A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome.

OBJECTIVE: This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients. DESIGN: A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial. SETTING: Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN). PARTICIPANTS: Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits. INTERVENTIONS: All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120,000 IU (72 mg) of beta-carotene daily. Follow-up was quarterly at routine clinic visits. RESULTS: Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration <1.0 micromol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P < 0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P = 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P = 0.04) or higher baseline CD4 T-lymphocyte counts (P = 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P = 0.03). CONCLUSIONS: Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.

HIV, hepatitis C and risk behaviour in a Canadian medium-security federal penitentiary. Queen's University HIV Prison Study Group.

In a voluntary anonymous HIV and hepatitis C serology screen in a Canadian male medium security federal penitentiary, 68% of 520 prisoners volunteered a blood sample and 99% of those giving a blood sample completed a risk behaviour questionnaire which was linked numerically to the blood sample. Compared to previous screenings for HIV (4 years earlier), and hepatitis C (3 years earlier) in the same institution, HIV seroprevalence had risen from 1% to 2% and hepatitis C seroprevalence from 28% to 33%. The overwhelming risk association for hepatitis C was with drug use outside prison, although there was a small group of men who had only ever injected drugs inside prison, over half of whom had been infected with hepatitis C. The proportion of prisoners who had injected drugs in prison rose from 12% in 1995 to 24% in 1998. The proportion of surveyed individuals sharing injection equipment at some time in prison was 19%, and while HIV rates in the prison are currently low, HIV prevalence amongst Canadian street i.v. drug users is rising rapidly, underlining the need for urgent preventative measures in prisons.

Thrombotic thrombocytopenic purpura as an initial presentation of limited systemic sclerosis.

Thrombotic thrombocytopenic purpura (TTP) is a rare complication of scleroderma (systemic sclerosis, SSc). In the 5 reports documenting the association of TTP and SSc, the TTP syndrome developed on a background of well established SSc. We describe a 51-year-old woman with a 5 month history of an evolving connective tissue disease syndrome who presented initially with TTP, followed 4 months later by limited cutaneous SSc and Raynaud's phenomenon.

Lightweight, mobile E-mail for intra-clinic communication.

We have developed a mobile messaging system designed for use in the clinic setting. The system is designed to facilitate quick, informal, interactions that occur in a clinical setting, e.g., requests for assistance or information. The system includes safeguards to make sure that the sender of a message is aware if a message is not read in a timely fashion. Evaluation of the system shows message delivery was about 50% slower than our target of 30 seconds. Although the mobile device used is fairly small when combined with a radio unit, it is too bulky and users did not necessarily carry the system with them. This led to delays (over eleven minutes on average) before messages were seen. We expect that improvements in hardware and clinical software will lead to more common use of such adjunct software systems.

Malignant hyperthermia--a large kindred linked to the RYR1 gene.

Malignant hyperthermia susceptibility is genetically heterogeneous. The ryanodine receptor gene on the long arm of chromosome 19 represents an important candidate gene but not all families with malignant hyperthermia demonstrate ryanodine receptor mutations or linkage to this region of 19q. Linkage to chromosome 17 in the region of the adult muscle sodium channel alpha subunit gene has been suggested in some families; others are not linked to either of these loci. For most families the in vitro muscle contracture test remains the only reliable method of predicting susceptibility to malignant hyperthermia. We have performed linkage analysis in a large family group with malignant hyperthermia in which the in vitro muscle contracture test had been carried out using the procedure standardised by the European Malignant Hyperthermia Group. None of the published ryanodine receptor gene mutations associated with malignant hyperthermia susceptibility were detected in affected individuals but linkage to intragenic ryanodine receptor markers strongly suggest that this gene is involved in malignant hyperthermia susceptibility in this family. This enabled accurate predictive testing by DNA analysis in 11 untested subjects at 50% risk.

Voluntary anonymous linked study of the prevalence of HIV infection and hepatitis C among inmates in a Canadian federal penitentiary for women.

