Evaluation of novel renal biomarkers with a cisplatin model of kidney injury: gender and dosage differences.

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We use two novel multiplex assays to quantify biomarker concentration in multiple urine collections made prior to and following administration of cisplatin, a common nephrotoxicant, to rats. We investigate the correlation of the magnitude of biomarker changes with the severity of histopathological observations and explore the relationship of these to both dose and sex. The novel biomarkers evaluated are urinary albumin, alpha glutathione s-transferase (α-GST), glutathione S-transferase-yb1 (GSTYb1), lipocalin-2, kidney injury molecule-1 (KIM-1), osteopontin, and renal papillary antigen 1 (RPA-1) and plasma cystatin C, alongside the traditional biomarkers of plasma urea, creatinine, and urinary n-acetyl-beta-d-glucosaminidase (NAG), total protein, and glucose. We show for all time points, and for almost all doses, that male rats consistently had either more severely graded or a higher incidence of histologically observed lesions than females; that changes in urinary glucose, total urinary protein, NAG, and the novel urinary biomarkers albumin, osteopontin, and KIM-1 are clearly temporally associated; and that changes are related to the severity of injury. We also found that receiver operating characteristic curve analysis and area under the curve are significantly higher than urea or creatinine for all new biomarkers except aGST, GSTYb1, cystatin c, and total protein in both sexes.

Cerebral venous sinus thrombosis following cervical disc arthroplasty.

Cerebral venous sinus thrombosis is a rare condition, which is difficult to diagnose. It has not previously been reported following surgery to the cervical spine . We report such a case in a 45-year-old man after cervical disc replacement. A high index of suspicion, with early imaging of the brain and prompt treatment, can produce a favourable outcome, albeit not in this case.

Considering the impact of medicine label design characteristics on patient safety.

Medication errors involving patients receiving the wrong medicines, the wrong dosages or failure to take medicines according to the prescribed schedule are a substantial threat to patient safety. In the medical domain, research evidence on the benefits of improved labelling are piecemeal and often single-product or single-manufacturer driven and often do not inform the more general process of label design. Government and other guidelines on this topic are often low level and non-specific, often failing to give evidence-based guidance. However, there is a wealth of evidence-based research findings in related areas such as food labelling, chemical labelling and more general warnings research, which can provide systematic evidence on the effects of design characteristics such as font size, colour, signal words and linguistic usage on crucial performance variables such as compliance, understandability and discriminability. This research is reviewed and its relevance to medicine labelling is presented.

Opportunistic screening for abdominal aortic aneurysm.

OBJECTIVE: To contribute to the current debate on screening for abdominal aortic aneurysm (AAA). SETTING: Radiology department of the John Radcliffe Hospital, Oxford. METHODS: The prevalence of AAA in 317 clinically referred male patients aged 65-74 undergoing abdominal ultrasonography with no clinical suspicion of an AAA was investigated over a period of one year. RESULTS: Over the year 15/317 (5%) patients were found to have an aneurysm (defined as aortic diameter (> or = 30 mm), with eight (3%) patients having an aortic diameter of > or = 40 mm. Six months later appropriate management for the AAA had been started for only four patients. A knowledge assessment questionnaire sent to 245 hospital clinicians and general practitioners showed that 17 (12%) of the 139 respondents would initiate no review of patients found to have an aneurysm of 30-39 mm and two would take no action with aneurysms of 40-49 mm. Thirty two (23%) respondents would seek advice on management for all categories of aneurysm, 14% from the radiologist. CONCLUSIONS: Opportunistic screening for AAA in men undergoing clinically indicated abdominal ultrasonography is easy, productive, without discernible cost, and discloses a prevalence of AAA comparable with that of population screening programmes. Routine opportunistic measurement of aortic diameter during abdominal ultrasonography in the at risk group would allow 12-15% of men aged 65-74 to be screened for AAA within five years without the need for any additional resources.

Retrieval and allocation of organs for transplantation: the Michigan experience.

The Organ Procurement Agency of Michigan (OPAM) is now in its twenty-third year of service to the transplant community in Michigan. From a beginning with one coordinator in 1971, it now employs 53 individuals, including 8 laboratory technologists for its own on-site histocompatibility laboratory, a dozen procurement coordinators stationed throughout the state, 6 organ placement coordinators in the main office, 6 screening coordinators who provide around-the-clock coverage at the office, a tissue recovery section, as well as additional finance, education, and administrative support staff. This chapter outlines the history and growth in organ recoveries of the organization. More importantly, the chapter also analyzes the Michigan experience regarding racial distribution of kidneys. While African-Americans comprise 14% of the general population of the state, they comprise 40% of the waiting kidney recipients and only 26% of the actual recipients. Depending upon blood type, average waiting time for a kidney for African-Americans can be up to 4 months longer than for Whites. The analysis attributes this variance primarily to the allocation methodology for kidney distribution, which is largely driven by antigen matching and secondarily to the generally greater frequency and higher degree of blood sensitization among African-Americans, which causes a substantially higher frequency of positive-crossmatch results between potential donor and recipient. The authors conclude that changes in the present allocation system could be made to achieve greater equity for African-American patients, without removing the advantages inherent in transplanting kidneys with closely matched antigens.

A role for ultrasound in limb lengthening.

The distraction gap at eight sites in six patients undergoing limb lengthening was monitored by both standard radiographs and ultrasound. Using the measurements obtained we were able to assess the rate and quality of callus formation at the distraction site, something that radiographs alone do not enable one to do. We suggest that ultrasound has a valuable role to play in guaging the optimum rate of lengthening for a particular patient and commend it as a technique to complement radiographs in the follow-up of the increasing numbers of patients undergoing distraction osteogenesis.

Pharmacokinetics of teicoplanin in subjects with varying degrees of renal function.

The pharmacokinetics of teicoplanin were studied in 20 subjects with varying degrees of renal function after administration of a single 200 mg intravenous dose. Pharmacokinetic parameters were calculated with a three compartment open model and by non-compartmental analysis. The elimination half-life increased as creatinine clearance decreased (rs = -0.87, P less than 0.001). The distribution volume was 1.0 (+/- 0.3) 1/kg of actual body weight and did not vary with changes in creatinine clearance. In normal subjects the main route of elimination was renal. The plasma clearance of teicoplanin correlated with creatinine clearance (rs = 0.91, P less than 0.001). At lower levels of creatinine clearance the variation in elimination half-life was such that we recommend individualization of the teicoplanin dosage following the measurement of the drug concentration in plasma.

Hypercalcaemia as a manifestation of malignant urothelial change in analgesic nephropathy.

We report two cases of patients with analgesic nephropathy presenting with the symptoms of hypercalcaemia, and who were found to have transitional cell carcinomas of the renal pelvis. On removal of the tumours, calcium levels fell to normal, indicating that a humoral factor produced by the tumour caused the hypercalcaemia. We suggest that hypercalcaemia in a patient with analgesic nephropathy may indicate a malignant change, and that serum calcium should be assessed when such patients are reviewed.