Standardized mortality ratios and fatal pulmonary embolism rates following total knee replacement: a cohort of 936 consecutive cases

Mortality and fatal pulmonary embolism rates in 936 consecutive primary total knee replacements (TKR) were determined during a 3-month postoperative period. Postmortem examinations verified the cause of death in all but 3 patients, and follow-up was performed on all but 1 patient. All patients had elastic stockings as mechanical prophylaxis. No deaths occurred from pulmonary embolism confirmed by postmortem examinations. At worst, the fatal pulmonary embolism rate was 0.43% (4/936; confidence interval [CI]=0.14%-1.17%). The all-cause mortality rate was 0.64% (6/936; CI=0.26%-1.46%). The patient mortality was compared with the population mortality of England and Wales using standardized mortality ratios. The standardized mortality ratios for both sexes combined was 0.74 (CI=0.29-1.52). A lower mortality was observed in women (0.67) than in men (0.84) during the first 3 postoperative months compared to the general population. Fatal pulmonary embolism after TKR with the routine use of graded elastic stockings and early mobilization is rare. In this series, the death rate in patients undergoing TKR appears to be lower than that in the general population.     

Prevalence of bronchial asthma among bank employees of Vellore using questionnaire-based data

Asthma and related allergic disorders are reported to be rare in poor and developing countries and their prevalence is expected to rise with urbanisation. Investigation was carried to see the prevalence of asthma and asthma-related symptoms by using a simple questionnaire-based data collection. One hundred and twenty bank employees were studied in the age group 25-55 years in 4 centres of Vellore town. A one-page questionnaire in English regarding asthma and allergic symptoms was used to assess the prevalence and the details of medical care utilisation by those who were asthmatics. The prevalence of self-reported bronchial asthma was 8.3% and that of asthma-related symptoms 15.8%. A significant number of subjects with symptoms suggestive of asthma self-reported themselves as non-asthmatic. There was a significant association between those who had symptoms of asthma and a positive family history of asthma. Most of the asthmatic subjects using allopathic medicines reported a poor quality of life, despite treatment. The prevalence of asthma in Vellore town is more than that reported in other studies carried out at different centres in India. The prevalence may actually be higher since a significant number of subjects with symptoms suggestive of asthma reported themselves as non-asthmatic subjects. As expected, positive family history was forthcoming in subjects with asthma symptoms. Most asthmatic subjects have not experienced a significant improvement in their quality of life, which could indicate sub-optimal management. These findings can form the basis for further studies to investigate factors that lead to these variations.     

Socioeconomic inequality of cancer mortality in the United States: a spatial data mining approach

Background  

The objective of this study was to demonstrate the use of an association rule mining approach to discover associations between selected socioeconomic variables and the four most leading causes of cancer mortality in the United States. An association rule mining algorithm was applied to extract associations between the 1988–1992 cancer mortality rates for colorectal, lung, breast, and prostate cancers defined at the Health Service Area level and selected socioeconomic variables from the 1990 United States census. Geographic information system technology was used to integrate these data which were defined at different spatial resolutions, and to visualize and analyze the results from the association rule mining process.     

A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies

Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies is a neurodegenerative disease that resembles corticobasal degeneration. It is characterized by the presence of abundant neuronal and glial tau protein deposits. Here we describe a novel silent mutation in exon 10 of tau (N296N) in this familial dementia. By exon trapping, the mutation produced an increase in the splicing in of exon 10, indicating that it probably causes disease through an overproduction of four-repeat tau.     

Role of cysteinyl leukotrienes in airway inflammation and responsiveness following RSV infection in BALB/c mice

Cysteinyl leukotrienes (CysLTs) contribute to the development of airway obstruction and inflammation in asthma; however little information is available on the role of these molecules in the pathophysiology of respiratory syncytial virus (RSV) bronchiolitis. This study was designed to evaluate the effects of RSV infection on CysLTs production in a well-established mouse infection model. Furthermore, we assessed the effect of anti-inflammatory agents (a leukotriene receptor antagonist, MK-571, and dexamethasone) on the functional and immune changes induced by RSV infection. Six to 8-wk-old BALB/c mice were infected with human RSV (strain A2). Measurements of airway function were performed using whole body plethysmography. Lung inflammation was assessed by cell counts, measurement of cytokines and CysLTs in bronchoalveolar lavage fluid (BALF) in the absence and presence of treatment with MK-571 or dexamethasone. RSV infection produced a marked increase in CysLTs in the BALF and lung tissue, recruitment of neutrophils and lymphocytes into the airways, increased IFN-gamma levels and airway hyperresponsiveness (AHR). Treatment with MK-571 decreased RSV-induced AHR without affecting the cellular and inflammatory responses to RSV. Dexamethasone decreased AHR and markedly reduced the recruitment of inflammatory cells and production of IFN-gamma. Our findings suggest CysLTs play an important role in the pathogenesis of RSV-induced airway dysfunction. Treatment with MK-571 decreases RSV-induced AHR but does not appear to alter the lung inflammatory responses to RSV. In contrast, dexamethasone decreases RSV-induced AHR but interferes with recruitment of inflammatory cells, resulting in decreased Th1 cytokines (a potentially Th2-prone environment) in this model. These studies support recent reports on the beneficial effects of CysLT receptor antagonist in human trials and provide a model for investigating the role of CysLTs in RSV bronchiolitis.     

A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy

OBJECTIVE: To investigate the analgesic efficacy of lamotrigine in the treatment of painful HIV-associated distal sensory polyneuropathy (DSP). BACKGROUND: The pathogenesis of HIV-associated DSP is unknown and there is no effective treatment. A novel anticonvulsant, lamotrigine, blocks voltage-sensitive sodium channels and inhibits the release of glutamate and aspartate. There have been anecdotal reports of efficacy of lamotrigine in the treatment of painful neuropathy and trigeminal neuralgia. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, lamotrigine was initiated at 25 mg per day and slowly titrated over 7 weeks to 300 mg per day. Study duration was 14 weeks. The primary outcome measure was change in pain on the modified Gracely scale with secondary outcome measures including change in neurologic examination, use of concomitant analgesic medications, and global pain relief. RESULTS: Of 42 enrolled subjects, 13 did not complete the 14-week study endpoint. In five of these, rash was the cause for dropout. In the remaining 29 evaluable subjects, 20 patients received placebo and 9 received lamotrigine. The pain scores at baseline were not significantly different. The reduction in average pain from baseline to week 14 was greater (p = 0.03) in the lamotrigine group (-0.55) than in the placebo group (-0.18), adjusting for baseline levels of pain. There was no difference between the groups on the change in peak worst pain. CONCLUSIONS: In this small trial, lamotrigine showed promise in the treatment of pain associated with HIV-related DSP. The frequency of rash was greater than in lamotrigine studies in epilepsy. A larger controlled study of lamotrigine is warranted.     

A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma.

PURPOSE: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)-bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. EXPERIMENTAL DESIGN: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting <6 months). I.V. rituximab was given at 375 mg/m(2) (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). RESULTS: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcgammaR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. CONCLUSIONS: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.     

Seizures in children with low-grade tumors： outcome after tumor resection and risk factors for uncontrolled seizures

OBJECT： The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS： The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses.