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Biomedical subjects

S Strasser

Publications and source records attributed to S Strasser.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of mechanisms contributing to AraC-mediated chemoresistance and re-establishment of drug sensitivity by the novel heterodinucleoside phosphate 5-FdUrd-araC.

Chemoresistance is a biological response of cells to survive toxic stress. During cancer treatment the development of chemoresistance is a major problem. The mechanisms how cells become insensitive, and which downstream pathways are affected are not completely understood. Since it has not been well analysed which and how many regulative disorders are subsummised under the term "chemoresistance", we examined and measured arabinosylcytosine (AraC)-mediated desensitation of two mechanisms relevant for tissue homeostasis, cell cycle inhibition and apoptosis induction. MCF-7 cells harbouring ectopic mutated p53 were suitable for this investigation because they activated these mechanisms subsequently and became insensitive to AraC with regard to cell cycle inhibition and apoptosis induction. The major causal mechanism of acquired resistance against AraC was most likely through the inhibition of the first step of AraC phosphorylation within the cell, which is rate limiting for its activation. With regard to cell cycle inhibition AraC-resistant cells were also resistant against 5-fluorodeoxyuridine (5-FdUrd), but fully responsive to 5-FdUrd-induced apoptosis, evidencing that cell cycle and apoptosis are independent of each other. Apoptosis correlated with AIF-activation and was independent of Caspase 7, whereas cell cycle inhibition correlated with cyclinD1 expression but not with induction of p21 or p27. The phosphate conjugated 5-FdUrd-araC heterodimer (5-Fluoro-2'-desoxyuridylyl-(3'-->5')-Arabinocytidine), which is a prodrug of AraC-monophosphate, reactivated AIF and down-regulated cyclin D1 in AraC-resistant cells and circumvented resistance to apoptosis and to cell cycle inhibition. Also, cells which were resistant to 5-FdUrd or doxorubicin were sensitive to 5-FdUrd-araC. This investigation demonstrates that chemoresistance affects apoptosis induction and cell cycle inhibition independently and that detailed knowledge about the affected downstream pathways would enable the design of targeted intervention with small molecules to restore chemosensitivity.

Antimetabolites, Antineoplastic↗
PubMed2004

Subcellular localisation of Cdc25A determines cell fate.

Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKB-protein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.

Animals↗
PubMed2001

Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model.

OBJECTIVE: To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation. DESIGN: Prospective, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Thirteen fasted, anesthetized, mechanically ventilated landrace pigs. MEASUREMENTS AND MAIN RESULTS: Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in tPo2 failed to gain statistical significance (p =.08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2 gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade. CONCLUSIONS: Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.

Animals↗
PubMed2001

Evaluating the clinical management of severely malnourished children--a study of two rural district hospitals.

BACKGROUND: Severe malnutrition is an important cause of preventable mortality in most South African hospitals. Work recently done in two rural Eastern Cape hospitals supports the literature which shows that many deaths occur as a result of outdated clinical practices and that improving these practices reduces case fatality rates. Rapid assessment of clinical management in paediatric wards is necessary to highlight areas for improvement. OBJECTIVE: To assess the management of severely malnourished children in two rural district hospitals and to recommend improvements for their care. METHODS: Based on draft World Health Organisation (WHO) guidelines for inpatient care of children with severe malnutrition, data collection instruments were developed in conjunction with the district nutrition team to assess the quality of care given to malnourished children in two Mount Frere hospitals, Eastern Cape. Data were collected through retrospective review of case records, with detailed studies of selected cases, structured observations of the paediatric wards, and interviews with ward sisters and doctors. RESULTS: The combined case fatality rate for severe malnutrition was 32%. Inadequate feeding, poor management of rehydration and infection, lack of resources, and a lack of knowledge and motivation among staff were identified as areas that need attention. CONCLUSION: The clinical management of severely malnourished children can be rapidly assessed to highlight areas for improvement. Involving staff in the assessment process has led to their active involvement in improving the management of malnourished children in their hospitals.

Child↗
PubMed1999

Transcranial sonography in a patient with a persistent trigeminal artery.

Transcranial ultrasonography was performed in a patient with a persistent trigeminal artery, a remnant of fetal cerebral circulation that bridges the carotid and basilar territories. The study revealed low flow and reversal of flow in the vertebral and basilar arteries, respectively. The interpretation and significance of these findings are discussed.

Adult↗
PubMed1997

Improving the quality of the NCQA (National Committee for Quality Assurance) Annual Member Health Care Survey Version 1.0.

The National Committee for Quality Assurance (NCQA) developed a standardized survey instrument in 1995 designed to measure enrollee satisfaction with the care and services received from health plans across the United States. After the survey was administered for a large number of health plans and thousands of responses were received, some areas for survey improvement have emerged. The objective of this research was to evaluate the NCQA Annual Member Health Care Survey Version 1.0 (the standard form) relative to an alternate survey form created in cooperation with the HMO Group, Maritz Marketing Research, Inc., and Healthcare Research Systems, Ltd. The alternate form of the NCQA survey was constructed to test several theories of measurement improvement via rewording of items, reordering of items, deletion of items, and addition of items. The most important findings of the research project are reported herein. Ten geographically dispersed member health maintenance organizations (HMOs) of The HMO Group took part in the project. A split-half design was used to test the standard and alternate survey forms concurrently. Surveys were administered by using the NCQA-recommended mail methodology of survey and cover letter, reminder card, and second survey. Assuming a 50% response rate, a target of 400 responses (200 for each survey form) per HMO was planned. The window for responding was allowed to remain open 4 weeks beyond the mailing of the second survey to achieve the desired response rate. A total of 4,056 responses were collected (2,022 for the standard form and 2,034 for the alternate form). It was found that the addition of "No Experience" and "No Opinion" response options to the majority of satisfaction items reduced the random error associated with informed responses and produced statistically significant higher correlations with the global satisfaction items relative to the standard form items. Only four of the eight Short Form 12 summary scales, General Health, Reported Health Transition, Mental Health, and Social Functioning, were useful for adjusting data (covariation). The entire set of comorbidities (chronic disease checklist) could be eliminated without losing significant data adjustment capability. The multiple linear regression models generated by using the global satisfaction items on the alternate form had higher adjusted R2 values than the standard-form models. The alternate-form item Overall Value correlated highly with cost items and general satisfaction item, making it a useful global satisfaction variable for predictive modeling.

Health Care Surveys↗
PubMed1996

Transformational leadership of clinical nutrition managers.

OBJECTIVE: To identify leadership qualities of clinical nutrition managers and associate these leadership qualities with selected demographic variables (eg, training/degree, length of time in management, number of people supervised, income, and participation in advanced practice activities). DESIGN: The theory of transformational leadership, that is, leadership that incorporates specific interpersonal behaviors of the leader and his or her actions within the organization, provided the framework for the study. Specific transformational leadership qualities--leader behavior, leader personal characteristics, and the effect of the leader on organizational functioning and culture--were measured using the Leadership Behavior Questionnaire (LBQ). The reliability and validity of the LBQ have been reported previously. Other data were obtained using two demographic surveys. SAMPLE: Demographic surveys were mailed to 1,599 members of the Clinical Nutrition Management dietetic practice group. From the 951 (59.8%) respondents, a study sample of 150 clinical nutrition managers and their subordinates was selected to receive the LBQ; 116 (77.3%) instrument sets were used for analysis. STATISTICAL ANALYSIS: Descriptive statistics were used to analyze the demographic surveys. A specified mixed linear model repeated measures Statistical Analysis System procedure was used to compare the clinical manager and subordinate LBQ scores. Association of the selected demographic variables with leadership qualities was measured by lambda, a predictive value measure, using the BMDP 4F program. RESULTS: Clinical nutrition managers exhibited transformational leadership qualities as rated by the LBQ, rating lowest on the communication leadership score and highest on the respectful leadership score. Most of the clinical nutrition manager self LBQ scores were significantly higher than the clinical nutrition manager LBQ scores rated by subordinates. The selected demographic variables appeared to have the strongest predictive effect for the visionary culture building subscore of the LBQ. The visionary culture building subscore is a measure of how well the leader interacts with and affects the functioning of an organization. APPLICATIONS/CONCLUSIONS: More research is needed to define leadership in dietetics: this study can serve as a possible model. One way clinical nutrition managers may be able to enhance their leadership behaviors is to strengthen their skills in communicating their vision. Programs are needed to help clinical nutrition managers shape their organizations to foster leadership development in their subordinates.

