Glycoprotein E (gE) specified by bovine herpesvirus type 5 (BHV-5) enables trans-neuronal virus spread and neurovirulence without being a structural component of enveloped virions

Bovine herpesvirus 5 (BHV-5) is a neurovirulent alpha-herpesvirus that causes fatal encephalitis in calves. We previously demonstrated that deletion of a glycine-rich epitope in the gE ectodomain dramatically reduced BHV-5 neurovirulence. To investigate the role of gE cytoplasmic tail sequences in the neuropathogenesis of BHV-5 in rabbits, we constructed a BHV-5gE recombinant virus with a short residual cytoplasmic domain lacking the YXXL motifs and the acidic (BHV-5gEAm480). In vitro, BHV-5gEAm480 produced on the average smaller plaques, compared with wild-type BHV-5, but it produced on the average substantially larger plaques than the gE ORF-deleted BHV-5. The truncated gE was not phosphorylated, and was not endocytosed from the cell surface. Importantly, the truncated gE was not incorporated into enveloped infectious virions, but its glycosylation and interaction with gI were not affected. In a rabbit model of infection, the BHV-5gEAm480 remained highly virulent, while the gE-null virus was avirulent. The gEAm480 mutant virus invaded most of the central nervous system (CNS) structures that are invaded by the wild-type BHV-5. The number of neurons infected by BHV-5gEAm480 was very similar to the number infected by BHV-5 wild-type and gEAm480-rescued viruses. Collectively, the results suggest that gE functions in transsynaptic transmission of BHV-5 and neurovirulence without being a structural component of the virion particle.     

Resectoscopic surgery may be an alternative to hysterectomy in high-risk women with atypical endometrial hyperplasia

STUDY OBJECTIVE: Endometrial hyperplasia is found in 2% to 10% of women with abnormal uterine bleeding (AUB). Up to 43% of patients with cytologic atypia harbor coexisting adenocarcinoma, and approximately 20% to 52% of atypical hyperplasias, if untreated, progress to cancer. The objective of this study was to estimate the incidence of atypical endometrial hyperplasia encountered during routine resectoscopic surgery in women with AUB and to evaluate the role of resectoscopic surgery in the management of women with AUB and atypical endometrial hyperplasia who refused and/or were at high risk for hysterectomy. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the senior author (GAV) performed primary resectoscopic surgery in 3401 women with AUB. Among these, there were 22 women with atypical (17 complex, 5 simple) endometrial hyperplasia. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n = 3) or complete (n = 19) endometrial electrocoagulation and/or resection. Subsequently, 6 women had hysterectomy and bilateral salpingo-oophorectomy (BSO). MEASUREMENTS AND MAIN RESULTS: The median (range) for age, parity, and body mass index were 55 years (24-78 years), 2 (0-4), and 30.1 kg/m2 (22.5-52.2 kg/m2), respectively. Among the 3401 women, there were 22 cases of atypical endometrial hyperplasia, 12 of which were incidentally diagnosed at the time of hysteroscopy (complex 10, simple 2, incidence 0.35%). After hysteroscopic diagnosis or confirmation of diagnosis, 6 women underwent hysterectomy and BSO. Of the remaining 16 women, followed for a median of 5 years (range 1.5-12 years), 1 was lost to follow-up, 1 had only a biopsy to preserve fertility, 1 died from lung cancer after 4 years, and 1 died from colon cancer after 5 years. One patient developed endometrial cancer after 10.5 years with postmenopausal bleeding. She remains alive and well 3.5 years after hysterectomy and BSO. The remaining 11 patients are amenorrheic at a median follow-up of 6 years (range 1.5-12 years). CONCLUSIONS: Resectoscopic surgery in 3391 women with AUB detected 12 incidental cases of atypical endometrial hyperplasia (incidence 0.35%). Skillful resectoscopic surgery may be an alternative to hysterectomy in women with AUB and atypical endometrial hyperplasia, who refuse or are at high-risk for hysterectomy and who are compliant with regular and long-term follow-up.     

