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Biomedical subjects

L Neville

Publications and source records attributed to L Neville.

15 recordsLinked to original sources
PubMed2001

High group A streptococcal carriage in the Orthodox Jewish community of north Hackney.

BACKGROUND: General practitioners and the microbiologist serving north Hackney in north east London formed the impression, that of throat swabs sent to the laboratory, a disproportionate number of those positive for group A streptococcus appeared to come from Orthodox Jewish patients. AIM: To confirm the clinical impression that the pharyngeal carriage of group A streptococci was higher in the Orthodox Jewish population than in other members of the population in the same locality. DESIGN OF STUDY: A general practice questionnaire survey of all patients aged three years or over attending two practices that are about one kilometre apart, over a five-week period. SETTING: Two general practices in north London, one of which had a significant Orthodox Jewish patient list. METHODS: Throat swabs were taken from eligible patients who were invited to participate by completing a questionnaire and having a throat swab taken. RESULTS: Swabs were taken from 1223 people. After correction for age (child or adult) and history of recent sore throat, the Orthodox Jewish community had a significantly higher carriage rate of group A streptococci than the rest of the population (odds ratio = 5.0 [2.1 to 11.9]). The proportion of adults with group A streptococci with and without sore throats was 6.4% and 2.4% respectively in the Orthodox Jewish group and 0.45% and 1% respectively in the 'others' group. The proportion of children with group A streptococci with and without sore throats was 17.4% and 5.9% respectively and 3.4% and 0% respectively in the others. These differences were not explained by the larger family size and domestic overcrowding in the Orthodox Jewish group. CONCLUSIONS: Orthodox Jews in north London have a higher pharyngeal carriage rate of group A streptococci than the neighbouring population. These results may have implications for the diagnosis and treatment of acute sore throat in Orthodox Jewish patients, especially children.

Adolescent↗
PubMed1999

The hepatitis B virus-trimera mouse: a model for human HBV infection and evaluation of anti-HBV therapeutic agents.

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals 1 month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. The HBV-Trimera model was used to evaluate the therapeutic effects of human polyclonal anti-HBs antibodies (Hepatect) and of two reverse-transcriptase inhibitors, lamivudine (3TC) and beta-L-5-fluoro-2',3'-dideoxycytidine (beta-L-5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both the percentage of infected animals and the viral load in their sera. Treatment cessation resulted in rebound of viral load, indicating HBV replication upon drug withdrawal. These results show that the HBV-Trimera model represents a novel experimental tool for simulating human HBV infection and evaluating potential anti-HBV therapeutic agents.

Animals↗
PubMed1998

Infection rates with and without T-tube splintage of common bile duct anastomosis in liver transplantation.

Stenting the bile duct over a T-tube after orthotopic liver transplantation (OLT) is the preferred method of biliary reconstruction. However, because of complications associated with the use of the T-tube, we evaluated the effect of various biliary anastomoses following 100 consecutive OLT (83 records were available for long-term evaluation) and assessed the clinical outcome of abandoning routine T-tube splintage. Of 16 OLT recipients with T-tube splintage (one died immediately following OLT and was excluded from the study), 6 patients (40%) developed six episodes of septicaemia secondary to biliary and/or intra-abdominal sepsis. Four of these six patients had a biliary leak (27%). Of 57 patients with duct-to-duct anastomosis without T-tube splintage, 7 patients developed biliary leak (12.3%) and only 1 developed septicaemia (1.7%) secondary to biliary and intra-abdominal sepsis (P = 0.0002). Of 11 patients with either a gallbladder conduit or Roux loop, only 1 patient had a biliary leak (9%) and there were no septicaemic episodes. In conclusion, direct duct-to-duct anastomosis resulted in significantly less morbidity due to infection without T-tube splintage than the use of a T-tube following OLT, but there were no significant differences in leakage and stricture rates.

Anastomosis, Roux-en-Y↗
PubMed1998

Effect of liposome-encapsulated hemoglobin on the development of endotoxin-induced shock in the rat.

Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying resuscitation fluid. Because LEH is cleared from the circulation primarily by the reticuloendothelial system, its effect on the development of sepsis remains a major concern. Thus, the present study aimed to evaluate whether LEH modifies consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at 10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05) and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by 3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later. In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin-induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor necrosis factor-alpha response without modifying its peak levels. LEH (n = 20) did not exacerbate the endotoxin-induced tachycardia, leukopenia, and thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin-induced responses was dependent on the time interval between LEH and endotoxin administration as well as the endotoxin dose. The clinical relevance of these results should be further investigated.

