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PubMed2007

Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression.

Trypanosoma cruzi undergo PCD (programmed cell death) under appropriate stimuli, the mechanisms of which remain to be established. In the present study, we show that stimulation of PCD in T. cruzi epimastigotes by FHS (fresh human serum) results in rapid (<1 h) externalization of phosphatidylserine and depletion of the low molecular mass thiols dihydrotrypanothione and glutathione. Concomitantly, enhanced generation of oxidants was established by EPR and immuno-spin trapping of radicals using DMPO (5,5-dimethylpyrroline-N-oxide) and augmentation of the glucose flux through the pentose phosphate pathway. In the early period (<20 min), changes in mitochondrial membrane potential and inhibition of respiration, probably due to the impairment of ADP/ATP exchange with the cytosol, were observed, conditions that favour the generation of O2*-. Accelerated rates of mitochondrial O2*- production were detected by the inactivation of the redox-sensitive mitochondrial aconitase and by oxidation of a mitochondrial-targeted probe (MitoSOX). Importantly, parasites overexpressing mitochondrial FeSOD (iron superoxide dismutase) were more resistant to the PCD stimulus, unambiguously indicating the participation of mitochondrial O2*- in the signalling process. In summary, FHS-induced PCD in T. cruzi involves mitochondrial dysfunction that causes enhanced O(2)(*-) formation, which leads to cellular oxidative stress conditions that trigger the initiation of PCD cascades; moreover, overexpression of mitochondrial FeSOD, which is also observed during metacyclogenesis, resulted in cytoprotective effects.

Animals↗
PubMed1998

Molecular genetic analysis of von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is a dominantly inherited multisystem family cancer syndrome predisposing to retinal and central nervous system haemangioblastomas, renal carcinoma, phaeochromocytoma, pancreatic islet cell tumours and endolymphatic sac tumours. In addition, renal, pancreatic and epididymal cysts occur. Morbidity and mortality from VHL disease can be reduced by the identification and surveillance of affected individuals and at-risk relatives so that complications are diagnosed at an early presymptomatic stage. The detailed mapping and subsequent isolation of the VHL tumour suppressor gene has enabled molecular genetic analysis in families and patients with definite or possible VHL disease. Initially, linked DNA markers were used in informative families to modify individual risks and then to make appropriate alterations in surveillance programs. However, currently most DNA analysis involves the characterisation of germline mutations. World-wide, mutations have been identified in almost 500 families (including 132 in our laboratory). These studies have revealed considerable heterogeneity both in the type and in the location of mutations within the VHL gene. In our experience, most recurrent mutations result from de novo mutations at hypermutable sequences, although a founder effect for the Tyr98His ('Black Forest') mutation has been reported in German and American families. Although many mutations are predicted to impair the ability of pVHL to combine with the elongin regulatory subunits, analysis of genotype-phenotype relationships suggests that the VHL protein has multiple and tissue specific functions. Calculation of tumour risks for different classes of VHL mutations has provided important prognostic information especially with respect to the likelihood of phaeochromocytoma. However, there is evidence that retinal involvement does not correlate with allelic heterogeneity, but that the variability in retinal angiomatosis is influenced by modifier gene effects. VHL gene mutation analysis also provides a basis for investigating the genetic basis of familial phaeochromocytoma and renal cell carcinoma, and apparently isolated retinal angiomas. Results to date suggest that a substantial proportion of patients with familial pheochromocytoma have VHL gene mutations but in contrast, most familial clusters of clear cell renal cell carcinoma (RCC) without evidence of VHL do not have germline VHL mutations.

Age of Onset↗
PubMed2000

Infantile autism: adult outcome.

