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PubMed1997

Tuberculosis care in community care organizations in sub-Saharan Africa: practice and potential.

SETTING: Community care organizations in sub-Saharan Africa. OBJECTIVES: To evaluate current tuberculosis (TB) care in community health care organizations in sub-Saharan Africa, to assess their potential contribution to tuberculosis care, and to develop a model for expanded community participation in effective TB control. DESIGN: Quantitative assessment of tuberculosis care and cross-sectional assessment of qualitative measures in 14 community care organizations in Uganda, Zambia, South Africa and Malawi. RESULTS: The community care organizations assessed mainly provided care for human immunodeficiency virus (HIV) and aquired immune deficiency syndrome (AIDS) patients, and received funding from non-governmental organizations. Shortcomings in tuberculosis care included delays in diagnosis (which was often not based on sputum examination), drug shortages, low completion rates, high default rates, inadequate recording, little interaction with government tuberculosis programmes, and inadequate training of staff. However, one organization that provided primarily tuberculosis care and collaborated closely with the district tuberculosis programme and hospital attained a high treatment completion rate. The strong points of the community care organizations that favour a potential role of community participation in tuberculosis care were accessibility and staff motivation. CONCLUSION: Despite most community care organizations' shortcomings in tuberculosis care, they do have the potential to improve the care of tuberculosis patients, thus reducing the load on overstretched health facilities. Their potential impact on tuberculosis control depends on their population coverage and sustainability. HIV/AIDS community care organizations with strengthened management of tuberculosis care could serve as a model for expanded community participation in tuberculosis control. Operational research is needed to assess the feasibility and cost-effectiveness of community-based TB care.

AIDS-Related Opportunistic Infections↗
PubMed2000

Methylphenylethynylpyridine (MPEP) Novartis.

SIBIA and Novartis are investigating the use of excitatory amino acid agonists and antagonists for the metabotropic receptor and the ionotropic receptors AMPA and NMDA. Preliminary experiments indicate they may have potential in the treatment of epilepsy, stroke, anxiety, pain and neurodegenerative disease. Methylphenylethynylpyridine (MPEP) is the lead compound in the series [347212]. Other compounds in the series that arose from the collaboration were SIB-1893, and its equipotent analog, SIB-1757, both of which are subtype-selective, potent antagonists of mGluR5. Chemical derivation of SIB-1893 resulted in the discovery of MPEP, a selective, systemically active noncompetitive mGluR5 antagonist. Studies using these agents have yielded data to support the involvement of mGluR5 in inflammatory mechanical hyperalgesia [311829], [311828], [311823], [311880], [319655]. MPEP is the most potent of these compounds with an IC50 value of 12 nM for inhibition of quisqualate-stimulated phosphoinositide hydrolysis in recombinant human mGluR5a-expressing cells. MPEP exhibited no cross reactivity with mGluR1 and other mGluRs, or against representative NMDA, AMPA and kainate receptors up to concentrations of 100 microM. The compound, administered orally (100 mg/kg) produced a 70% reversal of mechanical hyperalgesia in the Freund's complete adjuvant model of inflammatory pain [319261]. By October 1999, investigations with SIB-1757 and SIB-1893 had been discontinued in favor of MPEP [347212].

Analgesics, Non-Narcotic↗
PubMed1998

Synaptic changes in rat maculae in space and medical imaging: the link.

Two different space life sciences missions (SLS-1 and SLS-2) have demonstrated that the synapses of the hair cells of rat vestibular maculae increase significantly in microgravity. The results also indicate that macular synapses are sensitive to stress. These findings argue that vestibular maculae exhibit neuroplasticity to macroenvironmental and microenvironmental changes. This capability should be clinically relevant to rehabilitative training and/or pharmacological treatments for vestibular disease. The results of this ultrastructural research also demonstrated that type I and type II hair cells are integrated into the same neuronal circuitry. The findings were the basis for development of three-dimensional reconstruction software to learn details of macular wiring. This software, produced for scientific research, has now been adapted to reconstruct the face and skull directly from computerized tomography scans. In collaboration with craniofacial reconstructive surgeons at Stanford University Medical Center, an effort is under way to produce a virtual environment workbench for complex craniofacial surgery. When completed, the workbench will help surgeons train for and simulate surgery. The methods are patient specific. This research illustrates the value of basic research in leading to unanticipated medical applications.

Acoustic Maculae↗
PubMed2002

Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice.

