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Biomedical subjects

Malathi Srinivasan

Publications and source records attributed to Malathi Srinivasan.

At least 19 recordsLinked to original sources
PubMed2007

Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model.

Exposure to a high-carbohydrate (HC) milk formula during the suckling period results in permanent metabolic programming of hyperinsulinemia in HC rats. Previous studies have shown that hyperinsulinemia in HC rats involves a programmed hyperresponsiveness to glucose. However, the immediate onset and persistence of enhanced insulin secretion throughout life suggests a role for numerous factors that control insulin secretion. Present in vivo and in vitro studies have shown a role for altered autonomic activity, including increased parasympathetic and decreased sympathetic activities, in the maintenance of hyperinsulinemia in 100-day-old HC rats. HC rats were shown to be more sensitive to cholinergic-induced potentiation of glucose-stimulated insulin secretion (GSIS) in response to acetylcholine and showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic-type 3 receptor-specific antagonist 4-diphenylacetoxy-N-methylpiperidine. In addition, HC rats were less sensitive to adrenergic-induced inhibition of insulin secretion by oxymetazoline, whereas treatment with yohimbine resulted in increased GSIS. Furthermore, HC rats showed greater reductions in plasma insulin levels after vagotomy, as well as an attenuation of yohimbine-induced potentiation of GSIS, suggesting that yohimbine-mediated changes are mediated by parasympathetic activity. Changes in autonomic regulation of GSIS are supported by increased mRNA levels of the parasympathetic signaling molecules muscarinic-type 3 receptor, phospholipase Cbeta1, and protein kinase C-alpha and decreased levels of alpha(2a)-adrenergic receptors in islets from adult HC rats. In conclusion, metabolic programming of hyperinsulinemia throughout adulthood of HC rats involves changes in autonomic activity in response to the HC dietary intervention in the suckling period.

Acetylcholine↗
PubMed2007

Comparing problem-based learning with case-based learning: effects of a major curricular shift at two institutions.

PURPOSE: Problem-based learning (PBL) is now used at many medical schools to promote lifelong learning, open inquiry, teamwork, and critical thinking. PBL has not been compared with other forms of discussion-based small-group learning. Case-based learning (CBL) uses a guided inquiry method and provides more structure during small-group sessions. In this study, we compared faculty and medical students' perceptions of traditional PBL with CBL after a curricular shift at two institutions. METHOD: Over periods of three years, the medical schools at the University of California, Los Angeles (UCLA) and the University of California, Davis (UCD) changed first-, second-, and third-year Doctoring courses from PBL to CBL formats. Ten months after the shift (2001 at UCLA and 2004 at UCD), students and faculty who had participated in both curricula completed a 24-item questionnaire about their PBL and CBL perceptions and the perceived advantages of each format RESULTS: A total of 286 students (86%-97%) and 31 faculty (92%-100%) completed questionnaires. CBL was preferred by students (255; 89%) and faculty (26; 84%) across schools and learner levels. The few students preferring PBL (11%) felt it encouraged self-directed learning (26%) and valued its greater opportunities for participation (32%). From logistic regression, students preferred CBL because of fewer unfocused tangents (59%, odds ration [OR] 4.10, P = .01), less busy-work (80%, OR 3.97, P = .01), and more opportunities for clinical skills application (52%, OR 25.6, P = .002). CONCLUSIONS: Learners and faculty at two major academic medical centers overwhelmingly preferred CBL (guided inquiry) over PBL (open inquiry). Given the dense medical curriculum and need for efficient use of student and faculty time, CBL offers an alternative model to traditional PBL small-group teaching. This study could not assess which method produces better practicing physicians.

Academic Medical Centers↗
PubMed2006

Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats.

