Search PubMed⌕ Search

Biomedical subjects

S R Johnson

Publications and source records attributed to S R Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Job satisfaction and workplace characteristics of primary and specialty care physicians at a bimodal medical school.

PURPOSE: A few medical schools are highly successful in obtaining research funding and producing primary care physicians. The authors compared the job satisfaction of primary and specialty care faculty at one of these bimodal schools. METHODS: In 1998, all full-time physician-faculty (n = 408) in 15 clinical departments at the University of Iowa College of Medicine (a bimodal medical school) were sent a questionnaire based on the Price-Mueller model of job satisfaction. Faculty rated their global job satisfaction and perceptions about 18 workplace characteristics, stressors, and supports. Responses of primary and specialty care physicians were compared in these domains. RESULTS: A total of 71% of surveyed faculty (n = 341) returned usable questionnaires. Primary and specialty care faculty reported similar levels of job satisfaction (p =.20), and similar percentages (51% versus 54%, p =.63) reported overall satisfaction with their jobs at the medical school. However, primary care faculty perceived less opportunity to advance (p <.01), greater professional-role ambiguity (p =.02), less collegiality (p =.02), and less ability to make full use of their clinical skills (p =.01). Primary and specialty care faculty reported similar intentions of leaving the medical school within the coming year (p =.41). CONCLUSIONS: Primary and specialty care physicians at one bimodal medical school reported similar levels of job satisfaction. However, the primary care physicians rated several important job-related domains lower than did their specialty care colleagues, most notably the opportunity to advance within the medical school.

Adult↗
PubMed2001

Defining benefits and risks for SERMs in clinical trials and clinical practice.

Differences between clinical trials and clinical practice with respect to defining benefits and benefit/risk ratios for SERMs are discussed. These differences stem from the perception that there is discordance between the statistical significance and the "clinical meaningfulness" of research data in the minds of the practitioner and patient. One way that we can obtain data that are more clinically meaningful is to solicit input in the planning stages of clinical trials from practicing community clinicians and their patients. However, there are drawbacks to community input, such as potentially unrealistic expectations. A further issue is the need to characterize clinically meaningful drug benefits and acceptable benefit/risk ratios for a drug. Individual patients have differences regarding their views of optimal benefits and acceptable risks, so a method or tool for determining what is clinically meaningful would be helpful in presenting comprehensive information to the patient. To present useful information to clinicians, head-to-head comparisons of a new drug with a standard agent should be undertaken. NIH's support in this area of comparator trials is critical to their implementation. Estrogen has been considered the standard for comparison of agents for conditions associated with menopause in clinical trials. Estrogen has been the "gold standard" in clinical practice as well. In fact, challenging the position of estrogen, even where scientifically supported, has proven to be an uphill battle. In the practice setting, we elaborate the challenges of keeping up with the scientific literature and of then communicating this information in a fashion that is relevant to the individual patient.

Clinical Trials as Topic↗
PubMed2001

Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells.

Airway remodeling complicates longstanding asthma. It is characterized by an increase in the number of airway smooth muscle cells (SMCs) as well as an increase in and alteration of the type of extra-cellular matrix (ECM) in the airways. Although the number of SMCs in the airways depends on the balance of cell proliferation and cell death, studies to date have concentrated on factors affecting SMC proliferation. Here we report the first study on airway SMC survival factors: these cells receive a strong survival signal, which is not dependent on the known growth factor mitogens. We identified the ECM factors fibronectin, laminin, and collagens I and IV as important anti-apoptotic elements, and characterized the expression of the ECM receptors (integrins) on cultured SMC. Functionally blocking antibody and peptide studies revealed the alpha(5)beta(1) integrin to be an important transducer of the ECM-derived survival signal in these cells. Confocal microscopy confirmed the striking effects that discrete ECM factors have on SMC phenotype, notably the cytoskeleton. In summary, our data improves the understanding of the mechanisms underlying airway remodeling by outlining the key survival factors for airway SMC and by highlighting the impact of the cell-matrix interactions on cell death and phenotype.

