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Biomedical subjects

M Charlton

Publications and source records attributed to M Charlton.

At least 19 recordsLinked to original sources
PubMed2003

Positron plasma diagnostics and temperature control for antihydrogen production.

Production of antihydrogen atoms by mixing antiprotons with a cold, confined, positron plasma depends critically on parameters such as the plasma density and temperature. We discuss nondestructive measurements, based on a novel, real-time analysis of excited, low-order plasma modes, that provide comprehensive characterization of the positron plasma in the ATHENA antihydrogen apparatus. The plasma length, radius, density, and total particle number are obtained. Measurement and control of plasma temperature variations, and the application to antihydrogen production experiments are discussed.

Journal Article↗
PubMed2002

Production and detection of cold antihydrogen atoms.

A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem-experimental investigations involving comparisons of particles with antiparticles are numerous. Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN) and at Fermilab, but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.

Journal Article↗
PubMed2002

Characterisation of an antibody coated microcantilever as a potential immuno-based biosensor.

In this study, we investigated the activity, stability, lifetime and re-usability of monoclonal antibodies to myoglobin covalently immobilised onto microfabricated cantilever surfaces. These sensing surfaces are of interest to us in the development of novel cantilever-based immunosensors. For such sensors the antibody layer represents the sensing element while the microcantilever acts as a mechanical transducer. A procedure for producing re-usable biological coatings has been tested with different independent techniques. An Enzyme Linked Immunosorbent Assay (ELISA) was used to determine the presence of an active antibody coating, and to monitor the lifetime and stability of the immobilised antibody. Through this analysis, the activity of the immobilised antibody layer was found to be more stable with the introduction of sucrose, as a stabilising agent. Sucrose was applied to the immobilised antibody layer after each regeneration step. The immobilised antibody was found to have a stable active lifetime for up to 7 weeks. Fluorescence microscopy was used to give information on the distribution of the coating on the gold and silicon nitride sides of the cantilever. Atomic Force Microscopy was used to determine the presence of the biological coating on the cantilever and to obtain information on the surface morphology of the biological element of the sensor. The combined results provide valuable information on the development of an optimised sensing element and demonstrate a set of methods to use for future sensor-to-sensor characterisation. Preliminary experimental results showing the antibody activity against myoglobin, detected with a microcantilever based sensor prototype confirmed the motivations and potentialities of the proposed immunosensing technique.

Biosensing Techniques↗
PubMed2002

Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without maintenance.

PURPOSE: Data concerning the relative efficacy of intravesical bacillus Calmette-Guerin (BCG) on subgroups of carcinoma in situ of the bladder are limited. We report the outcome of primary carcinoma in situ and carcinoma in situ associated with Ta or T1 transitional cell carcinoma of the bladder treated with BCG. MATERIALS AND METHODS: Between 1987 and 1997, 135 patients (median age 70 years) with biopsy proven bladder carcinoma in situ underwent a standard course of 6 BCG instillations. Patients were divided into group 1-23 patients with primary carcinoma in situ, group 2-37 with carcinoma in situ associated with Ta transitional cell carcinoma and group 3-75 with carcinoma in situ associated with T1 transitional cell carcinoma. RESULTS: Median followup was 41 months. For groups 1 to 3, complete response rates at 3 months were 74% (17 of 23 cases), 70% (26 of 37) and 75% (56 of 75), respectively. The overall progression rates at 5 years were 20% (3 of 15 cases), 18% (4 of 22) and 49% (25 of 51). Cancer specific survival rates were 83% (10 of 12 patients), 86% (12 of 14) and 59% (17 of 29), and the numbers of patients alive with the bladder intact were 60% (9 of 15), 58% (11 of 19) and 30% (12 of 40). Patients in group 3 treated with BCG had progression significantly earlier than those in groups 1 and 2 (log-rank test p = 0.013). A complete response to BCG in group 3 patients significantly delayed time to progression (Cox regression p = 0.001) but did not reduce death from transitional cell carcinoma. Indeed, only 38% (8 of 21) of complete responders were alive with the bladder intact at 5 years. CONCLUSIONS: A single course of BCG is remarkably effective for primary carcinoma in situ and carcinoma in situ associated with Ta transitional cell carcinoma but is suboptimal in patients with carcinoma in situ associated with T1 transitional cell carcinoma. Better outcomes in each of the 3 groups may have occurred with maintenance BCG.

