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Biomedical subjects

David Voss

Publications and source records attributed to David Voss.

7 recordsLinked to original sources

Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases.

AIM: Although proton pump inhibitors (PPI) are usually safe and effective therapeutic agents, serious adverse effects can occur. The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years. METHODS: The clinical presentation, therapeutic drugs, demographic details and renal outcome of the patients were considered. The population at risk and total PPI exposure were able to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal. RESULTS: The median patient age was 78 years. The mean baseline serum creatinine level was 83 micromol/L, peak level 392 micromol/L, and recovery level 139 micromol/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6-18.7 per 100 000 patient years). Although four patients presented with an acute systemic allergic reaction, 11 were asymptomatic with an insidious development of renal failure. CONCLUSION: PPI are now the most commonly identified cause of AIN in the Auckland area. Recovery occurs after withdrawal of the drug but is often incomplete. Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Role of p16 and p14ARF in radio- and chemosensitivity of malignant gliomas.

In addition to cytoreductive surgery, most patients with malignant gliomas also undergo radio- and chemotherapy. An improved understanding of the molecular genetic mechanisms underlying the radio- and chemosensitivity of gliomas may help to identify glioma patients who will benefit from aggressive and, therefore, potentially toxic adjuvant treatment. It may also allow for the development of new therapies aimed at improving the response of these tumors towards chemo- and radiotherapy. The INK4a gene products, p16 and p14ARF, have been suggested as potential regulators of glioma chemo- and radiosensitivity. We have used tetracycline controlled expression of p16 and plasmid-based p14ARF expression to study the chemo- and radiosensitivity of glioma cell lines. Ectopic p16 sensitized U-87MG cells towards treatment with vincristine and possibly also BCNU by approximately 1.5 to 2-fold, and towards ionizing radiation by a factor of 1.5. p14ARF expression was found to render U-87MG cells 2-fold more radioresistant than controls. These findings support a role for p16 and p14ARF as modulators of the radio-and chemosensitivity of gliomas. Further studies of the role of cell cycle regulators in glioma chemo- and radio-sensitivity seem warranted. We would like to point out that such candidate genes which may code for potent growth suppressors (like p16) or even toxic gene products can be successfully investigated using the approach detailed in this manuscript.

Antineoplastic Agents, Alkylating↗

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement.

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function. The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%. The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.

Journal Article↗

Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial.

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.

Anemia↗