Bupropion for the treatment of methamphetamine dependence.

Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a methamphetamine-free week. Secondary outcomes included: urine for quantitative methamphetamine, self-report of methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p=0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of methamphetamine use at baseline (p<0.0001). Comorbid depression and attention-deficit/hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence, mainly male patients, regardless of their comorbid condition.     

Rubratoxin B mycotoxicosis in the Syrian hamster

The LD50 for rubratoxin B dissolved in dimethylsulphoxide and administered to Syrian golden hamsters by ip injection was 0.4 (0.2-0.8) mg/kg body weight. The greatest number of deaths occurred 6-24 hr after administration. Gross alterations consisted of congestion of the liver, spleen and kidneys and histopathological alterations involved congestion of the spleen and congestion and mild degenerative changes in hepatocytes. In a second study, rubratoxin B was administered ip daily for 1 wk at doses of 25, 50 and 75% of the ip LD50. Mortality was greatest in the 50 and 75% dose groups. Toxicity was cumulative with multiple doses. Gross alterations were similar to those found in the LD50 study. Histopathological alterations included renal tubular degeneration and necrosis and focal necrosis of hepatocytes. The morphopathogenesis of lesions following a single ip LD50 dose was evaluated in a third study. Histopathological alterations were limited to the kidney and were characterized by renal tubular degeneration and necrosis. Renal lesions were first seen at 2 hr after administration and increased in severity to a maximum at 20 hr. Tubular regeneration was first seen at 24 hr and was found to the end of the test period (72 hr). Serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and serum concentrations of total and indirect bilirubin were increased by 8 hr after dosing and returned to control values by the end of the test period. In a fourth study, rubratoxin B was administered ip daily for 1 wk at a dose of 25% of the ip LD50. Gross alterations were similar to those in the other studies. Histopathological alterations included progressive renal tubular degeneration and necrosis. Serum activities of AST and ALT and concentration of blood urea nitrogen (BUN) were progressively increased with increasing numbers of doses. Urinalysis indicated progressive renal tubular damage.     

The injury profile after the 2008 earthquakes in China

The 8.0 magnitude earthquake that struck China on May 12, 2008, was the deadliest earthquake in 30 years. Most hospitals were destroyed and limited facilities were available for medical service in the earthquake regions. Over the first 5 days, three general hospitals and one children's hospital admitted 1770 injured individuals.MethodsWe retrospectively collected data on 1770 injured subjects in three general hospitals (n = 1723) and one children's hospital (n = 47) in the quake-area during the first 5 days after the event. The diagnosis for the injuries was based on the final hospital diagnosis made by the physicians and classified by two-independent researchers using the International Statistical Classification of Diseases and Related Health Problems ICD-10 (WHO ICD-10 Code.1993). To ensure the accuracy of the information, any questionable data was reviewed by phone with hospital staff.ResultsIn three general hospitals, 848 patients (48%) were male and 922 (52%) were female. Nine percent (n = 84) of females and 8.8% (n = 75) of males were over the age of 75. Four (0.4%) females and 5 (0.5%) males were less than 1-year old. The most common injuries were the injuries of the knee, lower leg, ankle and foot (36%), followed by head injuries (18%). In the children's hospital, 31 (65%) of the patients were males and 16 (35%) were females. 40% of the subjects were 10–14, while 21% were less than 1-year old. The most frequently seen injuries were also of the knee, lower leg, ankle or foot (19%), and of the abdomen, lower back, lumbar spine and pelvis, and hip and thigh (15%).ConclusionsWe gathered information from resources in Chinese, which at the time contained more records on this event than any documents in English. The age of the patients ranged from 7 days to 84 years old. Subjects over age 75 and children between 10 and 14 were the largest population in their respective hospitals, indicating that these groups required the greatest medical resources. The injury profile presented here serves as a reference not only for present injury intervention but also for future earthquake disaster response.     

Molecular diagnosis and molecular profiling to detect treatment-resistant ovarian cancer

Introduction: Epithelial ovarian cancer remains the gynecologic tumor with the highest rate of recurrence after initial optimal cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately, with the development of recurrent ovarian cancer often comes the discovery of chemo-resistant disease. The absence of improvement in long term survival, notwithstanding the use of newer agents as is seen in other cancers, emphasizes the need for improved understanding of the processes that lead to chemo-resistant disease.

