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Biomedical subjects

G Abel

Publications and source records attributed to G Abel.

At least 19 recordsLinked to original sources

Limitations and uses of gastrojejunal feeding tubes.

BACKGROUND: Gastrostomy feeding is a well established alternative method to long term nasogastric tube feeding. Many such patients have gastro-oesophageal reflux (GOR) and require a fundoplication. A transgastric jejunal tube is an alternative when antireflux surgery fails, or is hazardous or inappropriate. AIMS: To review experience of gastrojejunal (G-J) feeding over six years in two regional centres in the UK. METHODS: Retrospective review of all children who underwent insertion of a G-J feeding tube. RESULTS: There were 18 children, 12 of whom were neurologically impaired. G-J tubes were inserted at a median age of 3.1 years (range 0.6-14.7) because of persistent symptoms after Nissen fundoplication (n = 8) or symptomatic GOR where fundoplication was inappropriate. Four underwent primary endoscopic insertion of the G-J tube; the remainder had the tube inserted via a previous gastrostomy track. Seventeen showed good weight gain. There was one insertion related complication. During a median follow up of 10 months (range 1-60), four experienced recurrent aspiration, bilious aspirates, and/or diarrhoea. There were 65 tube related complications in 14 patients, necessitating change of the tube at a median of 74 days. Jejunal tube migration was the commonest problem. Five died from complications of their underlying disease. CONCLUSIONS: Although G-J feeding tubes were inserted safely and improved nutritional status, their use was associated with a high rate of morbidity. Surgical alternatives such as an Roux-en-Y jejunostomy may be preferable.

Adolescent↗

Flow cytometric analysis of lymphocyte subpopulations in bronchoalveolar lavage fluid after repeated ozone exposure.

As known from studies in animal and human subjects, ozone can exert effects on the immune response including allergic sensitisation and allergen responsiveness. The objective of the present study was to assess the changes in lymphocyte subsets in bronchoalveolar lavage fluid (BALF) after single and repeated ozone exposures. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone or filtered air (FA), as well as repeated exposures to 200 ppb ozone on four consecutive days, each during 4 h of intermittent exercise. Bronchoalveolar lavage was performed 20 h after the single exposure or the last of the repeated exposures. Lymphocytes were identified by sideward scatter and CD45 expression, and their subsets by eight different panels of antibodies. Checksums were calculated to assess the validity of the results. The percentage and the absolute number of lymphocytes, mostly comprising T-lymphocytes (CD2+; overall mean 98.8%), increased after single (P < 0.05; each), but not after repeated ozone exposure, compared with FA (7.4 vs 5.8 vs 6.5%; 680 vs 419 vs 301 x 10(3)). In addition, we observed small but statistically significant changes in the proportions of lymphocyte subpopulations. The percentage of CD4+ lymphocytes increased after single (P < 0.05) and repeated ozone exposure (P < 0.01), whereas the percentage of CD8+ cells decreased after repeated exposure (P < 0.05). The proportion of activated lymphocytes (CD25+) was elevated after repeated, compared with single, ozone exposure (P < 0.01), and the percentages of natural killer (NK) cells were decreased after both single (P < 0.05) and repeated (P < 0.01) exposures. Our data suggest that single but not repeated ozone exposures cause a change in absolute numbers of lymphocytes in BALF, whereas the proportions of lymphocyte subsets are affected by single as well as repeated exposures.

Adult↗

A 'segmented' sex industry in New Zealand: sexual and personal safety of female sex workers.

