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Biomedical subjects

J Hughes

Publications and source records attributed to J Hughes.

At least 109 records · Page 6Linked to original sources
PubMed2000

Trends in the rate of emergency room admissions for preventable cardiovascular conditions among african american men and women over the past decade. Continuation of negative trends.

PURPOSE: The objective of this retrospective analysis was to compare secular changes in the rate of emergency room admissions (per 100,000) for selected acknowledged preventable cardiovascular conditions among African Americans (AA) men and women aged >/=21 from 1991-1998, and rate of change for Caucasian (Cau), Hispanic (Hisp), and Asian (Asi) men and women aged >/=21; conditions included angina, congestive heart failure (CHF), diabetes, and hypertension.METHODS: Results are derived from calendar-year California hospital data based on a selection of specified ICD-9 codes that correspond to the principal diagnosis for admission. The combined study sample size included a total of 21,016 individuals who were admitted to a hospital via the ER. Separate standardized and age-adjusted Poisson regression models were employed for each condition to assess race and time main effects and race x time interaction terms (P </= 0.01). Age and payer-source were entered as covariates to control for confounding effects. Men and women were analyzed separately.RESULTS: Mean overall rates of ER admission due to angina were significantly lower among AA men compared to Cau men (17.8 vs 18.2); however, rates were higher among Hisp and Asi men (6.03 and 7.1, respectively). Rates for CHF were higher among AA men compared to Cau, Hisp, and Asi men (23.7 vs, 11.0, 3.7, 4.8, respectively); similar results were observed for diabetes (8.6 vs 2.7, 2.3, 1.2, respectively) and hypertension (5.1 vs, 1.6, 0.9, 1.5, respectively). Differentials in 1991 resulted in widening disparities overtime for each condition. For women, mean overall rates due to angina were significantly higher among AA women compared Cau, Hisp, and Asi women (17.0 vs 13.5, 5.7, 5.7, respectively). Similar patterns were observed for CHF (23.1 vs, 11.0, 3.7, 4.8, respectively), diabetes (6.4 vs 2.0, 1.8, 1.1, respectively) and hypertension (5.8 vs 1.9, 1.1, 1.5), respectively). As observed among AA men, differentials in 1991 resulted in widening disparity overtime.CONCLUSIONS: Findings reveal higher rates of ER admissions for preventable cardiovascular conditions among AA men and women during the 1990s with evidence of widening health status disparities into the new millennium.

Journal Article↗
PubMed2000

Supercritical-fluid extraction of synthetic pyrethroids from wool.

A stepwise approach was used to develop a supercritical fluid extraction (SFE) method for analysis of synthetic pyrethroids (SPs) on a wool matrix, commencing with a simple inert matrix to examine the solubility of the pyrethroids in the extraction fluid CO(2) and then extended to the real wool matrix. Chemometric approaches were used to determine the SFE optimum conditions. It was found that pyrethroids were readily extractable from an inert matrix over a wide range of pressure (170-350 atm) and at low temperature (<90 degrees C). Subambient hexane efficiently trapped the compounds from the depressurised fluid. Excessively high pressure and temperature resulted in poor trapping, isomerisation and possibly degradation of some components. With spiked wool samples method modifications focused on reducing the coextraction of grease, a bulk matrix component of raw wool. By using alumina (containing 8% moisture) and operating the extraction at 50 degrees C, 200 atm for 60 min, sufficiently clean extracts of pyrethroids suitable for gas chromatography-electron-capture detection analysis were obtained. The recoveries of all SPs were satisfactory (78-101%) over the range of 0.5-5 microg/g levels of these compounds. The precision of the entire analysis procedure was comparable to the conventional Soxhlet extraction method. Detection limits of some commonly used SPs for sheep treatment were also evaluated. Comparable results relative to those achieved by solvent extraction for incurred wool samples were obtained with a recovery of 81-85%. The results, however, suffered high uncertainties (R.S.D. approximately 19-24%) due to the small amount of wool sample taken in each extraction and the suspected inhomogeneity of the wool. Different persistences of cypermethrin isomers in wool were observed.

Aluminum Oxide↗
PubMed2000

The chemical stain removal properties of 'whitening' toothpaste products: studies in vitro.