Dual inactivation of PTEN and INK4a/ARF tumor suppressor genes is a common feature observed in a broad spectrum of human cancer types. To validate functional collaboration between these genes in tumor suppression, we examined the biological consequences of Pten and/or Ink4a/Arf deficiency in cells and mice. Relative to single mutant controls, Ink4a/Arf-/-Pten+/- mouse embryonic fibroblast cultures exhibited faster rates of growth in reduced serum, grew to higher saturation densities, produced more colonies upon low density seeding, and showed increased susceptibility to transformation by oncogenic H-Ras. Ink4a/Arf deficiency reduced tumor-free survival and shortened the latency of neoplasias associated with Pten heterozygosity, specifically pheochromocytoma, prostatic intraepithelial neoplasia, and endometrial hyperplasia. Compound mutant mice also exhibited an expanded spectrum of tumor types including melanoma and squamous cell carcinoma. Functional synergy between Ink4a/Arf and Pten manifested most prominently in the development of pheochromocytoma, prompting an analysis of genes and loci implicated in this rare human neoplasm. The classical pheochromocytoma genes Ret, Vhl, and Nf-1 remained intact, a finding consistent with the intersection of these genes with pathways engaged by Pten and Ink4a/Arf. Notably, conventional and array-comparative genomic hybridization revealed frequent loss of distal mouse chromosome 4 in a region syntenic to human chromosome 1p that is implicated in human pheochromocytoma. This study provides genetic evidence of collaboration between Pten and Ink4a/Arf in constraining the growth and oncogenic transformation of cultured cells and in suppressing a wide spectrum of tumors in vivo.

Adrenal Gland Neoplasms↗
PubMed2001

An approach to modelling in immunology.

Like most other fields in biology, immunology has been revolutionised by the techniques of molecular biology and the resulting explosion in available experimental data. It is argued that efforts to integrate the data to gain insight into how various subsystems in the immune system interact and function require mathematical modelling and computer simulation in close collaboration with experimentalists. This paper illustrates some of the techniques available for modelling immune systems, and highlights the issues that should be borne in mind by anyone starting down the modelling path.

Animals↗
PubMed2001

The role of correctional officers in multidisciplinary mental health care in prisons.

Prisons have become the homes of thousands of inmates who have mental disorders. The stress of incarceration can cause morbidity among these individuals, resulting in more severe symptoms and more disruptive behavior. Effective treatment for such inmates often involves services provided by a multidisciplinary treatment team that includes correctional officers. Correctional officers can assist in observations and interventions, and they play a unique role on specialized housing units. Successful collaboration between correctional officers and treatment teams requires a foundation of mutual respect, shared training, and ongoing communication and cooperation. With these elements in place, correctional officers can assist the treatment team and make important and constructive contributions to the assessment and management of offenders who have mental disorders.

Adult↗
PubMed2003

The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital.

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) in Toronto, which began on Mar. 7, 2003, resulted in extraordinary public health and infection control measures. We aimed to describe the psychological and occupational impact of this event within a large hospital in the first 4 weeks of the outbreak and the subsequent administrative and mental health response. METHODS: Two principal authors met with core team members and mental health care providers at Mount Sinai Hospital, Toronto, to compile retrospectively descriptions of the experiences of staff and patients based on informal observation. All authors reviewed and analyzed the descriptions in an iterative process between Apr. 3 and Apr. 13, 2003. RESULTS: In a 4-week period, 19 individuals developed SARS, including 11 health care workers. The hospital's response included establishing a leadership command team and a SARS isolation unit, implementing mental health support interventions for patients and staff, overcoming problems with logistics and communication, and overcoming resistance to directives. Patients with SARS reported fear, loneliness, boredom and anger, and they worried about the effects of quarantine and contagion on family members and friends. They experienced anxiety about fever and the effects of insomnia. Staff were adversely affected by fear of contagion and of infecting family, friends and colleagues. Caring for health care workers as patients and colleagues was emotionally difficult. Uncertainty and stigmatization were prominent themes for both staff and patients. INTERPRETATION: The hospital's response required clear communication, sensitivity to individual responses to stress, collaboration between disciplines, authoritative leadership and provision of relevant support. The emotional and behavioural reactions of patients and staff are understood to be a normal, adaptive response to stress in the face of an overwhelming event.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Modified immunoassays for polyether toxins: implications of biological matrixes, metabolic states, and epitope recognition.

Polyether marine toxins are responsible for the seafood intoxication phenomena known as neurotoxic shellfish poisoning (due to brevetoxins), ciguatera (due to ciguatoxin), and diarrheic shellfish poisoning (due to okadaic acid). Using traditional techniques of hapten (pure toxin) conjugation to protein to create complete antigen, animal immunization and antibody isolation, and specific antibody subpopulation purification, discriminating antibodies have been isolated that detect brevetoxins and ciguatoxin, but not okadaic acid, in a dose-dependent fashion. Using microorganic chemistry and purified toxins, a unique set of tools has been created for the study of polyether ladder toxin accumulation; depuration; and specific site localization in tissues, food sources, and clinical samples. Developed test protocols can detect toxin in dinoflagellate cells, in extracts from food sources, in seawater and culture media, and in human serum samples. Enzyme-linked immunosorbent assay protocols developed for eventual collaborative testing have been successful in limited applications within the laboratory (correlation coefficient of 0.92 excluding 2 outliers), and alternative formats are being developed to optimize the basic test for use in research laboratories, regulatory laboratories, and field inspections.