Adjuvants, Immunologic↗
PubMed2001

Hepatitis C infection in liver transplantation.

Hepatitis C-associated liver failure is the most common indication for liver transplantation and recurs nearly universally following transplantation. Histological evidence of recurrence is apparent in approximately 50% of HCV-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft secondary to hepatitis C-associated allograft failure in the medium term. While the choice of calcineurin inhibitor and/or the use of azathioprine have not been clearly shown to affect histological recurrence of hepatitis C or the frequency of rejection in hepatitis C-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histological recurrence. In contrast to nonhepatitis C-infected recipients, treatment for acute cellular rejection is associated with attenuated patient survival among recipients with hepatitis C. The development of steroid-resistant rejection is associated with a greater than five-fold increased risk of mortality in HCV-infected liver transplant recipients. In lieu of large studies in a post-transplant population therapy with pegylated interferon (+/- ribavirin) should be considered in recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dL. The role of hepatitis C immunoglobulin and new immunosuppression agents in the management of post-transplant hepatitis C infection is still evolving. Overall, HCV-infected recipients who undergo retransplantation experience 5-year patient and graft survival rates that are similar to recipients undergoing retransplantation who are not HCV-infected.

Hepatitis C↗
PubMed2001

Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease.

Although nonalcoholic steatohepatitis (NASH) has generally been considered a benign condition, the increasing prevalence and severity of obesity has heightened concerns about the frequency with which NASH progresses to end-stage liver disease. The aim of this study is to determine the frequency, clinical features, and posttransplantation history of decompensated liver disease secondary to NASH. The frequency of NASH as a cause of end-stage liver disease was prospectively determined in patients evaluated for liver transplantation. NASH was considered to be the primary cause of liver disease in patients who had histological evidence of steatohepatitis and in whom chronic liver diseases other than NASH were excluded. Posttransplantation histological characteristics were also determined in patients with NASH and compared with those of patients with pretransplantation diagnoses of cholestatic liver diseases, alcoholic disease, and hepatitis C. Of 1,207 patients evaluated for liver transplantation during the study period, 31 patients (2.6%) had NASH as the primary cause of liver disease. In the same period, 546 liver transplantations were performed, 16 of which (2.9%) were for end-stage disease secondary to NASH. Posttransplantation steatosis was seen in 60% of transplant recipients with NASH versus 5% of those with cholestatic disease, 15% of those with alcoholic disease, and 15% of those with hepatitis C. Steatohepatitis recurred in 33% of transplant recipients with NASH, with progression to cirrhosis in 12.5%. NASH can progress to end-stage liver disease in a minority of affected patients and was the primary cause of liver disease in 2.9% of patients evaluated for liver transplantation at our center. Recurrence of steatosis and NASH is frequent and can be severe after liver transplantation.

Adult↗
PubMed2001

Tissue-specific regulation of mitochondrial and cytoplasmic protein synthesis rates by insulin.

In vivo studies have reported conflicting effects of insulin on mixed tissue protein synthesis rates. To test the hypothesis that insulin has differential effects on synthesis rates of various protein fractions in different organs, we infused miniature swine (n = 8 per group) with saline, insulin alone (at 0.7 mU/kg(-1). min(-1)), or insulin plus an amino acid mixture for 8 h. Fractional synthesis rate (FSR) of mitochondrial and cytoplasmic proteins in liver, heart, and skeletal muscle, as well as myosin heavy chain (MHC) in muscle, were measured using L-[1-(13)C]leucine as a tracer. The FSR of mitochondrial and cytoplasmic proteins were highest in liver, followed by heart and then muscle. Mitochondrial FSR in muscle was higher during insulin and insulin plus amino acid infusions than during saline. Insulin had no significant effect on FSR of MHC in muscle. In contrast, FSR of both mitochondrial and cytoplasmic proteins were not stimulated by insulin in liver. Insulin also did not increase FSR of mitochondrial in heart, whereas insulin and amino acid stimulated FSR of cytoplasmic protein. In conclusion, insulin stimulates the synthesis of muscle mitochondrial proteins, with no significant stimulatory effect on synthesis of sarcoplasmic and MHC. These results demonstrate that insulin has different effects on synthesis rates of specific protein fractions in the liver, heart, and skeletal muscle.

