Improved outcome after intestinal transplantation: an 8-year, single-center experience.
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Biomedical subjects
Publications and source records attributed to S Dawson.
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The antimicrobial sensitivities of 78 recent (1995-1998) canine isolates of Bordetella bronchiseptica from 13 separate sources were determined. Minimum inhibitory concentrations were assessed using the E-test method or by agar dilution. All 78 isolates were sensitive to tetracycline, doxycycline, enrofloxacin, and amoxycillin/clavulanic acid; the majority were sensitive to ampicillin (63/78; 81%), trimethoprim (57/78; 73%), and sulphadiazine (63/78; 81%). Plasmids were detected in 14 out of the 24 isolates tested. There was no correlation between the presence of plasmids and antibiotic resistance, but there was some correlation between the presence of plasmids and the origin of the isolates. Three sizes of plasmid were found: 20, 14, and 5.5 kb. Eight of the isolates contained all three plasmids, the remainder one or two, Thirteen isolates demonstrated beta-haemolysis, of which six produced a soluble haemolysin. Except for one isolate, haemolysin production correlated with plasmid carriage. Pulsed-field gel electrophoresis showed that all except one isolate could be grouped in the same genotype. Within this genotype isolates could be divided into three subtypes, generally corresponding to their place of origin.
Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa, where hepatitis virus infection and exposure to specific liver carcinogens are prevalent. Although inactivation of some tumor suppressor genes such as p53 and p16INK4Ahas been identified, no known oncogene is commonly activated in hepatocellular carcinomas. Here we have isolated genes overexpressed in hepatocellular carcinomas by cDNA subtractive hybridization, and identified an oncoprotein consisting of six ankyrin repeats (gankyrin). The expression of gankyrin was increased in all 34 hepatocellular carcinomas studied. Gankyrin induced anchorage-independent growth and tumorigenicity in NIH/3T3 cells. Gankyrin bound to the product of the retinoblastoma gene (RB1), increasing its phosphorylation and releasing the activity of the transcription factor E2F-1. Gankyrin accelerated the degradation of RB1 in vitro and in vivo, and was identical to or interacted with a subunit of the 26S proteasome. These results demonstrate the importance of ubiquitin-proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1.
A cross-sectional survey of a convenience sample of cats was carried out to determine the prevalence of and risk factors for respiratory tract disease, feline calicivirus (FCV) infection and feline herpesvirus (FHV) infection. Seven hundred and forty cats were studied; samples for isolation of FCV and FHV were obtained from 622 (84%). Data on individual cat and household variables were obtained by questionnaire for each cat and analysed using univariable and logistic regression analysis. Thirty-eight percent (282/740) of cats surveyed had respiratory tract disease. Eighteen of 24 predictor variables were found to be significantly (P<0.05) associated with the presence of respiratory tract disease in a cat on univariable analysis. Following logistic regression, several factors retained significance including isolation of FCV and FHV, younger cats (4-11 months of age) and multiple cat households. A negative association was found with breeding catteries and other types of household in comparison with rescue catteries. Overall, feline calicivirus was isolated from 162/622 (26%) of cats sampled; 33% of the cats with respiratory tract disease were FCV positive compared to 21% of healthy cats. Variables significantly associated with FCV isolation on logistic regression were the presence of respiratory tract disease and contact with dogs with and without respiratory tract disease. Feline herpesvirus was isolated from 30/622 (5%) of all cats sampled; 11% of cats with respiratory tract disease were FHV positive compared to 1% of healthy cats. Variables significantly associated with FHV isolation on univariable analysis included age, gender, and the presence of respiratory tract disease. Vaccination showed a negative association. Logistic regression analysis of the data for FHV was limited by the sample size and the low prevalence of FHV.
Orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) infection was limited until recently by poor graft and patient outcomes caused by recurrent HBV. Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) dramatically improved post-OLT survival, but recurrent HBV still occurred in up to 36% of the recipients. More recently, combination HBIG and lamivudine has been shown to effectively prevent HBV recurrence in patients post-OLT. The aim of the current study is to determine long-term outcome and cost-effectiveness of using combination HBIG and lamivudine compared with HBIG monotherapy in patients who undergo OLT for HBV. A retrospective chart review identified 59 patients administered combination HBIG and lamivudine and 12 patients administered HBIG monotherapy as primary prophylaxis against recurrent HBV. Lamivudine, 150 mg/d, was administered orally indefinitely. HBIG was administered under a standard protocol (10,000 IU intravenously during the anhepatic phase, then 10,000 IU/d intravenously for 7 days, then 10,000 IU intravenously monthly) indefinitely. A decision-analysis model was developed to evaluate the potential economic impact of prophylaxis against HBV with combination therapy compared with monotherapy. Recurrent HBV was defined as the reappearance of hepatitis B surface antigen (HBsAg) after its initial disappearance post-OLT. In the combination-therapy group, no patient redeveloped serum HBsAg or HBV DNA during mean follow-ups of 459 and 416 days, respectively. In the monotherapy group, 3 patients (25%) had reappearance of HBsAg in serum during a mean follow-up of 663 days. Combination therapy resulted in a dominant, cost-effective strategy with an average cost-effectiveness ratio of $252,111/recurrence prevented compared with $362,570/recurrence prevented in the monotherapy strategy. Combination prophylaxis with HBIG and lamivudine is highly effective in preventing recurrent HBV, may protect against the emergence of resistant mutants, and is significantly more cost-effective than HBIG monotherapy with its associated rate of recurrent HBV.
OBJECTIVE: To determine the factors that influence patient survival after in vivo split liver transplantation (SLT). SUMMARY BACKGROUND DATA: Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. METHODS: During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. RESULTS: Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. CONCLUSIONS: Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.
Key issues addressing appropriateness of triage decisions and the tools needed to support those decisions are identified in this article. The limitations of current approaches to appropriate utilization such as admission and continued-stay criteria, medical management models, bed control and bed management strategies, and rounding practices are discussed, and a systemic model to examine the placement of patients is proposed. Determining which patients can benefit from critical care and which can benefit from an alternative level of care is analyzed through the use of clinical decision support tools that provide both retrospective analysis of current patterns and predictive models to assist the clinician in making continued-stay decisions. Patient populations who are considered for alternative placement are defined. Those populations identified as having the potential to gain limited benefit from the level of intensity of an intensive care unit are managed in alternative sites. The role played by the advanced practice clinician in using clinical decision support tools is discussed.
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The study determines the sequence evolution of feline calicivirus both in cell culture and in persistently infected cats and relates this to changes in virus neutralisation.
A cross-sectional survey of a convenience-sample of 740 cats was undertaken to obtain an estimate of the prevalence of Bordetella bronchiseptica infection, and to identify risk factors that might predispose them to the infection. Data on individual cats and household variables, including disease status and animal contacts were obtained by questionnaire. B bronchiseptica was isolated from 82 (11 per cent) of the cats sampled. The prevalence of B bronchiseptica varied with the type of household sampled, being 19.5 per cent in rescue catteries, 9 per cent in breeding catteries, 13.5 per cent in research colonies, and 0 per cent in household pets. On the basis of a univariable analysis, 19 of 29 predictor variables were found to be significantly associated with the isolation of B bronchiseptica, including an association with cats in rescue catteries, and with cats from premises with larger numbers of animals. Separate analysis of the rescue cattery subpopulation showed a highly significant association on multivariable analysis with current respiratory disease, suggesting that different risk factors may operate in this type of environment. In the whole sample there was also strong association with cats from households containing a dog with recent respiratory tract disease. The clinical signs observed in the B bronchiseptica-positive cats included sneezing, ocular and nasal discharges and coughing, although only the association with sneezing was statistically significant. There was no significant association between the isolation of B bronchiseptica and the isolation of respiratory viruses, suggesting that in some circumstances B bronchiseptica may be able to cause disease independently.
Each 19S regulator of the 26S proteasome contains six ATPase subunits as well as many (>14) non-ATPase protein subunits. The ATPase subunits have been detected in other complexes which may regulate transcription and possibly other cellular processes. The S10b (yeast SUG2 or human p42) and the S6' (TBP1) ATPases have been found in an activator complex (modulator) prepared from bovine red cells. We have identified and partially characterised a similar activator from different human tissues (from soluble extracts of human brain, placenta and human embryonic kidney cells) and an insect: an activator is present in soluble extracts of abdominal intersegmental muscle from Manduca sexta. Activation is ATP and concentration dependent. There is no stimulation of human red cell-derived 20S proteasome by the Manduca activator ruling out 11S regulator in the preparations. Additionally, cross-species activation occurs: the Manduca activator increases the activity of rat skeletal muscle 26S proteasomes and the human placental activator similarly increases the activity of 26S proteasomes prepared from muscles from Manduca sexta. Finally, there is no evidence for other ATPases in the activator complex.
