Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Risk of infectious complications in well-appearing children with transient neutropenia

To determine whether well-appearing children found incidentally to be neutropenic are at risk for an infectious complication, 44 consecutive months of hematology laboratory records were reviewed. One hundred nineteen patients had medical record documentation regarding clinical course, serial white blood cell counts, and the absence of serious infections, chronic illnesses, or a family history known to be associated with neutropenia. The median duration of documented neutropenia was 13 days (range, 1 to 491 days). Infectious complications occurred in 4 of the 36 patients who had neutropenia for more than 30 days (2 with stomatitis, 1 with cellulitis, and 1 with pneumonia) but in none with shorter durations of neutropenia. There were no significant associations between the development of an infectious complication and either the initial absolute neutrophil count or the lowest documented absolute neutrophil count, nor was there a correlation between the initial absolute neutrophil count and the duration of neutropenia. These data indicate that infectious complications occur in otherwise well children with unexplained neutropenia that persists, but these infections are infrequent and usually are superficial.     

Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.

An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.     

Rubella virus strains show no major antigenic differences.

To determine whether antigenic differences occur among rubella virus strains, five wild-type strains of rubella virus isolated in the UK, the USA, and in Japan between 1964 and 1987 and four attenuated vaccine strains were compared employing a panel of 28 monoclonal antibodies in neutralization, haemagglutination-inhibition, enzyme immunoassay, and indirect immunofluorescence assays. No antigenic differences were detected which confirms that rubella vaccines will protect against circulating strains and that rubella antigens used in serological tests for screening and diagnosis will detect antibodies induced by all strains.     

Diabetic retinopathy.

Diabetic retinopathy is the commonest cause of blindness amongst individuals of working age. The onset of retinopathy is variable. Regular ophthalmic screening is essential in order to detect treatable lesions early. Retinal laser therapy is highly effective in slowing the progression of retinopathy and in preventing blindness. As the sufferers of diabetes mellitus, the commonest endocrine disorder, now constitute approximately 1-2% of Western populations, concerted multidisciplinary effort must be made towards cost-effective community screening by the medical community.     

Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline

Ninety-day inhalation studies were conducted on 50:50 weight percent (wt %) mixtures of n-butane:n-pentane and isobutane:isopentane, respectively, and on a distillation cut boiling below 145 degrees F of a reference unleaded gasoline blend to assess the nephrotoxicity of these volatile mixtures. The mixtures of butanes and pentanes were selected because these four hydrocarbons are the most prevalent components of gasoline vapors encountered under typical occupational exposures. The 0-145 degrees F gasoline distillation fraction was tested because it reasonably approximates the composition of gasoline vapors measured under occupational settings. Male and female F-344 rats were exposed to 2 levels of each mixture, 6 hours per day, 5 days per week, for 13 weeks. The target concentrations for the butane:pentane mixtures were 4500 and 1000 parts per million (ppm), while 5200 and 1200 ppm were set for the gasoline distillation fraction. An interim sacrifice was conducted after 28 days. The rats were not significantly affected by the exposures, and there was no evidence of hydrocarbon-induced nephropathy in either sex at the termination of each study. However, at the 28-day interim sacrifice period for both butane:pentane mixtures, mild, transient treatment-related but not exposure-related kidney effects were observed in the male rats. These perturbations were absent at the interim sacrifice period for the gasoline distillation fraction.     

Biosynthesis of adipokinetic hormones (AKHs): further characterization of precursors and identification of novel products of processing

Two adipokinetic hormones (AKH I: pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2, and AKH II: pGlu-Leu-Asn-Phe-Ser-Thr-Gly-Trp-NH2) are synthesized by the neurosecretory cells of the corpora cardiaca (CC) of the locust Schistocerca gregaria. Both AKHs are released into the blood during flight and serve to regulate lipid metabolism and other physiological processes involved in flight. By in vitro "pulse-chase" experiments we show that 2 precursors (P1 and P2) are involved in AKH biosynthesis. These are about 8.4 kDa polypeptides which are AKH immunoreactive but also contain an amino acid (tyrosine) not present in the AKH peptides. By following the fate of 14C-tyrosine incorporated into P1 and P2, we have identified 2 novel products of precursor processing. These are called AKH-Precursor Related Peptides or APRP 1 and APRP 2. Size exclusion chromatography shows that the APRPs are about 6.5 kDa large and therefore represent major fragments of the precursors. The optical density peaks corresponding to P1, P2, APRP 1, and APRP 2 on a reverse-phase chromatogram are identified. The precursors being metabolic intermediates are represented by minor optical density peaks that disappear when de novo protein synthesis is blocked by cycloheximide. In contrast, the APRPs are represented by major optical density peaks consistent with their being accumulating end products of AKH precursor processing. The function of the APRPs is as yet unknown. They are, however, co-synthesized and also co-released with the AKHs, and may therefore also have hormonal functions related to flight.