Amino Acids↗
PubMed2001

Insulin's effect on synthesis rates of liver proteins. A swine model comparing various precursors of protein synthesis.

Insulin's effect on the synthesis of liver proteins remains to be fully defined. Previous studies using various surrogate measures of amino acyl-tRNA have reported variable results of insulin's effect on liver protein synthesis. We determined the effect of insulin with or without amino acid supplementation on the synthesis rates of liver proteins (tissue, albumin, and fibrinogen) using L-[1-13C]Leu as a tracer in 24 male miniature swine. In addition, we compared the isotopic enrichment of different precursors of liver proteins with that of amino acyl-tRNA using L-[1-13C]Leu and L-[15N]Phe as tracers. Although liver tissue fluid enrichment of [13C]Leu and [15N]Phe and that of plasma [13C]ketoisocaproatic acid (KIC) were very similar to that of tRNA, plasma isotopic enrichment of both Leu and Phe were substantially higher (P < 0.01) and VLDL apolipoprotein-B100 enrichment was lower (P < 0.01) than the respective amino acyl-tRNA enrichment. Plasma KIC enrichment most accurately predicted leucyl-tRNA enrichment, whereas plasma Leu enrichment was best correlated with that of tRNA. Neither insulin alone nor insulin plus amino acid infusion had an effect on liver tissue protein synthesis. In contrast, insulin alone decreased the albumin synthesis rate, and insulin with amino acids maintained the albumin synthesis rate. Insulin with or without amino acids inhibited the fibrinogen synthesis rate. These results, based on synthetic rates using amino acyl-tRNA, were consistent with those obtained using KIC or tissue fluid Leu or Phe as precursor pools. These studies demonstrated that plasma KIC enrichment is a convenient and reliable surrogate measure of leucyl-tRNA in liver. We also concluded that insulin has differential effects on the synthesis rates of liver proteins. Whereas insulin with or without amino acid supplement has no acute effect on the synthesis of liver tissue protein, insulin has a substantial inhibitory effect on fibrinogen synthesis. In contrast, insulin administration along with amino supplement is necessary to maintain albumin synthesis rate.

Amino Acids↗
PubMed2000

Impact of nutritional status on outcomes after liver transplantation.

BACKGROUND: Poor preoperative nutritional status has been reported to be associated with adverse outcomes after liver transplantation. Published data are, however, conflicting, with methods of preoperative nutritional assessment and postoperative outcomes varying between studies. METHODS: We prospectively studied the predictive value of preoperative nutritional status for adverse outcomes after liver transplantation. Assessment of preoperative nutritional status included: body cell mass determination, subjective global assessment, anthropometry, handgrip dynamometry, biochemical and amino acid profile, Child's score, and dual-energy x-ray absorptiometry. Death, intensive care unit (ICU) length of stay > or =4 days, hospital length of stay > or =15 days, blood usage > or =36 U of blood products, infection, rejection, and global resource utilization (an index of cost) greater than the median were considered poor outcomes. RESULTS: Fifty-three patients were studied. Longer ICU stay was associated with lower handgrip strength (P<0.01) and lower aromatic amino acid levels (P<0.01). Longer total hospital stay and the development of infections were associated with lower branched chain amino acid levels (P<0.01 and <0.001, respectively). Acute cellular rejection was associated with lower total body fat (P<0.001) and higher triglyceride levels (P<0.02). Neither death nor higher global resource utilization was associated with any preoperative nutritional parameter. CONCLUSIONS: Lower preoperative handgrip strength and branched chain amino acid levels are associated with longer ICU stays and increased likelihood of posttransplant infections. In our program, in which nutritional support was provided to potential recipients exhibiting malnourishment, none of the measured nutritional parameters were associated with mortality or greater global resource utilization.

Adult↗
PubMed2000

The effect of insulin on human small intestinal mucosal protein synthesis.

