Endostatin plus interferon-alpha2b therapy for metastatic melanoma: a novel combination of antiangiogenic and immunomodulatory agents

In patients with stage IIB-III disease, adjuvant high-dose interferon-alpha2b has shown clinical benefit, although metastatic melanoma is currently without any known survival-prolonging therapy. Angiogenesis has been considered important in melanoma progression, and endostatin is an angiogenesis inhibitor with antitumor activity that has shown promising results in murine model systems, prompting investigation of a formulation of rh-Endostatin (EntreMed, Rockville, Maryland, USA) alone and with interferon in metastatic melanoma. Patients were randomly assigned to receive interferon alpha2b (Schering-Plough) 10 million units/m(2) subcutaneously three times a week plus rh-Endostatin 45 mg/m(2) subcutaneously every 12 h (arm A) vs. rh-Endostatin alone (arm B). Twenty-one patients (age range 31-77 years, median age 54, 12 men and nine women, 17 cutaneous, and four ocular melanomas) were enrolled. No antitumor responses were observed, and no significant differences were noted in time to progression or overall survival. Two patients had stable disease enduring more than 30 weeks on treatment. Serum endostatin levels increased significantly 4 weeks after treatment in both groups. Basic fibroblast growth factor levels in urine were significantly lower following treatment in patients on arm B (P=0.043). The percentage of circulating endothelial cells was increased in five evaluable patients 4 weeks after treatment. Low titer (相似文献   

Synthesis of Poly[(ethylene carbonate)‐co‐(ethylene oxide)] Copolymer by Phosphazene‐Catalyzed ROP

Poly[(ethylene carbonate)‐co‐(ethylene oxide)] is synthesized by ROP of 1,3‐dioxolan‐2‐one using 1‐tert‐butyl‐4,4,4‐tris(dimethylamino)‐2,2‐bis[tris(dimethylamino)phosphoranylidenamino]‐2Λ5,Λ5‐catenadiphosphazene as the catalyst. NMR spectroscopy shows that the copolymer chain consists of EO‐EC‐EO‐EO sequences. GPC measurements indicate a PDI of 1.43–1.66 and show that the molecular weight increases with monomer conversion. Thermal analysis demonstrates that the copolymer is amorphous with a glass transition temperature of about –42 °C and an onset decomposition temperature of about 200 °C.     

The Impact of Underweight Status on the Prognosis of Ovarian Cancer Patients: A Meta-Analysis

Malnutrition and underweight status pose an unfavorable prognosis for cancer patients. Several studies have addressed the impact of a low body mass index (BMI) (<18.5 kg/m²) on ovarian cancer progression. However, their results seem to be conflicting. The present meta-analysis investigates whether the underweight status negatively affects the progress of ovarian cancer. We conducted a systematic review searching the Medline (1966–2014), Scopus (2004–2014), Popline (1974–2014), ClinicalTrials.gov (2008–2014), and Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2014) databases together with reference lists from included studies. All prospective and retrospective observational cohort studies were included. Statistical meta-analysis was performed using the RevMan 5.1 software. Current evidence suggests that the stage of the disease does not differ between underweight and normal-weight patients [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.46–1.39 for stage I; OR 1.27, 95% CI 0.71–2.27 for stage II; OR 1.03, 95% CI 0.71–1.51 for stage III; and OR 1.05, 95% CI 0.63–1.76 for stage IV disease]. Concurrently, the risk of residual disease after surgery (OR 1.03, 95% CI 0.69–1.52) and the risk of dying due to ovarian cancer (OR 1.08, 95% CI 0.64–1.85) seem to be similar. According to the findings of our systematic review, the underweight status does not seem to have a detrimental impact on ovarian cancer prognosis. However, the methodological limitations of published studies and the small number of enrolled underweight patients preclude firm results. Thus, future research in this field is necessary.     

Systematic review of conservative management of postpartum hemorrhage: what to do when medical treatment fails

We performed a systematic review to identify all studies evaluating the success rates of treatment of major postpartum hemorrhage by uterine balloon tamponade, uterine compression sutures, pelvic devascularization, and arterial embolization. We included studies reporting on at least 5 cases. All searches were performed independently by 2 researchers and updated in June 2006. Failure of management was defined as the need to proceed to subsequent or repeat surgical or radiological therapy or hysterectomy, or death. As the search identified no randomized controlled trials, we proceeded to search for observational studies. This identified 396 publications, and after exclusions, 46 studies were included in the systematic review. The cumulative outcomes showed success rates of 90.7% (95% confidence interval [CI], 85.7%-94.0%) for arterial embolization, 84.0% (95% CI, 77.5%-88.8%) for balloon tamponade, 91.7% (95% CI, 84.9%-95.5%) for uterine compression sutures, and 84.6% (81.2%-87.5%) for iliac artery ligation or uterine devascularization (P = 0.06). At present there is no evidence to suggest that any one method is better for the management of severe postpartum hemorrhage. Randomized controlled trials of the various treatment options may be difficult to perform in practice. As balloon tamponade is the least invasive and most rapid approach, it would be logical to use this as the first step in the management.     

Female voiding dysfunction

Female voiding dysfunction unrelated to childbirth is common but poorly understood, and most often occurs as a result of detrusor hypotonia and less frequently in association with bladder outlet obstruction. Specific causes include anti-incontinence surgery, bladder over-distension, painful infective, allergic or chemical reactions of the urogenital tissues, bladder outlet obstruction, dyssynergia of the bladder-urethral sphincter mechanism, neurogenic, pharmacological, and psychogenic causes. A thorough history and examination is essential in the clinical assessment. It should be followed by investigations including urine microbiology, frequency volume diaries, ultrasound scan, uroflowmetry, and, when indicated, subtracted voiding cystometry, electromyography, and cystourethroscopy. The main treatment modalities are catheterization (self-intermittent, suprapubic, urethral, in order of preference), bladder retraining, biofeedback, and, rarely, surgery or sacral neuromodulation.     

Lip Ulceration Associated with Intravenous Administration of Zoledronic Acid: Report of a Case

Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H₂O₂ (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated.     

Are dexamethasone suppression test nonsuppression and thyroid dysfunction related to a family history of dementia in patients with major depression? An exploratory study.

OBJECTIVE: Recent data suggest that the low thyroid function syndrome in depression is nonspecific. They also suggest that depression may constitute a risk factor for the development of dementia, especially in atypical patients who have high rates of hypothalamo-pituitary-adrenal axis disorders. This study aimed to search for correlations among Dexamethasone Suppression Test (DST) cortisol levels, thyroid indices, and family history of dementia in patients with depression. METHODS: A sample of 30 patients, aged 21 to 60 years and suffering from major depression according to DSM-IV criteria, took part in the study. Three had a family history of dementia in first-degree relatives. We measured their serum levels of free T3, free T4, thyroid-stimulating hormone, thyroid binding inhibitory immunoglobulines, thyroglobulin antibodies, and thyroid microsomal antibodies (TMAs). We applied the 1-mg DST to all patients. The statistical analysis included 1-way multivariate analysis of covariance using t tests as the post hoc tests. RESULTS: Significantly higher levels of TMAs were found in patients with a family history of dementia, compared with those who did not have this family history. CONCLUSION: The results of this study suggest that a more pronounced autoimmune process may characterize depression patients with a family history of dementia.