BACKGROUND: A considerable number of toothpastes are available as tooth whitening products. Most appear to contain ingredients that might remove extrinsic stains rather than change natural tooth colour. Extrinsic stain removal could be achieved by physical or chemical means. AIM: The purpose of this study was to measure the chemical stain removal properties of a range of whitening toothpaste products and experimental formulations using a standardised method in vitro. MATERIALS AND METHOD: 5 separate studies were conducted involving a total of 39 agents of which 28 were whitening products, 7 were experimental formulations, 2 were oxidising mouthrinses used as positive controls, 1 was a popular fluoride toothpaste product as a benchmark control, and 1 was water as the negative control. The formulations and controls varied in each study. The stain model was saliva/chlorhexidine/tea stain developed on optically clear acrylic to an optical density of at least 2.0. Groups of stained specimens were exposed to standard slurries or solutions of each test agent for 1 minute periods up to 5 minutes. Optical density readings were taken at each 1 minute time point. Analyses were based on per cent stain remaining after 5 minutes and time to 75% stain remaining. RESULTS: 3 toothpaste products achieved 100% stain removal by 5 minutes; 2 of these in 3 out of 4 studies in which they were used. 4 experimental formulations also achieved 100% stain removal. In general agents with high total stain removal also had short times to 75% stain remaining. The majority of agents tested had low total chemical stain removal and prolonged times to 75% stain remaining. A few agents were little different from water and several similar in effect to the conventional fluoride toothpaste. This method in vitro tests agents under the best case scenario conditions for chemical stain removal. CONCLUSION: Only a small number of the whitening toothpaste products have good chemical stain removal potential; the majority are unlikely to achieve their claimed benefits through chemical stain removal. There is clearly a need for further data on the actual effects of such products using both methods in vitro and particularly in vivo or in situ.

Acrylic Resins↗
PubMed2000

Comparison of clinical features, CD4 and CD8 responses among patients with acute HIV-1 infection from Geneva, Seattle and Sydney.

OBJECTIVE: To compare the clinical features and T-cell subsets among 160 patients with acute HIV-1 infection not treated with antiretroviral agents from three different locations (Geneva, Seattle and Sydney). DESIGN: Patients with documented acute HIV-1 infection were enrolled in four prospective studies: one randomized placebo controlled trial (RCT) and three observational cohort studies. SETTING: All patients were diagnosed and followed in three university affiliated tertiary clinical care centers. METHODS: The chi-square test was used for comparing proportions and one way analysis of variance (ANOVA) for comparing continuous variables among these groups. Multiple regression analysis was used to identify the variables independently associated with the duration of acute HIV-1 infection. The differences in mean CD4 and CD8 load between centers were assessed using the random-effect models for the longitudinal data. RESULTS: Minor differences were noted in the frequency of symptoms among subjects enrolled at different locations. RCT patients reported a longer duration of symptoms (31 days) compared with that for observational patients (15 days; P < 0.0001). For the most common symptoms such as fever, skin rash, arthralgia, myalgia, and headaches, a longer duration was observed in the RCT group compared with that for observational patients (P range, 0.001 to < 0.0001). T-cells subsets within 100 days of seroconversion did not statistically differ by centre or by mode of recruitment. CONCLUSIONS: These results suggest a selection bias toward patients with longer symptomatic acute HIV-1 infection enrolled in the RCT. Data collected from RCT are not comparable to that collected in observational studies. However, data from collaborative international studies can be combined.

CD4 Lymphocyte Count↗
PubMed2000

Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial.

CONTEXT: Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries is unknown. OBJECTIVES: To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and formula-fed infants. DESIGN AND SETTING: Randomized clinical trial conducted from November 1992 to July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. PARTICIPANTS: Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points. INTERVENTIONS: Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213). MAIN OUTCOME MEASURES: Infant HIV-1 infection and death during the first 2 years of life, compared between the 2 intervention groups. RESULTS: Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative probability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P = .001). The estimated rate of breast milk transmission was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P = .30). The rate of HIV-1-free survival at 2 years was significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P = .02). CONCLUSIONS: The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-free survival.

AIDS Serodiagnosis↗
PubMed2000

beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics.

