'Obesity paradox' misunderstands the biology of optimal weight throughout the life cycle.

The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 g/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.

Incidence and lifetime costs of injuries in the United States.

BACKGROUND: Standardized methodologies for assessing economic burden of injury at the national or international level do not exist. OBJECTIVE: To measure national incidence, medical costs, and productivity losses of medically treated injuries using the most recent data available in the United States, as a case study for similarly developed countries undertaking economic burden analyses. METHOD: The authors combined several data sets to estimate the incidence of fatal and non-fatal injuries in 2000. They computed unit medical and productivity costs and multiplied these costs by corresponding incidence estimates to yield total lifetime costs of injuries occurring in 2000. MAIN OUTCOME MEASURES: Incidence, medical costs, productivity losses, and total costs for injuries stratified by age group, sex, and mechanism. RESULTS: More than 50 million Americans experienced a medically treated injury in 2000, resulting in lifetime costs of $406 billion; $80 billion for medical treatment and $326 billion for lost productivity. Males had a 20% higher rate of injury than females. Injuries resulting from falls or being struck by/against an object accounted for more than 44% of injuries. The rate of medically treated injuries declined by 15% from 1985 to 2000 in the US. For those aged 0-44, the incidence rate of injuries declined by more than 20%; while persons aged 75 and older experienced a 20% increase. CONCLUSIONS: These national burden estimates provide unequivocal evidence of the large health and financial burden of injuries. This study can serve as a template for other countries or be used in intercountry comparisons.

Advanced Cancer Patients' Prognostic Awareness and Its Association With Anxiety, Depression and Spiritual Well-Being: A Multi-Country Study in Asia.

AIMS: The associations between prognostic awareness, acceptance of illness and psychological outcomes (anxiety, depression and spiritual well-being) remain unclear. This study examined the associations between prognostic awareness and various psychological outcomes and how they can be moderated by patient acceptance of illness (cancer). MATERIALS AND METHODS: In total, 1184 patients with stage IV solid cancer were recruited at major public hospitals across four Asian countries (China, India, Sri Lanka, Vietnam). Prognostic awareness and acceptance of illness were assessed through self-reported understanding of treatment intent and acceptance of illness, respectively. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, whereas spiritual well-being was measured using the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being Scale. Multivariate regressions were used to estimate the associations while controlling for patient characteristics. RESULTS: Compared with being unaware of their prognosis (i.e. believing that their cancer is curable), being aware or unsure of their prognosis was associated with higher anxiety and depressive symptoms, and lower spiritual well-being scores. Acceptance of illness moderated these relationships and improved the psychological outcomes. CONCLUSIONS: The results suggest that disclosure of prognostic information should be provided in conjunction with psychological interventions that focus on acceptance of illness.

Strategies to improve survival outcomes of out-of-hospital cardiac arrest (OHCA) given a fixed budget: A simulation study.

BACKGROUND: Our study aimed to identify a strategy that maximizes survival upon hospital discharge or 30-days post out-of-hospital cardiac arrest (OHCA) in Singapore for fixed investments of S$1, S$5, or S$10 million. Four strategies were compared: (1) no additional investment; (2) reducing response time via leasing of more ambulances; (3) increasing number of people trained in cardiopulmonary resuscitation (CPR); and (4) automated external defibrillators (AED). METHODS: We estimated the effect of ambulance response time, bystander CPR and AED on survival based on Singapore's 2010-2015 OHCA registry data. We simulated the changes in ambulance response times and likelihood of (1) CPR and (2) AED usage as a function of their increased availability, which was then combined with the effect of each factor to determine the increase in survival for each strategy. RESULTS: Survival given no additional investment was 4.03% (95% CI: 3.96%, 4.10%). The investments in ambulances, CPR training and AEDs for a given budget of S$1M changed survival to 4.03% (95% CI: 3.96%, 4.10%), 4.04% (95% CI: 3.98%, 4.11%), and 4.44% (95% CI: 4.35%, 4.54%), respectively. This generated 0, 2 and 102 additional life years saved respectively. Given a budget of S$5M or S$10M, 509 or 886 additional life years could be saved, by investing in an additional 10,000 or 20,000 AEDs respectively. The strategies reached a saturation effect whereby improvement in survival was marginal when the budget was increased to ≥S$5M for investment in ambulances and CPR training. CONCLUSIONS: Investing in AEDs had the most gain in survival.

Superoxide reaction with nitroxide spin-adducts.

