Biomedical subjects
Publications and source records attributed to D Hull.
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BACKGROUND: Itraconazole is often given for fungal prophylaxis to renal transplant recipients, who require concomitant cyclosporine in the immediate posttransplant period. We determined the extent of the pharmacokinetic interaction between cyclosporine and itraconazole oral solution in renal transplant recipients and the effect on daily drug costs. METHOD: This was a single-center, open-label, nonrandomized study. Posttransplantation, renal transplant recipients received itraconazole solution 200 mg twice daily and cyclosporine, dosed to achieve target concentrations. Once at steady state, blood samples were collected over 12 hours for pharmacokinetic evaluation of cyclosporine, itraconazole, and hydroxy-itraconazole. Itraconazole was discontinued after approximately a 3-month prophylaxis regimen. Cyclosporine doses were titrated to achieve target concentrations and cyclosporine concentrations were once again determined when steady state was achieved. A noncompartmental analysis was used to analyze cyclosporine pharmacokinetic parameters. The pharmacoeconomic impact was measured based on the percent change in dose of cyclosporine when administered with and without itraconazole. Drug costs were calculated using the average wholesale price. The cost per patient, as well as the average cost, was calculated for the cyclosporine/itraconazole combination, as well as the cyclosporine regimen alone. RESULTS: Eight renal transplant recipients completed the study. All were included for itraconazole analyses and seven for cyclosporine analyses. Mean peak and trough itraconazole levels were 1.64 +/- 0.82 and 1.23 +/- 0.90 microg/mL respectively. Mean peak and trough hydroxy-itraconazole levels were 2.37 +/- 1.55 and 2.20 +/- 1.48 microg/mL, respectively. While on itraconazole, a 48% reduction in the mean total daily dose of cyclosporine was necessary to maintain target concentrations (171 +/- 63.6 versus 329 +/- 103.5 mg, P =.003). This reduction in cyclosporine dose resulted in a discounted itraconazole daily drug cost of approximately 29.5%. CONCLUSION: Administering itraconazole with cyclosporine allows for a decrease in the cyclosporine dose, thus lowering daily drug costs and providing adequate antifungal coverage with itraconazole and hydroxy-itraconazole trough concentrations above the MIC(90) of Candida and Aspergillus spp.
PURPOSE: Hand assisted laparoscopy combines aspects of open and laparoscopic surgery. A hand in the abdomen may facilitate laparoscopic live donor nephrectomy, allowing more urologists to participate. We report and compare our initial series of hand assisted laparoscopy donor nephrectomy with nephrectomy performed by standard open methods. MATERIALS AND METHODS: In the last 18 months 60 patients at 2 institutions underwent hand assisted laparoscopy donor nephrectomy. This cohort was compared to a contemporary group of 31 patients who underwent open donor nephrectomy via a flank incision at our 2 institutions. Demographic and outcome data were compared retrospectively in a nonrandomized fashion in the 2 groups. RESULTS: Demographic data on patient age, male-to-female ratio and body mass index were similar in the 2 groups. Operative time, transfusion rate, time to oral intake and complications were also similar. However, estimated blood loss, change in hematocrit preoperatively to postoperatively, hospitalization, parenteral and oral narcotic requirement, and donor convalescence were significantly less in the hand assisted laparoscopy versus open groups. In terms of allograft function, nadir creatinine, time to nadir creatinine, creatinine clearance at 6, 12, and 18 months, delayed graft function, episodes of acute rejection and ureteral stricture were similar in the groups. CONCLUSIONS: Hand assisted laparoscopy is safe, efficacious and reproducible for living related donor nephrectomy. Compared with the open technique hand assisted laparoscopy provides the donor with significantly decreased postoperative morbidity, while enabling excellent allograft function. Further randomized prospective studies are warranted.