An early dietary intervention in the form of a high-carbohydrate (HC) milk formula in neonatal rat pups results in immediate onset of hyperinsulinemia. While increased insulin secretion in HC rats has been shown to be related to hypersensitivity to glucose, the immediate onset of hyperinsulinemia and its persistence throughout the suckling period suggest involvement of multiple systems that enhance insulin secretion in response to increased demand. Evidence presented here in 12-day-old HC rats indicates that altered activity of the autonomic nervous system contributes to enhanced insulin secretory responses to glucose stimulation through increased parasympathetic and decreased sympathetic signaling. Both in vivo and in vitro studies have shown that HC rats secrete significantly higher levels of insulin in response to glucose in the presence of acetylcholine, a cholinergic agonist, while sensitivity to inhibition of insulin secretion by oxymetazoline, an alpha(2a)-adrenergic receptor (alpha(2a)AR) agonist, was reduced. In addition, HC rats showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic type 3 receptor (M3R) antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide, as well as increased potentiation of glucose-stimulated insulin secretion by treatment with yohimbine. Increases in islets levels of M3R, phospholipase C-beta1, and protein kinase Calpha mRNAs, as well as decreased alpha(2a)AR mRNA, in 12-day-old HC rats provide a mechanistic connection to the changes in insulin secretion seen in HC rats. In conclusion, altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.

Acetylcholine↗
PubMed2006

Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood.

Chronic consumption of a high-fat (HF) diet by female rats in their postweaning period resulted in significant increases in body weight and plasma levels of insulin, glucose, and triglycerides during pregnancy compared with female rats consuming a standard rodent laboratory chow (LC). On gestational day 21, plasma insulin levels and the insulin secretory response of islets to various secretogogues were significantly increased in HF fetuses. The HF male progeny weaned onto LC (HF/LC) demonstrated increases in body weight from postnatal day 60 onward. In adulthood, HF/LC male rats were significantly heavier than controls, had increased plasma levels of insulin, glucose, free fatty acids, and triglycerides, and demonstrated glucose intolerance. HF/LC male islets secreted increased amounts of insulin in response to low glucose concentrations, but their response to a high glucose concentration was similar to that of LC/LC islets. In another set of experiments, when the male progeny of HF female rats were weaned onto a high-sucrose diet (HF/HSu), their metabolic profile was further worsened. These results indicate that chronic consumption of a HF diet by female rats malprograms the male progeny for glucose intolerance and development of increased body weight in adulthood. The long-term high-fat feeding to female rats employed in this study bears resemblance to the dietary habits in Western societies. The results of this study implicate dietary practices of women in the etiology of the present epidemic of human obesity and related disorders.

Animals↗
PubMed2006

Spectrophotometric method for quantitative determination of nonionic, ionic and zwitterionic detergents.

Detergents serve as means of solubilizing biological membranes and thus play an important role in purification and characterization of membrane proteins. We report here a simple method to estimate the amount of detergent bound to a protein or present in an aqueous solution. The method is based on the turbidity caused by the addition of a detergent to triolein. Detergent bound to an integral membrane protein, lysophosphatidic acid acyltransferase, was separated by native gel electrophoresis and the amount of detergent bound to the same was estimated. This method is applicable for Triton X-100, sodium dodecyl sulfate and zwitterionic detergent, and was validated in the presence of reagents commonly used in membrane protein solubilization and purification.

Acyltransferases↗
PubMed2006

Connoisseurs of care? Unannounced standardized patients' ratings of physicians.

BACKGROUND: Patient satisfaction surveys can be informative, but bias and poor response rates may limit their utility as stable measures of physician performance. Using unannounced standardized patients (SPs) may overcome some of these limitations because their experience and training make them able judges of physician behavior. OBJECTIVES: We sought to understand the reliability of unannounced SPs in rating primary care physicians when covertly presenting as real patients. STUDY DESIGN: Data from 2 studies (Patient Centered Communication [PCC]; Social Influences in Practice [SIP]) were included. For the PCC study, 5 SPs made 192 visits to 96 physicians; for the SIP study, 18 SPs made 292 visits to 146 physicians. SPs visits to physicians were randomized, thus avoiding mutual selection bias. Each SP rated 16 to 38 physicians on interpersonal skills (autonomy support: PCC, SIP), technical skills (information gathering: SIP-only), and overall satisfaction (SIP-only). We evaluated SP evaluation consistency (physician vs. total variance rho), and SPs' overall satisfaction with specific dimensions of physician performance. RESULTS: Scale reliability varied from 0.71 to 0.92. Physician rhos (95% confidence intervals) for autonomy support were 0.40 (0.22-0.58; PCC) and 0.30 (0.14-0.45; SIP); information gathering rho was 0.46 (0.33-0.59; SIP). Overall SP satisfaction rho was 0.47 (0.34-0.60; SIP). SPs varied significantly in adjusted overall satisfaction levels, but not other dimensions. CONCLUSIONS: These analyses provide some evidence that medical connoisseurship can be learned. When adequately sampled by trained SPs, some physician skills can be reliably measured in community practice settings.