Although the core features of autism do not change qualitatively, a gradual overall symptomatic improvement including an increase in adaptive skills is observed in most cases with age. Follow-up studies show that the diagnostic features, the differential diagnosis, and clinical problems of adult autistics differ substantially from that of autistic children. The differential diagnosis of older autistics include personality disorders, learning disabilities, and mood disorder. Depression, epilepsy, and behavioral problems such as aggression and agitation may be major clinical problems during adolescence. The early indicators of a better outcome include a higher level of IQ and language. Among the neuropsychological variables, measures of flexibility and cognitive shift are important as prognostic factors. Early behavioral and educational intervention may especially increase the adaptive skills of the patients and promote the in-family communication. The outcome studies of autism are particularly helpful in addressing the appropriate and most effective programs of remediation for adult autistics.

Adult↗
PubMed2006

[Benefits of a multimodular outpatient training program for patients with COPD].

BACKGROUND: The partition and chronological sequence of the different training items and modalities necessary for an effective training of patients with chronic obstructive pulmonary disease (COPD) remains a subject of debate. We investigated the combination of effective components of pulmonary rehabilitation in the settings outpatient lung sports group, home-based training and training in a gym. METHODS: Subjects were randomized to a 12-month training program and a no training group. PATIENTS AND MAIN RESULTS: The training group (n = 10, mean age: 62.5 years, FEV1 53.4% predicted) reached an average increase in peakVO2 of 10% (p = 0.01) from 1.30 +/- 0.41 L/minute to 1.44 +/- 0.38 L/minute, in peak work rate of 14% (p = 0.007) from 82 +/- 39 W to 93 +/- 43 W and in the six-minute walking distance of 79 meters (p = 0.003), whereas in the control group (n = 9, mean age: 63.2 years, FEV1 53.7% predicted) no significant changes were observed. The quality of life obtained by use of the SF36-questionnaire and SGRQ also significantly improved in the training group, but not in the control group. CONCLUSION: This outpatient rehabilitation program is effective and appropriate for long-term rehabilitation of patients with COPD.

Aged↗
PubMed2003

Adherence to practice guidelines: the role of specialty society guidelines.

BACKGROUND: Physician adherence to guidelines is often poor, but the reasons have not been completely studied. We investigated whether physician adherence to guidelines for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) varied by source, development methods, or the extent of their evidence-base. METHODS AND RESULTS: We assessed adherence to guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) for PTCA (1988 and 1993) and for CABG (1990) and guidelines developed by RAND for PTCA and CABG in 1990. We randomly sampled patients on Medicare who were undergoing coronary angiography in 5 states in 1991 and 1992, extracting clinical and laboratory data from medical records and using computer programs to classify the appropriateness of each procedure. A total of 543 PTCA and 676 CABG procedures were studied. By use of the 1988 ACC/AHA guidelines, 30% of PTCAs were rated class III (inappropriate), whereas 24% were class III by use of the 1993 guidelines. Only 1.5% of CABG procedures were class III with ACC/AHA guidelines. By use of RAND guidelines, 12% of PTCA and 9% of CABG procedures were classified as inappropriate. CONCLUSIONS: Adherence to guidelines is higher when the recommendations are supported by evidence from randomized clinical trials (CABG). The credibility of the source and familiarity with the guidelines do not ensure compliance. When evidence is lacking, as with PTCA at the time of this study, guideline recommendations may lag behind appropriate changes in clinical practice. More frequent revisions coupled with on-line access have the potential to make guidelines more useful.

Aged↗
PubMed2000

Automated parallel DNA sequencing on multiple channel microchips.

We report automated DNA sequencing in 16-channel microchips. A microchip prefilled with sieving matrix is aligned on a heating plate affixed to a movable platform. Samples are loaded into sample reservoirs by using an eight-tip pipetting device, and the chip is docked with an array of electrodes in the focal plane of a four-color scanning detection system. Under computer control, high voltage is applied to the appropriate reservoirs in a programmed sequence that injects and separates the DNA samples. An integrated four-color confocal fluorescent detector automatically scans all 16 channels. The system routinely yields more than 450 bases in 15 min in all 16 channels. In the best case using an automated base-calling program, 543 bases have been called at an accuracy of >99%. Separations, including automated chip loading and sample injection, normally are completed in less than 18 min. The advantages of DNA sequencing on capillary electrophoresis chips include uniform signal intensity and tolerance of high DNA template concentration. To understand the fundamentals of these unique features we developed a theoretical treatment of cross-channel chip injection that we call the differential concentration effect. We present experimental evidence consistent with the predictions of the theory.