OBJECTIVE: To determine the seroprevalence of HIV infection and hepatitis C among inmates of a federal penitentiary for women. DESIGN: Voluntary, anonymous, linked, point-prevalence study involving testing of blood samples for antibodies to HIV and hepatitis C virus. PARTICIPANTS: All inmates of the multilevel security federal Prison for Women, Kingston, Ont., who volunteered to participate in the study. Inmates at this long-stay facility are from across Canada. OUTCOME MEASURE: Seroprevalence rate among participants of antibodies to HIV and hepatitis C virus. RESULTS: Of the 130 inmates available for study 113 (86.9%) agreed to donate a blood sample. One woman (0.9%) was HIV positive; 45 (39.8%) were positive for hepatitis C antibody. CONCLUSIONS: It is possible to obtain a high participation rate in a voluntary, anonymous, linked point-prevalence study in a long-stay penitentiary. The HIV seroprevalence rate of 0.9% is lower than that found in studies in provincial (short-stay) prisons. However, the high rate of antibodies to hepatitis C suggests a significant level of risk behaviour, most likely injection drug use, and suggests the potential for a rapid increase in the rate of HIV infection should the number of newly admitted HIV-positive inmates who use injection drugs rise.

The cardiovascular pathology of phospholipid antibodies: An illustrative case and review of the literature.

There is some confusion in the literature regarding the pathology associated with phospholipid antibodies. These antibodies, formed to a number of negatively charged phospholipids, are associated with an increased tendency to both arterial and venous thrombosis and embolism and may be manifest in a primary syndrome, a syndrome secondary to systemic lupus erythematosis, or as an isolated phenomenon, which may or may not be associated with thromboembolism. The pathogenesis of thrombosis in these syndromes has not yet been elucidated. Indeed it is not even clearly established that the antibodies have a pathogenic role, as opposed to existing as an epiphenomenon or arising secondary to some form of vascular damage. Clarification of the reported pathologic literature is needed as a basis for studying the pathogenesis of thrombosis in these syndromes, and therefore we present a review of papers that have reported pathology in association with phospholipid antibodies. In order to illustrate the review, we present a typical case of primary antiphospholipid antibody syndrome.

A comparative study of signal versus aggregate methods of outcome measurement based on the WOMAC Osteoarthritis Index. Western Ontario and McMaster Universities Osteoarthritis Index.

OBJECTIVE: To compare signal versus aggregate measurement strategies using the VA3.0S version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index. METHODS: Seventy patients with OA of the knee were asked to identify a signal item for each of the 3 dimensions of the WOMAC OA Index at baseline and termination of a 12-week, double blind, randomized, controlled trial. RESULTS: The signal method detected statistically significant alterations in health status at relatively small sample sizes and with a relative efficiency close to or at unity. In addition to a low prevalence of deterioration in nonsignal items, we observed some inconsistency in signal selection. CONCLUSION: Signal methods of measurement may provide an alternative approach to outcome measurement provided issues of nonsignal deterioration and the consistency of signal selection can be addressed.

Clinicopathologic correlations of antiphospholipid antibodies. An autopsy study.

The clinicopathologic correlations of antiphospholipid antibodies (aPLs) have so far only been examined in case reports and highly selected series. This study assessed the incidence of aPLs in 156 consecutive, unselected autopsies and correlated the pathological findings with the clinical histories. Elevations of aPLs were found in 20.5% of the autopsy population, compared with 9.6% of age- and sex-matched controls and 2% of healthy normal subjects. There was a higher incidence of thromboembolic disease in patients with elevated aPL levels compared with those without, but the histology of thrombi was similar in both groups, with no evidence of vasculitis in the aPL-positive individuals. Patients with transient ischemic attacks and cardiac valve lesions had a high incidence of aPLs, as reported previously. Five cases that fit the designation of primary antiphospolipid antibody syndrome were noted. The study concludes that aPLs are relatively common in a hospital autopsy population and are commonly associated with thromboembolic events, that the thromboemboli are not associated with vasculitis, and that primary aPL syndrome is more common than generally appreciated.

