Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.     

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.     

Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion

Platelet adhesion to the exposed surface of the extracellular matrix in flowing blood is the first and critical reaction for in vivo thrombus formation. However, the mechanism of this in vivo platelet adhesion has yet to be studied extensively. One of the reasons for this is the lack of a practical assay method for assessing platelet adhesion under flow conditions. We have devised an assay method (the fluorescent adhesion assay) that is based on the technique originally reported by Hubbell and McIntire (Biomaterials 7:354, 1986) with some modifications to make it more amenable for assaying small samples and have developed an analysis method to quantify the extent of platelet adhesion and aggregation from fluorescence images by using a computer-assisted image analysis system. In our assay, platelet adhesion, expressed as the percentage of the area covered by adhered platelets, was found to increase biphasically as a function of time. In the first phase, platelets interacted with the coated collagen, transiently stopping on the surface; we called this reaction the temporary arrest. In the second phase, platelets adhered much more rapidly and permanently on the surface, and this adhesion was dependent on the shear rate; platelets formed aggregates in this phase. We used our assay to analyze the effects of platelet aggregation inhibitors on platelet adhesion. All three examined inhibitors, EDTA (10 mmol/L), antiglycoprotein (GP) IIb/IIIa, and GRGDS peptide (1 mmol/L), inhibited the second phase adhesion in flowing blood. Furthermore, GPVI-deficient platelets also showed defective second-phase adhesion under the same conditions. These results suggested that GPIIb/IIIa activation and GPVI contribute to the reaction inducing the second phase. The second-phase adhesion has been extensively investigated, and the consensus is that this reaction is mainly attributable to the platelet-platelet interaction. In this report, we were able to detect an earlier reaction, the temporary arrest. This temporary arrest would reflect the fast and weak interaction between platelet GPIb/IX and collagen-von Willebrand factor complexes on the collagen-coated surface.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

National Patterns of Risk-Standardized Mortality and Readmission After Hospitalization for Acute Myocardial Infarction,Heart Failure,and Pneumonia: Update on Publicly Reported Outcomes Measures Based on the 2013 Release

BACKGROUND

The Centers for Medicare & Medicaid Services publicly reports risk-standardized mortality rates (RSMRs) within 30-days of admission and, in 2013, risk-standardized unplanned readmission rates (RSRRs) within 30-days of discharge for patients hospitalized with acute myocardial infarction (AMI), heart failure (HF), and pneumonia. Current publicly reported data do not focus on variation in national results or annual changes.

OBJECTIVE

Describe U.S. hospital performance on AMI, HF, and pneumonia mortality and updated readmission measures to provide perspective on national performance variation.

DESIGN

To identify recent changes and variation in national hospital-level mortality and readmission for AMI, HF, and pneumonia, we performed cross-sectional panel analyses of national hospital performance on publicly reported measures.

PARTICIPANTS

Fee-for-service Medicare and Veterans Health Administration beneficiaries, 65 years or older, hospitalized with principal discharge diagnoses of AMI, HF, or pneumonia between July 2009 and June 2012. RSMRs/RSRRs were calculated using hierarchical logistic models risk-adjusted for age, sex, comorbidities, and patients’ clustering among hospitals.

Results

Median (range) RSMRs for AMI, HF, and pneumonia were 15.1% (9.4–21.0%), 11.3% (6.4–17.9%), and 11.4% (6.5–24.5%), respectively. Median (range) RSRRs for AMI, HF, and pneumonia were 18.2% (14.4–24.3%), 22.9% (17.1–30.7%), and 17.5% (13.6–24.0%), respectively. Median RSMRs declined for AMI (15.5% in 2009–2010, 15.4% in 2010–2011, 14.7% in 2011–2012) and remained similar for HF (11.5% in 2009–2010, 11.9% in 2010–2011, 11.7% in 2011–2012) and pneumonia (11.8% in 2009–2010, 11.9% in 2010–2011, 11.6% in 2011–2012). Median hospital-level RSRRs declined: AMI (18.5% in 2009–2010, 18.5% in 2010–2011, 17.7% in 2011–2012), HF (23.3% in 2009–2010, 23.1% in 2010–2011, 22.5% in 2011–2012), and pneumonia (17.7% in 2009–2010, 17.6% in 2010–2011, 17.3% in 2011–2012).

Conclusions

We report the first national unplanned readmission results demonstrating declining rates for all three conditions between 2009–2012. Simultaneously, AMI mortality continued to decline, pneumonia mortality was stable, and HF mortality experienced a small increase.