Automation↗
PubMed1975

Complete translation of poliovirus RNA in a eukaryotic cell-free system.

Poliovirus RNA stimulates imcorporation of 35S from both [35S]methionine and formyl-[35S]methionyl-tRNAfMet in cell-free systems derived from HeLa cells or from poliovirus-infected HeLa cells. The largest product formed under the direction of the viral RNA is the same size as the polyprotein thought to represent translation of the entire RNA. Synthesis of this polyprotein and other large products was stimulated greatly by increasing the salt concentration during the reaction from the optimum for initiation (90 mM) to the optimum for elongation (155 mM). Only one initiation peptide could be identified, and a tryptic digest of the product contained mainly peptides that cochromatographed with peptides from authentic viral proteins. The RNA from a deletion mutant of poliovirus initiated protein synthesis at the same site used by standard RNA and programmed synthesis of an appropriately deleted set of polypeptides. The results strongly support the model of translation of poliovirus RNA from a single initiation site into a continuous polyprotein that is cleaved to form the functional proteins. It is suggested that uninfected HeLa cell extracts can carry out the cleavages of nascent polyprotein.

Cell-Free System↗
PubMed2005

Distinct role of calmodulin and calmodulin-dependent protein kinase-II in lipopolysaccharide and tumor necrosis factor-alpha-mediated suppression of apoptosis and antiapoptotic c-IAP2 gene expression in human monocytic cells.

Exposure of phagocytic cells to bacterial endotoxin (lipopolysaccharide; LPS) or inflammatory cytokines confers antiapoptotic survival signals; however, in the absence of the appropriate stimulus, monocytes are programmed to undergo apoptosis. Macrophage survival may thus influence inflammatory and immune responses and susceptibility to microbial pathogens. Herein, we demonstrate that LPS and the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), enhance monocytic cell survival through the induction of the antiapoptotic c-IAP2 gene in a human promonocytic THP-1 cell line. We also investigated the role of upstream signaling molecules including the mitogen-activated protein kinases, phosphatidylinositol 3-kinase, and the calcium signaling pathways in the regulation of c-IAP2 expression and eventual survival of monocytic cells. Our results suggest that LPS and TNF-alpha-induced c-IAP2 expression was regulated by calmodulin (CaM) through the activation of calmodulin-dependent protein kinase-II (CaMKII). In addition, CaM and CaMKII regulated c-IAP2 expression in LPSand TNF-alpha-stimulated cells through NF-kappaB activation. Moreover, the CaM/CaMKII pathway also regulated LPS- and TNF-alpha-mediated inhibition of apoptosis in these cells. Taken together, these results suggest that LPS- and TNF-alpha-induced c-IAP2 expression and its associated antiapoptotic survival signals in THP-1 cells are regulated selectively by CaM/CaMKII through NF-kappaB activation.

Apoptosis↗
PubMed1986

Post-polio syndrome. The battle with an old foe resumes.

How many of the thousands who contracted polio during the epidemics 30 and 40 years ago will experience post-polio syndrome? What causes these delayed effects, and how quickly will they progress? None of these questions can be answered with certainty. At present, several factors appear to be at work. Patients are generally in one of two groups: The first group has deterioration in the function of muscles that were affected by the disease. This muscle weakness may be caused by a loss of motor neurons, due to aging, from an already depleted neuron pool. The remaining motor units then become stressed from overuse. The second group has problems in new muscle groups or those thought to be recovered from the disease. Problems in the second group appear to have a cause other than simple aging, possibly autoimmune, but longer follow-up is required to assess these patients. Evaluation of post-polio patients should be based on differentiating new neuromuscular disorders from exacerbations of the original disability. Although changes associated with aging cannot be halted, once post-polio syndrome is diagnosed, patients can be encouraged to follow appropriate dietary and exercise programs to maintain their present function, and they can be reassured of the relatively benign course of their problems.