Pancreatitis arthritis with periarticular fat necrosis.

We describe the case of a 76-year-old man hospitalized for 14 months because of a complicated hip fracture who developed pancreatitis and polyarthritis. He had no evidence of subcutaneous fat necrosis away from his joints and his pancreatitis was virtually asymptomatic otherwise. Polyarthritis is a rare complication of this disorder, and rarer still is polyarthritis without evidence of subcutaneous fat necrosis elsewhere.

A multicenter study of tenoxicam and diclofenac in patients with osteoarthritis of the knee.

OBJECTIVE: To conduct the first Canadian study of the comparative efficacy and safety of tenoxicam and diclofenac in patients with primary osteoarthritis (OA) of the knee. METHODS: Tenoxicam 20 mg per os once daily (po od) was compared to diclofenac (Voltaren) 50 mg per os 3 times a day (po tid) in a 12-week, double blind, randomized, controlled, multicenter, parallel trial. The primary outcome measure was the pain dimension of the WOMAC OA Index. Following an initial screening visit and a 3 to 7 day NSAID-free washout period (i.e., baseline), patients were assessed at Weeks 2, 4 and 12; assessments including some 15 efficacy variables and safety variables. RESULTS: Ninety-eight patients [tenoxicam (n = 48), diclofenac (n = 50)] participated in the trial. Statistically significant (p < or = 0.05) improvements in all 3 dimensions of the WOMAC OA Index and six efficacy variables were noted in both treatment groups. No significant between drug differences were noted on any efficacy variable. Significantly fewer patients reported adverse events in the tenoxicam group (21 vs 33, p = 0.03). CONCLUSION: Tenoxicam is efficacious and well tolerated in patients with OA of the knee. In this group of patients it was similar in efficacy and superior in tolerability to diclofenac 150 mg/day (50 mg tid). Thus the benefit/risk ratio of tenoxicam was superior to that of diclofenac in this study.

Relationship between cell adherence and proteoglycan synthesis in cultures of human peripheral blood mononuclear cells: effects of concanavalin A.

Human, blood-derived mononuclear cells (MC), stimulated with Concanavalin A (Con A), synthesized a chondroitin sulfate (CS) proteoglycan (PG), which was elaborated largely by T-cells. Following Con A stimulation, the majority of MC adhered to the culture dish by day 2, but as incubation progressed to day 10 the proportion of non-adherent (NAd) MC increased in a fashion which approximately paralleled the accumulation of PG in the medium. Cell kinetic studies suggest that, following Con A stimulation, there was an inverse relationship between the amount of newly synthesized cellular PG and adherence, which appears to be related to a reciprocal effect on PG synthesis of the declining adherent (Ad) cell density with time of culture. In the stimulated cultures, NAd cells contained much more newly synthesized CS/cell than Ad cells up to day 6 of incubation. Cell type analysis, using monoclonal antibodies against specific cell surface markers, suggested that the higher PG synthesis in the NAd population may, at least in part, be due to a greater proportion of T-helper cells.

Double-blind randomized controlled trial of flurbiprofen-SR (ANSAID-SR) and diclofenac sodium-SR (Voltaren-SR) in the treatment of osteoarthritis.

A six week, double-blind, randomized, parallel group, multicentre study was conducted in 85 patients with osteoarthritis of the knee and hip to compare the efficacy, tolerability, and safety of Flurbiprofen-SR 200 mg with Diclofenac Sodium-SR 100 mg. Between group comparisons, based on change scores from baseline, we detected no significant differences between the two drugs with respect to efficacy for the majority of outcome measures. There was no significant difference between the groups in the proportion of patients experiencing at least one adverse medical event or in terminations from treatment. We conclude that Flurbiprofen-SR 200 mg is similar in efficacy, tolerability, and safety to Diclofenac Sodium-SR in this trial.