Apoptosis↗
PubMed2001

A foot care program for diabetic unilateral lower-limb amputees.

OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.

Aged↗
PubMed2001

Peripheral vascular and nerve function associated with lower limb amputation in people with and without diabetes.

Multiple factors, including peripheral vascular disease and neuropathy, contribute to the development and perpetuation of complications of the lower extremities in diabetes. The main aim of the present study was to assess the peripheral vascular and nerve status of diabetic and non-diabetic subjects that had undergone lower limb amputation. Various non-invasive tests of peripheral vascular and nerve function were carried out on subjects who had undergone unilateral lower limb amputation and were now attending a Rehabilitation Centre. The control group (n=23), the diabetic amputee group (n=64) and the non-diabetic amputee group (n=32) were age-matched. Only the diabetic amputee group had evidence of medial arterial calcification. Transcutaneous oxygen levels were significantly lower in the diabetic amputee group (median 43 mmHg; interquartile range 33-49 mmHg) than in the control (59; 56-74 mmHg) and non-diabetic amputee (57; 43-65 mmHg) groups (control compared with diabetic amputee group, P<0.001; diabetic amputee compared with non-diabetic amputee group, P<0.01). The same trend was found for carbon dioxide levels in the skin [mmHg: diabetic amputees, 25 (21-37); controls, 38 (32-42); non-diabetic amputee, 34 (31-39)] (control compared with diabetic amputee, P<0.01; diabetic amputee compared with non-diabetic amputee, P<0.05). Vibration and pressure perception measurements (which assess Abeta nerve fibre function) showed that both the diabetic amputee and non-diabetic amputee subjects had significantly greater impairment than the controls. However, measures of Aalpha and C nerve fibre function were abnormal only in the diabetic amputee group. Thus the peripheral vascular and nerve functions of age-matched diabetic and non-diabetic subjects having undergone lower limb amputation show specific differences, with non-diabetic amputees exhibiting signs of neuropathy. This indicates that factors characteristic of diabetes (such as hyperglycaemia and non-enzymic glycation) are associated with calcification, lower oxygen and carbon dioxide levels in the skin, and abnormal Aalpha and C nerve fibre function.

Aged↗
PubMed2000

Long-term results of surgical repair of bile duct injuries following laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is associated with an increased incidence of bile duct injuries when compared with the open surgical technique. Long-term results of repaired injuries and hepatic damage associated with chronic biliary obstruction are lacking. METHODS: From Aug 1, 1991 until Dec 1, 1999, there were 27 patients referred for management of complex biliary injuries that occurred during LC. Patients underwent percutaneous transhepatic cholangiography and placement of transhepatic catheters with computed tomography-guided biloma drainage when indicated. On the basis of the cholangiography findings, patients underwent Roux-en-Y hepaticojejunostomy (HJ) and liver biopsy or were treated with nonsurgical interventions. RESULTS: Twenty-one of 27 patients (77. 8%) underwent HJ, and 16 of these 21 patients (76.2%) also underwent hepatic biopsy. In 1 patient, a recurrent stricture developed at 20 months after the initial repair; and, in a second patient, an episode of cholangitis developed in the postoperative period with the transhepatic catheters in place. Five of 16 patients (31.2%) demonstrated marked hepatic fibrosis with 4 (25%) of these patients showing evidence of evolving cirrhosis at the time of HJ. CONCLUSIONS: In this series with 55 months of follow-up, HJ repair of LC injuries was associated with an initial 95.2% success rate and an ultimate success rate of 100%. Despite this, delayed referral, averaging 12 months, was associated with significant hepatic injury in 5 of 16 (31.3%) patients who underwent biopsy.

Adolescent↗
PubMed2000

Clinical experience of lymphangioleiomyomatosis in the UK.

