A Review of Clostridium difficile Infection at the University Hospital of the West Indies, Jamaica.

OBJECTIVES: This study examined the frequency of Clostridium difficile infection (CDI) among hospital admission and diarrhoeal stool samples over a six-year period. METHODS: A review of all suspected cases of C difficile positive patients from 2007 to 2012 at the University Hospital of the West Indies (UHWI), Jamaica, was performed. Clostridium difficile infection was confirmed by clinical features and a positive enzyme-linked immunosorbent assay (ELISA) stool test for Clostridium Toxins A and B. The demographics, clinical features, risk factors, treatment and outcomes were also examined. RESULTS: There were 56 patients reviewed. The most commonly affected age group was 40-59 years of age. The proportion of CDI cases per total stool samples increased from 0.5% in 2007 to 5.9% in 2010 then fell to 2.2% in 2011 but increased again to 4.3% in 2012. The proportion of cases per total UHWI admissions also increased from 0.12 cases per 1000 admissions in 2007 to 1.16 in 2010 and 1.36 in 2012 (p < 0.001). Most CDI cases were nosocomial (76% males, 48.6% females). Co-morbidities included hypertension and end-stage renal disease. Ceftazidime was the most common antibiotic associated with the development of CDI. Resolution occurred in 62.5% of patients. Duration of hospital stay was longer in males than females (≥ 21 versus < 7 days) and males had more adverse outcomes, with death in 23.8% versus 11.4%. CONCLUSION: There has been an increase in the frequency of CDI at UHWI with a greater than expected frequency of community acquired CDI. Increased awareness is needed of the increasing risk for CDI and measures must be taken to prevent the disease, especially in hospitalized patients.

A review of the HIV-infected homeless sub-population at the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies.

OBJECTIVE: The twin epidemics of HIV and homelessness present several challenging aspects to the development of programmes for the provision of treatment and care. This paper describes the characteristics of this population being managed by a collaborative effort between the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies and the National Council on Drug Abuse. SUBJECTS AND METHODS: A retrospective descriptive study was conducted via review of patients'medical files. Demographic and clinical data of the HIV-infected homeless population were summarized, highlighting issues related to the provision of care, rates of antiretroviral therapy (ART) uptake and subsequent adherence to treatment and known factors associated with HIV transmission. RESULTS: A total of 12 cases were included in the analysis. There was an average age of 38.0 years (IQR 32.5-49.25) with the majority being female, nine (75.0%). Late stage diagnosis was a common feature. The majority of cases were eligible for ART on first contact, with CD4 counts on average being 284.4 (95% CI 10.9.0, 459.8). Significant risk factors for HIV transmission were also identified as all cases reported being sexual active with limited condom use reported and high reported numbers of lifetime partners, 30 (IQR 25.0-100.0). Other factors identified include eight (66.6%) cases reporting sexually transmitted infection (STI) symptoms, 10 (83.3%) reporting substance abuse and nine (75.0%) reporting sex work. CONCLUSION: The implementation of combination interventions providing a comprehensive package of services that address the multitude of issues facing the HIV-infected homeless population is required in order to appropriately manage this population.

A review of the HIV-infected homeless sub-population at the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies / Una revisión de la subpoblación sin hogar de infectados por el VIH en el Centro para la Investigación, Educación y Servicios del VIH/SIDA, del Departamento de Medicina del Hospital Universitario de West Indies

OBJECTIVE: The twin epidemics of HIV and homelessness present several challenging aspects to the development of programmes for the provision of treatment and care. This paper describes the characteristics of this population being managed by a collaborative effort between the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies and the National Council on Drug Abuse. SUBJECTS AND METHODS: A retrospective descriptive study was conducted via review of patients'medical files. Demographic and clinical data of the HIV-infected homeless population were summarized, highlighting issues related to the provision of care, rates of antiretroviral therapy (ART) uptake and subsequent adherence to treatment and known factors associated with HIV transmission. RESULTS: A total of 12 cases were included in the analysis. There was an average age of 38.0 years (IQR 32.5-49.25) with the majority being female, nine (75.0%). Late stage diagnosis was a common feature. The majority of cases were eligible for ART on first contact, with CD4 counts on average being 284.4 (95% CI 10.9.0, 459.8). Significant risk factors for HIV transmission were also identified as all cases reported being sexual active with limited condom use reported and high reported numbers of lifetime partners, 30 (IQR 25.0-100.0). Other factors identified include eight (66.6%) cases reporting sexually transmitted infection (STI) symptoms, 10 (83.3%) reporting substance abuse and nine (75.0%) reporting sex work. CONCLUSION: The implementation of combination interventions providing a comprehensive package of services that address the multitude of issues facing the HIV-infected homeless population is required in order to appropriately manage this population.

