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Biomedical subjects

R Hogg

Publications and source records attributed to R Hogg.

At least 19 recordsLinked to original sources

Air bag injury as a cause of inflammatory myofibroblastic pseudotumour of the subglottic larynx progressing to myositis ossificans.

Inflammatory myofibroblastic pseudotumour (IMFPT) is a rare condition. The clinical presentation can be indistinguishable from that of a malignant neoplasm. The most frequently affected organ is the lung; a much less common site is the larynx and subglottic involvement is particularly rare. Trauma is purportedly one potential aetiological factor, although there have been no previous reports of IMFPT occurring in the larynx secondary to external laryngeal trauma. We present a case of IMFPT of the subglottis which occurred subsequent to external trauma of the neck sustained during air bag inflation in a road traffic accident. This mechanism has not been previously reported. Furthermore, the lesion progressed uniquely to show myositis ossificans-like maturation over time. The patient was ultimately treated by means of complete local excision.

Accidents, Traffic↗

Determinants of HAART discontinuation among injection drug users.

The objective of this study was to identify psychosocial determinants of, and self-reported reasons for, HAART discontinuation among HIV-positive injection drug users (IDUs). We examined correlates between sociodemographic characteristics, drug use and risk behaviors, outcome expectations, adherence self-efficacy, social support and HAART discontinuation among 160 HIV-positive participants in the Vancouver Injection Drug Users' Study (VIDUS). Logistic regression was used to identify the factors independently associated with discontinuation of HAART. Seventy-one (44%) study participants discontinued HAART during the study period. Factors independently associated with discontinuation of HAART included recent incarceration (OR = 4.84, p = 0.022), negative outcome expectations (OR = 1.41, p = 0.001), adherence efficacy expectations (OR = 0.70, p = 0.003) and self-regulatory efficacy (OR = 0.86, p = 0.050). The most frequently cited reasons provided for discontinuing HAART were being in jail (44%) and medication side effects (41%). The results of this study suggest that psychological constructs derived from self-efficacy theory are highly germane to the understanding of HAART discontinuation behavior and interventions that may change it. Incarceration may result in interruptions in HAART among IDUs, and programmatic changes may be needed to promote optimal retention on HAART among incarcerated HIV-infected IDUs.

Adult↗

An analysis of diagnostic delay in unilateral facial paralysis.

Bell's palsy or idiopathic facial palsy is the commonest cause of unilateral lower motor neuron facial palsy. Misdiagnosis of facial nerve palsy as Bell's palsy is still seen in clinical practice. The clinician should always consider the possibility of a potentially serious underlying pathology before making the diagnosis of Bell's palsy. We present a series of 13 patients referred to our ENT department with an initial diagnosis of Bell's palsy. Further clinical examination and investigation revealed the underlying cause. Many had additional symptoms and signs related to the ear. In all patients with unilateral facial palsy a detailed history should be taken and thorough clinical examination carried out. Where no recovery occurs within the expected time period further radiological investigations such as computerized axial tomography (CT) and magnetic resonance imaging (MRI) should be performed. Current scanning techniques provide good quality images, which can show occult lesions of the temporal bone, internal acoustic canal and/or cerebellopontine angle. Radiologists with a special interest and experience in otoneurological radiology should ideally report these images, and a close co-operation between ENT surgeon and radiologist is essential in arriving at a proper diagnosis.

Adolescent↗

Cerebellopontine angle arachnoid cysts in adult patients: what is the appropriate management?

Arachnoid cysts can occur at different intracranial sites, including the cerebellopontine angle (CPA). The incidence of arachnoid cysts is 1 per cent of all intracranial lesions. Recent advances in MRI (magnetic resonance imaging) scan techniques have led to CPA arachnoid cysts being more frequently diagnosed and with a higher degree of certainty. The need for further understanding of their natural history as well as for the development of a management rationale has been highlighted with this increased rate of diagnosis. We present a series of five adult patients with different clinical presentations attributed to CPA arachnoid cysts. These lesions have a characteristic location in the posterior-inferior aspect of the CPA below the facial and vestibulocochlear nerves. These cysts did not show change in size on repeated MRI scan and the patients' symptoms did not progress over the period of follow up. Our findings would support a conservative management approach to the majority of these cysts.

Adult↗

Pseudoaneurysm after total pharyngolaryngectomy with jejunal graft insertion: two different presentations.

Pharyngeal reconstruction after total pharyngolaryngectomy using a jejunal graft is now a common procedure in head and neck oncological surgery. The vascular supply of this graft comes from the anastomosis between a branch of the mesentric artery and a branch of the external carotid artery. We report two cases of pseudoaneurysm, one at the site of ligation of the lingual artery and the other at the site of arterial anastomosis. One presented with dramatic hematemesis and was managed by the interventional radiologist, and the second presented with a pulsating neck mass and required a surgical revision. In both cases, the jejunal graft survived.