OBJECTIVE: Assess differences in personal circumstances, risk exposure and risk-taking among female sex workers in different sectors of the New Zealand sex industry in regard to issues of sexual safety, drug use, violence and coercion. METHOD: A cross-sectional survey of 303 female sex workers was carried out in Christchurch, New Zealand, May-September 1999. RESULTS: There was evidence of 'segmentation': street workers were younger, had started work at a younger age and had less education than indoor workers. More street than indoor workers used money from sex work for drugs and used drugs at work. There was a high level of condom use but little 'negotiation' about them with clients. High levels of violent experiences were reported, but street workers reported more, and more extreme forms of, violence than indoor workers. IMPLICATIONS: Although knowledge of condom use and sexual safety appears generally high and women in both sectors report taking the initiative for safer sex, drug use, violence and coercion remain of concern. While sexual safety will need ongoing health promotion and education interventions to support and ensure the uptake of safer sex practice by new workers and prevent any relapse by more experienced workers, issues of violence and coercion also require attention to the power relationships between individuals. Legislation and policy directed at these issues should encourage the control women can exert over their work practice. Reducing exposure to personal risk may require different measures in different sectors.

Adolescent↗

Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study.

BACKGROUND AND PURPOSE: Stroke risk factors have been determined in large part through epidemiological studies in white cohorts; as a result, race-ethnic disparities in stroke incidence and mortality rates remained unexplained. The aim in the present study was to compare the prevalence, OR, and etiological fraction (EF) of stroke risk factors among white, blacks, and Caribbean Hispanics living in the same urban community of northern Manhattan. METHODS: In this population-based incident case-control study, cases (n=688) of first ischemic stroke were prospectively matched 1:2 by age, sex, and race-ethnicity with community controls (n=1156). Risk factors were determined through in-person assessment. Conditional logistic regression was used to calculate adjusted ORs in each race-ethnic group. Prevalence and multivariate EFs were determined in each race-ethnic group. RESULTS: Hypertension was an independent risk factor for whites (OR 1.8, EF 25%), blacks (OR 2.0, EF 37%), and Caribbean Hispanics (OR 2.1, EF 32%), but greater prevalence led to elevated EFs among blacks and Caribbean Hispanics. Greater prevalence rates of diabetes increased stroke risk in blacks (OR 1.8, EF 14%) and Caribbean Hispanics (OR 2.1 P<0.05, EF 10%) compared with whites (OR 1.0, EF 0%), whereas atrial fibrillation had a greater prevalence and EF for whites (OR 4.4, EF 20%) compared with blacks (OR 1.7, EF 3%) and Caribbean Hispanics (OR 3.0, EF 2%). Coronary artery disease was most important for whites (OR 1.3, EF 16%), followed by Caribbean Hispanics (OR 1.5, EF 6%) and then blacks (OR 1.1, EF 2%). Prevalence of physical inactivity was greater in Caribbean Hispanics, but an elevated EF was found in all groups. CONCLUSIONS: The prevalence, OR, and EF for stroke risk factors vary by race-ethnicity. These differences are crucial to the etiology of stroke, as well as to the design and implementation of stroke prevention programs.

Aged↗

Services and information utilised by female sex workers for sexual and physical safety.

AIMS: To examine services utilised by female sex workers in Christchurch for sexual and physical safety. METHOD: Estimates were made of the sex worker population in Christchurch before conducting a cross-sectional survey. RESULTS: 303 women responded. Almost all went for sexual health check-ups. Most (251) had a general practitioner, but only about half disclosed they were sex workers. Of the 135 women who used their own general practitioner for sexual health checks, 62% disclosed they were sex workers. In general, the women relied upon informal networks for information and advice, but the peer organisation of New Zealand Prostitutes Collective was also important. CONCLUSION: While general practitioners were used by the majority of sex workers, high levels of nondisclosure need to be understood and redressed. The preference of sex workers for informal, peer relationships should be considered in future health promotion efforts.

Adolescent↗

Children with neurological disorders do not always need fundoplication concomitant with percutaneous endoscopic gastrostomy.

