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Biomedical subjects

D Turner

Publications and source records attributed to D Turner.

At least 19 recordsLinked to original sources

Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram.

OBJECTIVE: To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection. METHODS: Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status. RESULTS: Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24-30 and 31-36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not. CONCLUSIONS: The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Aging↗

Lipid abnormalities in HIV/hepatitis C virus-coinfected patients.

BACKGROUND: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with increased rates of lipodystrophy and insulin resistance. Its impact on HIV-associated dyslipidaemia is less clear. METHODS: The lipid profiles of all HIV-infected patients and a subset of HCV-infected patients seen at the VA Medical Center in Dallas from January 2003 to March 2004 were analysed. Demographic data, HCV serostatus, and HIV treatment history were recorded. Lipid profiles of HIV/HCV-coinfected patients were compared with those of HIV-monoinfected and HCV-monoinfected patients. RESULTS: A total of 359 HIV-infected patients, 91 (25.3%) of whom were HCV coinfected, and 112 HCV-infected patients were included in the analysis. Among the HIV-infected patients, HCV coinfection was associated with a reduced risk of hypercholesterolaemia [9.9% vs 24.8%; relative risk (RR)=0.333; 95% confidence interval (CI)=0.158-0.699; P<0.001] and hypertriglyceridaemia (48.4% vs 60.3%; RR=0.616; 95% CI=0.382-0.994; P=0.031). After controlling for duration of protease inhibitor (PI) therapy, race, alanine aminotransferase (ALT) concentration and platelet count, HCV remained an independent predictor of hypercholesterolaemia (RR=0.369; P=0.01) and any dyslipidaemia (RR=0.531; P=0.019). In addition, the rate of dyslipidaemias was lower among HCV-monoinfected than HIV/HCV-coinfected patients (29.5% vs 50.5; P=0.002). White race was also an independent predictor of dyslipidaemia (73.8% vs 50.7%; RR=2.32; 95% CI=1.44-3.76; P=0.001). CONCLUSIONS: HCV coinfection independently predicted lower rates of dyslipidaemia among HIV-infected patients. An analysis of lipid kinetics among mono- and coinfected patients may elucidate the mechanisms of the apparent protective effect of HCV infection.

Adult↗

Anastomotic ulceration following small bowel transplantation.

We describe, for the first time, anastomotic ulcers (AU) following bowel transplantation at the Hospital for Sick Children. Two children presented with rectal bleeding, 6 and 9 months, following the transplantation. Isolated ulcers were identified at the ileo-colonic and the colo-colonic anastomosis site. The ulcers resolved, but recurred 6 and 7 months after the initial presentation. Both patients were positive for adenovirus in the stool and were treated with rapamycin. The histology revealed granulation tissue formation with mild inflammation in the adjacent mucosa, without evidence of rejection or infection. A literature search revealed 10 studies reporting 29 patients who developed AU following various surgical etiologies, none of which was bowel transplant. Numerous factors that are unique to the post-transplant period may predispose to such ulcer and are discussed in detail. Physicians and surgeons should be aware of this multifactorial complication, among other etiologies, as a cause of anemia or rectal bleeding following intestinal transplantation.

Anastomosis, Surgical↗

Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality.

Candidaemia due to non-albicans Candida species is increasing in frequency. We describe 272 episodes of candidaemia, define parameters associated with Candida albicans and other Candida species, and analyse predictors associated with mortality. Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy. The overall fatality rate was 36%, and predictors of death by multi-variate analysis were shock, impaired performance status, low serum albumin and congestive heart failure. Isolation of non-albicans Candida species, prior surgery and catheter removal were protective factors. When shock was excluded from analysis, antifungal therapy was shown to be protective. Unlike previous concerns, infection with Candida species other than C. albicans has not been shown to result in an increased fatality rate.

Adolescent↗

Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation.

