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Biomedical subjects

I Grant

Publications and source records attributed to I Grant.

At least 19 recordsLinked to original sources

Diminished somatostatin gene expression in individuals with HIV and major depressive disorder.

In analyzing the expression of 15 candidate genes for HIV encephalitis (HIVE) by the presence or absence of major depressive disorder (MDD), we noted significant reductions in the expression of four cytoskeletal genes and somatostatin. Whereas disruption of cytoskeletal genes has been noted in HIVE, dysregulation of somatostatin has not, indicating that dysregulation of somatostatin is part of the molecular pathologic process of MDD in the setting of HIV.

AIDS Dementia Complex↗

Cognitive deficits and degeneration of interneurons in HIV+ methamphetamine users.

The cellular basis for cognitive deficits in HIV+ patients with and without a history of methamphetamine (METH) use is unclear. We found that HIV+ METH users had more severe loss of interneurons that was associated with cognitive impairment. Compared with other markers, loss of calbindin and parvalbumin interneurons in the frontal cortex was the most significant correlate to memory deficits, suggesting a role in neurobehavioral alterations of HIV+ METH users.

Amphetamine-Related Disorders↗

Interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders in an HIV-infected cohort: experience of the National NeuroAIDS Tissue Consortium.

The interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was assessed in a multicentre study. Four sites of the National NeuroAIDS Tissue Consortium performed blinded reratings of audiotaped PRISM interviews of 63 HIV-infected patients. Diagnostic modules for substance-use disorders and major depression were evaluated. Seventy-six per cent of the patient sample displayed one or more substance-use disorder diagnoses and 54% had major depression. Kappa coefficients for lifetime histories of substance abuse or dependence (cocaine, opiates, alcohol, cannabis, sedative, stimulant, hallucinogen) and major depression ranged from 0.66 to 1.00. Overall the PRISM was reliable in assessing both past and current disorders except for current cannabis disorders when patients had concomitant cannabinoid prescriptions for medical therapy. The reliability of substance-induced depression was poor to fair although there was a low prevalence of this diagnosis in our group. We conclude that the PRISM yields reliable diagnoses in a multicentre study of substance-experienced, HIV-infected individuals.

Adult↗

Severe acidosis in patients taking metformin--rapid reversal and survival despite high APACHE score.

BACKGROUND: Metformin has been shown to reduce complications and mortality from Type 2 diabetes mellitus, and is increasingly used to treat this condition. This agent is, however, associated with a rare but serious risk of lactic acidosis. CASE REPORT: We present cases of 10 patients with Type 2 diabetes mellitus who developed acute renal failure and severe lactic acidosis. Despite the severity of their illness, all patients but one survived. CONCLUSIONS: The increasing prevalence of Type 2 diabetes and its treatment with metformin might result in more cases of lactic acidosis. However our case report demonstrates that early and aggressive treatment with haemofiltration can improve outcomes even in the presence of severe acidosis.

APACHE↗

Significance testing of a cluster of multivariate binary variables: comparison of the tripartite T index to three common similarity measures.

Similarity measures quantify resemblance between pairs of items when each consists of a pattern of two-state (eg, presence versus absence) variables. Numerous similarity measures, many of which are straightforward to calculate and interpret, have been developed and characterized. Methods for testing if items within a specified cluster are significantly more similar to each other than to items outside the cluster have not been extensively developed for binary responses, but a permutation test procedure using a measure of distinctness is available to do this. We compare three well known similarity measures, the Dice, Jaccard and simple matching coefficients, with the more complex tripartite T similarity index recently proposed by Tulloss. Each measure is used in significance tests of whether hypothesized subsets of items are legitimately grouped for resemblance. Theoretically derived measures reflecting diverse scenarios found in medical research and data from neuropsychological research illustrate the methods. Results for the tripartite T measure were comparable to the other methods in some settings, and essentially the same as the Dice coefficient overall when compared theoretically and on the same clinical data. Some shortcomings with the Tulloss algorithm were found and limit the usefulness of the tripartite T index in medical applications.

Brain↗

Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine.

OBJECTIVE: To examine the contribution of hepatitis C virus (HCV) infection to neurocognitive dysfunction in individuals with comorbid HIV infection or methamphetamine (METH) dependence. METHODS: Neurocognitive functioning was examined in 430 study participants who were either normal controls or had HCV infection, HIV infection, history of METH dependence, or combinations of these factors as risks for cognitive deficits. RESULTS: Rates of global and domain-specific neuropsychological (NP) impairment increased with the number of risk factors. HCV serostatus was a significant predictor of NP performance both globally and in the areas of learning, abstraction, and motor skills, with trends in speeded information processing and delayed recall. HCV serostatus did not predict scores in attention/working memory or verbal fluency. CONCLUSION: Hepatitis C virus infection contributes to the neuropsychological deficits observed among HIV-infected and stimulant-dependent populations.