BACKGROUND & AIMS: Insulin deficiency was recently shown to stimulate splanchnic protein synthesis in vivo, whereas insulin enhances small intestinal mucosal cell proliferation in vitro. Because insulin is a postprandial hormone, it was hypothesized that it has an important role in regulating small intestinal protein synthesis in humans. METHODS: Small intestinal mucosal protein synthesis was measured in C-peptide-negative patients with type 1 diabetes mellitus during insulin deprivation (n = 6) and during insulin treatment (n = 6) and in nondiabetic control subjects (n = 6). Mucosal protein synthesis was measured from the increment of [(13)C]leucine enrichment in endoscopically obtained duodenal mucosa samples during a primed continuous infusion of L-[1-(13)C]leucine. RESULTS: During insulin treatment, the rate of mucosal protein synthesis in patients with type 1 diabetes was similar (1.32% +/- 0.05%/h) to that of nondiabetic controls (1.33% +/- 0.06%/h). However, during insulin deprivation, the mucosal protein synthesis rate in patients with type 1 diabetes was significantly lower (1.15% +/- 0.33%/h) than during either insulin treatment (P = 0.01) or in nondiabetic controls (P = 0.04). CONCLUSIONS: These studies show that insulin is required for the maintenance of normal rates of protein synthesis in small intestinal mucosa. Because protein synthesis is an essential component of the remodeling process of this fast turning over tissue, the decline in the synthesis rate of small intestinal mucosa during insulin deprivation may be a contributing factor in the development of gastrointestinal complications that occur in poorly controlled type 1 diabetic patients.

Adult↗
PubMed2000

A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice.

PURPOSE: The commonly accepted diagnostic algorithm for hematuria includes excretory urography (IVP) and cystoscopy. Some have suggested that ultrasound of the upper urinary tract is adequate and that cystoscopy is not necessary in younger patients with microscopic hematuria. We ascertain whether a less intensive algorithm could be adopted while retaining diagnostic efficacy. MATERIALS AND METHODS: A total of 1,930 patients were enrolled prospectively in the study at a hematuria clinic between October 1994 and March 1997. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis and cytology. All patients underwent plain abdominal radiography, renal ultrasound, IVP and flexible cystoscopy. RESULTS: A total of 1,194 males and 736 females with a mean age of 58 years (range 17 to 96) were included in the study. Overall, 61% of patients had no basis found for hematuria, 12% had bladder cancer, 13% had urinary tract infection and 2% had stones. Kidney and upper tract tumors were noted in 14 patients (0.7%), including 4 who presented with microscopic hematuria. If only ultrasound or IVP had been performed 4 of these cases would have been missed. Of 982 patients presenting with microscopic hematuria 51 had cancer. Bladder cancer was found in 7 patients younger than 40 years. CONCLUSIONS: Our findings suggest that cystoscopy cannot be safely avoided even in younger patients with microscopic hematuria. Only a combination of ultrasound and IVP detected all upper tract tumors.

Adolescent↗
PubMed1999

Impact of immunosuppression and acute rejection on recurrence of hepatitis C: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

Whereas the impact of early (first 6 postoperative weeks) acute cellular rejection on patient survival among liver transplant recipients as a whole has been reported to be favorable, we hypothesized treatment for acute cellular rejection may have differing impacts on patient and graft survival in hepatitis C virus (HCV)-infected and HCV-negative transplant recipients. We studied the impact of immunosuppression and rejection on patient and graft survival among the 166 HCV-infected and 602 HCV-negative transplant recipients enrolled onto the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. All data were collected prospectively. The association of early acute cellular rejection with mortality was determined using a Cox proportional hazards model with a time-dependent covariate. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative transplant recipients. HCV-infected transplant recipients experienced similar frequencies of acute cellular and steroid-resistant rejection as patients undergoing liver transplantation for most other indications. The mortality risk was significantly increased (relative risk = 2.4; P =.03) for HCV-infected transplant recipients who developed early acute cellular rejection compared with HCV-negative transplant recipients. None of the HCV-infected transplant recipients developed allograft failure secondary to chronic rejection. The choice of calcineurin inhibitor did not affect posttransplantation outcomes. Early acute cellular rejection occurs at similar frequencies in HCV-infected and HCV-negative transplant recipients. Although an episode of early acute cellular rejection is associated with a lower cumulative mortality among HCV-negative transplant recipients, the opposite is true for HCV-infected transplant recipients, who experience an increased risk for mortality after an episode of early acute cellular rejection. The adverse impact of early acute cellular rejection on patient survival should be considered in developing primary immunosuppression and acute cellular rejection treatment protocols for HCV-infected transplant recipients.

Databases, Factual↗
PubMed1998

Predictors of patient and graft survival following liver transplantation for hepatitis C.