The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting alpha-subunit of the channel is regulated by two known auxiliary subunits, beta1 and beta2. We have identified rat and human forms of an additional subunit, beta3. It is most closely related to beta1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, beta3 inactivates sodium channel opening more slowly than beta1 does. Structural modeling has identified an amino acid residue in the putative alpha-subunit binding site of beta3 that may play a role in this difference. The expression of beta3 within the central nervous system differs significantly from beta1. Our results strongly suggest that beta3 performs a distinct neurophysiological function.

Amino Acid Sequence↗
PubMed2000

Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse.

Adenovirus-mediated gene transfer may hold much promise in the treatment of human cancer. However, concerns regarding vector dissemination beyond the target tissue, particularly with replication-competent viruses, require an evaluation of the persistence of viral infection in collateral tissue and vector-associated toxicities. In addition, for indications such as prostate cancer, the proximity of the point of viral administration to organs of the male reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To address these concerns, the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent adenovirus (Ad5-CD/TKrep) following intraprostatic administration in the mouse was examined. Ad5-CD/TKrep (10(10) vp, 5 x 10(11) vp/kg) was injected intraprostatically on Day 1 of the study and its presence in the major organs of the male urogenital tract (prostate, testes, seminal vesicles, and urinary bladder) and liver was determined on Days 8 and 29. For comparison, a parallel group of animals was injected with the same dose of a related replication-defective Ad5-FGNR virus. To evaluate germ-line transmission, Ad5-CD/TKrep-injected males were mated to females on Days 8 and 29 and resulting embryos were examined for AdS-CD/TKrep viral DNA. Ad5-CD/TKrep viral DNA was detected in all major organs of the adult male urogenital tract and liver 7 and 28 Days postinjection. Interestingly, relative to the replication-defective Ad5-FGNR adenovirus, the replication-competent Ad5-CD/TKrep virus accumulated to a much greater level (approximately 300-fold) and persisted for a longer period of time in prostate, testes, and liver. This difference could not be explained on the basis of differences in viral infectivity, suggesting that the AdS-CD/TKrep virus may be capable of replicating in mouse tissues in vivo. In vitro infection of six mouse cell lines representing prostate, testes, and liver demonstrated that the Ad5-CD/TKrep virus was indeed capable of replicating in these mouse cell types, albeit with reduced efficiencies relative to human cells. Despite the fact that the Ad5-CD/TKrep vector persisted in the adult male gonads and may have replicated in vivo, we observed no evidence of germ-line transmission in 149 offspring examined. To evaluate the toxicity of combining Ad5-CD/TKrep viral therapy with CD/5-FC and HSV-1 TK/GCV suicide gene therapies as a prerequisite for a human trial, an escalating dose (10(8), 10(9), 10(10) vp) of Ad5-CD/TKrep was administered intraprostatically followed by 7 days of 5-FC and GCV double prodrug therapy. Although the virus persisted in the mouse urogenital tract and liver for up to 28 days postinjection, most of the toxicities observed were expected, minimal, and self-limiting. These results lead us to believe that intraprostatic administration of the Ad5-CD/TKrep virus to humans concomitant with double suicide gene therapy will be associated with acceptable toxicities and will not result in vertical transmission of viral-encoded genes through the germ line.

Adenoviridae↗
PubMed2000

In vitro transport and delivery of antisense oligonucleotides.

A variety of techniques are currently available to enhance the cellular uptake and pharmacological effectiveness of antisense oligonucleotides in the in vitro setting. The choice of technique will depend on the context of investigation, the likelihood of cytotoxity due to the delivery agents, and the ease and convenience of the approach. The considerations for the delivery of antisense molecules in the in vivo setting are likely to be quite different from the cell culture situation emphasized in this article.

Amino Acid Sequence↗
PubMed2000

Prolonged changes in neurochemistry of dopamine neurones after chronic ethanol consumption.

