Reflex Cardiorespiratory Effects of Nociceptive Oesophageal Distension in the Decerebrate Rat

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.     

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.     

The Disablement Experienced by Traumatically Brain-Injured Adults Living in the Community

The disablement that occurs following traumatic brain injury (TBI) can be extensive and severe and consequently has been difficult to report on in a comprehensive and thorough manner. We were able to address this difficulty by analysing a sub group of data from the Canadian Health and Activity Limitation Survey (HALS) using the theoretical framework of disablement developed by the World Health Organization, the International Classification of Impairment, Disability and Handicap (ICIDH). There were 454 survey respondents (representing 12290 in the Canadian population) with disability resulting from a TBI and a mean time post-injury of 13 years. Three handicaps identified in the ICIDH were the focus of the study: physical independence, work, social integration. The prevalence of long term handicap was very high with 66% of the sample reporting the need for ongoing assistance with some activities of daily living, 75% not working, and 90% reporting some limitations or dissatisfaction with their social integration. Multivariate regression analysis was used to investigate the determinants of the handicaps. The determinants included: age, gender, level of education, living alone, physical environment, and specific disabilities. The implications of these findings are discussed in relation to rehabilitation issues, the usefulness of the ICIDH as a model to investigate outcomes, and directions for future research.     

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.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

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.