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Biomedical subjects

J Dudley

Publications and source records attributed to J Dudley.

At least 19 recordsLinked to original sources
PubMed2002

The effect of extended in-sewer storage on wastewater treatment plant performance.

A project funded by UKWIR is under way in the UK to develop a relatively simple methodology whereby the effects of the introduction of extended in-sewer storage at CSOs on downstream sewerage and treatment can be assessed. Recent legislation (UK and European) has compelled many sewer system operators to introduce systems which increase in-sewer retention times, and also retain more flow and load within sewer networks. The project has reviewed existing knowledge about the interaction between in-sewer flow and treatment plants, together with available models. The study is utilising a "benchmark" of 3 configurations of treatment plant and dynamic simulation using the WRc STOAT software, with minor modifications to ensure that effects on odour generation and nutrient removal processes are adequately modelled. As no existing sewer flow quality model can represent the range of conditions possible in sewer networks, a combined application of the Hydroworks model and a new model developed at Aalborg University is being used for this part of the study.

Benchmarking↗
PubMed2002

Experience and extensions to the ASM2 family of models.

The development of ASM2 has created a complex model for biological phosphorus removal. Most of the published work on calibrating this model has focused on the design of experiments to maximise information with which to calibrate the model, or the use of hourly data collected around and within an aeration tank. But many sewage works do not collect such data, nor have such instrumentation. The application of ASM2 with sparse data collected at a low frequency, and mostly only input-output, is considered in this paper, based on data collected at a Swedish sewage works. This paper shows that ASM2 can be calibrated with such measurements. This paper also looks at a modification to ASM2d to better handle heterotrophic usage of volatile fatty acids, and the use of this model to study the effects of large increases in in-sewer storage on sewage treatment works. Concern about the generation of large quantities of VFAs, and their effect on the sewage treatment processes, was unfounded.

Calibration↗
PubMed2001

Co-prescribing of SSRIs and TCAs in Australia: how often does it occur and who is doing it?

AIMS: To determine the frequency with which the selective serotonin re-uptake inhibitor (SSRI) antidepressants are used as add-on therapy to the tricyclic antidepressants (TCA) rather than as replacement therapy. METHODS: The data analysed were profiles of prescription records by date of supply to the patient. From within the national administrative dispensing claims database, the subset eligible for social security entitlements was identified as individuals by means of their coded permanent identification numbers (PINs). Following the initial supply of an SSRI in January 1996, the subsequent 6 months dispensing of SSRI and TCA antidepressants to these individuals was examined. The main outcome measure was the proportion of individuals to whom SSRIs and TCAs were dispensed concurrently, as an indirect measure of coprescription. In instances where a patient was receiving prescriptions for SSRIs and TCAs that had been written by the one doctor only, the major specialty of the doctor was investigated. RESULTS: 55 271 PINs were dispensed 63 865 SSRI prescriptions in January 1996 which represented over half (52%) of the total community SSRI prescriptions dispensed in that month. The number of these patients meeting the criteria for coprescription of SSRIs and TCAs over the next 6 months was 2773 (5%). The coprescribing instances were highest in Queensland and the prescribers most frequently involved had psychiatry major specialty codes. CONCLUSIONS: Among SSRI users there is a cohort of patients who, within the same time frame, are receiving supplies of a TCA, the nonselective drug that the SSRIs were designed to replace. This is indirect evidence of probable coprescription. Such combination use is of uncertain clinical and cost effectiveness, and carries additional risks. The SSRIs were included on the subsidy list in Australia on the basis of reasonable cost effectiveness as monotherapy compared with the TCAs. Our data imply that for some patients, antidepressant prescribing is inconsistent with the basis on which government subsidy was approved.

Adult↗
PubMed2000

Quantitation of cyclosporine-sensitive and -resistant allospecific cytotoxic cells at birth.

In the absence of clinically relevant models of acute rejection we have attempted to develop an assay to measure cyclosporine-resistant allospecific cytotoxic cells in vitro, beginning at birth. The principle of limiting dilution analysis was applied to investigate umbilical cord bloods as responders. Responders were incubated for 1 h in different concentrations of cyclosporine and irradiated HLA mismatched stimulator cells from healthy adults added, followed by recombinant IL-2. After 7 days, responders were tested against three europium-labelled PHA blasts: stimulator, responder and third party. A significant number of cyclosporine-resistant allospecific cytotoxic cell precursors were found in cord blood indicating prior activation. They may have been primed in utero against non-inherited maternal HLA antigens. Cyclosporine-resistant allospecific cytotoxic cell precursors were demonstrated in human umbilical cord blood using a quantitative assay. These cells may influence the reaction to subsequent transplants.