The effects of 3 weeks of chronic ethanol consumption in mice on brain concentrations and turnover of monamine transmitters was examined. The measurements were made at 24 h, 6 days and 2 months after cessation of the ethanol intake to examine changes that might be relevant to relapse drinking. Increases in noradrenaline and dopamine concentrations, and decreases in the ratios of dopamine metabolites to dopamine, were seen in ventral tegmental tissue at 24 h after alcohol consumption. Increased noradrenaline was also evident at the 6-day interval, but no other changes were seen at this time. At the 2-month interval, the ventral tegmentum from ethanol-treated animals showed decreases in metabolite/dopamine ratios. No changes were seen in 5-hydroxytryptamine or its metabolite. In striatal tissue, none of these changes were seen, but at 24 h decreases occurred in the content of dopamine and its metabolites and a decrease in 5-hydroxyindoleacetic acid. The results indicate changes occur in monoamine turnover in the VTA as long as 2 months after cessation of chronic ethanol consumption; such changes may be related to the prolonged nature of alcohol dependence.

Alcoholism↗
PubMed2000

Pressure sores in children--the acute hospital perspective.

There is very little published literature on pressure sores in children and most of the existing literature is qualitative. Using literature from paediatric and adult studies, a schedule was designed to collect quantitative data on aspects that may predispose children to pressure injury. The schedule was piloted in an incidence and a prevalence study at the Royal Liverpool Children's NHS Trust. The sample size was 82 children for the incidence study and 183 children for the prevalence study. Six children in the incidence study and 12 children in the prevalence study sustained pressure injury. Data indicated that factors most strongly associated with pressure injury were nutritional status, mobility and consciousness level. Other factors that were implicated in increasing susceptibility to pressure injury were skin condition, body weight, haemodynamic status and hydration. Infants and young children most frequently sustained pressure injury on the occipital scalp area and heels. Although this was a small study, it produced some useful preliminary data, and was a valuable exercise to develop a tool for data collection on a larger scale.

Acute Disease↗
PubMed2000

Recombinant phytochrome of the moss Ceratodon purpureus (CP2): fluorescence spectroscopy and photochemistry.

The recombinant phytochrome of the moss Ceratodon purpureus (CP2) expressed in Saccharomyces cerevisiae and reconstituted with phycocyanobilin (PCB) was investigated using fluorescence spectroscopy. The pigment had an emission maximum at 670 nm at low temperature (85 K) and at 667 nm at room temperature (RT) and an excitation maximum at 650-652 nm at 85 K (excitation spectra could not be measured at RT). Both spectra had a half-band width of approx. 30-35 nm at 85 K. The fluorescence intensity revealed a steep temperature dependence with an activation energy of fluorescence decay (Ea) of 5.9-6.4 and 12.6-14.7 kJ mol(-1) in the interval from 85 to 210 K and from 210 to 275 K, respectively. The photochemical properties of CP2/PCB were characterised by the extent of the red-induced (lambda(a) = 639 nm) Pr conversion into the first photoproduct lumi-R at 85 K (gamma1) of approximately 0.07 and into Pfr at RT (gamma2) of approximately 0.7. From these characteristics, CP2/PCB can be attributed to the Pr" photochemical type with gamma1 < or = 0.05, which comprises the minor phyA fraction (phyA"), phyB, Adiantum phy1 and Synechocystis Cph1 in contrast to the major phyA' fraction (Pr' type with gamma1 = 0.5). Within the Pr" type, it is closer to phyA" than to phyB and Cph1.

Bryopsida↗
PubMed2000

Further evidence for the role of the alpha(2)delta subunit of voltage dependent calcium channels in models of neuropathic pain.

