Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

Determinants In HIV Counselling And Testing In Couples In North Rift Kenya

Background: Voluntary HIV counselling and testing (VCT) has been shown to be an acceptable and effective tool in the fight against HIV/AIDS. Couple HIV Counselling and Testing (CHCT) however, is a relatively new concept whose acceptance and efficacy is yet to be determined.Objective: To describe factors that motivate couples to attend VCT as a couple. Design: A cross sectional qualitative study.Setting: Moi Teaching and Referral Hospital and Moi University, School of Medicine, Eldoret, KenyaSubjects: Seventy one individuals were interviewed during KII (9) and dyad interviews (31 couples). Ten FGDs involving a total of 109 individuals were held. Results: Cultural practices, lack of CHCT awareness, stigma and fear of results deter CHCT utilisation. Location of centre where it is unlikely to be associated with HIV testing, qualified professional staff and minimal waiting times would enhance CHCT utilisation.Conclusions: CHCT as a tool in the fight against HIV/AIDS in this region of Kenya is feasible as the factors that would deter couples are not insurmountable

Stakeholders perception of HIV sero-discordant couples in western Kenya

Objective: To describe the perceptions of key stakeholders regarding the counselling needs of HI V sero-discordant couples as part of preparation for a clinical trial involving HIV sero-discordant couples. Design: Qualitative study using key informant and couple interviews. Setting: Moi Teaching and Referral Hospital (MTRH). Subjects: A purposive sample of nine key informants and 31 couple interviews totaling 71 participants. The couple interviews consisted of HI V untested, HI V concordant (positive and negative) and discordant couples. Results: Seventy one individuals participated in nine key informant and 31 couple interviews. The responses identified the following as key issues in counselling HIV discordant couples: The need for education on the meaning of HI V sero-discordancy including potential sources of infection; assistance in disclosing HIV test results to one\'s partner; discussion of the stigma surrounding formula feeding. Overall, the participants supported safer sexual practices in discordant partnerships. Conclusions: Psychosocial support of HI V sero-discordant couples should include messages about the meaning, mechanisms and implications of sero-discordancy. Culturally appropriate HI Vdisclosure and safer sex messages are also needed to support these partnerships. East African Medical Journal Vol. 85 (7) 2008: pp. 326-33

A Needs Assessment to Build International Research Ethics Capacity at Moi University

International Research Ethics Partnership. This online version is the post-print version (final, peer-reviewed and accepted for publication version) of the published article. For the published version, refer to the article citation within the item record.International collaborators in biomedical sciences face ethical challenges in the design,review, and conduct of research. Challenges include differences in research ethics capacity, cultural differences in interpretation and application of ethical principles, and cooperation between ethics review boards at collaborating institutions. Indiana University School of Medicine (Indianapolis, USA) and Moi University Faculty of Health Sciences (Eldoret, Kenya)developed a Memorandum of Understanding (MOU) to establish greater cooperation between their ethics review boards, followed by a joint needs assessment to assess barriers to implementing the MOU. Focus groups and interviews at each institution revealed that while each side verbalized understanding and respect for the other's culture, there were misunderstandings deeply rooted in each culture that could potentially derail the collaboration. Although the participants at each university agreed on the major principles and issues in research ethics and on the importance attributed to them, a more in-depth evaluation of the responses revealed important differences. Methods to address these misunderstandings are outlined in the recommended Best Practices.Fogarty International Center at the NIH, Indiana University Division of General Internal Medicine and Geriatrics, Indiana University School of Medicine, Indiana University International Development Fund, Indiana Genomics Initiative, Lilly Endowment, Inc

Admission Characteristics, Diagnoses And Outcomes Of HIV-Infected Patients Registered In An Ambulatory HIV-Care Programme In Western Kenya

Objective: To determine admissions diagnosis and outcomes of HIV-infected patients attending AMPATH ambulatory HIV-care clinics. Design: Prospective cohort study. Setting: Academic Model for Prevention and Treatment of HIV/ AIDS (AMPATH) ambulatory HIV-care clinic in western Kenya. Results: Between January 2005 and December 2006, 495 HIV-infected patients enrolled in AMPATH were admitted. Median age at admission was 38 years (range: 19 - 74), 62% females, 375 (76%) initiated cART a median 56 days (range: 1- 1288) before admission. Majority (53%) had pre-admission CD4 counts 200 cells/ml. Common admissions diagnoses were: tuberculosis (27%); pneumonia (15%); meningitis (11%); diarrhoea (11%); malaria (6%); severe anaemia (4%); and toxoplasmosis (3%). Deaths occurred in 147 (30%) patients who enrolled at AMPATH a median 44 days (range: 1 - 711) before admission and died a median 41 days (range: 1 -713) after initiating cART. Tuberculosis (27%) and meningitis (14%) were the most common diagnoses in the deceased. Median admission duration was six days (range: 1 - 30) for deceased patients and eight days (range: I - 44) for survivors (P=0.0024). Deceased patients enrolled in AMPATH or initiated cART more recently, had lower CD4 counts and were more frequently lost to follow-up than survivors (

Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by motor neuron loss, resulting in muscle wasting, paralysis and eventual death. A key pathological feature of ALS is cytoplasmically mislocalized and aggregated TDP-43 protein in >95% of cases, which is considered to have prion-like properties. Historical studies have predominantly focused on genetic forms of ALS, which represent ∼10% of cases, leaving the remaining 90% of sporadic ALS relatively understudied. Additionally, the role of astrocytes in ALS and their relationship with TDP-43 pathology is also not currently well understood. We have therefore used highly enriched human induced pluripotent stem cell (iPSC)-derived motor neurons and astrocytes to model early cell type-specific features of sporadic ALS. We first demonstrate seeded aggregation of TDP-43 by exposing human iPSC-derived motor neurons to serially passaged sporadic ALS post-mortem tissue (spALS) extracts. Next, we show that human iPSC-derived motor neurons are more vulnerable to TDP-43 aggregation and toxicity compared with their astrocyte counterparts. We demonstrate that these TDP-43 aggregates can more readily propagate from motor neurons into astrocytes in co-culture paradigms. We next found that astrocytes are neuroprotective to seeded aggregation within motor neurons by reducing (mislocalized) cytoplasmic TDP-43, TDP-43 aggregation and cell toxicity. Furthermore, we detected TDP-43 oligomers in these spALS spinal cord extracts, and as such demonstrated that highly purified recombinant TDP-43 oligomers can reproduce this observed cell-type specific toxicity, providing further support to a protein oligomer-mediated toxicity hypothesis in ALS. In summary, we have developed a human, clinically relevant, and cell-type specific modelling platform that recapitulates key aspects of sporadic ALS and uncovers both an initial neuroprotective role for astrocytes and the cell type-specific toxic effect of TDP-43 oligomers

A model for extending antiretroviral care beyond the rural health centre

<p>Abstract</p> <p>Background</p> <p>A major obstacle facing many lower-income countries in establishing and maintaining HIV treatment programmes is the scarcity of trained health care providers. To address this shortage, the World Health Organization has recommend task shifting to HIV-infected peers.</p> <p>Methods</p> <p>We designed a model of HIV care that utilizes HIV-infected patients, community care coordinators (CCCs), to care for their clinically stable peers with the assistance of preprogrammed personal digital assistants (PDAs). Rather than presenting for the standard of care, monthly clinic visits, in this model, patients were seen every three months in clinics and monthly by their CCCs in the community during the interim two months. This study was conducted in Kosirai Division, western Kenya, where eight of the 24 sub-locations (defined geographic areas) within the division were randomly assigned to the intervention with the remainder used as controls.</p> <p>Prior to entering the field, CCCs underwent intensive didactic training and mentoring related to the assessment and support of HIV patients, as well as the use of PDAs. PDAs were programmed with specific questions and to issue alerts if responses fell outside of pre-established parameters. CCCs were regularly evaluated in six performance areas. An impressionistic analysis on the transcripts from the monthly group meetings that formed the basis of the continuous feedback and quality improvement programme was used to assess this model.</p> <p>Results</p> <p>All eight of the assigned CCCs successfully passed their training and mentoring, entered the field and remained active for the two years of the study. On evaluation of the CCCs, 89% of their summary scores were documented as superior during Year 1 and 94% as superior during Year 2. Six themes emerged from the impressionistic analysis in Year 1: confidentiality and "community" disclosure; roles and responsibilities; logistics; clinical care partnership; antiretroviral adherence; and PDA issues. At the end of the trial, of those patients not lost to follow up, 64% (56 of 87) in the intervention and 52% (58 of 103) in the control group were willing to continue in the programme (p = 0.26).</p> <p>Conclusion</p> <p>We found that an antiretroviral treatment delivery model that shifted patient monitoring and antiretroviral dispensing tasks into the community by HIV-infected patients was both acceptable and feasible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov ID NCT00371540</p

Risk factors for death in HIV-infected adult african patients recieving anti-retroviral therapy

Objective: To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART).Design: Retrospective Case-control study.Setting: The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya.Results: Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p&lt;0.0148). Mediantime from enrollment at AMPATH to initiation of ART was two weeks for both groups while median time on ART was eight weeks for the deceased and fourty two weeks for the living (p&lt;0.0001). Patients with CD4 cell counts &lt;100/mm3 were more likely to die than those with counts &gt;100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p&lt;0.003). Patientsattending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p&lt;0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level &lt;10 grams% were associated with time to death while age, marital status, educational level, employment status andweight were not.Conclusion: Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital

Lipodystrophy in HIV infected patients on long term Antiretroviral therapy in western Kenya

Changes in fat distribution has been observed in patients on highly active antiretroviral therapy. The frequently reported drugs that cause fat redistribution are stavudine and protease inhibitors. Stavudine also causes a high incidence of metabolic complications and peripheral neuropathy