Adult↗
PubMed2000

Polymorphism of the ACE gene in Henoch-Schönlein purpura nephritis.

Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5-15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.

Child↗
PubMed2000

Pretransplant blood transfusions with cyclosporine in pediatric renal transplantation.

Pretransplant transfusions were repeatedly shown to be associated with improved graft survival in the "pre-cyclosporine era," and have recently been shown to be beneficial in patients on modern immuno-suppressive regimes. In an attempt to improve this transfusion effect and minimize the potential development of cytotoxic antibodies, we have given these transfusions, with concomitant cyclosporine cover, prior to transplantation. Ninety-two renal transplantations were performed in 91 children in the study group (group 1) and all received pretransplant transfusions with cyclosporine cover. Results were compared with a preceding group of 102 children (104 transplantations) who had received pretransplant transfusions without cyclosporine cover (group 2). There were 70 cadaver and 22 living-related donor (LRD) transplants in group 1, and 88 cadaver and 16 LRD transplants in group 2. Graft survival rates (1- and 5-year) for cadaver transplantation were 96% and 90% in group 1 compared with 78% and 64% in group 2 (P = 0.001). For LRD transplantation, these figures were 95% and 87% in group 1 and 81% and 69% in group 2. There was no difference between the two groups in terms of age at transplantation, sex, donor age, HLA-A, -B, -DR mismatches, or cold and warm ischemia times. All cadaver graft recipients received quadruple, sequential immunosuppression post transplant. However, 9 patients in group 1 were changed to tacrolimus for recurrent rejection episodes. No patient developed persistent lymphocytotoxic antibodies post transfusion or side effects of cyclosporine. Cyclosporine can be safely given with whole blood prior to transplantation with no adverse effect and no sensitization. Graft survival was significantly improved in this group of patients and graft loss due to rejection was exceptional. This effect should be further evaluated in prospective studies.

Anticoagulants↗
PubMed2000

Impact of increasing the re-supply interval on the seasonality of subsidised prescription use in Australia.

OBJECTIVE: To evaluate the impact of increasing the minimum re-supply period for prescriptions on the Pharmaceutical Benefits Scheme (PBS) in November 1994. The intervention was designed to reduce the stockpiling of medicines used for chronic medical conditions under the PBS safety net. METHODS: Interrupted times series regression analyses were performed on 114 months of PBS drug utilisation data from January 1991 to June 2000. These analyses assessed whether there had been a significant interaction between the onset of the intervention in November 1994 and the extreme levels of drug utilisation in the months of December (peak utilisation) and January (lowest utilisation) respectively. Both serial and 12-month lag autocorrelations were controlled for. RESULTS: The onset of the intervention was associated with a significant reduction in the December peak in drug utilisation; after the introduction of the policy there were 1,150,196 fewer prescriptions on average for that month (95% CI 708,333-1,592,059). There was, however, no significant change in the low level of utilisation in January. The effect of the policy appears to be decreasing across successive post-intervention years, though the odds of a prescription being dispensed in December remained significantly lower in 1999 compared to each of the pre-intervention years (11% vs. 14%). CONCLUSION: Analysis of the impact of increasing the re-supply period for PBS prescriptions showed that the magnitude of peak utilisation in December had been markedly reduced by the policy, though this effect appears to be decreasing over time. Continued monitoring and policy review is warranted in order to ensure that the initial effect of the intervention be maintained.

Australia↗
PubMed1999

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients.

