Relationship of childhood physical and sexual abuse to adult bipolar disorder

Objectives: To characterize whether adult depressives with either bipolar or unipolar disorder differ in the prevalence of childhood sexual or physical abuse.

Method: The investigators reviewed data from patients who were evaluated over a 2-year period by a semi-structured clinical interview. In total, 333 cases with a bipolar or unipolar diagnosis were included in the present study.

Results: A childhood history of abuse, in particular sexual abuse, was significantly more frequent in bipolar subjects compared with unipolar subjects. Consistent with previous studies, women reported higher rates of sexual abuse than men, although no interaction by diagnosis was shown. Sexual abuse incidence in male samples was markedly dissimilar, with male bipolar subjects demonstrating a significantly increased rate of sexual abuse and combined sexual and physical abuse compared with unipolar male subjects.

Conclusion: The increased incidence of sexual abuse in women supports growing evidence of gender differences in sexual abuse among adult depressives. In contrast to literature reports, the finding that male bipolar patients have significantly increased rates of sexual abuse histories suggests differences in psychiatric depressive subgroups. This result may reflect the particular characteristics of our cohort (treatment resistant, privately insured, and educated). Further work will aid in characterizing sexual abuse prevalence in other male bipolar samples.     

Cadet basic training: an ethnographic study of stress and coping

Cadet basic training (CBT) at the U.S. Military Academy at West Point is an initial cadet experience designed to transition freshmen (new cadets) into the military. Challenge is an inherent component of CBT, and some challenging activities may be stressful. However, the nature and the impact of stress on health status have not been systematically investigated. An ethnographic technique, participant observation, was used to identify stressors and coping strategies among cadets aged 18 to 21 years participating in CBT. A company of 183 cadets, consisting of 123 new cadets and 60 supervising upperclass cadets from the U.S. Military Academy, was followed throughout the 6-week CBT in the summer of 1993. The investigator observed daily activities and participated in select field training experiences. Daily field observations were taped, and field notes were generated chronicling the experience. After CBT, 10 of the 60 upperclass cadets participated in a 20-minute structured interview. Field and interview notes were systematically reviewed to identify and categorize stressors and coping techniques. Stressors included anticipatory stress, time management pressures, sleep deprivation, performance evaluations, conflicts between teamwork and competitive grading, and inexperience in the leadership role. Coping techniques identified included perceiving social support, humor, and rationalization. Three new hypotheses were generated from the observations.     

Dismal rehabilitation in predominantly type II diabetics on dialysis in Inner-City Brooklyn

AIM: In order to define their demographics and medical conditions, 218 diabetic patients undergoing hemodialysis in Brooklyn were interviewed and their charts reviewed. METHODS: Patient rehabilitation was assessed with the Karnofsky score, and the urea reduction rate as well as serum albumin and hematocrit levels evaluated adequacy of hemodialysis. RESULTS: The majority of patients (167) were African-American, 25 were Whites, 19 patients were Hispanic and 6 were Asian. One patient was a Native American. The mean age was 60.5 years (range 16-88), and the majority, 52%, were women. Rehabilitation was poor, the mean Karnofsky score being 65.1+/-20.8, and only 6% of patients were working. By linear regression, there was no difference in the Karnofsky score according to gender, age, race, type of diabetes, education, family income or hematocrit level. Only the patients' self-perception of their psyche function, or how well they thought they were doing, was significant. CONCLUSION: Further work is needed to examine the reasons for the poor rehabilitation of diabetics on dialysis in Brooklyn.     

Treatment of Anthracycline-Resistant Breast Cancer

The anthracyclines are commonly used for the treatment of early stage and advanced stage breast cancer, but many patients develop resistance to therapy. The definition of anthracycline resistance varies considerably in the literature, but in most cases includes disease progression during or within 6–12 months after completion of anthracycline therapy. Some authors have distinguished true anthracycline resistance (defined as progression during anthracycline therapy) from anthracycline pretreatment (defined as progression after completion of therapy). Single agents that have demonstrated response rates of at least 15–20% in anthracycline pretreated or resistant disease include the antitubulin agents (docetaxel, paclitaxel, vinorelbine), antimetabolites (capecitabine, fluorouracil), nucleoside analogues (gemcitabine), and trastuzumab (for HER2/neu positive disease only). Phase III studies have demonstrated that docetaxel is more effective than paclitaxel, mitomycin/vinblastine, and methotrexate/fluorouracil, and that the docetaxel/capecitabine combination is more effective than docetaxel alone. The decision regarding which agent(s) to use should be based upon the patient’s prior treatment history, tumor biology (HER2/neu and hormone receptor expression), comorbid conditions (e.g. neuropathy, heart disease), and other considerations (e.g. insurance coverage for oral medication). The choice of a specific treatment regimen must be individualized based upon these considerations.     

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.     

Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance

INTRODUCTION: Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability. MATERIALS AND METHODS: Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability. RESULTS: A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38. CONCLUSIONS: Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.     

Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer.

PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats HER2-overexpressing extracerebral breast neoplasms. Delivery of such macromolecule therapeutic agents to intracerebral metastases, however, is limited by the tight junctions characteristic of the cerebral vasculature. Direct intracerebral microinfusion (ICM) is a technique that bypasses this blood-brain barrier and allows for a greater delivery of drugs directly into intracerebral tumors. EXPERIMENTAL DESIGN: A human breast cancer cell line transfected to overexpress HER2, MCF-7/HER2-18, was transplanted into the cerebrum of athymic rats. Saline, trastuzumab, or an isotype-matched control MAb was delivered systemically or by ICM to assess toxicity and efficacy. RESULTS: No clinical or histological toxicity related to trastuzumab was evident under any of the conditions studied. Delivery of trastuzumab (2 mg/kg) i.p. led to a median survival of 26.5 days, whereas treatment with trastuzumab (2 mg/kg) by ICM increased the median survival by 96% to 52 days, with two of nine rats surviving >120 days (P = 0.009). Treatment with an isotype-matched control MAb (16 mg/kg) resulted in a median survival of 21 days, which did not differ significantly from the survival of rats treated by ICM with saline (16 days; P = 0.42). Treatment by ICM with trastuzumab (16 mg/kg) led to a median survival of 45 days, with 2 of 10 rats surviving >120 days. These results represent 181% and 114% increases in median survival over the saline and MAb controls, respectively (P < 0.001). CONCLUSION: ICM of trastuzumab is safe and superior to systemic delivery as therapy for HER2-overexpressing intracerebral neoplasms in an athymic rat model.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.