BACKGROUND: Lymphangioleiomyomatosis is a rare lung disease that affects only women. No controlled trials of management have been performed and, until such data are available, management must be based on clinical experience. This study provides data on the natural history of lymphangioleiomyomatosis in the UK and compares this with experience from other centres. METHODS: We tried to identify all cases of lymphangioleiomyomatosis in the UK over a five year period by contacting all chest physicians. Cases were confirmed by lung biopsy or history and high resolution computed tomographic (CT) scanning. Details of disease and management were obtained from hospital notes. RESULTS: The 50 patients who fitted the diagnostic criteria for lymphangioleiomyomatosis had a median age at onset of 35 years (range 22-50). Five presented when postmenopausal (four taking hormone replacement therapy). Pneumothorax and dyspnoea were the most common presenting features. Extrapulmonary presentations included renal angiomyolipomas (3) and lymphangiomyomas (2). Only half the patients were assessed for renal angiomyolipoma and six were identified. Thirty patients had had one or more pneumothoraces, of which two thirds recurred if treated conservatively. Chylous effusions occurred in 11 patients, five requiring surgery. Pregnancy was uncommon once the diagnosis was made (n=7), but was associated with an increase in complications. Half the patients were taking a beta agonist and many showed a bronchodilator response in the laboratory. Thirty six patients had received hormone treatment. CONCLUSIONS: Our UK five year period prevalence was one per 1.1 million population. Since prophylactic interventions are sometimes indicated for renal angiomyolipoma, these data suggest that screening for angiomyolipoma, ideally by CT scanning, may be underused. Patients need to be aware of the increase in complications associated with pregnancy. Recurrence rate of pneumothorax was high in those not treated surgically. Hormone treatment was used variably and controlled trials are needed to determine their role and the optimum duration and dose.

Adult↗
PubMed2000

A human pituitary tumor-derived folliculostellate cell line.

Pituitary cells have been used for the study of hormone synthesis, secretion, and regulation. However, the lack of human cell lines of pituitary origin has made such studies in humans very difficult. Activin, a member of the transforming growth factor-beta cytokine family, is secreted by the pituitary and serves, in addition to regulating hormone biosynthesis, as a regulator of cell growth and differentiation. In the human pituitary, folliculo-stellate cells secrete an activin-binding and -neutralizing protein, follistatin. However, the role of these cells in the autocrine/paracrine regulatory mechanisms of activin is poorly understood. We describe a human pituitary-derived folliculostellate cell line, designated PDFS, that was developed spontaneously from a clinically nonfunctioning pituitary macroadenoma. PDFS cells showed an epithelial-like morphology with long cytoplasmic processes. Electron microscopy revealed frequent intercellular junctions, including desmosomes, and cytogenetic analysis showed clonal characteristics with chromosomal abnormalities. These cells express vimentin and the nervous tissue-specific S-100 protein, specific markers of folliculostellate cells in the anterior pituitary, but no secretory pituitary cell markers. PDFS cells formed large colonies in an anchorage-independent transformation assay. They express follistatin and activin A and have an intact activin intracellular signaling pathway as determined by reporter assays. Therefore, this human cell line provides a useful model for studying the regulation of cell growth and cytokine production by factors endogenously produced in pituitary folliculostellate cells.

Activin Receptors↗
PubMed2000

Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling.

Activin, a member of the transforming growth factor beta (TGFbeta) superfamily of cytokines, inhibits cell proliferation in a variety of cell types. The functions of activin are mediated by type I and type II serine/threonine kinase receptors. The main type I receptor mediating activin signaling in human cells is ActRIB, also called Alk4. We have previously reported that several truncated Alk4 receptor isoforms are exclusively expressed in human pituitary tumors, and that the majority of such tumors did not exhibit activin-induced growth arrest in culture. We therefore studied the function of these truncated receptor isoforms. Transient expression of these truncated receptors inhibited activin-activated transcription from an activin-responsive reporter construct, 3TPLux. When each of these truncated Alk4 receptors was stably transfected into K562 cells, activin-induced expression of an endogenous gene, junB, was blocked, indicating that inhibition of gene expression also occurred at the chromosomal level. Furthermore, activin administration failed to cause growth inhibition and an increase of the G1 population in these cells. Coimmunoprecipitation experiments showed that the truncated Alk4 receptors formed complexes with type II activin receptors, but were not phosphorylated. These data indicate that the truncated activin type I receptors, predominantly expressed in human pituitary adenomas, function as dominant negative receptors to interfere with wild-type receptor function and block the antiproliferative effect of activin. This may contribute to uncontrolled pituitary cell growth and the development of human pituitary tumors.