Whether antireflux surgery should be routinely performed at the time of gastrostomy in children with neurological disorders is debatable because of the risk of gastroesophageal reflux. Some argue that these children should be screened for occult gastroesophageal reflux as this will determine the need for fundoplication. This study retrospectively examines outcome in 29 children with neurological disorders who underwent percutaneous endoscopic gastrostomy (PEG) without concomitant fundoplication. Children were included if they had no clinical evidence of severe gastroesophageal reflux before PEG insertion. The median age of children at PEG insertion was 5.6 years (range 1.1 to 18.0). The children were followed for a median of 2.6 years (range 0.4 to 4.9). Insertion of PEG was technically impossible in two children; and an asymptomatic gastrocolic fistula in another child led to subsequent tube removal. Fourteen of the 26 remaining children developed symptomatic gastroesophageal reflux after PEG; five of these showed no reflux on pH monitoring prePEG. Control of symptoms was achieved by medical intervention in 12, but two required fundoplication. Our findings indicate that in the child with neurological disabilities without symptoms indicating severe gastroesophageal reflux, fundoplication is unlikely to be necessary as a consequence of PEG insertion. We conclude that routine investigation for gastroesophageal reflux in the child without severe vomiting can be avoided and the number of antireflux procedures reduced.

Child, Preschool↗

Management of septicaemic infants during long-term parenteral nutrition.

Young infants, particularly following gastrointestinal surgery, are at high risk of septicaemia during parenteral nutrition. Febrile illness in the absence of focal infection inevitably raises suspicion of central venous catheter sepsis and poses the following dilemma: remove the catheter (which may then prove uninfected) and lose venous access, or leave the catheter and risk clinical deterioration? We examined retrospectively the isolates from blood culture during febrile episodes in 13 children who received long-term (> 2 months) parenteral nutrition via a central venous catheter, and assessed the effectiveness of through-catheter antibiotic treatment during 76 episodes of blood culture positive sepsis. Coagulase-negative Staphylococci accounted for only 16% of positive isolates, with yeasts accounting for 5%, and Gram-negative organisms accounting for 46%, suggesting that infection was often associated with bacterial translocation from the gastrointestinal tract. Treatment with the central venous catheter left in situ was successful in resolving infection in 53 (70%) of septic episodes. These findings indicate that, in this specific group of patients, through-catheter antibiotic treatment is often effective in treating septicaemia. When long-term venous access is essential, this approach should be tried before recourse to central venous catheter removal.

Anti-Bacterial Agents↗

Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor.

Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV system indicated that the LDL receptor may be the main but not exclusive means of cell entry of these viruses. Studies on other types of viruses indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associate with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.

Animals↗

Limited ileal resection in infancy: the long-term consequences.

BACKGROUND/PURPOSE: The longer-term sequelae of short bowel syndrome in infancy are reasonably well documented, but little is known about the long-term nutritional and metabolic effects of limited (less than 50 cm) ileal resection. This makes it difficult to formulate a rational follow-up policy in such children. METHODS: All children who underwent limited ileal resection for either necrotizing enterocolitis (NEC) or intussusception at our institution between 1984 and 1992 were invited to attend a detailed clinical, anthropometric, hematologic, and biochemical assessment, together with a biliary and renal ultrasound scan and measurement of bone mineral density. RESULTS: Twenty-four children (NEC, 17; intussusception, 7) of median age 7.4 years (range, 5.5 to 13.7 years) agreed to participate. Nine previously had undergone an isolated ileal resection, and 15 also had had variable lengths of colon removed. The length of resected ileum ranged from 3 to 44 cm, with a median of 10 cm. Seven control subjects in whom neonatal NEC developed but recovered without surgery were also evaluated. Median height, weight, and body mass index after ileal resection were between the 25th and 50th percentiles; no child was stunted or wasted. After ileal resection, one boy was found to have asymptomatic vitamin B12 deficiency, and three children had low plasma concentrations of vitamin A. Hematologic and biochemical parameters were otherwise normal apart from a few marginally low trace element levels in both subjects and controls. No renal calculi were detected, and bone mineral density measurements were normal in all except one child. Four children had cholelithiasis, all of whom had previously undergone limited ileal resection for NEC (two isolated, two ileocolic). Thus, the prevalence of cholelithasis after limited ileal resection for NEC was 24% at a median age of 7.0 years. CONCLUSIONS: Growth and nutritional status are well preserved after limited ileal resection in infancy. Limited ileal resection for NEC is associated with a subsequent high prevalence of cholelithiasis and a risk of vitamin B12 deficiency. These findings are important when planning strategies for long-term follow-up.

