Psychometric and utility-based measures of health status of asthmatic patients with different disease control level

OBJECTIVE: To explore the relationship between asthma control level and health-related QOL (HR-QOL), and to understand the role of various psychometric and utility-based methods in studying this relationship. METHODS: Two hundred and twenty-eight consecutive adult outpatients and inpatients at four sites participated in the study. Physicians identified the level of disease control according to the Global Initiative for Asthma (GINA) classification system. Patients filled in three different HR-QOL questionnaires (EuroQol 5-D [EQ-5D], Short-Form 36-item health survey [SF-36], and St George's Respiratory Questionnaire [SGRQ]) and a direct time trade-off question. The Short Form-6D (SF-6D) was used to derive utility values from SF-36 data. RESULTS: All patient-reported evaluation methods could discriminate between patients with different disease control levels, and both generic and disease-specific instruments strongly correlated to each other. The magnitude of differences in HR-QOL between groups with different disease control levels was clinically meaningful. All three HR-QOL measures reflected a relationship between disease control level and HR-QOL, but the actual pattern of the relationship depended on the instrument used. Utilities gained from the EQ-5D index, compared with the SF-6D index, had higher values in the patient group with the best disease control and lower values in the patient group with poor disease control. CONCLUSION: When choosing an instrument to measure the health status of asthmatic patients in clinical studies, the severity range of the study population should be considered. Researchers might prefer to use the EQ-5D in asthma patients with severe disease or poor disease control and the SF-6D in patients with mild disease or good disease control.     

Gonadal function in patients treated for leukemia in childhood

Ovarian and testicular function were assessed in 67 long-term survivors (37 females, 30 males) treated for leukemia between 1973 and 1992. At diagnosis they were 1 - 16 (median 5) years old and had evaluation of gonadal function 4 - 25 (median 13) years later at the age of 13 - 31 (median 19). All had been treated with various combinations of chemotherapy (ChT) (including cyclophosphamide (CYC) and cytarabine in 32 patients), 62 patients had received prophylactic cranial irradiation with 12 - 49 (median 18) Gy, 2 patients had had craniospinal irradiation with 24 and 10 Gy respectively. Nine patients were treated for relapse; 2 boys had testicular irradiation (RT) with 12 Gy in 3 fractions and 1 girl whole-abdomen RT with 20 Gy as a part of this treatment. Three patients were treated for second malignancies. Gonadal function was assessed by clinical examination and measurement of serum concentrations of estradiol and testosterone. Serum levels of LH and FSH were determined in basal state and after stimulation. Primary hypogonadism was found in 6 (9%) patients. Five (16,5%) males had primary hypogonadism with evidence of damage to the germinal epithelium, 2 of them, treated with testicular RT, had evidence of damage to the Leydig cells and 2 had evidence of dysfunction of Leydig cells as well. Primary hypogonadism was found in 1 female, who was heavily treated for relapse (ChT containing CYC, abdominal RT and craniospinal RT). She was amenorrhoic and needed substitutional estrogen therapy but delivered a child anyway. Five females had early puberty after cranial RT. One female had secondary hypogonadism and hyposomatotropism after cranial RT with 30 Gy, one male had hyposomatotropism after receiving cranial RT twice (49 Gy total). Primary treatment for leukemia does not produce primary hypogonadism in girls, but it does in boys. Alkylating agents and gonadal RT are the most damaging factors. Not only RT to gonads but also alkylating agents alone cause dysfunction of Leydig cells.     

Characterization of HER2/neu and topoisomerase IIα status by FISH in locally advanced breast cancer

Background

HER2/neu encodes a receptor related to breast cancer pathogenesis and topoisomerase IIα is an enzyme involved in response to anthracycline chemotherapy. The aim of this study is to analyse HER2/neu and topoisomerase IIα in a homogenous series of 49 patients with locally-advanced breast cancer (LABC) to determine their status and predictive value with respect to response to treatment.

Material and methods

Paraffin-embedded tissues samples from patients with LABC (prior to their neoadjuvant chemotherapy programme) were analysed using the FISH technique.

Results

HER2 amplification was noted in 29% of cases of which 77% presented amplification in the topoisomerase IIα gene, 15% had deletion and 8% did not show any aberration in topoisomerase IIα status.

Conclusions

These preliminary analyses show a correlation between HER2 amplification and topoisomerase IIα status (92%), and suggest that patients with non-amplified HER2/neu or topoisomerase IIα have better response and have and increase (albeit not statistically significant) in disease-free survival (DFS). However, the limited numbers of patients in the study preclude definitive conclusion regards the value of these genes in predicting patient response to anthracycline-based chemotherapy.     

Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.     