Dietetics↗
PubMed1995

Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. Results of the first multicentre Australian trial. Australia Hepatitis C Study Group.

Two hundred and thirty patients with histologically proven chronic hepatitis C were randomized to receive one of the following treatment protocols: (a) 3 million units of interferon alfa-2b thrice weekly for 6 months, (b) 5 million units thrice weekly for 6 months, or (c) 3 million units thrice weekly for 2 years. The short-term response to treatment was defined by normal alanine aminotransferase for at least 3 months and until the end of treatment, and was confirmed by loss of hepatitis C viraemia in 42 (91%) of 46 cases as determined by reverse transcription-polymerase chain reaction. Short-term response to interferon alfa-2b was independent of the incremental dose, being 64% for 5 million units and 58% for 3 million units. Long-term response to interferon alfa-2b was defined by continued normality of alanine aminotransferase levels for at least 6 months after treatment withdrawal. The long-term response rates among responders treated for 6 months and those treated for 2 years were 29% and 54%, respectively (p < 0.001). Among all 18 patients tested, serum HCV-RNA was negative at both 6 and 12 months of follow-up in all long-term responders, and none have subsequently relapsed. Improvement in hepatic necroinflammatory changes was confirmed by quantitative histology (Scheuer score) in responders at the end of interferon alfa-2b treatment. The changes were significantly greater among those who had been treated for 2 years compared with those treated for 6 months (p < 0.05 and p < 0.02, respectively, for portal and lobular inflammation scores). Several pretreatment characteristics could be correlated with a favourable response to interferon alfa-2b. Thus, absence of cirrhosis was associated with a short-term response of 75%, while only 42% of patients with cirrhosis had a short-term response (p < 0.001). The frequency of short-term response to interferon alfa-2b also differed according to mode of disease acquisition, being best for injecting drug use (71%), less favourable for blood transfusion (56%) and worst for sporadic cases (43%) (p < 0.01). This observed difference, however, was not independent of histology on multivariate analysis. In summary, a 5 million unit dose of interferon alfa-2b failed to improve the short-term or long-term response to interferon alfa-2b treatment, but prolongation of interferon alfa-2b treatment to 2 years resulted in substantially improved long-term response rate.

Adolescent↗
PubMed1995

Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation.

OBJECTIVE: Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol-induced liver disease. We have evaluated hypothalamic-pituitary-testicular function in patients with end-stage non-alcoholic liver disease before and at 6 and 12 months after hepatic transplantation. DESIGN: A prospective study of hypothalamic-pituitary-testicular endocrine function before and after cadaveric hepatic transplantation. PATIENTS: Fifty four consecutive patients with end-stage, non-alcoholic liver disease were evaluated before and after liver transplantation. MEASUREMENTS: Hypothalamic-pituitary-testicular (HPT) axis function was evaluated under basal conditions by single morning measurements of plasma total and free testosterone, sex hormone-binding globulin and by plasma LH and FSH responses to 100 micrograms i.v. GnRH. RESULTS: Men with chronic non-alcoholic liver disease had reduced levels of total and free testosterone and increased levels of SHBG compared with controls with normal liver function. Total and free testosterone were positively correlated with basal and stimulated LH (but not FSH) concentrations. Gonadotrophin responses to GnRH were preserved but delayed compared with healthy controls consistent with a predominantly hypothalamic defect in regulation of pituitary-testicular function. Increasing severity of underlying liver disease was associated with declining total and free testosterone as well as peak GnRH-stimulated LH concentrations. Spironolactone treatment was associated with decreased circulating testosterone levels only in men with liver disease of intermediate severity (Child-Pugh class B). Following hepatic transplantation, total and free testosterone and SHBG concentrations returned progressively towards eugonadal control levels over the first 12 months but total and free testosterone levels remained subnormal. CONCLUSIONS: Hypothalamic-pituitary regulation of testicular function is impaired in end-stage non-alcoholic liver disease in proportion to the severity of underlying liver disease. Spironolactone reduces circulating testosterone but only among men with Child-Pugh B liver cirrhosis. Gonadal function improves, but is not normalized, over the first year following successful liver transplantation.