Chronic allograft rejection is the major problem encountered in solid organ transplantation and is the end point of several complex processes. A number of recent studies show both alloimmune and autoimmune responses may have roles to play. The importance of HLA antibodies in transplantation is well documented, but despite the introduction of very sensitive HLA screening assays, antibody-mediated allograft rejection still occurs without detectable HLA antibodies. The target for antibody-mediated allograft rejection in these circumstances remains elusive, perhaps due to the variety of potential targets presented on endothelial cells. Recent studies identifying C4d and immunoglobulin deposits in patients undergoing late allograft loss provide evidence that chronic rejection involves humoral as well as cellular components. Several endothelial cell antigens that might be important in chronic rejection have been suggested, including MHC class I chain-related genes; Lewis; and the intermediate filament protein, vimentin. Vimentin is an ideal candidate antigen for antibody-mediated rejection as it is found in endothelial cells and is exposed to the immune system following surgery or by chronic allograft rejection due to endothelial cell breakdown, where the development of antibodies may cause further damage. We have developed a flow cytometric assay for the detection of antibodies to vimentin and have investigated whether HLA or vimentin antibodies are present in renal transplant recipients undergoing chronic rejection.

Graft Rejection↗

Diagnosis of transfusion-associated graft-vs.-host disease: the importance of short tandem repeat analysis.

Transfusion-associated graft-vs.-host disease (TA-GvHD) can occur following transfusion of blood products containing immunocompetent lymphocytes, usually from HLA homozygous donors, into immunocompromised patients sharing one HLA haplotype with the donor. The diagnosis of TA-GvHD may be delayed due to the initial nonspecific clinical features involved. Investigations to detect the presence of donor-derived cells in the blood and/or affected tissues of the recipient are essential to confirm the diagnosis. We report the investigation of suspected TA-GvHD using short tandem repeat (STR) analysis, to detect the presence of donor cells (chimerism), in an immunocompetent patient admitted for coronary artery bypass surgery. Peripheral blood and skin biopsies (from affected and nonaffected sites) from the patient and peripheral blood samples from the implicated donors were taken for HLA typing and STR analysis. STR analysis revealed the presence of donor material in the patient's peripheral blood sample and in DNA extracted from the affected skin biopsy but not the unaffected biopsy, suggesting lymphocytes from this donor were responsible for the development of TA-GvHD. Furthermore, HLA typing results supported the diagnosis of TA-GvHD. These data demonstrate the use of STR and HLA analysis as effective tools in the diagnosis of TA-GvHD.

Aged↗

Isolation and characterization of structural components of Aloe vera L. leaf pulp.

The clear pulp, also known as inner gel, of Aloe vera L. leaf is widely used in various medical, cosmetic and nutraceutical applications. Many beneficial effects of this plant have been attributed to the polysaccharides present in the pulp. However, discrepancies exist regarding the composition of pulp polysaccharide species and an understanding of pulp structure in relation to its chemical composition has been lacking. Thus, we examined pulp structure, isolated structural components and determined their carbohydrate compositions along with analyzing a partially purified pulp-based product (Acemannan hydrogel) used to make Carrisyn hydrogel wound dressing. Light and electron microscopy showed that the pulp consisted of large clear mesophyll cells with a diameter as large as 1000 microm. These cells were composed of cell walls and cell membranes along with a very limited number of degenerated cellular organelles. No intact cellular organelles were found in mesophyll cells. Following disruption of pulp by homogenization, three components were isolated by sequential centrifugation. They were thin clear sheets, microparticles and a viscous liquid gel, which corresponded to cell wall, degenerated cellular organelles and liquid content of mesophyll cells based on morphological and chemical analysis. These three components accounted for 16.2% (+/-3.8), 0.70% (+/-0) and 83.1% of the pulp on a dry weight basis. The carbohydrate composition of each component was distinct; liquid gel contained mannan, microparticles contained galactose-rich polysaccharide(s) and cell walls contained an unusually high level of galacturonic acid (34%, w/w; Gal A). The same three components were also found in Acemannan Hydrogel with mannan as the predominant component. Thus, different pulp structural components are associated with different polysaccharides and thus may potentially be different functionally. These findings may help lay a basis for further studies and development of better controlled processing methods and applications for this well-accepted medicinal plant.

Aloe↗

Retinal and extraocular cytomegalovirus end-organ disease in HIV-infected patients in Europe: a EuroSIDA study, 1994-2001.