Acute Disease↗
PubMedDate not supplied

Risk factors of violent death in rural Bangladesh, 1990-1999.

This study attempts to improve our understanding of the prevalence and determinants of violent death in rural Bangladesh. Data came from a demographic surveillance system covering a population of nearly 62,000 in 10 districts of the country. Findings reveal that drowning and homicide were the leading causes of death followed by traffic accident and suicide. Significant sociodemographic differentials in violent death existed. The probability to become the victim of violent death was 61.2 per 100,000 if the person was very young, male, poor, illiterate and Muslim. The author concludes that the public health program should consider the appropriate mechanisms to prevent many avoidable events of death in rural Bangladesh.

Accidents, Traffic↗
PubMed1999

Secondary school tobacco policy and prevention curricula in South Carolina.

The primary purpose of this study was to describe tobacco control policy in secondary schools in South Carolina, and sanctions imposed on students for violation of these policies; and to explore potential associations between policies and sanctions. A secondary purpose was to explore the use of tobacco education curricula in the state. This study employed a cross-sectional design in which two surveys were mailed to all secondary schools in South Carolina (n = 437): the School Principal Questionnaire (SPQ) and the Lead Health Education Teacher Questionnaire (LHETQ). The SPQ elicited information about tobacco control policies and the sanctions imposed on violators of such policies. The LHETQ was sent to lead health education teachers to elicit information about use of packaged curricula addressing tobacco use and prevention. Over 95% of respondents reported having school policies that prohibited use of tobacco inside buildings, and explicitly prohibited the use of cigarettes for students anywhere on school grounds. Sanctions imposed for violation of tobacco policy were severe. For a second offense, nearly 68% of students were suspended out-of-school or expelled, and for a third offense, almost 28% of students were expelled. There is some evidence to suggest that more stringent policies were associated with more severe sanctions. Cessation from tobacco programs were rarely used as a sanction, and in fact, tobacco education curricula were rarely used by health education teachers. In South Carolina secondary schools, tobacco policies are prevalent. Student violators of such policies are punished by means that potentially detract from their educational experience (e.g., out-of-school suspension, expulsion). It is recommended that school administrators and school health education teachers implement tobacco cessation programs as part of appropriate sanctions for violations of school tobacco use policy.

Adolescent↗
PubMed1985

Development and application of a long dynamic range nitrous oxide monitoring system.

The laboratory and field evaluation of a nitrous oxide monitor for an extremely wide range of cumulative exposures are reviewed. The passive sampling behavior and high analyte capacity show it to be useful for short-term and full workweek exposure monitoring. The monitor has application for both area and personnel surveillance. The principal criterion is for an accurate report of exposure time of the monitor. Application of the monitor to real workplace environments--with and without a reference method--demonstrated the ability of workweek monitoring as a valuable and potentially superior way of documenting exposure stress of employees. Environmental factors such as humidity and temperature variation are shown to have acceptably small effects on both short- and long-term exposure data; barometric pressure affects the data in a predictable manner. Paired dosimeters show good agreement in the workplace environment throughout the range of 6-40 cumulative hours of exposure. In both hospital and dental operating suites, work logistics and work group relationships were readily traceable on a week-by-week basis during a continuous weekly monitoring program. Source emissions and appropriate worker and work area exposure relationships were clearly evident, with appropriate reduction of all exposures as a result of an abbreviated work schedule. The ability to effectively track employee and area exposure excursions in an integrated weekly manner leads to a whole series of new applications and concepts of industrial hygiene surveillance. Such approaches could effectively replace the speculative statistical approaches currently in use with actual data on a cost effective basis.

