The direct health care costs of obesity in the United States.

OBJECTIVES: Recent estimates suggest that obesity accounts for 5.7% of US total direct health care costs, but these estimates have not accounted for the increased death rate among obese people. This article examines whether the estimated direct health care costs attributable to obesity are offset by the increased mortality rate among obese individuals. METHODS: Data on death rates, relative risks of death with obesity, and health care costs at different ages were used to estimate direct health care costs of obesity from 20 to 85 years of age with and without accounting for increased death rates associated with obesity. Sensitivity analyses used different values of relative risk of death, given obesity, and allowed the relative costs due to obesity per unit of time to vary with age. RESULTS: Direct health care costs from 20 to 85 years of age were estimated to be approximately 25% lower when differential mortality was taken into account. Sensitivity analyses suggested that direct health care costs of obesity are unlikely to exceed 4.32% or to be lower than 0.89%. CONCLUSIONS: Increased mortality among obese people should be accounted for in order not to overestimate health care costs.     

Neuroanatomic substrates of late-life mental disorders

Advances in magnetic resonance imaging (MRI) techniques have made it possible to quantify anatomic brain abnormalities in neuropsychiatric disorders. This review focuses on controlled, quantitative MRI studies in depression, degenerative disorders, and psychosis in the elderly. Although many of the anatomic abnormalities detected are observed across disorders, the patterns of regional involvement may be more selective and disorder specific. We integrate MRI findings with relevant clinical and neurobiologic observations in an attempt to develop a cohesive model of late-life psychiatric illness. Although the model primarily alludes to the pathophysiology of late-life depression, it may have broader biologic implications for other mental disorders in the elderly.     

Tumors of the Osseous Spine

Recent advances in molecular biology with the development of novel therapeutic agents, as well as fundamental understanding of the mechanisms of bone metastases have greatly altered the therapeutic options in patients with spine tumors. Improvements in spine instrumentation as well as the development of recombinant Bone Morphogenetic Protein for spine reconstruction and fusion offers promising hope for curative strategies in selected patients. A clearer application of the fundamentals of surgical oncology applied to spine tumors should result in a greater proportion of patients undergoing surgically appropriate en bloc resections for spine tumors. Finally, the superiority of surgery over external irradiation in the controlled clinical trial setting should greatly expand the pool of patients requiring surgery. In this review, we consider the recent advances in primary bone tumors including chordoma, sarcomas, multiple myeloma, as well as metastatic cancer to the spine.     

A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma.

A randomized prospective clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated, short course radiotherapy in poor prognosis patients with high grade glioma. The primary endpoint was overall survival.     

Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.     

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Olanzapine-induced mania

This report describes a case of manic symptoms induced by olanzapine in an 85-year-old female with a 3 year history of delusional disorder. She was treated in the past with trifluoperazine and risperidone. Symptoms were severe enough to require detention in hospital. Florid manic symptoms resolved two weeks after stopping olanzapine while only using 1 mg of haloperidol as required.