Active surveillance of Q fever in human and animal population of Cyprus

Background  

A long-term active surveillance of Q fever was conducted in Cyprus organized in two phases.     

Phase I/II Trial of External Irradiation plus Medium-Dose Brachytherapy Given Concurrently to Liposomal Doxorubicin and Cisplatin for Advanced Uterine Cervix Carcinoma

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.     

HLA-DRB1 first domain sequence for a novel DR4 allele designated DRB1*0413

A novel DR4 allele, DRB1*0413, was identified in a Caucasian individual "LEV" having the HLA phenotype A2; B51,14; DR4,7; DQw3,w2. DRB1*0413 is a DRB1*0401-variant differing from DRB1*0401 only at codon 86 where valine is present instead of glycine.     

Men's Perceptions of Delivery Care in Rural Malawi: Exploring Community Level Barriers to Improving Maternal Health

In this cross-sectional survey with qualitative components (n = 389), we explored how husbands perceive delivery care in rural Malawi. Most husbands decide on maternal health care seeking, believe in antenatal care, and prefer institutional delivery. Men acknowledge that their unfaithfulness and violence can harm the pregnancy. Most husbands feel responsible for birth preparedness, but poor availability and unforeseeable transport costs hinder care seeking in pregnancy complications. Our findings suggest that innovative birth preparedness and transport interventions that involve men, as well as the extension of antenatal care (ANC) services to men, can help overcome obstacles to improving maternal health at the community level.     

The MHC in the era of next-generation sequencing: Implications for bridging structure with function

The MHC continues to have the most disease-associations compared to other regions of the human genome, even in the genome-wide association study (GWAS) and single nucleotide polymorphism (SNP) era. Analysis of non-coding variation and their impact on the level of expression of HLA allotypes has shed new light on the potential mechanisms underlying HLA disease associations and alloreactivity in transplantation. Next-generation sequencing (NGS) technology has the capability of delineating the phase of variants in the HLA antigen-recognition site (ARS) with non-coding regulatory polymorphisms. These relationships are critical for understanding the qualitative and quantitative implications of HLA gene diversity. This article summarizes current understanding of non-coding region variation of HLA loci, the consequences of regulatory variation on HLA expression, the role for evolution in shaping lineage-specific expression, and the impact of HLA expression on disease susceptibility and transplantation outcomes. A role for phased sequencing methods for the MHC, and perspectives for future directions in basic and applied immunogenetic studies of the MHC are presented.     

The effect of intraventricularly administered GnRH on plasma beta-endorphin levels of the rat.

This study investigates the effects of intraventricularly administered gonadotropin-releasing hormone (GnRH) on plasma beta-endorphin levels in female proestrous rats. Adult female Wistar rats (220-250 g) were implanted with an indwelling cannula in the third ventricle. Approximately 20 days later, the animals which had established a regular 4-day cycle were implanted with two indwelling catheters, one intracarotid and one intrajugular, on the morning of proestrus. A single injection of 100 ng GnRH dissolved in 5 microliters distilled water or 5 microliters of saline (control) was infused slowly through the cannula in the third ventricle. Blood was withdrawn via the intracarotid catheter just before the infusion (12.30 h) and at 14.00, 15.30, 16.30 and 17.30 h for the determination of plasma beta-endorphin levels. The results indicated that intracerebroventricular infusion of GnRH causes a significant decline of plasma beta-endorphin levels at all time points. It is postulated that GnRH possibly causes desensitization of GnRH receptors, due to the continuous GnRH supply to the pituitary via the blood circulation.     

The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice

There are two major defects in type 2 diabetes: 1) insulin resistance and 2) insulin deficiency due to loss of beta-cell function. Here we demonstrated that treatment with muraglitazar (a dual peroxisome proliferator-activated receptor alpha/gamma activator), when initiated before or after the onset of diabetes in mice, is effective against both defects. In study 1, prediabetic db/db mice were treated for 12 weeks. The control mice developed diabetes, as evidenced by hyperglycemia, hyperinsulinemia, reduced insulin levels in the pancreas, blunted insulin response to glucose, and impaired glucose tolerance. The muraglitazar-treated mice had normal plasma glucose, and insulin levels, equivalent or higher pancreatic insulin content than normal mice, showed a robust insulin response to glucose and exhibited greater glucose tolerance. In study 2, diabetic db/db mice were treated for 4 weeks. The control mice displayed increased glucose levels, severe loss of islets, and their isolated islets secreted reduced amounts of insulin in response to glucose and exendin-4 compared with baseline. In muraglitazar-treated mice, glucose levels were reduced to normal. These mice showed reduced loss of islets, and their isolated islets secreted insulin at levels comparable to baseline. Thus, muraglitazar treatment decreased both insulin resistance and preserved beta-cell function. As a result, muraglitazar treatment, when initiated before the onset of diabetes, prevented development of diabetes and, when initiated after the onset of diabetes, prevented worsening of diabetes in db/db mice.     

Allogeneic hematopoietic stem cell transplantation for myelofibrosis

Fifty-six patients, 10 to 66 years of age, with idiopathic myelofibrosis (IMF) or end-stage polycythemia vera or essential thrombocythemia received allogeneic hematopoietic cell transplants from related (n = 36) or unrelated (n = 20) donors. Forty-four patients were prepared with busulfan plus cyclophosphamide and 12 with total body irradiation plus chemotherapy. The source of stem cells was marrow in 33 and peripheral blood in 23 patients. All but 3 patients achieved engraftment. While 50 patients showed complete donor chimerism, 3 patients were found to be mixed chimeras at 26, 48, and 86 months after transplantation, respectively. Two patients died from relapse/progressive disease, and 18 died from other causes. There are 36 patients surviving at 0.5 to 11.6 (median, 2.8) years, for a 3-year Kaplan-Meier estimate of 58% (CI, 43%-73%). Dupriez score, cytogenetic abnormalities, and degree of marrow fibrosis were the most significant risk factors for posttransplantation mortality. Patients conditioned with a regimen of busulfan targeted to plasma levels of 800 to 900 ng/mL plus cyclophosphamide had a higher probability of survival (76% [CI, 62%-91%]) than other patients. Results with unrelated donors were comparable with those with HLA-identical sibling transplants. Thus, allogeneic hematopoietic cell transplantation offers long-term relapse-free survival for patients with myelofibrosis.