Air Pollutants, Occupational↗
PubMed2005

Incarceration, addiction and harm reduction: inmates experience injecting drugs in prison.

Within Canadian prisons HIV/AIDS is becoming more common among inmates. While injection drug use in correctional facilities is documented to be a problem, qualitative research into the HIV risks faced by inmates is lacking. The goal of this research was to qualitatively examine HIV risk associated with injecting inside British Columbia prisons. A sample of 26 former male inmates who had recently used drugs within correctional facilities were recruited from a ongoing cohort study of injection drug users in Vancouver, Canada. Data for this study were collected through in-depth interviews conducted in 2001/2002. Analysis of these data involved identifying emergent themes and then exploring these central concepts in further interviews to confirm the accuracy of interpretation. The harms normally associated with drug addiction, and injection drug use are exacerbated in prison. Interpersonal relationships and the possession of exchangeable resources determine access to scarce syringes. The scarcity of syringes has resulted in patterns of sharing amongst large numbers of persons. Continual reuse of scarce syringes poses serious health hazards and bleach distribution is an inadequate solution. The findings of this study emphasize the need for effective harm reduction programs that provide an appropriate response to the problem of injection drug use among inmates.

Anecdotes as Topic↗
PubMed2003

Do resident physicians use antibiotics appropriately in treating upper respiratory infections? A survey of 11 programs.

We surveyed resident physicians of 11 primary care programs regarding the management of upper respiratory infections and antibiotic resistance. Although they viewed excess antibiotic use as the most important factor increasing resistance, they had little knowledge regarding antimicrobial resistance and were willing to prescribe antibiotics for common viral illnesses.

Data Collection↗
PubMed1990

Variation in risk for falls by clinical department: implications for prevention.

To examine rates of falls and injuries by clinical department, a retrospective analysis was performed of 874 inpatient falls during a one-year period in a 1,000-bed acute-care hospital. Incident reports were reviewed, and for those patients injured, medical records were abstracted. Fall rates were calculated by age, sex and service using total patient days as the denominator. During 1983, 874 falls occurred during 282,713 adult patient days (31/10(4) days). Fall rates were significantly higher (odds ratio = 2.12; 95% confidence interval [CI]: 1.84, 2.45) in the neuroscience and psychiatry departments (53/10(4) days) compared with other adult services combined (25/10(4) days); this difference persisted after direct adjustment for age. Differences by clinical department persisted throughout four additional years of surveillance, although fall rates for the oncology service increased. Injuries following falls occurred among 200 (22.8%) patients. These data indicate that falls are not random events, and that falls and injury prevention programs can be more appropriately focused by consideration of clinical department.

Accidental Falls↗
PubMed1995

Multidrug-resistant Mycobacterium tuberculosis in an HIV dental clinic.

OBJECTIVE: To investigate possible transmission of multidrug-resistant tuberculosis (MDR-TB) in a dental setting. DESIGN: A retrospective, descriptive study of dental workers (DWs), patients, and practice characteristics. PATIENTS: Two dental workers (DW1 and DW2) with acquired immunodeficiency syndrome and MDR-TB. SETTING: A hospital-based (Hospital X) human immunodeficiency virus (HIV) dental clinic in New York City. METHODS: To identify dental patients with tuberculosis (TB), patients treated in the dental clinic at Hospital X during 1990 were cross-matched with those listed in the New York City Department of Health Tuberculosis Registry. Mycobacterium tuberculosis isolates from both DWs and from dental patients with TB were tested for antimicrobial susceptibility and typed by restriction fragment length polymorphism (RFLP) analysis. Infection control practices were reviewed. RESULTS: M tuberculosis isolates infecting DW1 and DW2 were resistant to isoniazid and rifampin and had identical RFLP patterns. DW1 and DW2 worked in close proximity to each other in a small HIV dental clinic in Hospital X during 1990. Of 472 patients treated in the dental clinic in 1990, 41 (8.7%) had culture-proven M tuberculosis infection. Of these 41, 5 had isolates with resistance patterns similar to both DWs; however, for four available isolates, the RFLP patterns were different from the patterns of the DWs. Sixteen of the 41 patients received dental treatment while potentially infectious. Dental patients were not routinely questioned about TB by dental staff, nor were all dental staff screened routinely for TB. No supplemental environmental measures for TB were employed in the dental clinic in 1990. CONCLUSIONS: Our investigation suggests that MDR-TB transmission may have occurred between two DWs in an HIV dental clinic. Opportunities for transmission of TB among dental staff and patients were identified. TB surveillance programs for DWs and appropriate infection control strategies, including worker education, are needed to monitor and minimize exposure to TB in dental settings providing care to patients at risk for TB.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Population-based medical and disease management: an evaluation of cost and quality.