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1994, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P = .02 and P = .003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P = .001). Recipients who had a pretransplantation HCV-RNA titer of > or = 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of < 1 x 10(6) vEq/mL (P = .0001). Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While long-term patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients.

Adult↗
PubMed1998

TT-virus infection in North American blood donors, patients with fulminant hepatic failure, and cryptogenic cirrhosis.

A novel DNA virus, TT-virus (TTV), has been reported in patients with non-A-G posttransfusion hepatitis in Japan. We sought to determine whether TTV infection occurs in North American blood donors and to further determine the prevalence of TTV infection in several groups of patients with liver disease, including patients with cryptogenic cirrhosis and idiopathic fulminant hepatic failure. TTV infection was sought by detection of TTV DNA in serum by polymerase chain reaction (PCR) using primers generated from a conserved region of the TTV genome. Blood donors, patients with cryptogenic cirrhosis, idiopathic fulminant hepatic failure, and patients with other forms of advanced liver disease with and without a history of parenteral exposures were studied. TTV infection was present in 1% (1 of 100) of blood donors, 15% (5 of 33) of patients with cryptogenic cirrhosis, 27% (3 of 11) of patients with idiopathic fulminant hepatic failure, 18% (2 of 11) of patients with a history of exposure to blood products, and 4% (1 of 25) of patients without parenteral risk factors. For all patients tested, a history of prior exposure to blood products was associated with an increased risk of TTV infection (relative risk, 4.5; 90% confidence intervals, 0.6-43.9). We conclude that TTV infection is present among North American blood donors and is common in patients with liver disease, including cryptogenic cirrhosis and fulminant hepatic failure. Further studies are required to determine the role of TTV in the pathogenicity of acute and/or chronic liver disease.

Adult↗
PubMed1998

Pyrithione biocide interactions with bacterial phospholipid head groups.

Sodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively) are antimicrobial agents widely used in both the cosmetics and fuel industries. They are also utilized in the mining industry because of their metal chelating properties. They have been shown to depolarize membrane electropotential in fungi and are also known to inhibit fungal and bacterial substrate transport processes. Recent work has shown that both pyrithiones cause the leakage of intracellular material (potassium ions and O.D.260 nm absorbing material) from exposed bacterial cells. The work here reports studies on the interactions between the pyrithiones and the bacterial phospholipid head group structures, at both a practical and a theoretical level, utilizing tube dilution neutralizer studies, scanning spectrophotometry and molecular modelling. The tube dilution neutralizer studies exhibited a decrease in minimum inhibitory concentration (MIC) for both pyrithiones in the presence of extracellular phosphatidyl-ethanolamine and EDTA. Scanning spectrophotometry exhibited the chelation of the central zinc atom from the ZnPT chelate by the addition of EDTA. Molecular modelling studies exhibited the chelation of the phosphatidyl-ethanolamine head group by ZnPT. Zinc pyrithione also exhibited an interaction with the ammonium tail of the head group structures. Sodium pyrithione exhibited electrostatic interactions with the phospholipid head groups in the molecular modelling studies.

Antifungal Agents↗
PubMed1998

Protein metabolism in insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes are in a catabolic state without insulin replacement. The mechanism of insulin's anticatabolic effect has been investigated in whole-body and regional tracer kinetic studies. Whole-body studies have demonstrated that there are increases in both protein breakdown and protein synthesis during insulin deprivation. Because the magnitude of the increase in protein breakdown is greater than the magnitude of the increase in protein synthesis, there is a net protein loss during insulin deprivation. Regional studies have shown that insulin replacement inhibits protein breakdown and synthesis in splanchnic tissue but only inhibits protein breakdown in skeletal muscle. Because the increase in protein synthesis in splanchnic tissues is greater than the increase in protein breakdown, insulin deprivation results in a net accretion of protein in the splanchnic bed. In contrast, in skeletal muscle, there is a net increase in protein breakdown during insulin deprivation, resulting in a net release of amino acids. There are no human data concerning the site of protein accretion in the splanchnic bed or the specific protein whose synthesis is increased during insulin deprivation. It appears that insulin exerts its overall anticatabolic effect in insulin-dependent diabetes mainly through the inhibition of muscle protein breakdown.

Diabetes Mellitus, Type 1↗