OBJETIVO: Las epidemias gemelas del VIH y las personas sin hogar, presentan varios aspectos desafiantes para el desarrollo de programas que ofrecen atención y tratamiento. Este trabajo describe las características de esta población, y su manejo como parte de un esfuerzo de colaboración entre el Centro para la investigación, educación y servicios del VIH/SIDA, del Departamento de Medicina del Hospital Universitario de West Indies, y el Consejo Nacional para el Abuso de Drogas. SUJETOS Y MÉTODOS: Se realizó un estudio descriptivo retrospectivo mediante revisión de expedientes médicos de los pacientes. Se resumieron los datos clínicos y demográficos de la población sin hogar infectada por el VIH, destacando las cuestiones relacionadas con la prestación de asistencia, las tasas de adopción de terapia antirretroviral (TAR), y la posterior adherencia al tratamiento, además de factores conocidos, asociados con la transmisión del VIH. RESULTADOS: Un total de 12 casos se incluyeron en el análisis. La edad promedio fue de 38.0 años (IQR 32.5-49.25), siendo mujeres la mayoría, 9 (75.0%). El diagnóstico en etapa tardía fue una característica común. La mayoría de los casos fueron elegibles para TAR desde el primer contacto, con conteos CD4 de 284.4 (95% CI 10.9.0, 459.8) como promedio. También se identificaron factores de riesgo significativos para la transmisión del VIH, ya que todos los casos reportaron actividad sexual con un uso limitado de condón, y un gran número de parejas sexuales durante toda la vida, 30 (IQR 25.0-100.0). Otros factores identificados incluyen 8 (66,6%) casos que reportaron síntomas de infección de transmisión sexual (ITS), 10 (83,3%) que reportaron abuso de sustancias, y 9 (75.0%) que reportaron trabajo sexual. CONCLUSIÓN: Se requiere la implementación de intervenciones de combinación que ofrezcan un paquete integral de servicios que respondan a los numerosos problemas que enfrenta la población sin hogar infectada por VIH, a fin de tratar adecuadamente a esta población.

CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression.

Recent advances in oligonucleotide microarray technology ("gene chips") permit rapid screening for DNA sequence variation. The CYP2D6 gene encodes debrisoquine hydroxylase, which metabolizes the antidepressant nortriptyline and other psychotropic medications. Nortriptyline plasma concentrations were obtained after at least three weeks of treatment in 36 geriatric patients with major depression who were taking a mean of 8.6 other medications besides nortriptyline. Oligonucleotide microarrays were used to detect 16 CYP2D6 alleles that affect debrisoquine hydroxylase activity. Subjects carrying alleles encoding impaired debrisoquine hydroxylase activity had significantly greater nortriptyline concentrations and lower nortriptyline doses than did other subjects. Significant correlations were found between the numbers of alleles encoding decreased metabolism and nortriptyline plasma concentration, nortriptyline dose, and nortriptyline plasma concentration standardized for dose, indicating a gene dosage effect. These results demonstrate that CYP2D6 genotyping on a microarray platform can be used to predict plasma antidepressant concentrations despite advanced patient age and numerous concurrent medications.

Rate of cognitive decline in AD is accelerated by the interleukin-1 alpha -889 *1 allele.

The reason for differences in rate of cognitive decline in AD is unknown. The interleukin-1 alpha (IL-1 alpha) -889 *2 allele is associated with increased risk for AD. Surprisingly, in a sample of 114 patients followed for an average of 3.8 years, individuals homozygous for the IL-1 alpha -889 *1 allele declined significantly more rapidly on the Mini-Mental State Examination than did others. There was no difference in rate of decline between patients with and without the APOE epsilon 4 allele. These results support the hypothesis that inflammation is important in the clinical course of AD.

N-acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid.

N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 microM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 microM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful.

Passage of MHPG from plasma to CSF in a non-human primate.

In experimental protocols with humans and non-human primates, cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the predominant end-product of norepinephrine metabolism in the mammalian central nervous system (CNS), have been widely used as an index of the rate of CNS norepinephrine metabolism. However, an earlier investigation showed that there was slow but free exchange between plasma and CSF MHPG. To define more precisely the time-course of equilibration of plasma and CSF MHPG, we intravenously administered 100 micrograms/kg of [2H3]-MHPG to drug-naive squirrel monkeys. Measurements were made of the concentrations of [2H3]- and [1H]-MHPG in plasma and cervical CSF samples collected at time points from 10 min to 4 hr thereafter. The results indicated that neither plasma nor CSF concentrations of [1H]-MHPG changed during the course of the experiment, and that [2H3]-MHPG appeared in the CSF within 10 min of intravenous administration. The maximal plasma and CSF concentrations of [2H3]-MHPG were 7.6- and 2.3-fold higher than the respective concentrations of [1H]-MHPG. The plasma and CSF pools of [2H3]-MHPG reached concentration equilibrium within 30 min, and thereafter the temporal decline in concentration of [2H3]-MHPG was the same in plasma and CSF. These results demonstrate that MHPG rapidly crosses from plasma to CSF, and support the suggestion that this factor be included in any attempts to estimate norepinephrine turnover in the CNS from measurements of steady-state MHPG concentrations in CSF or plasma.