Clinical Competence↗
PubMed2006

Saving time, improving satisfaction: the impact of a digital radiology system on physician workflow and system efficiency.

The objective of the study was to assess UC Davis Health System's transition to digital radiology. The study involved pre- and post-PACS analyses of workflow and costs, physician satisfaction surveys, and self-recorded radiology interactions by on-call residents. The study revealed significant results. Before the PACS implementation, physicians spent one to three hours searching for films daily and were dissatisfied with radiology services. After implementation, images were readily available, physicians were more likely to view and interpret images themselves, and they reported increased satisfaction. From real-time reporting, residents viewed studies with radiologists 90.2 percent less often. Average image search time decreased, from 16 to 2 minutes, saving 21.5 physician years, worth dollar 1,034,150 annually. Reductions in film printing (73.4 percent) and file clerk full-time equivalents (50.3 percent) saved dollar 1,001,452 annually, and freed up 1,218 hospital and 8,108 warehouse square feet, worth dollar 2,018,320. As a result, UCDHS's digital radiology system improved clinician satisfaction and workflow, increased clinician image viewing, and decreased clinician engagement with radiologists. System implementation saved 21 physician years and dollar 2 million annually.

California↗
PubMed2005

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype.

We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that mal-programming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny.

Animals↗
PubMed2005

Patient desires: a model for assessment of patient preferences for care of severe or terminal illness.

OBJECTIVE: Patient-centered care is better achieved through a comprehensive understanding of patients' preferences for how they want to live their life and how they want to influence their own death. Though much has been written on identifying goals of care, it is often difficult for clinicians to articulate patient goals to guide care planning. We explored the literature on patient's preferences for their care in chronic or life-limiting illness to develop a model for assessment of patient perspectives. We then illustrated our model with composite patients from our clinics and we provide questions to guide patient discussion. METHODS: We searched MEDLINE from 1986 to 2004 for primary research articles that relate primarily to a patient's preferences for his or her care. We reviewed over 3500 titles, abstracts, and research papers. Hundreds of articles described patients' quality of life, health status, or satisfaction. We excluded consensus guidelines, non-English papers, reviews, and articles focused on medical professional perspectives. Forty-eight studies focused primarily on patient preferences. Using an iterative process, we identified unique issues and broader themes in patients' desires for their care. RESULTS: Studies focused on patients with cancer, those in hospice or those with terminal disease. Three domains emerged: patient feelings about disease, feelings about suffering, and feelings about the circumstances of death. Attention was given to the differences between patients in terms of the strength and persistence of feelings in each domain. SIGNIFICANCE OF RESULTS: Based on existing data, there are three fundamental domains of patient perspective that influence preferences for care. These domains can be assessed by the care team to guide the development of a plan of care and to identify areas of conflict. Our review identifies gaps in the end-of-life literature and areas for future work in patient preferences.

Attitude to Death↗
PubMed2005

Factors affecting resident performance: development of a theoretical model and a focused literature review.

PURPOSE: The clinical performances of physicians have come under scrutiny as greater public attention is paid to the quality of health care. However, determinants of physician performance have not been well elucidated. The authors sought to develop a theoretical model of physician performance, and explored the literature about factors affecting resident performance. METHOD: Using expert consensus panel, in 2002-03 the authors developed a hypothesis-generating model of resident performance. The developed model had three input factors (individual resident factors, health care infrastructure, and medical education infrastructure), intermediate process measures (knowledge, skills, attitudes, habits), and final health outcomes (affecting patient, community and population). The authors used factors from the model to focus a PubMed search (1967-2002) for all original articles related to the factors of individual resident performance. RESULTS: The authors found 52 original studies that examined factors of an individual resident's performance. They describe each study's measurement instrument, study design, major findings, and limitations. Studies were categorized into five domains: learning styles/personality, social/financial factors, practice preferences, personal health, and response to job environment. Few studies examined intermediate or final performance outcomes. Most were single-institution, cross-sectional, and survey-based studies. CONCLUSIONS: Attempting to understand resident performance without understanding factors that influence performance is analogous to examining patient adherence to medication regimens without understanding the individual patient and his or her environment. Based on a systematic review of the literature, the authors found few discrete associations between the factors of individual resident and the resident's actual job performance. Additionally, they identify and discuss major gaps in the educational literature.