This multicentre prospective cohort study by the EuroSIDA study group was designed to determine the factors affecting the incidence of cytomegalovirus (CMV) end-organ disease (CMVD) and the rate of survival after diagnosis in patients with AIDS during the years 1994-2001. This period includes two eras, the pre-HAART era and the HAART era, because HAART affects the natural history of HIV infection, especially with respect to opportunistic infections, including CMV infection. Clinical and laboratory data were collected from the charts of 8,556 patients in 63 AIDS clinics in Europe. A total of 707 patients had CMVD at recruitment and at follow-up: 449 with retinitis (CMVR), 190 with extraocular CMV disease (EOCMVD), and 58 with both. Of the cases of EOCMVD, 66% involved the gastrointestinal tract and 17% the central nervous system. Of patients with a CD4+ count of < or =200 mm(-3) initially, 1.8% on HAART developed CMVD within a 24-month period, as compared to 11.1% on dual therapy and 14.3% without treatment (P<0.0001). There were highly significant differences in survival according to the calendar year (P<0.0001), with mortality declining from 79% during the years 1994-1995 to 42% in 2000-2001. The incidence of death after any CMVD was 28.4 per 100 patient-years of follow-up. Median survival of CMVR patients and EOCMVD patients was 11 and 7 months, respectively, the prognosis being better among patients with gastrointestinal rather than neurological CMVD. The initiation of HAART was associated with a 37% decrease in mortality (P<0.05). Eighteen percent of all deaths were caused by EOCMVD itself. This study describes a decline in the incidence and mortality of CMVR and EOCMVD during the HAART era of the HIV epidemic. It furthermore serves as a reminder of the importance of EOCMVD as a cause of morbidity and mortality in AIDS in the pre-HAART era.

AIDS-Related Opportunistic Infections↗

Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells.

The enteric nervous system, which regulates multiple aspects of digestive activity, is composed of two major cell types, neurons and glial cells. Enteric glia, but not enteric neurons, respond to bioactive lipids with calcium signaling. The sphingomyelin metabolite sphingosine-1-phosphate (S1P) caused dose-dependent calcium (Ca(2+)) signaling using extracellular and intracellular Ca(2+). The signal transduction cascade was pertussis toxin-insensitive and involved an extracellular receptor since repetitive exposure yielded diminished responsiveness. Inhibition of either phospholipase C or the inositol 1,4,5-trisphosphate receptor abolished S1P effects. RT-PCR analysis demonstrated the presence of S1P-coupled endothelial differentiation gene (EDG) receptor mRNAs (EDG-1, EDG-3, and EDG-5) within the enteric nervous system. Immunocytochemical analysis demonstrated strong expression of both EDG-1 and EDG-3 and weak expression of EDG-5 in enteric glial cells. Other sphingomyelin cycle components, including sphingomyelin, sphingomyelinase, and sphingosine caused Ca(2+) transients in enteric glia. Related lipids lysophosphatidic acid and sphingosylphosphorylcholine also induced Ca(2+) signaling in enteric glia, suggesting that multiple lipid-activated signaling mechanisms exist in these cells.

Animals↗

Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10.

Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of these responses. The aim of this study was to determine whether cytokine gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty-six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-2 promoter region polymorphism. TNF-a, TNF-d, and IL-10 microsatellite polymorphisms were also analyzed. The frequency of the anti-inflammatory cytokine IL-10 promoter (-1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA-TT-AA homozygous genotype combination of three single-nucleotide polymorphisms at -1082, -819, and -592 in the IL-10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF-alpha, IL-6, and IL-2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL-10 genotypes with differences in IL-10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide-stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position -1082 produced lower levels of IL-10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL-10 promoter, -1082 A-positive genotype in patients with renal artery stenosis, suggests that IL-10 may protect against the development of atherosclerotic renovascular disease.

Aged↗

Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action.

BACKGROUND: Acne affects 83-95% of 16-year-olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. OBJECTIVES: To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. METHODS: Ten patients (nine men and one woman, age range 16-40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm(-2), 15 J cm(-2)). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. RESULTS: There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site. CONCLUSIONS: ALA-PDT is capable of clinically improving acne. An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study.

Acne Vulgaris↗

The human leucocyte antigen (HLA) system.

Since the discovery of the HLA system, over 40 years ago, we now have an understanding of the role of HLA molecules in the adaptive immune response, as well as in the alloimmune response experienced when foreign HLA is introduced into an individual via transplant, transfusion or pregnancy. Retrospective studies in the 1970s and 1980s illustrated the importance of matching for HLA antigens in transplantation and platelet transfusion. The huge degree of polymorphism in the system has driven the development of sensitive HLA typing and HLA antibody screening methods in H & I laboratories in order to improve transplant and transfusion outcomes.

