Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.     

Time course of symptom resolution in patients with community-acquired pneumonia

The majority of patients with community-acquired pneumonia are at low risk for short-term mortality or serious morbidity and are increasingly managed in the outpatient setting. Efforts to improve the quality of care for these patients will need to measure patient outcomes such as disease-specific symptom resolution. The aims of this study were to (1) develop a self-administered daily version of a symptom questionnaire for patients with pneumonia, (2) measure the reliability of this instrument, and (3) provide estimates for recovery rates based on symptom resolution in a cohort of low-risk patients with community-acquired pneumonia. This study was conducted as part of a prospective study of a new emergency department protocol for pneumonia at the Massachusetts General Hospital. Eligible study subjects included all adult patients with pneumonia presenting to the emergency department with a predicted low risk of short-term mortality. The main outcome measures were based on a new five item symptom questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from the time of diagnosis of pneumonia. The symptom questions were also administered during patient interviews on days 0, 7, 14 and 28 in order to assess the questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to participate in this study. The mean intra-class reliability coefficient of the symptom questionnaire was 0.75. The median times to resolution of individual symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty-five percent of patients had at least one symptom still present at the end of the 28-day study period. We found that a daily self-report questionnaire is a reliable measure of symptom resolution for patients with pneumonia. Full resolution of symptoms takes more than 28 days for a significant proportion of patients with pneumonia.     

Vitamin E deficiency intensifies the myocardial injury of coxsackievirus B3 infection of mice

Feeding a vitamin E-deficient diet increases pathology in hearts of mice infected with a myocarditic coxsackievirus B3 (CVB3/20). Hearts from infected mice fed a vitamin E-deficient diet rich in highly unsaturated fat (menhaden oil) exhibited more severe pathology than hearts from infected mice fed a vitamin E-deficient diet based largely on saturated fat (lard). Furthermore, a cloned and sequenced amyocarditic coxsackievirus B3 (CVB3/0), which caused little or no pathology in the hearts of vitamin E-supplemented mice, induced extensive cardiac pathology in vitamin E-deficient mice. In infected mice, both mitogen and antigen responses were depressed by vitamin E deficiency, although neutralizing antibody responses were unaffected. Natural killer cell responses were comparable in infected mice fed a lard-based diet with or without supplemented vitamin E. However, a menhaden oil-based diet, whether supplemented with vitamin E or not, significantly depressed natural killer cell activity in infected mice compared with mice fed the lard-based diet. Coxsackievirus B3/0 recovered from the heart of a vitamin E-deficient donor mouse, passaged one time onto HeLa cells, caused significant heart damage when passed back into vitamin E-supplemented recipient mice, demonstrating that the amyocarditic CVB3/0 had changed to a virulent phenotype. Enhanced virulence was also seen with CVB3/20 virus similarly passaged in a vitamin E-deficient donor. Our work demonstrates the important role of host nutritional antioxidant status in determining the severity of certain viral infections.     

A phase II study of BTI-322, a monoclonal anti-CD2 antibody, for treatment of steroid-resistant acute graft-versus-host disease

BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen on T cells and natural killer (NK) cells, blocks primary and memory alloantigen proliferative responses in vitro. We have evaluated the pharmacokinetics and safety of BTI-322 during treatment of 20 transplant recipients with steroid-refractory acute graft-versus-host disease (GVHD). Treatment consisted of BTI-322 by intravenous (IV) bolus or 30-minute infusion at approximately 0.1 mg/kg/d for 10 days in addition to continuing high-dose steroids and tacrolimus or cyclosporine. Pharmacokinetic sampling was performed in 10 patients; the t1/2 +/- SE was 9.1 +/- 1.3 hours, the Cmax was 2,549 +/- 291 ng/mL, the Vd was 3.97 +/- 0.95 L, and the Vd/kg was 0. 05 +/- 0.01 L/kg. Ten patients experienced transient dyspnea sometimes accompanied by nausea, vomiting, diarrhea, and tachycardia shortly after the initial bolus dose of drug, but serious drug-related adverse events were not seen during the remainder of the infusions. At the end of treatment (day 11), there were six patients with complete responses and five with a reduction in grade of GVHD for a total response rate of 55% (95% confidence interval [CI], 32% to 77%). Antibodies targeting CD2 may be active in the treatment of acute GVHD, and evaluation of a humanized form of BTI-322 is warranted.     

Old patients with hypertension. A 25-year observational study of a geographically defined population (Dalby), aged 67 years at entry

OBJECTIVES: To evaluate the impact of hypertension and other risk factors on mortality, in particular cardiovascular mortality, in a geographically defined population of elderly subjects. DESIGN: An observational 25-year study of a total population. SETTING: The local health centre in the village of Dalby in southern Sweden. SUBJECTS: All men and women born in 1902 or 1903, living in Dalby, were, at the age of 67, invited for medical and psychological examinations. The population comprised 188 subjects (109 men and 79 women); 156 (83%) of them took part in the first medical examination. Blood pressure, heart rate, weight and height were measured and laboratory tests performed at entry. Blood pressures were thereafter recorded six times, and this report is based on a 25-year follow-up period ending in October 1994. MAIN OUTCOME MEASURES: Survival analyses were performed, based on definition of underlying causes of death, divided into all-cause and cardiovascular. RESULTS: At entry, females had higher blood pressure than males, both at baseline and during the first 16 years of the study, regardless of whether they were hypertensives or not. Most men smoked but only a few women. At the end of the follow-up of the present study in 1994, 138 out of 156 (88%) subjects had died and only 18 (12%) remained alive; 78 (57%) had died of a cardiovascular disease. In men, a diagnosis of hypertension as well as increased blood pressure at entry was associated with increased mortality. In women this was the case for blood pressure and risk of cardiovascular mortality. In men, both systolic and diastolic blood pressures during the study were significant risk factors for death, whereas in women this was not the case. CONCLUSIONS: Elderly male hypertensives ran an increased mortality risk even though they were treated according to the then current guidelines; female hypertensives seemed to run the same risk of dying as normotensive females.     

Structural and experiential neighborhood contexts, developmental stage, and antisocial behavior among urban adolescents in poverty

This study explored the effects of structural and experiential neighborhood factors and developmental stage on antisocial behavior, among a sample of poor urban adolescents in New York City. Conceptually and empirically distinct profiles of neighborhood experience were derived from the data, based on measures of perceived neighborhood cohesion, poverty-related hassles, and involvement in neighborhood organizations and activities. Both the profiles of neighborhood experience and a measure of census-tract-level neighborhood hazard (poverty and violence) showed relationships to antisocial behavior. Contrary to expectation, higher levels of antisocial behavior were reported among adolescents residing in moderate-structural-risk neighborhoods than those in high-structural-risk neighborhoods. This effect held only for teens in middle (not early) adolescence and was stronger for teens perceiving their neighborhoods as hassling than for those who did not. Implications for future research and preventive intervention are discussed.     

Light distribution by linear diffusing sources for photodynamic therapy

The distribution of the light emitted by linear light diffusers commonly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser.     

Culture medium for protocorm differentiation in Dendrodium candidum Wall. ex Lindl

Effects of basal culture medium, sucrose concentration, natural extracts and phytohormones on protocorm differentiation were studied. The suitable medium for protocorm differentiation has been found to be 1/2Ms basal medium plus 2% w/v sucrose, 2mg/L BA, 0.2mg/L NAA and 20% (w/v) potato extract.