Analgesic nephropathy

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.     

Inhibition of Na/Ca exchange stimulates insulin release from isolated rat pancreatic islets

Summary— Na/Ca exchange was recently shown to regulate cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) in the pancreatic B-cell. The aim of the present study was to provide direct evidence that inhibition of the activity of the exchange may also increase insulin release. In the presence of extracellular Na+, caffeine stimulated ⁴⁵Ca outflow but did not increase insulin release from islets perifused in the presence of 2.8 mM glucose. By contrast, in the absence of extracellular Na+, caffeine almost failed to increase ⁴⁵Ca outflow and reversibly stimulated insulin release despite the fact that the absence of extracellular Na+ per se reduced basal insulin release. Similar findings were observed in islets perifused at a higher glucose concentration (8.3 mM) except that, in the presence of extracellular Na+, caffeine more markedly increased ⁴⁵Ca outflow and stimulated insulin release. Our data provide direct evidence that inhibition of Na/Ca exchange with resulting blockade of Ca²⁺ outflow may increase insulin release from the pancreatic B-cell under suitable experimental conditions.     

A survey of the effectiveness of the assessment of the welfare of the child in UK in-vitro fertilization units

Seventy-one clinics in the UK offering in-vitro fertilization (IVF) treatment were surveyed for their protocols on the assessment of the welfare of the children produced. A total of 44 (62%) responded. Of these, five (12%) did not have operational protocols, seven (16%) declined to provide their protocols, and 32 (73%) provided information used in the survey. The information was in the form of a protocol for only 16 (50%) of these clinics. The remaining clinics submitted as their 'protocols' letters to general practitioners, patient information, patient questionnaires and/or a copy of their policy on the assessment of child welfare. From the submitted material, it was possible to determine that 94% of clinics seek information on aspects of child welfare assessment, 78% have a procedure for making further enquiries where there is any cause for concern, 44 % include counselling opportunities explicitly in protocols, 30-38% of clinics see a full medical and social history from each prospective parent as part of the child welfare assessment, 16% include explicit consideration of the impact of multiple births on the welfare of the child, and 3% include consideration of the issue of disclosure of the mode of conception of the child on its welfare. Most clinics did not have clearly defined procedures on how to reach a decision on whether or not to treat. Eight clinics (25%) made explicit in their protocols any exclusion criteria. It is concluded that clinics are not currently producing completely effective protocols. Two possible reasons for this are considered: lack of technical knowledge about what constitutes an effective protocol, and lack of clear policy development and propagation underlying protocols within clinics. Possible approaches to improving the situation are considered.