Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND)

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.     

Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1)

Regulation of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion. Both EEA1 and Rabenosyn-5 contain a distinctive N-terminal C₂H₂ zinc finger that binds Rab5. How these C₂H₂ zinc fingers recognize Rab GTPases remains unknown. Here, we report the crystal structure of Rab5A in complex with the EEA1 C₂H₂ zinc finger. The binding interface involves all elements of the zinc finger as well as a short N-terminal extension but is restricted to the switch and interswitch regions of Rab5. High selectivity for Rab5 and, to a lesser extent Rab22, is observed in quantitative profiles of binding to Rab family GTPases. Although critical determinants are identified in both switch regions, Rab4-to-Rab5 conversion-of-specificity mutants reveal an essential requirement for additional substitutions in the proximal protein core that are predicted to indirectly influence recognition through affects on the structure and conformational stability of the switch regions.     

In vitro and in vivo anti-inflammatory activity of Tetrastigma sulcatum leaf extract,pure compound and its derivatives

Inflammopharmacology - The severity and perseverance of inflammation have been demonstrated in many health conditions. The limitations of existing medications suggest the need for new alternative...     

Postoperative auras and the risk of recurrent seizures

PURPOSE: Little is known about the prognostic significance of persistent auras following temporal lobe surgery in determining the recurrence of complex partial seizures (CPS) or generalized tonic-clonic seizures (GTCS). METHODS: In a retrospective analysis of temporal lobectomy patients who had preoperative auras associated with CPS or GTCS and who were seizure-free following surgery, the predictive value of auras was assessed at 3 months and 2 years following surgery. Medication use, in relation to the presence of auras, was also assessed. RESULTS: Three hundred and forty-seven patients were seizure-free for 3 months following surgery (247 aura-free, 101 with persistent auras). KM analysis yielded no difference in outcome (p=0.65) and current outcome class was also similar (p=0.99). Patients with persistent auras were somewhat more likely to be on medication at the time of recurrence (p=0.06) and at last follow-up (p=0.09). 224 patients were seizure-free for 2 years following surgery (163 aura-free, 61 with persistent auras). KM analysis yielded no difference in outcome (p=0.86) and current outcome class was also similar (p=0.35). Patients with persistent auras were more likely to be on medication at the time of recurrence (p<0.001) and at last contact (p<0.01). CONCLUSIONS: Auras were not associated with increased risk of recurrence, although increased rates of AED use were seen in these patients. However, any medication effect appears to be quite small, so we consider it reasonable to advise cessation of AEDs in patients with persistent auras who are otherwise seizure-free.     

Laparoscopic excision of Mullerian structures in a neonate with mixed gonadal dysgenesis: a case report

Excision of Mullerian structures in children with disorders of sexual differentiation is an operative challenge. We report our experience with laparoscopic excision of Mullerian structures in a neonate with mixed gonadal dysgenesis. The salient features of the procedure were excellent visualisation and ease of dissection.     

Mortality rates in geriatric patients with spinal cord injuries

OBJECT: The authors undertook this study to evaluate the incidence of spinal cord injury (SCI) in geriatric patients (> or = 70 years of age) and examine the impact of patient age, extent of neurological injury, and spinal level of injury on the mortality rate associated with traumatic SCI. METHODS: A prospectively maintained SCI database (3481 patients) at a single institution was retrospectively studied for the period from 1978 through 2005. Parameters analyzed included patient age, admission American Spinal Injury Association (ASIA) motor score, level of SCI, mechanism of injury, and mortality data. The data pertaining to the 412 patients 70 years of age and older were compared with those pertaining to the younger cohort using a chi-square analysis. RESULTS: Since 1980, the number of SCI-related hospital admissions per year have increased fivefold in geriatric patients and the percentage of geriatric patients within the SCI population has increased from 4.2 to 15.4%. In comparison with younger patients, geriatric patients were found to be less likely to have severe neurological deficits (greater percentage of ASIA Grades C and D injuries), but the mortality rates were higher in the older age group both for the period of hospitalization (27.7% compared with 3.2%, p < 0.001) and during 1-year follow-up. The mortality rates in this older population directly correlate with the severity of neurological injury (1-year mortality rate, ASIA Grade A 66%, Grade D 23%, p < 0.001). The mortality rate in elderly patients with SCI has not changed significantly over the last two decades, and the 1-year mortality rate was greater than 40% in all periods analyzed. CONCLUSIONS: Spinal cord injuries in older patients are becoming more prevalent. The mortality rate in this patient group is much greater than in younger patients and should be taken into account when aggressive interventions are considered and in counseling families regarding prognosis.     

Radiotherapy-induced depigmentation in a patient with breast cancer

Vitiligo is a common dermatological disorder. A middle-aged woman with preexisting vitiligo was diagnosed with breast carcinoma. After surgery and chemotherapy she received regional radiotherapy. Six months after the completion of radiotherapy she developed depigmentation in the irradiated area. This article discusses the etiology for this phenomenon and the literature in this regard.     

Airway pressure release ventilation for in-vivo donor lung management and lung transplant outcomes

Background:Airway pressure release ventilation (APRV) can be used for cadaveric donor lung recruitment. APRV elevates PaO₂ in donor lungs; however, reported outcomes in recipients with APRV-managed donor lungs are limited. Methods:We retrospectively reviewed patients who underwent lung transplantation (LTx) from 2012 to 2013 and divided them into two groups based on mode of ventilation used during donor management and organ extraction (A: non-APRV; B: APRV). Kaplan-Meier method and multivariate Cox regression were used for analysis. Results:We found 126 LTx recipients (LTxRs); 9 were excluded for use of portable ventilation perfusion systems. Of the remaining 117 patients, 81 (69%) were in Group A; 36 (31%) were in Group B. Preoperative LTxR characteristics (age, sex, lung allocation score, end-stage lung disease type) were comparable between groups. Donors for Group B were older (P=0.03) and had higher body mass index (BMI) (P<0.001), higher incidence of death from chest trauma (P=0.008), longer ventilation duration after brain death (P<0.001), and higher pre-explant PaO₂/FiO₂ ratios (P<0.001). Post-LTx duration of mechanical ventilation, hospital stay, and median survival were similar in both groups. Risk of death was comparable between the two groups at the end of follow-up (HR =1.42; 95% CI: 0.57-3.56; P=0.45). Conclusions:APRV is a safe and effective pre-LTx donor lung management strategy. Short- and long-term survival outcomes were comparable in LTx recipients, irrespective of donor ventilation mode. APRV may help recruit lungs from older donors with higher BMI who die from chest trauma and have anticipated longer ventilation duration.