2 patients was not at chromosome 10 but at chromosome 1p. Molecular genetic testing of multiple endocrine neoplasia type 1 and type 2 family members at risk provides a powerful tool for early identification and treatment of susceptible individuals. Efforts to clarify familial neuroendocrine tumors without associated multiple endocrine neoplasia syndromes continue. The best characterized tumor of this type is familial medullary thyroid carcinoma. Familial paraganglioma, neuroblastoma, and carcinoid also are reviewed. Potential barriers to genetic screening for familial neuroendocrine tumors are discussed.
Sexually active adolescents are at high risk for unintended pregnancy and sexually transmitted diseases. We identified a cohort of 6089 women aged 13 to 21 years who in 1985 either delivered an infant at Parkland Hospital (3154) or used the outpatient clinics (2935). We reviewed those records and others in the Dallas County sexually transmitted disease (STD) clinic for the period 1983 through 1988 to determine the prevalence of visits to the Dallas County STD clinic by pregnant and nonpregnant adolescents, STD diagnoses at initial visit, whether STD visits and diagnoses varied by pregnancy status or ethnic background, and how the women were referred to the STD clinic. Similar percentages of nonpregnant (13%) and pregnant (11%) women had an STD visit, and most adolescents who visited the STD clinic had an STD diagnosis made. Gonorrhea and syphilis were the STDs diagnosed most frequently in both pregnant and nonpregnant adolescents. Regardless of pregnancy status, black adolescents were 7.3 times more likely to have an STD visit. Referral by a sexual partner was the second most common reason that adolescents sought STD care. Our study provides only minimal estimates of STDs among adolescents but indicates STDs, regardless of pregnancy status, are a more common medical problem than has been reported previously. Referral by sexual partners may be an important way to reach adolescents at risk for STDs.
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OBJECTIVE: To compare the cumulative effects of oral methotrexate (MTX) therapy (after 6-8 weeks) with the acute effects (24 hours after a dose) on arachidonic acid metabolism by the 5-lipoxygenase (5-LO) pathway in neutrophils from patients with active rheumatoid arthritis (RA) who were beginning therapy with MTX. METHODS: Neutrophils and monocytes were isolated from whole blood from 7 patients with RA, immediately before and 24 hours after their first weekly dose of 7.5 mg of MTX, and again after their dose at 6-8 weeks. RESULTS: Total immunoreactive leukotriene B4 (LTB4) formation in neutrophils activated ex vivo with calcium ionophore A23187 was significantly suppressed (by 33%) before the 6-8-week dose, compared with the level before the first dose (mean +/- SEM 8.29 +/- 1.24 ng/10(6) cells at predose 6-8 weeks versus 12.29 +/- 2.13 ng/10(6) cells at predose 1; P = 0.03). Reductions were also observed after the first dose (27%; P = 0.07) and after the 6-8-week dose (43%; P = 0.05) compared with the respective predose levels. MTX treatment produced significant reductions in the total generation of 5-LO pathway products (5-hydroxyeicosatetraenoic acid + 6-trans-LTB4 + LTB4 + omega-oxidation products of LTB4) by calcium ionophore-activated neutrophils, as quantitated by integrated optical density after resolution on reverse-phase high-performance liquid chromatography. Decreases were observed after the first dose (26%; P = 0.025), immediately before the 6-8-week dose (23%; P = 0.05), and after the 6-8-week dose (47%; P = 0.0033) compared with levels before the first dose, and after the 6-8-week dose compared with the level before it (32%; P = 0.04). The generation of LTB4 by calcium ionophore-activated monocytes was not significantly affected by MTX therapy. CONCLUSION: The significant decreases in the formation of omega-oxidation products of LTB4 and in the total generation of neutrophil 5-LO pathway products in the absence of a significant change in the release of 3H-arachidonic acid or the generation of platelet-activating factor suggest that the activity of the 5-LO enzyme in neutrophils is inhibited. We conclude that weekly oral MTX therapy in patients with active RA inhibits neutrophil 5-LO pathway product generation in a pattern consistent with inhibition of the activity of the 5-LO enzyme; an effect is observed after the first dose. The inhibition of 5-LO is cell-selective and cumulative, with a superimposed incremental inhibition observed after the weekly MTX dose.
OBJECTIVE: Two methods which only consider bacterial morphotypes and require counting various types of bacteria, for interpreting Gram stains of vaginal secretions for the purpose of diagnosing bacterial vaginosis were previously described. A new interpretative method, which combines clue cells with bacterial morphotypes as diagnostic markers, is offered. STUDY DESIGN: One hundred twenty patients were tested with the new interpretative method and clinical criteria of bacterial vaginosis as the reference standard. RESULTS: The new method was found comparable to older methods when all were compared with clinical diagnostic methods. The sensitivity of the clue cell method was 86.1% and the specificity was 92.8%. The predictive value of a positive test was 83.7% for a population with a prevalence of bacterial vaginosis of 30%. The negative predictive value was 94.0%. CONCLUSION: If clue cells are present and the nonlactobacilli morphotypes exceed lactobacilli morphotypes, bacterial vaginosis can be diagnosed without the need for exact bacterial counts.