Gas chromatography/electron impact mass spectrometry, fast atom bombardment mass spectrometry, mass-analyzed ion kinetic energy spectroscopy and B/E linked scan analysis of triaryl phosphates and triethylene glycol fatty acid esters.

Tris(isopropylphenyl/phenyl) phosphates and triethylene glycol dicaprate/caprylate mixtures of typical industrial compositions have been analyzed by fast atom bombardment (FAB) mass spectrometry, FAB collisional activation (CA) mass-analyzed ion kinetic energy spectroscopy and FAB/electron impact (EI) CA B/E linked scans. Data obtained by these state-of-the-art methodologies are compared qualitatively and semi-quantitatively with those provided by classical gas chromatography (GC)/EI MS. To identify the plasticizers in cases of suspected contamination, GC/EI MS still appears to be the method of choice whenever ultimate sensitivity and specificity are needed. In cases where these requirements are less demanding, FAB mass spectrometry and FAB tandem mass spectrometry may be sufficient and more convenient.

Measurement of phenylacetic acid in cerebrospinal fluid and plasma using combined gas chromatography/electron capture chemical ionization mass spectrometry.

Details are presented of an ultra-sensitive gas chromatographic/mass spectrometric assay for phenylacetic acid in plasma and cerebrospinal fluid based on measurements of the relative intensities of the carboxylate anions, derived from the penta- and tetrafluorobenzyl esters under electron capture chemical ionization conditions, of unlabeled and a (13C2)-labeled internal standard. The limits of detection for the penta- and tetrafluorobenzyl esters are 0.85 and 4.0 pg respectively, and the assay is capable of measuring phenylacetic acid concentrations in samples as small as 20 microliter of CSF and plasma. The penta- and tetrafluorobenzyl esters are chromatographically separated on the gas chromatograph column, which allows for their co-injection and independent measurement from the same chromatogram.

Modification of renal cortical subcellular membrane phospholipids induced by mercuric chloride.

Administration of mercuric chloride (HgCl2, 6 mg/kg) to rabbits produced renal failure, with changes in serum creatinine from 1.01 +/- 1 in controls to 6.46 +/- 0.91 mg/dl 24 hr after administration. Mitochondria isolated from HgCl2-treated rabbits exhibited alterations in acceptor control ratios, with reduction to 1.9 +/- 0.2 from 3.9 +/- 1.2 in controls. Ultrastructurally, the mitochondria showed swelling and loss of inner mitochondrial membranes. Total lipids from mitochondria of control and treated rabbits were obtained by modified Folch extraction and phospholipids analyzed by TLC. Brush border membranes and basolateral membranes were prepared from control and HgCl2-treated kidneys 2 and 24 hr after HgC12 administration. At 24 hr mitochondria showed a 36% fall in phosphatidylcholine (PC), a 36% fall in phosphatidylethanolamine (PE), and a 27% fall in cardiolipin. Brush border showed a decrease in phosphatidylserine (PS) of 29% and in PE of 40%. The basolateral membranes showed a reduction only in PE of 35%. At 2 hr post HgCl2, early changes are confined to the BBM and consist of a reduction in PE in this membrane. This changes in membrane phospholipids may be important in the functional derangements that occur at the cellular level after HgCl2 administration.

Biochemical alterations of membrane lipids associated with renal injury.

Ureteral obstruction and partial renal vasoconstriction are associated with increased prostaglandin biosynthesis and arachidonate release from cellular phospholipids. HgCl2-induced renal injury was associated with changes in respiratory control of mitochondria with loss of acceptor control and with marked morphological changes seen ultrastructurally. The mitochondrial lipids showed losses of 29 and 46%, respectively, of phosphatidylethanolamine and cardiolipin. These biochemical changes may be the markers of the functional and ultrastructural derangements seen in toxic renal injury.

Metabolism of arachidonate through NADPH-dependent oxygenase of renal cortex.

In normal kidneys the renal medulla very efficiently converts arachidonic acid to prostaglandins. Although the renal cortex has only trace amounts of cyclooxygenase activity, we report here the existence of an active cortical NADPH-dependent monooxygenase that converts arachidonate primarily into 19-hydroxy- and 20-hydroxyarachidonate as well as 19-ketoarachidonate and a dicarboxylic acid. The enzyme is presumably a cytochrome P-450 monooxygenase and demonstrated marked resistance to inhibition by 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A), metyrapone, and carbon monoxide. In the rabbit kidney these products are produced only by the cortex in the presence of NADPH and represent the major metabolic products of arachidonate metabolism.