Feeding-related immune responsive brain stem neurons: association with CGRP

Using dual-labeling in situ hybridization histochemistry, the neurotransmitter expression of immune-responsive neurons in the pontine parabrachial nucleus, a major relay for interoceptive information, was investigated. Intravenous injection of bacterial wall lipopolysaccharide resulted in dense c-fos mRNA expression in the external lateral parabrachial nucleus, and a majority of the c-fos expressing cells also expressed calcitonin gene-related peptide (CGRP) mRNA. In contrast CGRP-positive cells in the adjoining external medial subnucleus were c-fos negative. Taken together with previous hodological and behavioral studies, these data suggest that CGRPergic parabrachial neurons may mediate lipopolysaccharide-induced anorexia by means of their projection to central nucleus of the amygdala.     

Mortality after appendectomy in Sweden, 1987-1996

OBJECTIVE: To study mortality after appendectomy. SUMMARY BACKGROUND DATA: The management of patients with suspected appendicitis remains controversial, with advocates of early surgery as well as of expectant management. Mortality is not known. METHODS: The authors conducted a complete follow-up of deaths within 30 days after all appendectomies in Sweden (population 8.9 million) during the years 1987 to 1996 (n = 117,424) by register linkage. The case fatality rate (CFR) and the standardized mortality ratio (SMR) were analyzed by discharge diagnosis. RESULTS: The CFR was 2.44 per 1,000 appendectomies. It was strongly related to age (0.31 per 1,000 appendectomies at 0-9 years of age, decreasing to 0.07 at 20-29 years, and reaching 164 among nonagenarians) and diagnosis at surgery (0.8 per 1,000 appendectomies after nonperforated appendicitis, 5.1 after perforated appendicitis, 1.9 after appendectomies for nonsurgical abdominal pain, and 10.0 for those with other diagnoses). The SMR showed a sevenfold excess rate of deaths after appendectomy compared with the general population. The relation to age was less marked (SMR of 44.4 at 0-9 years, decreasing to 2.4 in patients aged 20-29 years. and reaching 8.1 in nonagenarians). The SMR was doubled after perforation compared with nonperforated appendicitis (6.5 and 3.5, respectively). Nonsurgical abdominal pain and other diagnoses were associated with a high excess rate of deaths (9.1 and 14.9, respectively). The most common causes of deaths were appendicitis, ischemic heart diseases and tumors, followed by gastrointestinal diseases. CONCLUSIONS: The CFR after appendectomy is high in elderly patients. The excess rate of death for patients with nonperforated appendicitis and nonsurgical abdominal pain suggests that the deaths may partly be caused by the surgical trauma. Increased diagnostic efforts rather than urgent appendectomy are therefore warranted among frail patients with an equivocal diagnosis of appendicitis.     

BACH1 Ser919Pro variant and breast cancer risk

Background  

BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer.     

Brain tumours in Sweden 1996: care and costs

OBJECTIVES: Brain tumours cause considerable concern due to a high mortality and there are increasing efforts to provide adequate care, sometimes outside hospitals. Health care utilisation, direct costs of care, and the indirect social cost of morbidity and early mortality caused by brain tumours in Sweden in the year 1996 was analysed. METHODS: Quantification of ambulatory care, care in hospital, long term and palliative/terminal care, drug consumption, temporary as well as long term morbidity, and mortality from comprehensive national data sources. Direct costs were calculated using 1996 charges. Indirect costs were calculated by sex and age specific salaries. A sensitivity analysis considered the impact of alternative estimates of each item. RESULTS: Indirect costs were 75% of the total and were caused mainly by early mortality. Direct costs were predominantly for care in hospital, long term care, and home health care. Among direct costs, astrocytomas III-IV and meningiomas accounted for 42% and 30% respectively. CONCLUSIONS: The cost of illness from brain tumours reflects the characteristics of these malignancies. Despite their low incidence rate, the economic impact caused by high mortality among young persons is a predominant trait. Costs of acute hospital care and also long term care and home care are considerable.     

Tumour microvessel density as predictor of chemotherapy response in breast cancer patients

The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer.     

QALYs, standard gambles, and the expected budget constraint

This paper shows that when quality adjustment factors for use in constructing QALY indices are established through answers to standard-gamble questions or similar methods, the assumptions that are made by respondents about the financial consequences of changing probabilities of illness and death are critically important for the use of QALYs in cost-utility analysis (CUA). It qualifies Meltzer's [Journal of Health Economics 16 (1997) 33] result that the cost per quality-adjusted life-year (QALY) for life-saving medical interventions should include the future consumption of those who would otherwise not have survived, by showing that its validity depends on how the QALY index has been established. The paper also shows that, contrary to a widely held notion, allocation of a fixed health care budget through CUA does not generally result in a second-best efficient allocation. Another finding is that failure to specify carefully what respondents to standard-gamble questions are supposed to assume about the financial consequences of ill health may result in a bias against providing care to older individuals.