Animals↗
PubMed1997

Liposome-encapsulated hemoglobin modulates lipopolysaccharide-induced tumor necrosis factor-alpha production in mice.

OBJECTIVE: To investigate the effect of liposome-encapsulated hemoglobin, an experimental blood substitute, on the function of the mononuclear phagocytic system in normovolemic mic, in ex vivo murine splenocytes and in a transformed murine monocytic cell line, RAW 264.7. DESIGN: Prospective, randomized trial. SETTING: Center for Biomolecular Science and Engineering, Naval Research Laboratory, and the Thomas Jefferson University. SUBJECTS: Female Balb/c mice (n = 27). INTERVENTIONS: Mice were injected into the tail vein with liposome-encapsulated hemoglobin or liposome vehicle and were killed at varying time points for blood sampling and splenocyte isolation and culture. MEASUREMENTS AND MAIN RESULTS: Injection of liposome-encapsulated hemoglobin in mice (2.2 of lipid/kg and 0.56 g of hemoglobin/kg, n = 9) did not increase serum tumor necrosis factor (TNF)-alpha concentrations at 2, 8, 15, and 24 hrs after administration. In the ex vivo procedure, lipopolysaccharide (1 microgram/mL)-induced TNF-alpha production by splenocytes from mice injected with liposome-encapsulated hemoglobin was attenuated at 2 and 4 hrs (73%, p = .002 at 2 hrs), compared with TNF-alpha production by splenocytes from sham animals challenged with the same concentration of lipopolysaccharide. In the in vitro procedure, simultaneous exposure of liposome-encapsulated hemoglobin (0.88 to 8.8 mg/mL) and lipopolysaccharide (0.125 to 1 microgram/mL) to the murine-derived, peritoneal monocytic RAW 264.7 cell line showed significantly reduced TNF-alpha peptide, but not messenger RNA, 1 to 4 hrs after exposure as compared with cells challenged with lipopolysaccharide alone. This effect correlated with the rapid phagocytosis (1 hr to 4 hrs) of liposome-encapsulated hemoglobin by RAW 264.7 cells. Phagocytic activity in RAW 264.7 cells exposed to both liposome-encapsulated hemoglobin and lipopolysaccharide showed reduced uptake compared with uptake of liposome-encapsulated hemoglobin. The liposome-induced reduction in TNF-alpha peptide production elicited by lipopolysaccharide was countered by extending the time period to an overnight delay between liposome-encapsulated hemoglobin exposure and lipopolysaccharide challenge. Liposome-encapsulated hemoglobin incubated with lipopolysaccharide in vitro, and subsequently washed to remove free lipopolysaccharide, stimulated TNF-alpha expressed by RAW 264.7 cells. Incubation with liposome-encapsulated hemoglobin alone did not evoke TNF-alpha production in these cells. CONCLUSIONS: These data suggest that liposome-encapsulated hemoglobin modulates the response of the mononuclear phagocyte system to endotoxin, possibly through binding of lipopolysaccharide, presentation to macrophages with subsequent phagocytosis, and modulation of cytokine response by a posttranscriptional mechanism. This effect is attenuated by extending the period between exposure to liposome-encapsulated hemoglobin and endotoxin. The clinical relevance of these findings awaits further investigation.

Animals↗
PubMed1996

Liver biopsy in liver transplantation: no additional risk of infections in patients with choledochojejunostomy.

BACKGROUND/AIMS: This study aimed to determine whether there is an increased infectious risk following liver biopsy in liver transplant patients with choledochojejunostomy. METHODS: We evaluated the incidence of liver-biopsy-related sepsis in a consecutive series of 27 patients who underwent choledochojejunostomy, either during the transplant procedure (17 patients) or later following biliary complications (10 patients). We evaluated another 138 patients as a control group who had orthotopic liver transplantation during the same period and underwent duct-to-duct anastomosis. All liver biopsies had routine, prior ultrasound evaluation to detect dilated biliary ducts. RESULTS: In the 27 patients who underwent choledochojejunostomy, 96 liver biopsies were performed: the sepsis rate was 3.12% per biopsy (n = 96) or 7.4% per patient (n = 27). However, despite a normal ultrasound, subsequent ERCP demonstrated biliary obstruction in one patient. Thus the rate of sepsis was 2.1% per biopsy or 3.7 per patient. In the control group 338 liver biopsies were performed: the sepsis rate was 1.5% per biopsy (n = 338) or 2.9% per patient (n = 138). The difference was not significant. All septic episodes had positive blood cultures for a single enteric microorganism, and all responded to antibiotics CONCLUSIONS: Our data do not suggest that liver-transplanted patients with choledochojejunostomy are more at risk of sepsis following liver biopsy, providing there is no "occult" biliary obstruction; therefore, they do not require prophylactic antibiotics as has been suggested by other authors.