Arterial splenic calcifications in children with AIDS: two case reports

Splenic calcifications in AIDS patients are usually round and result from infections with opportunistic pathogens such as Pneumocystis carinii, Mycobacterium avium-intracellulare and Cytomegalovirus. We describe here a remarkable echopattern of the spleen in two pediatric patients, resulting from linear, branching calcifications in the splenic parenchymal arteries. We believe this echopattern represents the ultrasonographic manifestation of an HIV-associated vasculopathy.     

Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid obesity: prospective study of 500 consecutive patients

OBJECTIVE: To evaluate early and late morbidity of laparoscopic adjustable gastric banding for morbid obesity and to assess the efficacy of this procedure by analyzing its results. SUMMARY BACKGROUND DATA: Laparoscopic adjustable gastric banding is considered the least invasive surgical option for morbid obesity. It is effective, with an average loss of 50% of excessive weight after 2 years of follow-up. It is potentially reversible and safe; major morbidity is low and there is no mortality. METHODS: Between April 1997 and June 2001, 500 patients underwent laparoscopic surgery for morbid obesity with application of an adjustable gastric band. There were 438 women and 62 men (sex ratio = 0.14) with a mean age of 40.4 years. Preoperative mean body weight was 120.7 kg and mean body mass index (BMI) was 44.3 kg. m. RESULTS: Mean operative time was 105 minutes, 84 minutes during the last 300 operations. Mean hospital stay was 4.5 days. There were no deaths. There were 12 conversions (2.4%), 2 during the last 300 operations. Fifty-two patients (10.4%) had complications requiring an abdominal reoperation. Forty-nine underwent a reoperation for minor complications: slippage (n = 43, incisional hernias (n = 3), and reconnection of the catheter (n = 3). Three patients underwent a reoperation for major complications: gastroesophageal perforation (n = 2) and gastric necrosis (n = 1). Seven patients had pulmonary complications and 36 patients experienced minor problems related to the access port. At 1-, 2-, and 3-year follow-up, mean BMI decreased from 44.3 kg. m to 34.2, 32.8, and 31.9, respectively, and mean excess weight loss reached 42.8%, 52%, and 54.8%. CONCLUSIONS: Laparoscopic adjustable gastric banding is a beneficial operation in terms of excessive weight loss, with an acceptably low complication rate. It can noticeably improve the quality of life in obese patients. Half of the excess body weight can be effortlessly lost within 2 years.     

A fully automated [35S]GTPgammaS scintillation proximity assay for the high-throughput screening of Gi-linked G protein-coupled receptors

The diversity of physiological functions mediated by the GPCR superfamily provides a rich source of molecular targets for drug discovery programs. Consequently, a variety of assays have been designed to identify lead molecules based on ligand binding or receptor function. In one of these, the binding of [(35)S]GTPgammaS, a nonhydrolyzable analogue of GTP, to receptor-activated G-protein alpha subunits represents a unique functional assay for GPCRs and is well suited for use with automated HTS. Here we compare [(35)S]GTPgammaS scintillation proximity binding assays for two different G(i)-coupled GPCRs, and describe their implementation with automated high-throughput systems.     

Surviving breast cancer: the role of complementary therapies

Early detection and efficacious treatment have prolonged the lives of women diagnosed with breast cancer. Although many of these women have survived more than 5 years, there is minimal knowledge of their use of complementary and alternative medical (CAM) treatments. A qualitative focus group study was conducted with 66 breast cancer survivors, ranging in age from 32 to 85 years, with time since diagnosis 2 to 28 years. This article will discuss specific reasons breast cancer survivors reported for using CAM, the ways in which breast cancer survivors blended these therapies with conventional Western medicine, and health care providers' roles in supporting breast cancer survivors' use of CAM approaches.     

Acute sports-related spinal cord injury: contemporary management principles

Improvements in helmet and equipment design have led to significant decreases in overall injury incidence, but no available helmet can prevent catastrophic injury to the neck and cervical spine. The most effective strategy for preventing this type of injury appears to be careful instruction, training, and regulations designed to eliminate head-first contact. The incidence of football-related quadriplegia has decreased from a peak of 13 cases per one million players between 1976 and 1980 to 3 per million from 1991 to 1993, mostly as a result of systematic research and an organized effort to eliminate high-risk behavior. An episode of transient quadriparesis does not appear to be a risk factor for catastrophic spinal cord injury. Torg reported that 0 of 117 quadriplegics in the National Football Head and Neck Injuries Registry recalled a prior episode of transient quadriparesis, and 0 of the 45 patients originally studied in his transient quadriparesis cohort have subsequently suffered quadriplegia. The significance of developmental spinal stenosis is unclear. Plain radiographic identification of a narrow spinal canal in a player sustaining cervical cord neurapraxia warrants further evaluation by MRI to rule out functional stenosis. The presence of actual cord deformation or compression on MRI should preclude participation in high-risk contact or collision sports.