BACKGROUND: Body mass index (BMI) at its extremes contributes to morbidity and mortality in the general population. Its influence on morbidity and mortality in patients on hemodialysis is not clearly defined. METHODS: The BMI in 1346 patients attending limited-care hemodialysis units across the state of Mississippi was determined, and its relation to one-year mortality and hospital stay was assessed using the Cox proportional hazard model. RESULTS: Of these patients, 89% were black, and 11% were white. Thirty-eight percent of patients were overweight (BMI > 27.5), and 13% were underweight (BMI < 20). The highest (27.60 +/- 0.29, mean +/- SE) and the lowest (24.54 +/- 0.48) BMI were noted in black females and white males, respectively. BMI, race, hematocrit (Hct), and biochemical markers of better nutrition positively influenced the survival, whereas age, serum globulin, and diabetes had a negative influence. In a Cox multivariate analysis, BMI, age, diabetes, prealbumin, and creatinine, but not race, serum albumin, Hct, or serum globulin, retained significant influence on survival. Compared with the normal weight (BMI between 20 and 27.5), the one-year survival rate was significantly higher in the overweight patients and lower in the underweight patients. With a one-unit increase in BMI over 27.5, the relative risk for dying was reduced by 30% (P < 0.04), and with a one-unit decrease in BMI below 20, the relative risk was increased by 1.6-fold (P < 0.01). Furthermore, underweight patients had significantly lower levels of biochemical markers of nutrition and higher frequency and longer duration of hospital stay. CONCLUSION: Adequate dialysis with special attention to proper nutrition aimed to achieve the high end of normal BMI may help to reduce the high mortality and morbidity in hemodialysis patients.

Black or African American↗
PubMed1998

Benign methylmalonic acidemia in a sibship with distal renal tubular acidosis.

Two male infants born to consanguineous parents were investigated for feeding difficulties in the 1st month of life. Both were found to have distal renal tubular acidosis (dRTA) with hypercalciuria. Nephrocalcinosis was present in the first child but not in the second. Urinary organic acid profile demonstrated an excess of methylmalonic acid (MMA) in both children in the absence of any other organic acid. MMA mutase activity and propionate incorporation were normal. There have been no neurological symptoms in either child. The first child has normal growth and psychomotor development at 4 years. His brother, who also has significant gastrooesophageal reflux, has failed to thrive and currently requires nasogastric feeding and caloric supplements to maintain weight along the 3rd percentile. Urinary and plasma MMA continue to be raised in both cases. The association of increased urinary and plasma MMA and dRTA presenting in the 1st month of life has not previously been reported and may represent a new syndrome of autosomal recessive inheritance.

Acidosis, Renal Tubular↗
PubMed1998

Using the Quetelet body mass index as a mortality indicator for patients starting renal replacement therapy.

OBJECTIVE: The purpose of this study was to compare clinical profiles and mortality risk of patients starting renal replacement therapy (RRT) across three Quetelet body mass index (BMI) classifications: lean, normal, and obese. SAMPLE/SETTING: All patients applying for dialysis services using Health Care Financing Administration (HCFA) from 2728-U4 were sampled during the period of April 1, 1995 through June 30, 1995 in two end-stage renal disease (ESRD) Networks. These two ESRD networks encompassed 7 states and provided 846 patients for this analysis. DESIGN: A descriptive survival study was used with a follow-up period of 18 months. METHODS: The Quetelet BMI was calculated based on dividing the predialysis (i.e. before the first dialysis) weight in kilograms by the height in meters squared (kg/m2). Lean, normal, and obese groups were established by quartiles for each gender. A normal BMI consisted of all patients in which the observed BMI was greater than the 25th percentile or less than the 75th percentile. RESULTS: The lean risk group had more health problems than either the normal or obese group, most notably, a higher prevalence of chronic obstructive pulmonary disease (n = 35, 16.99%) [p = 0.007] and peripheral vascular disease (n = 51, 24.76%) [p = 0.005]. CONCLUSIONS: Death risk was higher in the lean group compared to the normal group after adjusting for age, sex, diabetes, coronary artery disease (CAD), and albumin ratio levels. Based on the simplicity of this technique, recommendations for using the Quetelet BMI as a part of routine patient screening is advocated. Obtaining height and weight are necessary assessment parameters for patients starting dialysis therapy. Using the Quetelet BMI will help nurses to identify those patients who are at nutritional risk.

Aged↗
PubMed1997

Mouse mammary tumor virus: a virus that exploits the immune system.