Reports by the Institute of Medicine and the Health Care Financing Administration have emphasized that the integration of medical care delivery, evidence-based medicine, and chronic care disease management may play a significant role in improving the quality of care and reducing medical care costs. The specific aim of this project is to assess the impact of an integrated set of care coordination tools and chronic disease management interventions on utilization, cost, and quality of care for a population of beneficiaries who have complementary health coverage through a plan designed to apply proactive medical and disease management processes. The utilization of health care services by the study population was compared to another population from the same geographic service area and covered by a traditional fee-for-service indemnity insurance plan that provided few medical or disease management services. Evaluation of the difference in utilization was based on the difference in the cost per-member-per-month (PMPM) in a 1-year measurement period, after adjusting for differences in fee schedules, case-mix and healthcare benefit design. After adjustments for both case-mix and benefit differences, the study group is $63 PMPM less costly than the comparison population for all members. Cost differences are largest in the 55-64 and 65 and above age groups. The study group is $115 PMPM lower than the comparison population for the age category of 65 years and older, after adjustments for case-mix and benefits. Health Plan Employer and Data Information Set (HEDIS)-based quality outcomes are near the 90th percentile for most indications. The cost outcomes of a population served by proactive, population-based disease management and complex care management, compared to an unmanaged population, demonstrates the potential of coordinated medical and disease management programs. Further studies utilizing appropriate methodologies would be beneficial.

Adolescent↗
PubMed2006

Health behaviors among American Indian/Alaska Native women, 1998-2000 BRFSS.

BACKGROUND AND OBJECTIVE: Minority populations, including American Indians and Alaska Natives (AI/AN), in the United States generally experience a disproportionate share of adverse health outcomes compared with whites. The prevalence of risk behaviors associated with these adverse health outcomes among AI/AN women is not well documented, especially for those who live outside areas serviced by Indian Health Service. We sought to describe the prevalence of selected health risk behaviors among AI/AN women, document the disparities between AI/AN women and all U.S. women, and demonstrate the efforts needed for AI/AN women to reach Healthy People 2010 goals. METHODS: Age-adjusted prevalence estimates for selected sociodemographic characteristics, current smoking, obesity, lack of leisure time physical activity, and binge drinking were calculated using Behavioral Risk Factor Surveillance System (BRFSS) data from 1998 to 2000, combined. Comparisons were made between prevalence estimates for AI/AN women and all women who participated in the BRFSS and Healthy People 2010 goals. RESULTS: The prevalences of current smoking (27.8%) and obesity (26.8%) were significantly higher among AI/AN women than among all U.S. women. AI/AN women did not meet Healthy People 2010 goals for current smoking, obesity, leisure time physical activity, or binge drinking. CONCLUSIONS: These data highlight both disparities in health risk behaviors between AI/AN women and all U.S. women and improvements needed for AI/AN women to meet Healthy People 2010 goals. This project demonstrates the overwhelming need for culturally appropriate and accessible prevention programs to address health risk behaviors associated with the leading causes of death among urbanized AI/AN women.

Alcohol Drinking↗