Bone Density↗

A competitive reverse transcription-polymerase chain reaction assay for quantitation of GB virus C/hepatitis G virus RNA that circumvents heteroduplex artifact.

The role of GB virus C (GBV-C)/hepatitis G virus (HGV) in hepatitis has been controversial. To investigate its possible pathogenicity and site(s) of replication, it is important to develop an accurate quantitative assay for both positive and negative strand GBV-C/HGV RNA. In this study, a competitive reverse transcription-polymerase chain reaction (RT-PCR) assay for both positive and negative strand GBV-C/HGV RNA quantitation was developed. In developing the quantitative assay, heteroduplex formation was repeatedly observed. A heterologous competitor RNA with GBV-C/HGV primer-binding sequences was introduced, and heteroduplex artifact was circumvented successfully. Two-hundred thirty-seven serum specimens were screened by RT-PCR for GBV-C/HGV RNA. Two of the 62 patients infected with chronic hepatitis C virus (HCV) were found to be positive for GBV-C/HGV RNA. None of the 50 other patients with no evidence of HCV infection and none of the 125 normal individuals were positive for GBV-C/HGV RNA. The sensitivity of RT-PCR was 3000 gE/ml (30 gE in RT-PCR). Alternate methods for residual DNA removal and its detection in synthetic RNA were introduced. A RT control containing no primer before PCR is necessary to evaluate the trace amounts of template DNA remaining in synthesized RNA. The method will differentiate reliably between positive and negative strand RNAs up to a 10(4)-fold difference in titer. The positive and negative strand GBV-C/HGV RNAs were detected in one patient by RT-PCR and hybridization analysis, and the strand titer was determined by RT-PCR.

Adult↗

Detection of widespread hepatocyte infection in chronic hepatitis C.

The controversial question of the extent of hepatocyte infection in chronic hepatitis C was re-examined in both chimpanzees and humans using a newly modified in situ hybridization (ISH) method for detecting hepatitis C virus (HCV) RNA. The specificity of the methodology for distinguishing positive- and negative-strand synthetic HCV RNA was at least six magnitudes greater than the reverse-transcription polymerase chain reaction (RT-PCR) assay for HCV. The sensitivity of the methodology as determined by cell culture assay was 14 +/- 2 genomic equivalents (gE) of HCV positive strand per cell, which was three magnitudes less sensitive than RT-PCR quantitation of HCV. In contrast to previous studies in both humans and chimpanzees with chronic hepatitis C, a high percentage of hepatocytes positive for both positive- and negative-strand HCV RNA was found in most specimens studied. In humans, the extent of hepatocyte infection varied with histological activity index (HAI). In the two chimpanzees studied, the liver biopsies showed minimal histological disease activity, but high percentages of hepatocytes were HCV-positive by ISH that correlated with hepatocyte ultrastructural changes associated with HCV infection. Hepatocyte infection was confirmed by RNA extraction and RT-PCR techniques for detecting HCV RNA that minimize the false detection of negative strands. In both human and chimpanzee liver biopsies showing minimal HAI, the hepatocyte concentration of HCV was estimated to be very low. These findings suggested the hypothesis that persistent infection in the liver may be caused in part by low-level HCV replication. The theoretical and clinical implications of these findings are discussed.

Adult↗

Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia.