Adolescent↗
PubMed1995

Satisfaction with medical care. It's easier to please patients than their family members and friends.

The authors conducted a multi-site study to compare the level of satisfaction with medical care and services between patients and their family/friends. Hierarchical regression results controlling for patient age, gender, medical service performed, and other factors suggest that inpatients are more satisfied with the care rendered by physicians and nurses, as well as with their overall hospital stay, than are their family members and friends. The authors speculate about why this is so and what health care providers can do about it.

Aged↗
PubMed1995

Functioning and well-being of patients before and after elective surgical procedures.

BACKGROUND: Recent changes in health care delivery and financing have prompted interest in medical outcomes research. This study was performed to assess the effect of general surgical procedures on the health status of patients over time. STUDY DESIGN: The functional health status of patients undergoing elective surgical procedures was measured preoperatively, in the immediate postoperative period, and three and six months after surgery. Complete data were collected for 82 patients presenting to the general surgery service at the Ohio State University Medical Center for symptoms related to gallbladder disease (21), hemorrhoids (10), inguinal and incisional hernias (37), and clinically severe obesity (14). The Short Form-36 health status questionnaire was administered before the surgical procedure, at the first postoperative visit, and by telephone three months and six months following surgery. Hospital records were reviewed following the procedures, and preoperative anesthesiologist's risk status, American Society of Anesthesiologists scores, and complications were noted. Patient satisfaction was assessed using a questionnaire developed by Ohio State University. RESULTS: For all four elective procedures, a significant improvement in health status was demonstrated when preoperative function was compared to measurements three and six months postoperatively. Improvement was significant in all eight categories assessed, encompassing physical, social, mental, emotional, and general health, and pain relief. Dramatic improvement was reported by patients undergoing Roux-en-Y gastric bypass for clinically severe obesity. CONCLUSIONS: The Short Form-36 health status questionnaire proved to be a useful tool in assessing patient outcomes following elective surgical procedures. The general health status assessment will be especially useful for documenting the effectiveness of routine and innovative therapies.

Activities of Daily Living↗
PubMed1994

The effective use of patient satisfaction data.

Demonstrating the importance of patient satisfaction as a measure of health services quality, health care organizations are increasingly investing in information systems for the collection and manipulation of patient satisfaction data. Unfortunately, these information resources are often squandered as a variety of methodological, organizational, and psychological obstacles work to prohibit the productive use of patient satisfaction data. This article discusses the challenges that health care managers and clinicians face in effectively using patient satisfaction data and identifies statistical, operations management, and managerial-specific skills that these individuals should possess to use satisfaction data successfully.

Computer Literacy↗
PubMed1993

Service recovery in health services organizations.

Service recovery is defined as that part of quality management designed to alter the negative perceptions of dissatisfied consumers and to ultimately maintain a business relationship with these consumers. This article explores the theoretical and operational implications of service recovery in health services organizations. A framework that defines the range of possible service recovery actions is presented. Next, the benefits of and obstacles to service recovery in health services firms are discussed, and solutions for overcoming these obstacles are presented. Finally, the critical components of an effective service recovery program are described, and an agenda for empirical research on the efficacy of service recovery activities is proposed.

Cost Savings↗