Activin Receptors, Type I↗
PubMed1999

Antiproliferative effects of NO and ANP in cultured human airway smooth muscle.

Airway smooth muscle (ASM) hypertrophy and hyperplasia are important determinants of bronchial responsiveness in asthma, and agents that interfere with these processes may prevent airway remodeling. We tested the hypothesis that activators of soluble and particulate guanylyl cyclases would inhibit human ASM cell (HASMC) proliferation. We report that the nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP; 10(-6) to 10(-4) M) and sodium nitroprusside (10(-5) to 10(-3) M) and human atrial natriuretic peptide [ANP-(1-28); 10(-8) to 10(-6) M], which activate soluble and particulate guanylyl cyclases, respectively, inhibited serum- and thrombin-induced proliferation of cultured HASMCs. The antimitogenic effect of SNAP was reversed by hemoglobin (10(-5) M), an NO scavenger, suggesting that NO donation was involved. The antiproliferative effects of SNAP and ANP-(1-28) were potentiated by the cGMP-specific phosphodiesterase zaprinast and mimicked by 8-bromo-cGMP (10(-6) to 10(-3) M), suggesting that cGMP-dependent mechanisms were involved. However, first, ANP-(1-28) produced a smaller antiproliferative effect than SNAP in contrast to their abilities to elevate cGMP, and second, rat ANP-(104-126), which binds selectively to ANP clearance receptors without elevating cGMP, had a small antiproliferative effect, suggesting that cGMP-independent mechanisms were also involved. These results provide evidence for a novel antiproliferative effect of NO and ANP in HASMCs mediated through cGMP-dependent and cGMP-independent mechanisms.

Asthma↗
PubMed1999

Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment.

The progression of lymphangioleiomyomatosis, a rare lung disease in women, is thought to be influenced by hormonal factors. We studied the rate of decline in FEV(1) and carbon monoxide transfer factor (TL(CO)) in a national cohort of patients with lymphangioleiomyomatosis in the United Kingdom and its relation to two factors that might influence the disease, menopausal status and progesterone treatment. We used retrospective data from hospital notes, and of the 50 patients identified 43 had suitable lung function data spanning at least 3 mo. Mean (SD) annual decline in FEV(1) was 118 (142) ml for all patients, and these figures changed little when only data spanning at least 2 and 3 yr were analyzed. There was considerable variation in the rate of decline between subjects, however, and although it tended to be less among postmenopausal women and those receiving progesterone, patient numbers were smaller and the findings were not significant. There was a significant reduction in decline in TL(CO) in premenopausal patients receiving progesterone and in both FEV(1) and TL(CO) after starting progesterone in six patients who had data before and after starting treatment. This study documents the rapid decline in lung function in lymphangioleiomyomatosis, confirms the wide variation between patients, and provides some support for the suggestion that disease progression may be reduced by progesterone. The data provide a basis for designing prospective studies of treatment for lymphangioleiomyomatosis.

Adult↗
PubMed1998

Menopause and hormone replacement therapy.

Menopause is a normal part of life of most women and can be made easier with appropriate information about the events that occur. For those women who desire help for bothersome menopausal symptoms, effective therapy can be offered. The use of HRT for prevention is more complex. Several large randomized clinical trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen Replacement Therapy Study (HERS) in the United States, are currently underway. These trials, which have as end points clinical events such as myocardial infarction, sudden death, fractures, and cancer, will provide answers to many of the questions raised in this discussion. Until the results of these trials are available, clinicians must be prudent in their recommendations and should keep their patients apprised of the relevant uncertainties of preventive HRT.