AIDS Dementia Complex↗

Internal fixation of unstable fracture dislocations of the proximal interphalangeal joint.

We report a group of 14 patients with fracture dislocations of the proximal interphalangeal joint with fracture fragments of adequate size to allow reduction of the proximal interphalangeal joint and internal mini screw fixation of the bone fragment attached to the palmar plate to the base of the middle phalanx. Three years after surgery, (range 25-52 months) the average total active range of motion of the proximal interphalangeal joint was 100 degrees (range 65-115 degrees) for the acute group (operation within 14 days of injury, n=7) and 86 degrees (range 60-110 degrees) for the chronic group (operation on average 46 days after injury, range 21-120 days, n=7). Longer delay from injury was associated with a decreased total range of motion (P=0.028). Further subluxation occurred in three chronic group patients, one required further surgery. The key to successful treatment of this injury is the re-establishment of joint congruity and early mobilization. With appropriate patient selection, pain free, satisfactory range of motion can be achieved. There is a risk of persistent subluxation or dislocation, particularly if treatment is delayed.

Adolescent↗

Effect of CLA supplementation on immune function in young healthy volunteers.

OBJECTIVES: This study investigated the effect of dietary CLA supplementation (3g/day; 50:50 mix of the two major isomers) on the immune system and plasma lipids and glucose of healthy human (male and female) volunteers. DESIGN: Double-blind, randomized, reference-controlled study. SUBJECT AND INTERVENTION: A total of 28 healthy male and female participants aged 25-50 y received either high oleic sunflower oil (reference) or 50% CLA 9-11 and 50% CLA 10-12 CLA isomers (50:50 CLA-triglyceride form). The treatments were given as supplements in soft-gel capsules providing a total 3 g (6 x 500 mg capsules) per day in treatment groups for 12 weeks. A 12-week washout period followed the intervention period. RESULTS: Levels of plasma IgA and IgM were increased (P < 0.05 and 0.01 respectively), while plasma IgE levels were decreased (P < 0.05). CLA supplementation also decreased the levels of the proinflammatory cytokines, TNF-alpha and IL-1beta (P < 0.05), but increased the levels of the anti-inflammatory cytokine, IL-10 (P < 0.05). Another aspect of immune function, delayed type hypersensitivity (DTH) response, was decreased during and after CLA supplementation (P < 0.05). However, plasma glucose, lipids, lymphocyte phenotypic results were not affected significantly by CLA. CONCLUSION: This is the first study to show that CLA, a fatty acid naturally found in dairy and meat products, can beneficially affect immune function in healthy human volunteers. SPONSORSHIP: This study was supported by Loders-Croklaan, The Netherlands and SEERAD (Scottish Executive Environmental Rural and Agriculture Department).

Adult↗

Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy.

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is a significant cause of morbidity. The requirements for HIV adaptation to the CNS for neuropathogenesis and the value of CSF virus as a surrogate for virus activity in brain parenchyma are not well established. We studied 18 HIV-infected subjects, most with advanced immunodeficiency and some neurocognitive impairment but none with evidence of opportunistic infection or malignancy of the CNS. Clonal sequences of C2-V3 env and population sequences of pol from HIV RNA in cerebrospinal fluid (CSF) and plasma were correlated with clinical and virologic variables. Most (14 of 18) subjects had partitioning of C2-V3 sequences according to compartment, and 9 of 13 subjects with drug resistance exhibited discordant resistance patterns between the two compartments. Regression analyses identified three to seven positions in C2-V3 that discriminated CSF from plasma HIV. The presence of compartmental differences at one or more of the identified positions in C2-V3 was highly associated with the presence of discordant resistance (P = 0.007), reflecting the autonomous replication of HIV and the independent evolution of drug resistance in the CNS. Discordance of resistance was associated with severity of neurocognitive deficits (P = 0.07), while low nadir CD4 counts were linked both to the severity of neurocognitive deficits and to discordant resistance patterns (P = 0.05 and 0.09, respectively). These observations support the study of CSF HIV as an accessible surrogate for HIV virions in the brain, confirm the high frequency of discordant resistance in subjects with advanced disease in the absence of opportunistic infection or malignancy of the CNS, and begin to identify genetic patterns in HIV env associated with adaptation to the CNS.