OBJECTIVE: To investigate the role of hepatitis C virus (HCV) in the pathogenesis of the cutaneous vasculitis in patients with type II cryoglobulinemia. METHODS: Using in situ hybridization detection of HCV, we studied 6 test patients and various control subjects. Serum HCV was quantitated, cryoglobulins were analyzed by column chromatography at 37 degrees C, and low-density lipoprotein (LDL) receptors on keratinocytes were detected using LDL labeled with fluorescent dye. RESULTS: In the cutaneous vasculitic lesions from test patients, but not control subjects, the HCV virion was found in association with IgM and IgG. HCV alone was detected in some vessel walls, and in skin and ductal epithelium and vascular endothelium in inflamed, but not normal, skin. Cryoglobulins showed HCV, monomeric IgM, and monomeric IgG, with little or no immune complexes. The extent of the lesions correlated with levels of viremia. Up-regulation of LDL receptors on keratinocytes was detected in inflamed, but not normal, skin. CONCLUSION: HCV was present in the cutaneous vasculitic lesions, most likely in complexes with IgM and IgG formed in situ. These findings and the correlation of the severity of the rash with the level of viremia suggest that HCV plays a major role in the pathogenesis of cutaneous vasculitis in these patients and strengthens the rationale for antiviral drug therapy. The presence of HCV in keratinocytes and ductal epithelial and vascular endothelial cells may be the in vivo manifestation of endocytosis of HCV by the LDL receptors that has recently been demonstrated in vitro. The up-regulation of LDL receptors on keratinocytes in inflamed skin is consistent with this postulation.

Biopsy↗

Organ-specific differences in the ratio of alternatively spliced chorismate synthase (LeCS2) transcripts in tomato.

The primary transcript of one of the two chorismate synthase genes (LeCS2) of tomato is differentially processed due to an alternative splicing of the third intron. A novel observation was made when the abundances of the two LeCS2-specific transcripts in different organs were analysed. The ratio of these two transcripts differs in RNA populations from different organs. Possible explanations for this finding and its potential physiological impact for plant metabolism are discussed.

Alternative Splicing↗

Mechanism of action of an orally administered platinum complex [ammine bis butyrato cyclohexylamine dichloroplatinum (IV) (JM221)] in intrinsically cisplatin-resistant human ovarian carcinoma in vitro.

Intrinsic resistance to existing clinical platinum drugs is a major cause of treatment failure; moreover, these agents have the drawbacks of cross-resistance and intravenous administration. The mechanism of intrinsic cisplatin resistance and the mechanism of circumvention of intrinsic resistance by a member (JM221) of the ammine/amine platinum (IV) dicarboxylate class of platinum complex was studied in intrinsically resistant (SKOV-3) and sensitive (41M) human ovarian carcinoma cell lines. JM221 reduced the cisplatin resistance factor nine- to 2.7-fold, was more potent than cisplatin and showed marked time-dependent cytotoxicity. Cellular platinum accumulation was 20- to 40-fold greater (P < 0.001), and DNA platination was fourfold greater (P < 0.02), immediately following 2 h equimolar exposure to JM221, compared with cisplatin. DNA platinum levels decreased following cisplatin exposure with a half-life approximating 48 h in both lines, while no net removal of DNA-bound platinum was recorded following JM221 exposure. JM221 caused DNA interstrand cross-linking, but this was 10-20% less frequent with JM221 than with cisplatin when expressed as a proportion of total DNA platinum lesions. Cisplatin DNA interstrand cross-linking was twofold greater in the intrinsically sensitive line (41M) than in the resistant line (SKOV-3) over a range of concentrations and time-points. Neither cellular platinum accumulation, levels of DNA platination nor the rate of removal of DNA-bound platinum in the two cell lines related to their ninefold difference in cisplatin sensitivity. Intrinsic cisplatin resistance appears to be attributable to the inhibition of formation of bifunctional DNA lesions, while the circumvention of intrinsic resistance by JM221 seems to be the result of both improved transport properties and circumvention of DNA repair mechanisms.

Antineoplastic Agents↗

Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron-withdrawing groups in place of methyl.

In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble.

Animals↗