Autoimmune Diseases↗

Implementing intensive insulin therapy: development and audit of the Bath insulin protocol.

Intensive insulin therapy to control blood glucose has been found to reduce mortality among critically ill patients in a surgical intensive care unit, though a simple prescriptive insulin infusion protocol to achieve this has not been published previously. This study documents the development and routine use of a simple prescriptive intravenous insulin infusion protocol for critically ill patients and compares the results with previous practice. During development the protocol was optimized and practical issues of implementation addressed. The optimized protocol was then used for all ICU admissions, and a prospectively defined retrospective chart audit performed for the first month of use. Results were compared with a similar time period the previous year. In September 2002, 27 admissions were started on the protocol. Blood glucose for the time on the protocol had a median value of 6.2 (IQR 5.9-7.1) mmol/l compared with 9.2 (IQR 8.1-10.2) mmol/l for those on insulin in 2001. Blood glucose for the whole ICU stay for those on the protocol in 2002 had a median value of 6.6 (IQR 6.0-7.4) mmol/l compared with 8.6 (IQR 8.0-9.4) mmol/l in 2001. Blood glucose for all ICU patients in 2002 had a median value of 6.5 (IQR 6.0-7.3) mmol/l compared with 7.2 (IQR 6.3-8.3) mmol/l in 2001. Three blood glucose recordings were less than 2.2 mmol/l in September 2002. This study provides initial effectiveness and safety data for the Bath Insulin Protocol Further audits in a larger patient population are now needed.

Blood Glucose↗

Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients.

The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. Interestingly, the presence of M184V is also associated with alteration of several mechanisms relating to RT function that include decreased RTprocessivity, reduced nucleotide-dependent primer unblocking, increased fidelity, hypersensitization to other NRTIs, impaired viral fitness, and delayed appearance of mutations in RT that are responsible for resistance to thymidine analogues (i.e. thymidine-associated mutations or TAMs). In addition, M184V may affect viral transmission and immunological response. Collectively, these factors might explain the residual antiviral effect and clinical benefit observed with continued use of 3TC in combination therapy regimens following the emergence of M184V.

Amino Acid Substitution↗

Group A streptococcal osteomyelitis: severe presentation and course.

AIM: To evaluate the course of group A streptococcal osteomyelitis associated with severe disease nowadays. METHODS: Three consecutive cases of severe group A streptococcal disease with osteomyelitis in children that were documented in Beer Sheva, Israel are described in detail. RESULTS: Two of the three cases were postvaricella. Early in the course of the disease, the presentation resembled that of severe cellulitis. All three patients had severe osteomyelitis and required surgery, and one patient developed chronic osteomyelitis. Sepsis was diagnosed in two cases. CONCLUSION: Our cases are distinguishable from typical haematogenous staphylococcal osteomyelitis by the severe course and the extensive involvement of bone and soft tissues. The increase in severity of invasive group A streptococcal infections documented throughout the world could account for the difference between our complex cases and the previous reports.

Chickenpox↗

Induced sputum for diagnosing Pneumocystis carinii pneumonia in HIV patients: new data, new issues.

The complexity of bronchoalveolar lavage (BAL) has motivated the search for noninvasive methodology to retrieve specimens for detecting the presence of various pulmonary diseases. Induced sputum (IS) has been shown to be a reliable tool in terms of sensitivity and specificity comparable to BAL. Investigators from institutions worldwide have published several reports providing evidence in support of one or the other or a combination of both approaches. Among them are studies demonstrating the sensitivity and specificity of IS in diagnosing Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS). In 1996, highly active antiretroviral therapy was introduced for routine use and the morbidity from opportunistic infections decreased sharply. An earlier study showed that cost-effectiveness depends on the prevalence of a given condition in the population. More recent studies have confirmed that prophylaxis against PCP can be stopped after increasing the CD4 cell count, thus reducing the attractiveness of IS as a preferred method for monitoring the course of disease. This review presents a brief description of the evolution of the bronchoalveolar lavage versus induced sputum controversy and reconsiders the strengths and weaknesses of the earlier arguments in light of newer data that have emerged with regard to Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome.

Antiretroviral Therapy, Highly Active↗