Alzheimer Disease↗
PubMed1998

Agreement in assessing endometrial pathology: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.

We report on agreement in interpreting endometrial biopsy specimens between the local and central pathologists of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. This trial was a 3-year, multicenter, randomized, double-masked, placebo-controlled trial of four groups taking estrogen or estrogen/progestin combinations. A total of 1804 follow-up biopsies were performed in 596 subjects. Relative sensitivity and relative specificity using the diagnosis from the central pathologist as the gold standard and overall agreement are presented. Almost 90% of the diagnoses were reported normal by both readers. There were significant differences in agreement among clinics and treatment arms (p < 0.0001). The visit at which the biopsy specimen was obtained, age at baseline, prior postmenopausal estrogen use, parity, and drug adherence were not associated with agreement between the two readers. Higher proportions of disagreement were seen in two clinics (13% and 11%) compared with the other five clinics (2%-5%). Biopsy specimens from participants who were taking conjugated equine estrogens (CEE) only were more likely to be diagnosed differently by both readers (11%) than biopsy specimens from women taking a placebo (2%) or CEE combined with progestins (5%). Relative specificity varied from 86.4% to 98.9% among the clinics (p < 0.0001). Relative sensitivity was based on a small number of diagnoses, as few biopsy specimens were classified abnormal by the central pathologist. In patients assigned to CEE combined with progestin, 5 of the 7 biopsy specimens that were recorded abnormal by the central pathologist received a normal diagnosis locally. Our findings show that sample size requirements for study designs in which a central reader is used can be at least threefold lower than the requirements for designs relying on local diagnoses. Centralized protocols for endometrial histopathology reading and staff training are highly desirable in multicenter trials.

Biopsy↗
PubMed1998

Detection of Neisseria gonorrhoeae infection by ligase chain reaction testing of urine among adolescent women with and without Chlamydia trachomatis infection.

BACKGROUND AND OBJECTIVES: Culture, the conventional method for detection of Neisseria gonorrhoeae, requires invasive sampling and stringent specimen transport conditions. The recently developed ligase chain reaction test (LCR; Abbott Laboratories; North Chicago, IL) allows noninvasive sampling and stable transport conditions, but has not been evaluated with specimens from adolescent populations. GOAL OF THIS STUDY: To perform a comparative evaluation of a commercial LCR test and culture for the diagnosis of N. gonorrhoeae in adolescent women. STUDY DESIGN: Urine and endocervical swab specimens from 330 teenage women seen in two public health adolescent clinics were tested by LCR and culture. For resolution of discordant results, a polymerase chain reaction (PCR) test was developed that directly amplifies N. gonorrhoeae DNA from urine samples processed for LCR. RESULTS: Thirty-one of 330 (9.4%) cervical specimens were culture-positive for N. gonorrhoeae, and 30 of 330 (9.1%) urine specimens were positive by LCR. After resolution of 13 discordant results, the sensitivity, specificity, and positive and negative predictive values of LCR for urine were 88.2%, 100%, 100%, 98.7%, respectively, and for culture of endocervical specimens were 82.3%, 98.9%, 90.3% and 98%, respectively. CONCLUSIONS: Although more expensive than culture, LCR offers a sensitive means for the detection of N. gonorrhoeae in urine samples and may be useful for this purpose in settings where pelvic examinations are difficult to perform and simultaneous detection of N. gonorrhoeae and Chlamydia trachomatis is advantageous.

Adolescent↗
PubMed1998

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta-agonists.

We studied the dose-dependent effects of inhaled isoetharine HCl, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Qbr) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Qbr. With a total dose of 17.5 mg, Qbr increased from baseline values of 22 +/- 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects beta-agonist-induced increases in Qbr, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased Qbr by approximately 80% of baseline, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (approximately 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Qbr in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.

Administration, Inhalation↗