BACKGROUND: Dimethyl sulfoxide-cryopreserved cadaveric vein allografts have recently been proposed as an alternative to prosthetic grafts in the problem hemodialysis population. The transfer of mismatched major histocompatibility complex I and II molecules in association with these allografts can potentially lead to allosensitization in nonimmunosuppressed individuals. METHODS: In a university-affiliated medical center, 20 consecutive patients receiving technically successful upper arm cadaveric vein allograft fistulas (CAVFs) for hemodialysis between April 1999 and April 2000 were studied. A control cohort of 20 patients on a kidney transplantation waiting list was selected by nurses blinded to the study. These patients were matched for age, sex, history of transfusion, pregnancy, cause of kidney failure, and prior transplantation. The panel reactive antibody (PRA) values were recorded in this group over the same time period as the CAVF group. RESULTS: Patients receiving CAVFs had a mean PRA assay value of 84.1% (median, 96.5%) at an average of 3.1 months after engraftment (median, 1.5 months). The preengraftment PRA values were available for seven patients who were on the transplant waiting list. Six of these patients had nonreactive PRA assays before CAVF creation. All of these patients converted to positive PRA assays after CAVF creation with a mean value of 92.3% (median, 98%) at 2.85 months follow-up (median, 1.3 months). The mean PRA value for the control cohort was 5.5% (median, 2.5%), with no patients converting from a nonreactive to a reactive PRA assay during this same time interval. CONCLUSION: The use of dimethyl sulfoxide-cryopreserved cadaveric vein allografts for hemodialysis access leads to broad allosensitization as measured by PRA assay. Cryopreserved cadaveric vein allografts should not be used for hemodialysis access in potential kidney transplant recipients.
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A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n=10) and standard Prematil (n=10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n=11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34g kg(-1) (82.0), 2.64g kg(-1) (82.9) and 1.65g kg(-1) (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n-6 LCP (p < 0.01). Nevertheless, excreted LCP equated to < 30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.
Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP (n = 20) and standard Aptamil (n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group (n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg[-1]) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil (p < 0.01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.
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Explore the source record for details and available documents.
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Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in today's health care climate, not an optimal use of scarce donor livers.
There is growing concern about adverse health effects of fungal bio-aerosols on occupants of water-damaged buildings. Accidental, occupational exposure in a nonagricultural setting has not been investigated using modern immunological laboratory tests. The objective of this study was to evaluate the health status of office workers after exposure to fungal bio-aerosols, especially Stachybotrys chartarum (atra) (S. chartarum) and its toxigenic metabolites (satratoxins), and to study laboratory parameters or biomarkers related to allergic or toxic human health effects. Exposure characterization and quantification were performed using microscopic, culture, and chemical techniques. The study population (n = 53) consisted of 39 female and 14 male employees (mean age 34.8 years) who had worked for a mean of 3.1 years at a problem office site; a control group comprised 21 persons (mean age 37.5 years) without contact with the problem office site. Health complaints were surveyed with a 187-item standardized questionnaire. A comprehensive test battery was used to study the red and white blood cell system, serum chemistry, immunology/antibodies, lymphocyte enumeration and function. Widespread fungal contamination of water-damaged, primarily cellulose material with S. chartarum was found. S. chartarum produced a macrocyclic trichothecene, satratoxin H, and spirocyclic lactones. Strong associations with exposure indicators and significant differences between employees (n = 53) and controls (n = 21) were found for lower respiratory system symptoms, dermatological symptoms, eye symptoms, constitutional symptoms, chronic fatigue symptoms and several enumeration and function laboratory tests, mainly of the white blood cell system. The proportion of mature T-lymphocyte cells (CD3%) was lower in employees than in controls, and regression analyses showed significantly lower CD3% among those reporting a history of upper respiratory infections. Specific S. chartarum antibody tests (IgE and IgG) showed small differences (NS). It is concluded that prolonged and intense exposure to toxigenic S. chartarum and other atypical fungi was associated with reported disorders of the respiratory and central nervous systems, reported disorders of the mucous membranes and a few parameters pertaining to the cellular and humoral immune system, suggesting a possible immune competency dysfunction.
An in vitro incubation technique was used to examine the release of lipids from the rabbit placenta. Free fatty acid, but not phospholipid or triacylglycerol, was released into the incubation media. In a second series of experiments, the addition of lipids to the umbilical circulation was studied in situ in the placenta of anaesthetized rabbits at late gestation. Each placenta was perfused from the fetal side in turn with two different perfusate solutions, either 4% bovine albumin solution or rabbit plasma. The rabbit plasma contained the appropriate carriers (lipoproteins) for esterified lipids, whereas the 4% albumin solution did not. The effluent perfusates were remarkably similar in free fatty acid concentration and composition, which closely matched the maternal free fatty acid profiles. The concentrations and fatty acid composition of the perfusate triacylglycerol and phospholipid fractions were unchanged by passage through the placenta, whether perfused with 4% albumin or with rabbit plasma. With this system, no evidence could be found for the addition of esterified lipids to the umbilical circulation in the rabbit despite the provision of appropriate carriers on the fetal side of the placenta.