Adult↗
PubMed2005

Effective organizational control: implications for academic medicine.

This article provides a framework for understanding the nature, role, functioning, design, and effects of organizational oversight systems. Using a case study with elements recognizable to an academic audience, the authors explore how a dean of a fictitious School of Medicine might use organizational control structures to develop effective solutions to global disarray within the academic medical center. Organizational control systems are intended to help influence the behavior of people as members of a formal organization. They are necessary to motivate people toward organizational goals, to coordinate diverse efforts, and to provide feedback about problems. The authors present a model of control to make this process more visible within organizations. They explore the overlap among academic medical centers and large businesses-for instance, each is a billion-dollar enterprise with complex internal and external demands and multiple audiences. The authors identify and describe how to use the key components of an organization's control system: environment, culture, structure, and core control system. Elements of the core control system are identified, described, and explored. These closely articulating elements include planning, operations, measurement, evaluation, and feedback systems. Use of control portfolios is explored to achieve goal-outcome congruence. Additionally, the authors describe how the components of the control system can be used synergistically by academic leadership to create organizational change, congruent with larger organizational goals. The enterprise of medicine is quickly learning from the enterprise of business. Achieving goal-action congruence will better position academic medicine to meet its multiple missions.

Academic Medical Centers↗
PubMed2004

Developing an OSTE to address lapses in learners' professional behavior and an instrument to code educators' responses.

PURPOSE: To develop an instrument for measuring medical educators' responses to learners' lapses in professional behavior. METHOD: In 1999, at the Indiana University School of Medicine, a 22-item checklist of behaviors was developed to describe common responses used by educators responding to learners' lapses in professional behavior. Four medical students were trained to portray lapses in professional behaviors. These students and seven clinical observers trained to categorize behaviors as present or absent. Interrater reliability was assessed during 18 objective structured teaching evaluations (OSTEs). Videotaped OSTEs were coded twice at a one-month interval for test-retest reliability. Items were classified as low, moderate, or high inference behaviors. Script realism and educator effectiveness were assessed. RESULTS: Educators rated OSTE scripts as realistic. Raters observed an average of 6 +/- 2 educator behaviors in reaction to learners' lapses in professional behavior. Educators' responses were rated as moderately effective. More experienced educators attempted more interventions and were more effective. Agreement was high among raters (86% +/- 7%), while intraclass correlation coefficients decreased with increasing inference level. From videotaped OSTEs, raters scored each behavior identically 86% of the time. CONCLUSIONS: Accurate feedback on educators' interactions in addressing learners' professionalism is essential for faculty development. Traditionally, educators have felt that faculty's responses to learners' lapses in professional behavior were difficult to observe and categorize. These data suggest that educators' responses to learners' lapses in professional behavior can be defined and reliably coded. This work will help provide objective feedback to faculty when engaging learners about lapses in professional behavior.

Education, Medical↗
PubMed2003

Neonatal nutrition: metabolic programming of pancreatic islets and obesity.