OBJECTIVES: Substance use during pregnancy causes significant morbidity and mortality. Screening for substance use provides opportunity for intervention and treatment, but is often overlooked in prenatal care with today's fiscal climate and preconceived ideas about who uses substances. The purpose of this study was to determine the effect of implementing a more comprehensive screening procedure for identifying substance-using pregnant women. METHODS: Two hundred randomly selected prenatal patients screened using the old procedure for substance use during pregnancy were compared to 400 randomly selected patients screened after implementation of a new, more detailed screening procedure. The old screening approach included three check-boxes concerning substance use during pregnancy: one for "Smoking/alcohol," one for "Drug use (any)," and one for "Drug addiction/alcoholism." The new screening procedure included more detailed questions about the frequency of cigarette, alcohol, and illegal drug use during pregnancy. RESULTS: Compared with the old approach, the new screening protocol increased reporting of smoking/alcohol use from 21% to 72% (relative risk = 2.63, 95% confidence interval = 2.231, 3.108); reporting of any drug use from 12% to 18% (relative risk = 1.07, 95% confidence interval = 1.002, 1.150); and reporting of alcoholism/drug abuse from 0% to 6% (relative risk = 1.06, 95% confidence interval = 1.038, 1.090). CONCLUSIONS: Our study suggests that more detailed screening using direct questions concerning the amount and frequency of substance use increases reporting of prenatal substance use as compared to screening approaches using only "yes/no" style check boxes.
Feline Bordetella bronchiseptica infection had received little consideration until recent years when it has been increasingly documented in association with respiratory disease. This article reviews current knowledge on the organism; its epidemiology, pathogenesis, and clinical, diagnostic and therapeutic features.
In order to map linear B-cell (LBC) epitopes in the major capsid protein of feline calicivirus (FCV), an expression library containing random, short (100- to 200-bp) fragments of the FCV F9 capsid gene was constructed. Analysis of this library showed it to be representative of the region of the capsid gene that encodes the mature capsid protein. The library was screened by using polyclonal antisera from a cat that had been challenged experimentally with F9 to identify immunoreactive clones containing LBC epitopes. Twenty-six clones that reacted positively to feline antisera in immunoblots were identified. FCV-derived sequence from these clones mapped to a region of the capsid that spanned 126 amino acids and included variable regions C and E. An overlapping set of biotinylated peptides corresponding to this region was used to further map LBC epitopes by using F9 antisera. Four principal regions of reactivity were identified. Two fell within the hypervariable region at the 5' end of region E (amino acids [aa] 445 to 451 [antigenic site (ags) 2] and aa 451 to 457 [ags 3]). However, the other two were in conserved regions (aa 415 to 421 [ags 1; region D] and aa 475 to 479 [ags 4; central region E]). The reactivity of the peptide set with antisera from 11 other cats infected with a range of FCV isolates was also determined. Ten of 11 antisera reacted to conserved ags 4, suggesting that this region may be useful for future recombinant vaccine design.
A case study of clinical practice in children with glue ear is presented. The case is part of a larger project, funded by the North Thames Research and Development Programme, that sought to explore the part played by clinicians in the implementation of research and development into practice in two areas: adult asthma and glue ear in children. What is striking about this case is the differences found in every area of the analysis. That is, diversity was found in views about diagnosis and treatment of glue ear; the organisation of related services; and in the reported practice of our interviewees, both between particular groupings of clinical staff and within these groupings. The challenge inherent in the case is to go beyond describing the complexity and differences that were found, and look for patterns in the accounts of practice and tease out why such patterns may occur.
A case study of clinical practice in adult asthma is presented. The case is part of a larger project, funded by the North Thames NHS Executive Research and Development Programme, that sought to explore the part played by clinicians in the implementation of research and development into practice in two areas: adult asthma and glue ear in children. The first case of glue ear in children was reported in a previous issue of this journal (Quality in Health Care 1999;8:99-107). Background information from secondary sources on the condition, treatment, and organisation and location of care is followed by an account of the results of semistructured interviews with 159 clinicians. The findings are reported in two sections: clinical management and the organisation of care, and clinicians' accounts of what, why, and how they introduce changes into their practice. The way clinicians talk about their learning, their expressed views on acceptable practice, and their willingness to change were shown to be informed by construction of legitimate and sufficient evidence, respected colleagues, and accumulated individual experience. There was little open acknowledgment of the influence of organisational factors in influencing practice. To investigate whether relationships between task performance and organisational arrangements found in other sectors apply to UK health, more robust measures by which performance can be evaluated are needed.