AIDS Dementia Complex↗

Rupture of the flexor digitorum profundus tendon to the small finger within the carpal tunnel.

We report three patients who sustained a rupture of the flexor digitorum profundus tendon to the small finger within the carpal tunnel. There was a common mechanism of injury, each rupture occurred during resisted flexion of the digit with the metacarpophalangeal joint in extension. All the patients were male, one patient had an asymptomatic undiagnosed fracture of the hook of hamate, one patient had radiological evidence of piso-triquetral osteoarthritis. In each case, an attrition rupture was confirmed at surgery.

Adult↗

A multimodal assessment of driving performance in HIV infection.

OBJECTIVE: To examine if HIV-seropositive (HIV+) individuals are at risk for impaired driving. METHODS: Sixty licensed drivers (40 HIV+, 20 HIV-) completed a neuropsychological (NP) test battery and driving assessments. Eleven HIV+ subjects were NP-impaired. Driving-related skills were assessed using 1) two driving simulations (examining accident avoidance and navigational abilities), 2) the Useful Field of View (UFOV) test, and 3) an on-road evaluation. RESULTS: HIV+ NP-impaired subjects had greater difficulty than cognitively intact subjects on all driving measures, whereas the HIV- and HIV+ NP-normal groups performed similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on Visual Processing and Divided Attention tasks but not in overall risk classification. They also had a higher number of simulator accidents (1.3 vs 2.0; p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2 blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs 36%; p = 0.02). Impairment in Executive Functioning was the strongest NP predictor of failing the on-road drive test. NP performance and both simulations independently contributed to a model predicting 48% of the variance in on-road performance. CONCLUSION: HIV+ NP-impaired individuals are at increased risk for on-road driving impairments, whereas HIV+ individuals with normal cognition are not at a significantly higher risk than HIV- subjects. Executive Functioning is most strongly associated with impaired on-road performance. Cognitive and simulator testing may each provide data in identifying driving-impaired individuals.

AIDS Dementia Complex↗

Vincristine as a treatment for a large haemangioma threatening vital functions.

We report the use of vincristine to treat a large steroid resistant haemangioma of the lower face and neck. At the time of treatment the lesion had shown no signs of involution. The haemangioma was not life threatening but extension within the mouth was associated with bleeding and ulceration, which was impairing feeding and speech development. A significant improvement was seen with vincristine treatment.

Antineoplastic Agents, Phytogenic↗

Coenzyme Q differentially modulates phospholipid hydroperoxide glutathione peroxidase gene expression and free radicals production in malignant and non-malignant prostate cells.

The aim of this study was to investigate the role of coenzyme Q on the mRNA abundance of PHGPx and the reactive oxygen species (ROS) production in two different cell lines from human prostate, a line of non cancer cells (PNT2) and a line of cancer cells (PC3). Results showed that malignant cells markedly differ in their response to coenzyme Q compared to non-malignant cells, with no changes in PHGPx expression and greater ROS production. Furthermore coenzyme Q supplementation significantly lowered cell growth of the PC3 cancer line without affecting the PNT2. If these results are confirmed with additional experiments, it could represent a novel and interesting approach on the biomedical use of coenzyme Q10 in cancer therapy.

Cell Line↗

End-to-side venous anastomoses....a patency test.

A hitherto unpublished means of testing the patency across an end-to-side venous anastomosis is described. It relies on the elasticity of the venous walls to produce ballooning when the appropriate segments of the veins are occluded and blood is flowing unimpeded across the end-to-side anastomosis. It is foolproof, easy to perform and has no ambiguity in its interpretation.

Anastomosis, Surgical↗

HIV-positive gay and bisexual men: predictors of unsafe sex.

This paper describes the sexual risk practices of 322 HIV-positive gay and bisexual men who reported having unprotected anal, oral or vaginal sex with an HIV-negative or unknown status partner(s) during the previous four months. Descriptive data on type of sex, partner types and number of partners are presented. Determinants of unprotected anal and oral intercourse were examined using a social cognitive framework. More unprotected anal sex was associated with having a steady versus a casual partner, not being on triple drug therapy, increased use of drugs and alcohol, and lower outcome expectancies for condom use and negotiation of safer sex practices. Unprotected oral sex was associated with partner type; men with casual partners had less unprotected oral sex as compared to men with steady partners. Findings are discussed in relation to the development of sexual risk reduction interventions for HIV-positive individuals.

Adult↗