The reactions of superoxide radical with persistent nitroxide spin-adducts or with stable spin-labels were studied using ESR spectrometry. Superoxide radicals were produced enzymatically using xanthine - xanthine oxidase or chemically by dissolving potassium superoxide in DMSO. Hydroxyl and methyl spin-adducts of the spin-trap DMPO were performed by sonolysis and subsequently reacted with superoxide radical. Superoxide-induced depletion of DMPO--OH obeyed second order kinetics. Contrary to previously published mechanisms, the reaction requires neither transition metal ions nor thiols. The depleted spin-adducts could not be restored by reoxidation with ferricyanide or copper +H2O2; thus, the superoxide-mediated destruction does not result in a mere one-electron reduction product. Superoxide also depletes other DMPO spin-adducts including DMPO--CH3 and DMPO--H, but not PBN--CH3. In addition, some 5-membered ring stable nitroxides are depleted by superoxide in a pseudo-zero order reaction. In studying systems which generate O2- and OH, the superoxide-induced destruction of DMPO--OH may well lead to erroneous conclusions regarding the primary radicals produced. In particular this reaction might be operative under circumstances where elevated rates of superoxide production take place, such as during oxygen consumption "burst" in phagocytosis, degranulation, or paraquat intoxication.

Identification of surface proteins on bovine leukocytes by a biotin-avidin protein blotting technique.

A method has been developed which covalently attaches biotin to proteins on the outer surface of leukocytes. These proteins are separated by polyacrylamide gel electrophoresis and transferred to nitrocellulose by protein blotting. Labeled proteins are detected using an avidin-peroxidase conjugate and color indicator. The method has been used to identify surface proteins specific to either polymorphonuclear leukocytes or mononuclear leukocytes prepared from bovine peripheral blood. The method provides a highly sensitive, non-radioactive means of examining alterations of surface proteins on leukocytes under differing functional and physiological conditions. Cell viability is not altered by this labeling method and labeled cells can be used to examine functions of surface proteins.

The effects of cellular glutathione elevation on the oxygen enhancement ratio.

The radiation responses at various oxygen tensions were evaluated in V79 Chinese hamster cells under conditions where their nonprotein thiols, primarily glutathione (GSH), were elevated by 2-oxothiazolidine-4-carboxylate (OTZ). OTZ, when cleaved by intracellular oxoprolinase, provides the cell with cysteine which stimulates GSH synthesis. A 2-hr pretreatment with 10 mM OTZ elevated GSH to 200% of controls. This elevation in GSH offered no protection to aerated cells; however, for O2 tensions less than or equal to 40,000 ppm modest protection was observed as evidenced by an increase in oxygen enhancement ratio. GSH elevation afforded maximal protection between 1000 and 10,000 ppm O2; however, the extent of protection was relatively small (protection factor = 1.3).

Griseofulvin and its uses.

Griseofulvin has been used in the treatment of dermatophyte infections for the past 30 years. The use of the drug in treating other medical conditions is reviewed.

Spontaneous orbital haemorrhage.

A 57-year-old housewife, with controlled hypertension, presented with acute right proptosis and visual loss with external ophthalmoplegia due to spontaneous orbital haemorrhage. Vision and ocular motility were returned to normal by the rapid surgical evacuation of the blood. Acute orbital haemorrhage is an ocular emergency requiring urgent treatment to prevent the usual previously reported outcome of permanent visual loss.

Cigarette smoke impairs neutrophil respiratory burst activation by aldehyde-induced thiol modifications.

Exposure to airborne pollutants such as tobacco smoke is associated with increased activation of inflammatory-immune processes and is thought to contribute to the incidence of respiratory tract disease. We hypothezised that cigarette smoke (CS) could synergize with activated inflammatory/immune cells to cause oxidative injury or result in the formation of unique reactive oxidants. Isolated human neutrophils were exposed to gas-phase CS, and the production of nitrating and chlorinating oxidants following neutrophil stimulation was monitored using the substrate 4-hydroxyphenylacetate (HPA). Stimulation of neutrophils in the presence of CS resulted in a reduced oxidation and chlorination of HPA, suggesting inhibition of NADPH oxidase or myeloperoxidase (MPO), the two major enzymes involved in inflammatory oxidant formation. Peroxidase assays demonstrated that neutrophil MPO activity was not significantly affected after CS-exposure, leaving the NADPH oxidase as a likely target. The inhibition of neutrophil oxidant formation was found to coincide with depletion of cellular GSH, and a similar modification of critical cysteine residues, such as those in NADPH oxidase components, might be involved in reduced respiratory burst activity. As alpha,beta-unsaturated aldehydes such as acrolein have been implicated in thiol modifications by CS, we exposed neutrophils to acrolein prior to stimulation, and observed inhibition of NADPH oxidase activation in relation to GSH depletion. Additionally, translocation of the cytosolic components of NADPH oxidase to the membrane, a necessary requirement for enzyme activation, was inhibited. Protein adducts of acrolein (or related aldehydes) could be detected in several neutrophil proteins, including NADPH oxidase components, following neutrophil exposure to either CS or acrolein. Alterations in neutrophil function by exposure to (environmental) tobacco smoke may affect inflammatory/infectious conditions and thereby contribute to tobacco-related disease.

Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid.

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system.

Medicare beneficiary satisfaction with durable medical equipment suppliers.