Areas Covered: This review will cover the following topics: 1. Molecular and cellular mechanisms in platinum and paclitaxel resistance 2. Other molecular mediators of chemo-resistance 3. Expression of stem cell markers in ovarian cancer and relationship to chemo-resistance 4. MicroRNA and long non-coding RNA expression in chemo-resistant ovarian cancer 5. Determination of chromosomal aberrations as markers of chemo-resistance 6. Molecular profiling in chemo-resistant disease.

A standard MEDLINE search was performed using the key words; ovarian cancer, chemo-resistant disease, molecular profiling, cancer stem cells and chemotherapy.

Expert Commentary: Over the next few years the challenge remains to precisely determine the mechanisms responsible for the onset and maintenance of chemo-resistance and to effectively target these mechanisms.     

Characteristics of pain managed at home in children and adolescents with sickle cell disease by using diary self-reports

Pain can begin in the first year of life for individuals with sickle cell disease (SCD) and continue in an unpredictably recurrent manner throughout their life span. Sickle vaso-occlusive pain (sickle pain) can also occur simultaneously with pain of other origins, complicating both assessment and management. Aims of this research were to describe the reliability and validity of a daily diary for data collection with children and adolescents with SCD and to describe characteristics of vaso-occlusive sickle pain episodes (VOE) and other pain reported by children and adolescents with SCD along with home pain management strategies. Thirty-nine children and adolescents (mean age, 10.9 +/- 3.6 years) completed diaries twice daily at home for up to 3 years (mean, 417.9 +/- 272.2 diary days) with excellent compliance. Sickle pain alone was reported on 8.4% of days (n = 1515 days), whereas other pain occurred on 2.7% of days (n = 490) and both sickle pain and other pain on 5.7% (n = 1041 days). Other pain only episodes were shorter and involved fewer sites than sickle pain only episodes. Sickle pain occurred in the extremities and hips, whereas most other pain occurred in the head-neck area. Analgesic medication was taken on 85% of days of sickle pain, whereas analgesics were taken on only 60% of days with other pain. The diary used in this study is a valid and reliable self-report tool. The use of home diaries will improve the understanding of sickle pain and its management and assist in identifying other pain syndromes that may require alternative management.     

Effect of cytochrome P450 3A4 inhibition on the pharmacokinetics of docetaxel

OBJECTIVE: In vitro studies indicate that the anticancer drug docetaxel is primarily eliminated by cytochrome P450 (CYP) 3A4-mediated metabolism. Coadministration of drugs that modulate the activity of CYP3A4 is, therefore, likely to have undesirable clinical consequences. We investigated the effects of the potent CYP3A4 inhibitor ketoconazole on the pharmacokinetics of docetaxel in patients with cancer. METHODS: Seven patients were treated in a randomized crossover design with docetaxel (100 mg/m(2)), followed 3 weeks later by docetaxel (10 mg/m(2)) given in combination with orally administered ketoconazole (200 mg once daily for 3 days), or the reverse sequence. Plasma concentration-time data were analyzed by noncompartmental analysis. RESULTS: Ketoconazole coadministration resulted in a 49% decrease in clearance of docetaxel (P =.018). The mean (+/-SD) clearance values were 35.0 +/- 11.8 L/h (95% confidence interval, 24.1-45.9 L/h) for docetaxel alone and 18.2 L/h (95% confidence interval, 9.22-27.1 L/h) in the presence of ketoconazole, respectively. The docetaxel clearance ratio in the presence and absence of ketoconazole was weakly related to the area under the curve of ketoconazole (R(2) = 0.529, P =.064). CONCLUSION: Inhibition of CYP3A4 by ketoconazole in vivo results in docetaxel clearance values that have previously been shown to be associated with a several-fold increase in the odds for febrile neutropenia at standard doses. Caution should be taken and substantial dose reductions are required if docetaxel has to be administered together with potent inhibitors of CYP3A4.     

The distinct longitudinal impact of pain catastrophizing on pain interference among youth living with sickle cell disease and chronic pain

Journal of Behavioral Medicine - Youth living with chronic sickle cell disease (SCD) pain are at risk for psychosocial distress and high levels of pain catastrophizing that contribute to functional...