Antibodies↗
PubMed2003

Students with chronic illnesses: guidance for families, schools, and students.

Developed by a work group representing several nonprofit and federal health and education organizations, Students with Chronic Illnesses: Guidance for Families, Schools, and Students provides cross-cutting action steps to facilitate full participation in learning and other school activities by students with chronic diseases. Between 10% and 15% of children in the United States are affected by at least one chronic disease. This guide offers practical tips to help ensure that schools are responsive to the health needs of children with chronic illnesses. Children with chronic health conditions are more likely to miss days from school, need specialized health care, and require special education services or homebound teaching. School health advocates agree that meeting the needs of these children requires collaboration among the students, their families, school personnel, and community health care providers. Such efforts can help students establish better attendance, improve their alertness and physical stamina, and face fewer restrictions on physical activity at school and fewer medical emergencies. The guide addresses issues such as routine and urgent care needs of students, medication access and administration, and school personnel training to ensure compliance with applicable local, state, and federal regulations. While emphasizing the value of adopting general policies for supporting students with chronic conditions, the guide also encourages schools to develop and implement condition-specific and individualized protocols. The responsibilities of family members, school district officials, teachers and school administrators, and students are outlined to help each constituent fulfill these objectives.

Child↗
PubMed2002

[Functional training of enfeebled elderly in their own homes. A cross-disciplinary and cross-sectorial model].

INTRODUCTION: Today it is a proven fact that rehabilitation of elderly people suffering from illness and loss of functional faculties helps. The very weakest group is unable to make use of existing offers of rehabilitation. The objective of the investigation was to develop and test a model for functional training of weak, elderly people in their own home. MATERIALS AND METHODS: The process was assessed in eight cases. The elderly were selected consecutively on discharge from two geriatric wards as those who could be rehabilitated, but who were too weak to undergo the usual process. Training was supported by the regular home help assigned to the old person and carried out under the supervision of a geriatrician and a physiotherapist. An external-qualitative evaluation of the programme is published elsewhere. RESULTS: In collaboration with the elderly people and the home help, the project team succeeded in forming and implementing a training scheme based on the expectations that the elderly people had to rehabilitation. Of the eight patients taking part in the investigation, five realised their wishes for a greater degree of mobility and for being able to get out-of-doors. DISCUSSION: The model developed, where the home help acts as the central figure in the implementation of the rehabilitation of enfeebled, old persons under the supervision of a physiotherapist and a geriatrician, is an interesting alternative to the existing programmes for rehabilitation of elderly people in their own home. The work should be investigated in monitored tests, with the focus on effectiveness and consumption of resources.

Activities of Daily Living↗
PubMed1982

Genetic control of sensitivity to moloney leukemia virus in mice. VI. Involvement of virus-specific T helper cells collaborating with B cells.

T cell responses to Moloney virus involve cytolytic and helper lymphocytes. In contrast to specific cytolytic T lymphocytes, few studies have been devoted to the characteristics of helper T cells for antibody production. The present experiments describe an assay for Moloney virus-specific help for B cells using dinitrophenylated virus. This method, using the Moloney virus as a carrier in a hapten-carrier system, allows to definition of the specific helper function of antibody responses. T helper cells were induced in murine sarcoma virus or inactivated Moloney murine leukemia virus-primed spleens or lymph nodes. T helper function was due to Thy-1.2, Lyt-1+2- cells and was macrophage-dependent. It was stimulated by whole virus of Moloney gp71 envelope protein but not Moloney p30 internal protein. Cross-reactive stimuli were obtained with other dinitrophenylated type C viruses. High and low responses were correlated respectively with resistance and susceptibility to Moloney leukemia virus. Cultures of helper T cells with preserved activity have been established and maintained for one month.

Animals↗
PubMed1991

Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group.

Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed.

Autoradiography↗
PubMed2001

Bone mineral density, biochemical markers of bone turnover, and hormonal status in men with systemic lupus erythematosus.

