Diurnal rhythms of serum total,free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men

BACKGROUND: Conflicting views are reported on the association between advancing age and gradually diminishing concentrations of serum total testosterone in men. The putative loss of diurnal rhythm in serum total testosterone in older men is reported to be in part due to low concentrations in the morning when compared to concentrations found in young men. We have measured total, free and bioavailable testosterone along with SHBG in samples taken every 30 min throughout a 24-h period in 10 young and eight middle-aged men. RESULTS: Both young and middle-aged men displayed a significant diurnal rhythm in all variables, with a minimum fall of 43% in total testosterone from peak to nadir in all subjects. Subjecting the data to a time series analysis by least squares estimation revealed no significant difference in mesor (P = 0.306), amplitude (P = 0.061) or acrophase (P = 0.972) for total testosterone between the two groups. Comparing bioavailable testosterone in the two groups revealed no significant difference in mesor (P = 0.175) or acrophase (P = 0.978) but a significant difference (P = 0.031) in amplitude. Both groups display a significant circadian rhythm (middle-aged group P < 0.001; young group P = 0.014). Free testosterone revealed a highly significant rhythm in both the young group (P < 0.001) and the middle-aged group (P = 0.002), with no significant difference between the groups in mesor (P = 0.094) or acrophase (P = 0.698). Although analysis of the SHBG data revealed a significant rhythm in the young group (P = 0.003) and the older group (P < 0.001), the acrophase occurred in the mid afternoon in both groups (15.12 h in the young and 15.40 h in the middle-aged). The older men had a significantly greater amplitude (P = 0.044) but again no significant difference was seen in mesor (P = 0.083) or acrophase (P = 0.477) between the two groups. Acrophases for total, bioavailable and free testosterone occurred between 07.00 h and 07.30 h; for SHBG the acrophase occurred at 15.12 h in the young group and 15.40 h in the middle-aged group. CONCLUSIONS: The study suggests that the diurnal rhythm in these indices of androgen status is maintained in fit, healthy men into the 7th decade of life.     

A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.     

Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of interleukin-4 transgenic mice. Evidence of mast cell histamine release in vivo by diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry

We used light and electron microscopy to analyze the eyelid inflammation that develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by routine transmission electron microscopy, indicated that the mast cells in the inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of secretion in which the cells' cytoplasmic granules exhibit characteristic morphologic changes that are thought to be associated with the prolonged, vesicle-mediated release of the granules' constituents. Moreover, by using a newly reported enzyme affinity-gold method, which stains histamine based on binding to diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show that these activated mast cells had released much of their histamine content. The eyelid lesions also exhibited increased numbers of mast cells; interstitial fibrosis, particularly around cutaneous nerves and blood vessels; activated fibroblasts; focal axonal damage; venules with endothelial cells containing numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo can result in eyelid lesions associated with piecemeal degranulation of mast cells, as well as tissue fibrosis and a variety of other pathologic changes. These results also represent the first direct morphologic evidence for histamine secretion by mast cells in vivo.     

Does pure robotic partial nephrectomy provide similar perioperative outcomes when compared to the combined laparoscopic–robotic approach?

Laparoscopic and robotic partial nephrectomy have become the preferred option for surgical management of incidentally discovered small renal tumors. Currently there is no consensus on which aspects of the procedure should be performed laparoscopically versus robotically. We believe that combining a laparoscopic exposure and hilar dissection followed by tumor extirpation and renorrhaphy with robotic assistance provides improved perioperative outcomes compared to a pure robotic approach alone. We performed a comparison of perioperative outcomes between combined laparoscopic–robotic partial nephrectomy—or hybrid procedure—and pure robotic partial nephrectomy (RPN). A multi-center retrospective analysis of patients undergoing RPN and hybrid PN using the da Vinci S system^® was performed. Patient data were reviewed for demographic and perioperative variables. Statistical analysis was performed using the Welch t test and linear regression, and nonparametric tests with similar significance results. Thirty-one patients underwent RPN while 77 patients underwent hybrid PN between 2007 and 2011. Preoperative variables were comparable in both groups with the exception of lesion size and nephrometry score which were significantly higher in patients undergoing hybrid PN. Length of surgery, estimated blood loss and morphine used were significantly less in the hybrid group, while warm ischemia time was significantly longer. The difference in WIT was accounted for in this data by adjusting for nephrometry score. In our multi-center series, the hybrid approach was associated with a shorter operative time, reduced blood loss and lower narcotic usage. We believe this approach is a valid alternative to RPN.     

Bubaline Aortic Matrix: Histologic,Imaging, Fourier Transform Infrared Spectroscopic Characterization and Application into Cattle Abdominal Hernia Repair

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Extracellular matrix (ECM) scaffolds have been shown to promote constructive remodeling response into a host....     

Detection of Sight-threatening Diabetic Eye Disease

Blindness due to diabetes mellitus is potentially preventable in the majority of patients. Early detection of sight-threatening changes is associated with a better outcome, indicating the need to screen for retinopathy. At least 50 % of diabetic patients do not attend a hospital, so that diabetologists and ophthalmologists are unable to screen the diabetic population comprehensively. Although in theory all patients have access to general practitioners, these may lack training or confidence to screen for retinopathy. Hospital based or community optometrists using direct ophthalmoscopy or slit lamps and technicians performing fundus photography are alternatives which may be more effective. Further studies are required to examine the effectiveness of optometry screening. Initial studies using fundus photography raised concerns about the sensitivity of the technique, but these have been partially addressed by improvements in methodology and technology. As well as technicological effectiveness, factors affecting patient uptake of screening services still need to be addressed.