Adolescent↗
PubMed1995

Fragile X mental retardation syndrome: DNA diagnosis and carrier detection in New Zealand families.

AIMS: To establish a DNA-based test for the diagnosis and carrier detection of fragile X syndrome, and to investigate the nature of the mutation and patterns of inheritance in New Zealand families. METHODS: A probe for the FRAXA region was generated by polymerase chain reaction, cloned in a plasmid vector, and its structure was confirmed by DNA sequencing. This probe was used in a Southern blot assay to detect full mutations or premutations associated with fragile X syndrome in DNA from peripheral blood samples submitted to our laboratory for routine testing. RESULTS: We tested 379 individuals from throughout New Zealand. Full mutations were found in 29 males, leading to a fragile X diagnosis, or confirmation of an earlier cytogenetic diagnosis. Premutations were detected in 45 females and 11 males, all of whom are asymptomatic carriers of the disease. CONCLUSIONS: The DNA test is rapid and accurate, in contrast to the cytogenetic test. It allows unequivocal detection of carriers, enabling effective counselling, prenatal testing, and more generalised screening of at-risk populations. Our discovery of one large pedigree with many carriers and no prior history of X-linked mental retardation demonstrates that the DNA test is appropriate even in apparently sporadic cases of mental retardation.

Blotting, Southern↗
PubMed1990

Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure.

To study the primary structure of human acetylcholinesterase (AcChoEase; EC 3.1.1.7) and its gene expression and amplification, cDNA libraries from human tissues expressing oocyte-translatable AcChoEase mRNA were constructed and screened with labeled oligodeoxynucleotide probes. Several cDNA clones were isolated that encoded a polypeptide with greater than or equal to 50% identically aligned amino acids to Torpedo AcChoEase and human butyrylcholinesterase (BtChoEase; EC 3.1.1.8). However, these cDNA clones were all truncated within a 300-nucleotide-long G + C-rich region with a predicted pattern of secondary structure having a high Gibbs free energy (-117 kcal/mol) downstream from the expected 5' end of the coding region. Screening of a genomic DNA library revealed the missing 5' domain. When ligated to the cDNA and constructed into a transcription vector, this sequence encoded a synthetic mRNA translated in microinjected oocytes into catalytically active AcChoEase with marked preference for acetylthiocholine over butyrylthiocholine as a substrate, susceptibility to inhibition by the AcChoEase inhibitor BW284C51, and resistance to the BtChoEase inhibitor tetraisopropylpyrophosphoramide. Blot hybridization of genomic DNA from different individuals carrying amplified AcChoEase genes revealed variable intensities and restriction patterns with probes from the regions upstream and downstream from the predicted G + C-rich structure. Thus, the human AcChoEase gene includes a putative G + C-rich attenuator domain and is subject to structural alterations in cases of AcChoEase gene amplification.

Acetylcholinesterase↗
PubMed1982

Single-dose slow-release aminophylline at night prevents nocturnal asthma.

Twelve asthmatic patients with nocturnal wheezing were given a single nocturnal oral dose of slow-release aminophylline or matched placebo in a double-blind crossover trial. A dose of slow-release aminophylline (mean 683 mg; 10.4 mg/kg) gave a therapeutic plasma-theophylline concentration 10 h later (mean 10.9 mg/l). This was not associated with any adverse effects. Mean peak expiratory flow on waking was significantly greater with aminophylline (332 +/- 31 l/min) than placebo (283 +/- 32 l/min), whereas evening values did not differ. There was a significant difference between morning and evening peak flow on placebo (mean 22%) but not on aminophylline (5%), indicating abolition of the morning fall in peak flow. This was not at the expense of response to beta-agonists, since the response to inhaled salbutamol was the same for both treatments. The use of extra metered doses of inhaled beta-agonist during the night was significantly less with aminophylline, and there was a subjective improvement in nocturnal symptoms in all patients. Slow-release aminophylline in adequate dosage appears to be the most effective treatment yet demonstrated for nocturnal asthma.

Adrenergic beta-Agonists↗