Aged↗

Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies.

BACKGROUND: We examined whether the initial virological and immunological response to highly active antiretroviral treatment (HAART) is prognostic in patients with HIV-1 who start HAART. METHODS: We analysed 13 cohort studies from Europe and North America including 9323 adult treatment-naive patients who were starting HAART with a combination of at least three drugs. We modelled clinical progression from month 6 after starting HAART, taking into account CD4 count and HIV-1 RNA measured at baseline and 6 months. FINDINGS: During 13408 years of follow-up 152 patients died and 874 developed AIDS or died. Compared with patients who had a 6-month CD4 count of fewer than 25 cells/microL, adjusted hazard ratios for AIDS or death were 0.55 (95%CI 0.32-0.96) for 25-49 cells/microL, 0.62 (0.40-0.96) for 50-99 cells/microL, 0.42 (0.28-0.64) for 100-199 cells/microL, 0.25 (0.16-0.38) for 200-349 cells/microL, and 0.18 (0.11-0.29) for 350 or more cells/microL at 6 months. Compared with patients who had a 6-month HIV-1 RNA of 100000 copies/mL or greater, adjusted hazard ratios for AIDS or death were 0.59 (0.41-0.86) for 10000-99999 copies/mL, 0.42 (0.29-0.61) for 500-9999 copies/mL, and 0.29 (0.21-0.39) for 6-month HIV-1 RNA of 500 copies/mL or fewer. Baseline CD4 and HIV-1 RNA were not associated with progression after controlling for 6-month concentrations. The probability of progression at 3 years ranged from 2.4% in the patients in the lowest-risk stratum to 83% in patients in the highest-risk stratum. INTERPRETATION: At 6 months after starting HAART, the current CD4 cell count and viral load, but not values at baseline, are strongly associated with subsequent disease progression. Our findings should inform guidelines on when to modify HAART.

Acquired Immunodeficiency Syndrome↗

Identification of lesion components that influence visual function in age related macular degeneration.

AIMS: To explore the relation between lesion composition as assessed by fundus photography and fluorescein angiography with clinical measures of vision in eyes of patients with age related macular degeneration (AMD). METHODS: A standardised visual function assessment along with colour stereo pair fundus photography was carried out in both eyes of 58 subjects with a confirmed clinical diagnosis of AMD. The size, location, and composition of the macular lesion (blood, exudate, subretinal fluid, pigment, membrane, atrophy, and fibrosis) were measured on the colour photographs using computer assisted image analysis. Of the 58 subjects, 44 also had concurrent fluorescein angiography. Classic and occult choroidal neovascularisation (CNV), blood, blocked fluorescence, fibrosis, geographic atrophy, and the total area of abnormal fluorescence were measured. Multiple linear regression was used to examine the relation between clinical measures of vision and the location and extent of lesion components identified by both colour and fluorescein image capture. RESULTS: The composition of the macular lesion strongly influenced visual function, with atrophy (p=0.001) and fibrosis (p=0.002) accounting for most of the variation. When the location of the lesion with respect to the fovea was examined, fibrosis within the fovea significantly influenced all clinical measures of vision (p=0.008). The regression model selected the total area of abnormal fluorescence and a composite parameter (a semiquantitative measure of the following characteristics: atrophy, exudates, blood, and fibrosis ) from colour photography (r(2) =0.52) as the variables that explained most of the variation in clinical measures of vision. CONCLUSIONS: The composition and extent of the macular lesion strongly influences visual function in eyes with AMD. Both colour photography and angiography yielded information, which together explained considerably more of the variation in the clinical measures of vision than either on its own.

Aged↗

A demographic and health profile of gay and bisexual men in a large Canadian urban setting.

The purpose of this study was to provide both a population estimate and a socio-economic and health profile of gay and bisexual men living with HIV/AIDS in a large Canadian urban centre. A random telephone survey was used to determine the number of men in the study area over the age of 20 identifying as gay or bisexual and to characterize their health and socio-economic status. Out of a total of 1,176 completed interviews, 300 males described themselves as gay or bisexual. Projecting this figure on recent census data we estimated the number of men identifying as gay or bisexual in this region of downtown Vancouver, BC, at 5,100. Among these men we found an HIV prevalence rate of 16%, with those who reported a positive serostatus being less likely to be employed full time and more likely to earn less than $20,000 per year. In terms of clinical characteristics, HIV-positive men had a median CD4 cell count of 397 cells/mm(3) and a median viral load of less than 500 copies/ml. Eighty-three per cent of the HIV-positive respondents were on antiretroviral therapy and the median number of drugs taken by these men was three. In summary, random surveys of populations affected by this epidemic are important for policy makers, clinicians and persons caring for those with HIV/AIDS as they paint a clearer picture of who is being affected and help to identify areas where increased services are needed.