The purpose of this study was to compare antipyretic activity and evaluate tolerability of ibuprofen and paracetamol suspension in the treatment of febrile children. It was designed as a double blind, parallel group, multiple dose study comparing ibuprofen (20 mg/kg/24 hours) with paracetamol (50 mg/kg/24 hours) given at six hourly intervals for a maximum of 12 doses. Children on paediatric wards between the ages of 0.2 and 12 years, with fever as defined by an axillary temperature > or = 37.5 degrees C, were included. The main outcome measures were: change in axillary temperature; palatability of medication; changes in irritability and clinical condition; overall efficacy at the end of treatment; and number and nature of adverse events. The mean temperature change from baseline at four hours was -1.8 degrees C and -1.6 degrees C in ibuprofen and paracetamol groups respectively. In both groups: median palatability score was 'no reaction'; median irritability score at end point was 'not irritable'; median score for change in clinical condition was 'improved'; and median score for overall efficacy was 'good effect'. The proportion of patients experiencing adverse events was similar in both groups, the majority of events having doubtful or no relationship to therapy and being mild in severity. In conclusion, ibuprofen suspension was as effective and well tolerated as paracetamol in treatment of fever in young children.
An open circuit indirect calorimeter was used to measure resting energy expenditure in febrile infants. Twelve infants admitted to hospital with fever (axillary temperature 37.5 degrees C) were studied on admission and then again at the same time of day and in similar environmental conditions after the fever had resolved. Mean age of the infants was 0.31 years (range 0.12-0.54) and the mean body weight 6.59 kg (range 4.50-8.88 kg). On average the infants' axillary temperatures were +2.1 degrees C higher when they were febrile. Overall the mean difference in oxygen consumption (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE) between the febrile and afebrile measurements was not statistically significant. Of eight infants with a greater REE when febrile, five were diagnosed as having viral illness and three had bacterial meningitis. Of the four with a lower REE when febrile, two had viral illness and two had bacterial infection (one chest infection and one meningitis). In conclusion, there was no consistent alteration of REE during a fever in infants 1 to 6 months of age. In particular, age and type of infection were not predictors of whether REE would increase or decrease during the illness.
AIM: To measure the sleeping metabolic rate (SMR) of healthy infants in the first year of life. METHODS: The SMR was measured on 73 infants aged 1 to 12 months in a special nursery using indirect calorimetry. One hundred satisfactory observations were made. The room air and radiative temperatures, humidity, and amount of insulation were measured. Parents chose the clothing and bedding that they judged their infant needed. RESULTS: The mean (SD) SMR was 2.4 (0.4) watts (W)/kg or 45 (10) W/m2. The mean SMR of infants aged 1-2 months was 38 compared with 44 W/m2 in infants of 8-12 months; the difference was not significant. There were no obvious differences in SMR between boys and girls. But there were wide differences in SMR between apparently similar infants, range 1.4 to 3.5 W/kg. Most parents selected insulation between 1 and 3 togs, and this was weakly negatively correlated with air temperature. CONCLUSION: These wide variations in SMR mean that it is impossible to give specific guidelines on the amount of clothing and bedding a particular infant will need for thermal comfort in a given room temperature.
AIM: To measure the variation in sleeping metabolic rate (SMR) of healthy infants in the first year of life. METHODS: Attempts were made to measure SMR in the home of one group of infants at monthly intervals over the first year of life and of another group in the 1 to 12 age range, over three consecutive days. Sixty one infants were recruited and 181 measurements made. In 11 infants six or more satisfactory measurements were made a monthly intervals and in another 11 infants, three consecutive daily measurements were obtained. Parents chose the clothing and bedding that they judged their infant needed to fall asleep. The room air and radiative temperatures, humidity, and amount of insulation were recorded. RESULTS: The mean (SD) SMR was 2.4 (0.4) watts (W)/kg or 45 (10) W/m2. The rate was the same for infants in the age groups 0.25, 0.5, 0.75, and 1 years; individual infants did not show a systematic change with age. There was wide variation. Ninety eight per cent of infants had a SMR between 1.8 and 3.1 W/kg. The mean SMR for the infants measured on three consecutive days varied from 1.7 to 3.1 W/kg, and SMR varied within infants, from 0.06 to 0.86 W/kg. The variation within six to 11 measurements on infants over the first year of life ranged from 0.38 to 1.05 W/kg. CONCLUSION: Infants in the first year of life exhibit wide variations in SMR from day to day and from month to month. As the range is wide, guidance on clothing and bedding for thermal comfort can be given only in broad terms.