PURPOSE: The effect of mydriasis on Goldmann visual field area in patients with retinitis pigmentosa has not been suitably defined. The aim of this study is to determine whether visual field area in these patients varies with pharmacologic mydriasis. METHODS: Fifteen adult patients with retinitis pigmentosa were studied prospectively. Goldmann visual fields with II4e and V4e isopters were obtained in both eyes before and after full pharmacologic mydriasis of the right eye. The isopter areas were quantified and analyzed to determine the effect of mydriasis on visual field area. RESULTS: The difference in the right eye isopter areas was compared with the difference in the left eye isopter areas using paired t tests, where the differences were computed from areas obtained before and after dilation of the right eye. Mydriasis had no significant effect on the visual field in terms of isopter area difference (II4e, P = 0.87; V4e, P = 0.45) and percent change in isopter area (II4e, P = 0.81; V4e, P = 0.24). CONCLUSION: Pharmacologic mydriasis had no appreciable effect on the Goldmann visual field area in a selected group of patients with retinitis pigmentosa. These findings suggest that visual fields of such patients obtained in the dilated or undilated state can be meaningfully compared.
Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H-arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A.
Release of results of a clinical study to the public press prior to dissemination in a professional journal is a substantive issue which must undergo continued scrutiny. This report analyzes the second National Acute Spinal Cord Injury Study (NASCIS-2) and its subsequent reportage. NASCIS-2 was an elaborate protocol consisting of the randomized blinded use of methylprednisolone (MP), naloxone or placebo in 487 patients within 12 hours of spinal cord injury. Analysis of the entire population failed to show a significant clinical difference among treatments although data stratification revealed a significant change in patients with a complete loss of function who received MP within 8 hours of injury. The administration of MP was associated with a 7.1% incidence of wound infection. While these results suggested clinical benefit, incomplete data and statistical descriptions reduced assertions. Discrepancies in the report included lack of radiological data or descriptions of time-dependent surgical manipulations and extent of rehabilitative therapy. Justification for the broad 8-hour stratum and multiple hypothesis testing was unclear; incomplete design details included level of statistical significance, study power, stopping rules, trial duration and odds ratio data. The hypothesis that press release prior to publication in a professional journal would result in rapid therapy remained unproven. Reasons for pre-release, including limited peer review, physician familiarity with drug and dosage, and lack of alternative treatment or treatment complications were either unjustified or problematic. Early disclosure to the press resulted in da ta misinterpretation and oversimplification, failure to recognize exclusion or appropriate legal ramifications,and lack of communication to appropriate physicians.
OBJECTIVE: To study the effect of a geriatric evaluation and management program on health care charges and Medicare reimbursement. DESIGN: Prospective randomized controlled trial during a 1-year study period. SETTING: Large medical school-affiliated public hospital in an urban community. SUBJECTS: Patients at least 70 years old admitted to the medicine service were screened and randomized into two groups of 100 patients each. INTERVENTION: Patients randomized to the experimental group underwent initial comprehensive geriatric evaluation and once discharged from the hospital were enrolled in a geriatric care management and treatment program. The control group received usual care only. The major intervention of this study was in outpatient long-term care. MAIN OUTCOME MEASURE: Total charges for services billed to Medicare Part A and Part B and total Medicare reimbursement. The Medicare charge and reimbursement data were obtained by use of the Medicare Automated Data Retrieval System, a linked Medicare Part A and Part B utilization file. RESULTS: Total charges and reimbursement were greater for the control group but not significantly so. Subset analysis revealed significantly greater inpatient charges (P < 0.03) and Medicare reimbursement (P < 0.005) for the control patients and a greater likelihood of utilization of home health care services in the experimental group (P < 0.01). CONCLUSION: A geriatric evaluation and management program appeared to shift utilization and Medicare expenditures from inpatient services to home health care services. There was no evidence that the experimental program resulted in increased expenditures for Medicare. In selected populations, geriatric evaluation and management programs may contribute to cost containment.
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The purpose of this study is to assess the advantages and disadvantages of various annual financial clinical contract options between the Atlanta metropolitan area hospital and the Mercer University Southern School of Pharmacy (Atlanta, GA). Forty-five surveys with 17 statements in a Likert scale format were mailed to all directors, clinical staff of each hospital (adjunct faculty), and full-time clinical faculty to validate the perceived advantages and disadvantages of financial contracts between their hospital and the School of Pharmacy. The survey questionnaire was returned by 84% of the participants. Survey results indicate that the School of Pharmacy and area hospital pharmacies appear to have benefited from this marriage of common interests in clinical program development with 79% agreeing that the overall benefits of the educational affiliation and contract out-weighed the disadvantages.
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