Mouse mammary tumor virus (MMTV) causes mammary carcinomas and T-cell tumors in mice. MMTV variants that induce T-cell tumors have a large deletion within the U3 region of the long terminal repeat (LTR) compared to MMTV strains that induce mammary tumors. We provide evidence here that T-cell tropic MMTV strains lack a redundant binding site for a cellular protein called NBP (negative regulatory element binding protein). The lack of NBP-binding sites in T-cell tropic MMTV strains presumably leads to higher levels of transcription in T-cells during the MMTV life cycle and an increased incidence of mutagenic integration events.

Animals↗
PubMed1996

Systemic lupus erythematosus presenting as congenital nephrotic syndrome.

A male Caucasian infant developed nephrotic syndrome at 10 weeks of age. He had high titres of antinuclear antibody (ANA) and anti-double-stranded DNA antibody, with hypocomplementaemia, antiplatelet antibodies and anticardiolipin antibodies. There were no detectable antibodies to extractable nuclear antigens (ENA). His mother was consistently seronegative for anti-ENA (anti-Ro) antibodies and ANA. He developed severe, progressive multisystem involvement, however renal function has remained stable. Immunosuppression has been the mainstay of therapy in this rare presentation of systemic lupus erythematosus.

Antibodies, Antinuclear↗
PubMed1995

The Multicenter AIDS Cohort Study: retention after 9 1/2 years.

In a longitudinal, multicenter study of 4,954 men at risk for human immunodeficiency virus infection and acquired immunodeficiency syndrome, data from the first 9.5 years of follow-up (April 1984 through September 1993) were used to determine differences between those who remained in the study and those who dropped out. Demographic variables (age, race, education, employment, and study center), health status (human immunodeficiency virus type 1 serostatus and depression), and behavioral characteristics (alcohol drinking, drug use, and anal-receptive intercourse) were analyzed. Strategies for promoting retention included having frequent contact with participants, generating trust, keeping participants well-informed, utilizing multiple resources for follow-up, and providing flexible methods of participation. After 9.5 years of follow-up, vital status was known for 4,385 (88.5%) of the participants. Results from multiple logistic regression showed that race, age, education, and smoking were each significantly associated with nonparticipation (p < 0.001). A high level of retention was maintained in this well-educated and highly motivated cohort of homosexual/bisexual men. Extensive follow-up methods may improve case-finding. Nonwhite race, younger age, less education, and smoking were important predictors of dropping out. These findings identify specific groups for targeting follow-up efforts to reduce potential bias due to dropout.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A redundant nuclear protein binding site contributes to negative regulation of the mouse mammary tumor virus long terminal repeat.

The tissue specificity of mouse mammary tumor virus (MMTV) expression is controlled by regulatory elements in the MMTV long terminal repeat (LTR). These regulatory elements include the hormone response element, located approximately between -200 and -75, as well as binding sites for NF-1, Oct-1 (OTF-1), and mammary gland enhancer factors. Naturally occurring MMTV deletion variants isolated from T-cell and kidney tumors, transgenic-mouse experiments with MMTV LTR deletions, and transient transfection assays with LTR constructs indicate that there are additional transcription regulatory elements, including a negative regulatory element (NRE), located upstream of the hormone response element. To further define this regulatory region, we have constructed a series of BAL 31 deletion mutants in the MMTV LTR for use in transient transfection assays. These assays indicated that deletion of two regions (referred to as promoter-distal and -proximal NREs) between -637 and -201 elevated basal MMTV promoter activity in the absence of glucocorticoids. The region between -637 and -264 was surveyed for the presence of nuclear protein binding sites by gel retardation assays. Only one type of protein complex (referred to as NRE-binding protein or NBP) bound exclusively to sites that mapped to the promoter-distal and -proximal NREs identified by BAL 31 mutations. The promoter-proximal binding site was mapped further by linker substitution mutations and transfection assays. Mutations that mapped to a region containing an inverted repeat beginning at -287 relative to the start of transcription elevated basal expression of a reporter gene driven by the MMTV LTR. A 59-bp DNA fragment from the distal NRE also bound the NBP complex. Gel retardation assays showed that mutations within both inverted repeats of the proximal NRE eliminated NBP binding and mutations within single repeats altered NBP binding. Intriguingly, the NBP complex was detected in extracts from T cells and lung cells but was absent from mammary gland cells. These results suggest that a factor contributing to high-level expression of MMTV in the mammary gland is the lack of negative regulation by NBP.

Animals↗