Obese individuals are more likely to suffer from diseases termed the "metabolic syndrome," which includes type 2 diabetes. It is now recognized that early life dietary experiences play an important role in the etiology of such diseases. In this context, the consequences of a high carbohydrate (HC) dietary intervention in neonatal rats is being studied in our laboratory. Artificial rearing of 4-day-old rat pups on a HC milk formula up to Day 24 results in the immediate onset of hyperinsulinemia, which persists throughout the period of dietary intervention. Several adaptations at the biochemical, cellular, and molecular levels in the islets of these HC rats support the onset and persistence of the hyperinsulinemic condition during this period. Some of these adaptations include a distinct leftward shift in the insulin secretory capacity, increased hexokinase activity, increased gene expression of preproinsulin and related transcription factors and specific kinases in 12-day-old HC islets, and alterations in the number and size of islets. These adaptations are programmed and expressed in adulthood thereby sustain the hyperinsulinemic condition in the postweaning period and form the basis for adult-onset obesity. HC females spontaneously transmit the HC phenotype (chronic hyperinsulinemia and adult-onset obesity) to their progeny. Collectively, our results indicate that even a mere switch in the nature of the source of calories (from fat rich in rat milk to carbohydrate rich in the HC milk formula) during critical phases of early development in the rat results in metabolic programming of islet functions leading to chronic hyperinsulinemia (throughout life) and adult-onset obesity. This metabolic programming, once established, forms a vicious cycle because HC female rats spontaneously transmit the HC phenotype to their progeny. The results from our laboratory in the context of metabolic programming due to neonatal nutritional experiences are discussed in this review.

Animals↗
PubMed2003

Programming of islet functions in the progeny of hyperinsulinemic/obese rats.

Neonatal female rat pups that were raised artificially on a high-carbohydrate (HC) milk formula during their suckling period developed hyperinsulinemia immediately, maintained chronic hyperinsulinemia in the postweaning period on laboratory diet, and developed obesity in adulthood. Pups (second-generation HC [2-HC]) born to such female rats (first-generation HC [1-HC]) spontaneously developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype) without the requirement for any dietary intervention in their suckling period. Leftward shift in the insulin secretory response to a glucose stimulus, increase in hexokinase activity, and increased preproinsulin gene transcription were observed in islets from 28-day-old 2-HC rats, and these adaptations are similar to those reported for islets from 12-day-old and 100-day-old 1-HC rats. Unlike 1-HC islets, the ability to secrete moderate amounts of insulin in the absence of glucose and calcium and the incretin input for augmentation of insulin secretion were not observed in 2-HC islets. These results show that a dietary modification in the early postnatal life of the 1-HC female rat sets up a vicious cycle of spontaneous transfer of the HC phenotype to its progeny, implicating a new component to the growing list of factors that contribute to the fetal origins of adult-onset diseases.

Animals↗
PubMed2002

Early introduction of an evidence-based medicine course to preclinical medical students.

Evidence-based Medicine (EBM) has been increasingly integrated into medical education curricula. Using an observational research design, we evaluated the feasibility of introducing a 1-month problem-based EBM course for 139 first-year medical students at a large university center. We assessed program performance through the use of a web-based curricular component and practice exam, final examination scores, student satisfaction surveys, and a faculty questionnaire. Students demonstrated active involvement in learning EBM and ability to use EBM principles. Facilitators felt that students performed well and compared favorably with residents whom they had supervised in the past year. Both faculty and students were satisfied with the EBM course. To our knowledge, this is the first report to demonstrate that early introduction of EBM principles as a short course to preclinical medical students is feasible and practical.

Adult↗
PubMed2002

Medicare financing of graduate medical education.

The past decade has seen ongoing debate regarding federal support of graduate medical education, with numerous proposals for reform. Several critical problems with the current mechanism are evident on reviewing graduate medical education (GME) funding issues from the perspectives of key stakeholders. These problems include the following: substantial interinstitutional and interspecialty variations in per-resident payment amounts; teaching costs that have not been recalibrated since 1983; no consistent control by physician educators over direct medical education (DME) funds; and institutional DME payments unrelated to actual expenditures for resident education or to program outcomes. None of the current GME reform proposals adequately address all of these issues. Accordingly, we recommend several fundamental changes in Medicare GME support. We propose a re-analysis of the true direct costs of resident training (with appropriate adjustment for local market factors) to rectify the myriad problems with per-resident payments. We propose that Medicare DME funds go to the physician organization providing resident instruction, keeping DME payments separate from the operating revenues of teaching hospitals. To ensure financial accountability, we propose that institutions must maintain budgets and report expenditures for each GME program. To establish educational accountability, Residency Review Committees should establish objective, annually measurable standards for GME program performance; programs that consistently fail to meet these minimum standards should lose discretion over GME funds. These reforms will solve several long-standing, vexing problems in Medicare GME funding, but will also uncover the extent of undersupport of GME by most other health care payers. Ultimately, successful reform of GME financing will require "all-payer" support.

Adult↗