1. Current analgesic therapy is dominated by NSAIDs and opiates, however these agents have limited efficacy in the treatment of neuropathic pain. The novel anticonvulsant agent gabapentin (Neurontin) has been shown to be an effective treatment for neuropathic pain in the clinic. Recent studies have demonstrated that gabapentin selectively interacts with the alpha(2)delta subunit of voltage dependent calcium channels (VDCCs) which may be important in its mechanism of action. 2. Previous studies have identified a gabapentin analogue, 3-methyl gabapentin, that stereoselectively interacts with the alpha(2)delta subunit of VDCCs. Thus, whilst (1S, 3R) 3-methyl gabapentin binds to the alpha(2)delta protein with high affinity (IC(50)=42 nM), the corresponding (1R,3R) isomer is 300 times weaker (Bryans et al., 1998: J. Med. Chem., 41, 1838 - 1845). The present study examines the activity of diastereoisomers of 3-methyl gabapentin in two rat models of neuropathic pain to assess the importance of an interaction with the alpha(2)delta subunit of VDCCs. 3. (1S,3R) 3-methyl-gabapentin dose-dependently (10 - 100 mg kg(-1), p.o.) blocked the maintenance of static allodynia in the rat streptozocin and Chung models of neuropathic pain with MEDs of 30 mg kg(-1). This isomer also dose-dependently blocked the maintenance of dynamic allodynia in both models with respective MEDs of 30 and 100 mg kg(-1). In contrast, (1R,3R) 3-methyl gabapentin (100 mg kg(-1), p.o.) failed to block either static or dynamic allodynia in the streptozocin model. 4. It is concluded that these data further support the hypothesis that the alpha(2)delta subunit of VDCCs plays an important role in the maintenance of mechanical hypersensitivity in models of neuropathic pain.

Acetates↗
PubMed2000

The treatment of atopic dermatitis with adjunctive high-dose intravenous immunoglobulin: a report of three patients and review of the literature.

There are few reports of the use of high-dose intravenous immunoglobulin (hdIVIg) in the treatment of atopic dermatitis (AD). We describe our experience using this therapy in three patients with severe AD, all of whom had steroid-related side-effects. These patients received either Alphaglobin(R) or Sandoglobulin(R) 2 g/kg monthly: all had improved skin scores, allowing reduction of their steroid dose. Total IgE fell in one of three patients. We discuss the side-effects of hdIVIg and their management, and detail the differences between the available immunoglobulin products available in the U.K. There are several proposed mechanisms of action of this therapy which may be operative, and those most important in AD are discussed. In view of the time and expense involved in the treatment of patients with hdIVIg, careful patient assessment is vital. We describe dose reduction strategies and methods for cost containment. In addition, one of the patients has embarked on IVIg home therapy training. This will be the first time this has been attempted for a dermatological indication. Training of this type may be available through an immunotherapy service such as exists for patients with primary immunodeficiencies.

Adult↗
PubMed2000

A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response.

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.

Adult↗
PubMed2000

Comparison between videofluoroscopy and milk-swallow endoscopy in the assessment of swallowing function.

The investigation of swallowing function and the detection of aspiration has evolved over the past 10 years with the introduction of the fibreoptic endoscopic assessment. Practical reasons can limit the use of videofluoroscopy in some patients. A prospective study of 20 sets of videofluoroscopic and endoscopic assessments of swallowing function were compared. Endoscopic assessment was found to be a highly sensitive and specific method of determining swallowing safety. Reduced or absent laryngeal sensation at endoscopy correlates with silent aspiration and thus a high risk of aspiration pneumonia.

Aged↗
PubMed2000

Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy.

BACKGROUND: Renal microvascular injury characterizes thrombotic microangiopathy (TMA). The possibility that angiogenic growth factors may accelerate recovery in TMA has not been studied. METHODS: TMA was induced in rats by the selective right renal artery perfusion of antiglomerular endothelial cell IgG (30 mg/kg). Twenty-four hours later, rats received vascular endothelial growth factor (VEGF121, 100 microg/kg/day) or vehicle (control) daily until day 14. To evaluate renal function, the unperfused left kidney was removed at day 14, and rats were sacrificed at day 17. RESULTS: The induction of TMA was associated with loss of glomerular and peritubular capillary endothelial cells and decreased arteriolar density at day 1. Some spontaneous capillary recovery was present by day 17; however, repair was incomplete, and severe tubulointerstitial damage occurred. The lack of complete microvascular recovery was associated with reduced VEGF immunostaining in the outer medulla. VEGF-treated rats had more glomeruli with intact endothelium, less glomerular ischemia (collapsed glomeruli), and greater peritubular capillary density with less peritubular capillary loss. This was associated with less tubulointerstitial fibrosis, less cortical atrophy, and improved renal function. CONCLUSIONS: VEGF accelerates renal recovery in this experimental model of TMA. These studies suggest that angiogenic growth factors may provide a new therapeutic strategy for diseases associated with endothelial cell injury.

Animals↗