CMS has recently launched a series of initiatives to control Medicare spending on durable medical equipment (DME) and prosthetics, orthotics, and supplies (DMEPOS). An important question is how these initiatives will affect beneficiary satisfaction. Using survey data, we analyze Medicare beneficiary satisfaction with DMEPOS suppliers in two Florida counties. Our results show that beneficiaries are currently highly satisfied with their DMEPOS suppliers. Beneficiary satisfaction is positively related to rapid delivery, training, dependability, and frequency of service. Results of our analysis can be used as baseline estimates in evaluating CMS initiatives to reduce Medicare payments for DMEPOS.

Pharmacokinetics of oral cephalosporins: cephradine cephalexin.

A crossover experiment was utilized to compare the pharmacokinetics of a 1-g dose of cephalexin tablets, cephalexin capsules, or cephradine capsules in nine normal human volunteers. These antibiotics were administered as three formulations: two 500-mg capsulin every 6 hr for five doses, and one 1000-mg tablet of cephalexin every 6 hr for five doses. Pharmacokinetic parameters in the experimental groups showed no statistical differences (p greater than 0.1), indicating that these drugs are equivalent pharmacokinetically.

Neoadjuvant chemotherapy for resectable non-small cell lung cancer.

Surgical therapy remains the only curative treatment of localized non-small cell lung carcinoma (NSCLC). Yet, the results of surgical therapy leave much to be desired. Recently, neoadjuvant chemotherapy for Stage III NSCLC had become an accepted therapeutic modality. Accordingly, a question is raised regarding the feasibility of neoadjuvant chemotherapy in resectable NSCLC (Stage I and II). In this paper we report three patients, in chronological order, with localized NSCLC who were treated with neoadjuvant chemotherapy. Neoadjuvant chemotherapy was given to the first case with poor pulmonary functions. Decrease in size of the tumor made it possible for him to undergo a more conservative lung resection. In the second case, chemotherapy was given with a presumptive diagnosis of metastatic lung lesion. A good response was noted and, histologically, it was a primary lung cancer. In the third case, chemotherapy was given to a patient with obviously resectable lung carcinoma, and an excellent response was observed. According to the results, neoadjuvant chemotherapy for resectable NSCLC may be feasible and beneficial.

Coexistence of vitiligo and morphea: a case report and review of the literature.

A patient with both vitiligo and morphea is described. These skin diseases rarely appear concurrently in the same patient, despite the fact that both are thought to an autoimmune etiology. Similar cases that have been reported in the literature are reviewed and discussed.

A case of pemphigus vulgaris with esophageal involvement.

Esophageal involvement in pemphigus vulgaris is rare, found more in women than in men, and can be the only manifestation of pemphigus. Esophageal involvement had been reported only among patients with pemphigus vulgaris and not in patients with other forms of pemphigus. We describe a case of pemphigus vulgaris in which the esophagus was severely involved with only few oral lesions and no involvement of the skin or oropharynx.

Keratosis lichenoides chronica: a variant of lichen planus.

In order to establish a possible relationship between keratosis lichenoides chronica (KLC) and lichen planus (LP), we performed a comparative study which included routine histologic examination, electron microscopy, and direct immunohistochemical studies from one case of KLC and several patients with LP. Our findings demonstrate that KLC and LP share many similarities; their differences are mostly quantitative. In KLC, the findings are more prominent; we therefore conclude that KLC is at one end of the spectrum of LP.

Bovine leukocytes in mammary secretions during involution: surface protein changes.

Changes in surface proteins of leukocytes in bovine mammary secretions were examined during mammary involution. Leukocytes were collected from mammary secretions from involution days (ID) 1 to 36 and were labeled with biotin. Labeled proteins were separated by polyacrylamide-gel electrophoresis, transferred to nitrocellulose by protein blotting, and detected with avidin-peroxidase and color reagent. The population of leukocytes in mammary secretions changed during involution from predominantly polymorphonuclear leukocytes (PMN) at ID 1 to predominantly mononuclear leukocytes by ID 36. The gel profile of surface proteins also changed during involution, and some of those changes may have been caused by shifts in leukocyte populations. Profiles of surface proteins of leukocytes from mammary secretions containing predominantly PMN (ID 1) were different from profiles of PMN from blood. A distinctive change in the pattern of surface proteins on the leukocytes occurred between ID 1 and 3, even though the proportion of PMN did not change appreciably between those days.

Myospherulosis of the mastoid antrum: a case report.

Myospherulosis is a recently discovered iatrogenic disease caused by the implantation during surgery of mineral oil- or petrolatum-based products into various tissues. The condition results from the action of lipid substances on extravasated erythrocytes. The case report presented is the first detailed description of this uncommon, unique inflammatory lesion occurring in the mastoid and is the second otitic case reported in the literature. The lesion mimicked recurrent cholesteatoma 6 years following an intact canal wall mastoidectomy. As in myospherulosis of the paranasal sinuses, the symptoms and findings of otitic myospherulosis are those of the preceding disease.

Think cutaneous leishmaniasis.

Cutaneous leishmaniasis is now seen in non-endemic areas, especially in travellers to and troops serving in the Middle East. It was a common problem among American troops returning from the Gulf war. This article presents the clinical manifestations, the laboratory findings and the treatment options for this disease.