Atypical presentation of adenosine deaminase 2 deficiency with bi‐allelic ADA2 mutation

Herein, we report a case of VAIHS with atypical clinical presentation of perianal abscess, fistula fever, and bi‐cytopenia including pathogenic ADA2 mutation suggesting that ADA2 deficiency be considered as a differential diagnosis of enlarging cutaneous abscess with no evidence of wound healing in the setting of leukopenia and neutropenia.     

Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients.

PURPOSE: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)-positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. EXPERIMENTAL DESIGN: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. RESULTS: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, chi(2) for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. CONCLUSIONS: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.     

Impedance Cardiography: Noninvasive Assessment of Hemodynamics and Thoracic Fluid Content During Bariatric Surgery

Background: The effects of pneumoperitoneum (ppm) on hemodynamic parameters during bariatric surgery were investigated using the impedance cardiography monitor. Methods: 11 patients with BMI 46.5±10 kg/m² (range 38.9-60.8 kg/m²) underwent laparoscopic adjustable gastric banding under general anesthesia. Besides routine monitoring, the impedance cardiography (ICG) monitor was used to monitor cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), and thoracic fluid content (TFC). Data were recorded at three stages: A) before ppm, B) during ppm, and C) after gas deflation. One-way analysis of variance (ANOVA) was used to analyze differences of the data before, during and after ppm, and post-hoc (Bonferoni test) for multiple comparisons of the data obtained. For all comparisons, P<0.05 was considered significant. Results: There were significant low mean values of heart rate (HR), CO and CI at stage B compared to stage A (P<0.05). The mean values of TFC at stages A, B, and C were 30.48 ± 4.69, 29.74 ± 2.86 and 31.72 ± 4.93 k/Ohm respectively, with a non-significant relationship (P>0.05). The mean values of SVR during the same stages A, B and C were 1299.18 ± 374.40, 1873.64 ± 276.26 and 1669.36 ± 537.92 dynes sec cm^-5 respectively, with significant high mean values at stages B and C compared to mean value at stage A (P<0.05). Conclusions: Morbid obesity and pneumoperitoneum have significant effects on hemodynamics. However, it appears that these changes were of marginal clinical significance.     

Evaluation of drug therapy and risk factors in diabetic hypertensives: a study of the quality of care provided in diabetic clinics in Bahrain

OBJECTIVE: To evaluate control of blood pressure (BP) and diabetes and the associated risk factors in diabetic hypertensives treated by diabetic clinic primary care physicians. METHODS: A retrospective analysis of the medical records of diabetic hypertensives from six primary care diabetic clinics in Bahrain. RESULTS: The recommended BP target <130/<85 mmHg and of glycosylated haemoglobin (HbA1C) <7% were achieved in 7.5% and 14.5%, respectively. Most of the patients with uncontrolled BP and HbA(1C) were at high cardiovascular risk. More patients were on antihypertensive monotherapy than on combination therapy (60.6% vs. 36.7%; P<0.0001). The recommended two- and three-antihypertensive drug combinations were less often prescribed. In high-risk patients glycaemic control achieved was poor: antidiabetic combination therapy vs. monotherapy did not significantly differ. Inappropriate prescribing practices, such as the use of immediate-release nifedipine monotherapy, use of sulphonylurea instead of metformin in obese patients, and a trend towards prescribing of glyburide rather than a gliclazide in the elderly, were observed. Lipid-lowering (13.5%) and antiplatelet (12.8%) drugs were infrequently prescribed. CONCLUSIONS: Hypertension and diabetes in patients treated at the primary care diabetic clinics were inadequately controlled. In several instances, mono- and combination antihypertensives prescribed were irrational. Lipid-lowering and platelet aggregation inhibition strategies have received little attention. Intensive antihypertensive and antidiabetic complementary combination therapy should be encouraged. Continuous professional education of diabetic clinic physicians and expert-supervised diabetic clinics are desirable.     

Lack of MERS Coronavirus Neutralizing Antibodies in Humans,Eastern Province,Saudi Arabia

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.