Adult↗

Mutation screening analysis of the retinoblastoma related gene RB2/p130 in sporadic ovarian cancer and head and neck squamous cell cancer.

AIMS: To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). METHODS: Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. RESULTS: No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. CONCLUSIONS: Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.

Carcinoma, Squamous Cell↗

CCR5Delta32 and promoter polymorphisms are not correlated with initial virological or immunological treatment response.

OBJECTIVE: Natural genetic polymorphisms within the CCR5 gene and promoter have been linked to patterns of HIV-1 clinical disease progression in untreated individuals. The objective of this retrospective study was to assess the influence of the CCR5Delta32 mutation and promoter polymorphisms on virological and immunological treatment outcome in 436 antiretroviral-naive individuals initiating their first therapy, over a mean follow-up time of 22 months. METHODS: Genotypes for the CCR5Delta32 and promoter were determined by polymerase chain reaction amplification of human DNA from plasma, followed by gel electrophoresis for CCR5Delta32 or DNA sequencing for the promoter polymorphisms. Time to virological failure [defined as the second plasma viral load > or = 400 copies HIV-1 RNA/ml) and immunological failure (defined as time to achieve two successive CD4 cell counts below baseline) were analyzed by Kaplan-Meier methods. RESULTS: The five most common CCR5 promoter polymorphisms were observed at positions 208(G/T), 303(A/G), 627(C/T), 676(A/G), and 927(C/T). Allele frequencies were 0.24(208T), 0.38(303G), 0.44(627T), 0.35(676G) and 0.18(927T). The CCR5Delta32 allele frequency was 0.08. The promoter polymorphisms existed in strong linkage disequilibrium with each other and the Delta32. No significant effect of the individual CCR5Delta32 or promoter polymorphisms could be demonstrated with respect to time to treatment failure as defined by virological or immunological parameters (P > or = 0.07). Similarly, when combined CCR5Delta32 and promoter genotypes were analyzed in order to account for linkage disequilibrium, no significant effect was observed on time to virological or immunological failure (P > 0.6). CONCLUSION: CCR5Delta32 and promoter genotypes may not be of clinical relevance in predicting initial virological or immunological response to antiretroviral therapy.

Alleles↗

Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons.

The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. In symmetrical 140 mM K+, the single-channel slope conductance was linear in the voltage range -60/+60 mV, and was 207+/-19 pS. Na+ ions were not measurably permeant through the open channel. Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half-saturating [Ca2+] (K0.5) of 1.35 microM and slope of approximately equals 3. The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 microM) increased BK channel activity in the cell-attached recording configuration. The resting activity was consistent with a [Ca2+]i <100 nM and the increased channel activity evoked by ionomycin was consistent with a rise in [Ca2+]i to > or =0.3 microM. TEA (0.2-1 mM) increased the action potential duration approximately equals 1.5-fold and reduced the amplitude and duration of the afterhyperpolarization (AHP) by 26%. Charybdotoxin (100 nM) did not significantly alter the action potential duration or AHP amplitude but reduced the AHP duration by approximately equals 40%. Taken together, these data indicate that BK channel activation contributes to the action potential and AHP duration in rat intracardiac neurons.

Action Potentials↗

The pharmacokinetics of enalapril in children and infants with hypertension.

Forty children with hypertension between the age of 2 months and 15 years received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was administered orally as a novel extemporaneous suspension in children younger than 6 years of age and as tablets in older children. First-dose and steady-state pharmacokinetics were estimated in children ages 1 to 24 months, 25 months to < 6 years, 6 to < 12 years, and 12 to < 16 years. Maximum serum concentrations for enalapril occurred approximately 1 hour after administration. Serum concentrations of enalaprilat, the active metabolite of enalapril, peaked between 4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The area under the concentration versus time curve (AUC), adjusted for body surface area, did not differ between age groups. Based on comparison of first-dose and steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13- to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in children ages 12 to < 16 years. Urinary recovery for children ages 2 to < 6 years was 66.8%. The mean percentage conversion of enalapril to enalaprilat ranged from 64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The median effective half-life for accumulation ranged from 14.6 hours in children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years. There were two serious adverse events, neither of which was attributed to enalapril or resulted in discontinuation of the study drug. The extemporaneous suspension used in this study was tolerated well. The pharmacokinetics of enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with normal renal function appears to be similar to that previously observed in healthy adults.

Adolescent↗