The aim of this study was to evaluate bone mineral density (BMD), biochemical markers of bone turnover, and hormone levels in men with systemic lupus erythematosus (SLE). BMD at L2-L4 lumbar vertebrae (LS), left proximal femur neck, and radius at the ultradistal and mid-33% region was measured by dual-energy X-ray absorptiometry in 23 men with SLE (mean age, disease duration, and cumulative corticosteroid dose were 45.6 years, 11.9 years, and 33.410 g, respectively) and 40 healthy, age- and sex-matched controls. Biochemical markers of bone turnover, parathyroid hormone and 25-hydroxyvitamin D (25-OH-D), testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels were measured. There was no difference in BMD between the SLE and control group. The prevalence of osteoporosis was 17.4% (4 out of 23), found at LS. Biochemical markers of bone turnover were within the reference range. There was a high prevalence of hypovitaminosis D (65.2%), hypotestosteronism (62.5%), and hypodehydroepiandrosterone sulfate (100%). There was no correlation between BMD and duration of disease, corticosteroid doses, SLE Disease Activity Index (SLEDAI), SLE Collaboration Clinics/American College of Rheumatology (SLICC/ARC) damage index, or markers of bone turnover. Bone-specific alkaline phosphatase (BSAP) (r, -0.500; P=0.018) and DHEAS (r, -0.511; P=0.013) correlated with the daily corticosteroid dose. Despite corticosteroid therapy, bone mass in men with SLE was not decreased.

Aged↗
PubMed2001

Surveillance of hospital-acquired infection in the Republic of Ireland: past, present and future.

There is increasing interest in the surveillance of hospital-acquired infection (HAI) in the Republic of Ireland due to a greater awareness of the consequences of antibiotic resistance, and consumer pressure in the form of public expectations of the quality of health care. To date there have been no nationwide prospective surveillance projects but surveillance has taken place in the form of participation in international and national studies, and the description of local outbreaks. Infection control teams and others have participated in projects such as a European study of HAI in intensive care units conducted in 1992, the second national prevalence study conducted in the UK in 1993 and two surveys of methicillin-resistant Staphylococcus aureus (MRSA) carried out in 1995 and 1999, the latter involving colleagues in Northern Ireland. There have been a number of local surveys of antibiotic-resistant bacteria including the molecular characterization of MRSA in Dublin hospitals, vancomycin-resistant enterococci, and Gram-negative bacteria such as Enterobacter spp. and Serratia spp. affecting compromised patients such as bone marrow transplant recipients. In the future, it is hoped to standardize case definitions, automate data entry, increase collaboration with surveillance initiatives in Northern Ireland and link in with European networks such as EARSS and HELICS. Apart from the need to improve the quality of health care in Irish hospitals, approximate costings suggest that there are potential savings of 7.5 pounds sterling -15 pounds sterling m to be made following a reduction of HAI rates of 15%.

Cross Infection↗
PubMed2002

The Protein Information Resource: an integrated public resource of functional annotation of proteins.

The Protein Information Resource (PIR) serves as an integrated public resource of functional annotation of protein data to support genomic/proteomic research and scientific discovery. The PIR, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the PIR-International Protein Sequence Database (PSD), the major annotated protein sequence database in the public domain, containing about 250 000 proteins. To improve protein annotation and the coverage of experimentally validated data, a bibliography submission system is developed for scientists to submit, categorize and retrieve literature information. Comprehensive protein information is available from iProClass, which includes family classification at the superfamily, domain and motif levels, structural and functional features of proteins, as well as cross-references to over 40 biological databases. To provide timely and comprehensive protein data with source attribution, we have introduced a non-redundant reference protein database, PIR-NREF. The database consists of about 800 000 proteins collected from PIR-PSD, SWISS-PROT, TrEMBL, GenPept, RefSeq and PDB, with composite protein names and literature data. To promote database interoperability, we provide XML data distribution and open database schema, and adopt common ontologies. The PIR web site (http://pir.georgetown.edu/) features data mining and sequence analysis tools for information retrieval and functional identification of proteins based on both sequence and annotation information. The PIR databases and other files are also available by FTP (ftp://nbrfa.georgetown.edu/pir_databases).

Amino Acid Sequence↗
PubMed1992

Epidemiologic approach to the study of dementing diseases: a nested case-control study in European incidence studies of dementia.

In 1994 several European studies will have available risk factor information on incident cases of dementia collected in prospective community-based studies. These centers will collaborate in a nested-case control study based on the pooled cases and a sample of the non-diseased respondents. This paper describes the general design and the risk factors to be studied in a European nested case-control study of Alzheimer's disease and vascular dementia.

Aged↗
PubMed2005

Analysis of alcoholism data using support vector machines.

A supervised learning method, support vector machine, was used to analyze the microsatellite marker dataset of the Collaborative Study on the Genetics of Alcoholism Problem 1 for the Genetic Analysis Workshop 14. Twelve binary-valued phenotype variables were chosen for analyses using the markers from all autosomal chromosomes. Using various polynomial kernel functions of the support vector machine and randomly divided genome regions, we were able to observe the association of some marker sets with the chosen phenotypes and thus reduce the size of the dataset. The successful classifications established with the chosen support vector machine kernel function had high levels of correctness for each prediction, e.g., 96% in the fourfold cross-validations. However, owing to the limited sample data, we were not able to test the predictions of the classifiers in the new sample data.

Alcoholism↗