Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

Therapeutic efficacy and tolerance of diclofensine in psychoreactive depression--a double-blind comparison with placebo

Diclofensine increases the availability of the three neurotransmitters dopamine, noradrenaline and serotonin by inhibiting their re-uptake into synaptosomes. In a randomized double-blind parallel-group comparative study, a total of 40 patients, some hospitalized (n = 11) and some ambulatory (n = 29), mean age of 39.6 years +/- 12 S.D., with psychoreactive depression were treated for 30 days with 2 X 25 mg/day of diclofensine or with placebo. The assessments of efficacy indicated superiority of diclofensine over placebo. The number of "improved" patients (reduction in the overall depression scores by 50% or better) relative to that of "not improved" patients, was found to be statistically significant (p less than 0.025) on day 10 of treatment. With respect to individual symptoms, anxiety showed a significantly (p less than 0.05) better improvement under diclofensine than under placebo. Side effects were observed in one patient in each group. One patient (diclofensine group) reported a transient slight somnolence, the other (placebo group) reported episodes of transient dizziness. Based on these data it can be concluded that diclofensine is a well tolerated and effective drug for the treatment of symptoms associated with reactive depressions.     

Effectiveness of Preventive Therapy for Persons Exposed at Home to Drug-Resistant Tuberculosis,Karachi, Pakistan

In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.     

The evaluation of acute kidney injury due to ischemia by urinary neutrophil gelatinase-induced lipocalin (uNGAL) measurement in patients who underwent partial nephrectomy

International Urology and Nephrology - To investigate the role of urinary neutrophil gelatinase-induced lipocalin (uNGAL) measurement in the early diagnosis of acute kidney injury that may occur...     

The effect of renal artery-only or renal artery–vein clamping during partial nephrectomy on short and long-term functional results: Is clamping technique important?

Purpose

To evaluate the effect of artery-only (AO) and artery–vein (AV) clamping during partial nephrectomy (PN) on short- and long-term renal function outcome.

Methods

Medical records of 154 patients in the AO group and 192 patients in the AV group who underwent open and minimally invasive (laparoscopic/robotic) PN between January 2011 and January 2018 were retrospectively assessed. Preoperative patient and tumor-specific characteristics in addition to perioperative factors and renal function outcomes were compared. The change in the estimated glomerular filtration rate (eGFR) from postoperative 1–3 days, 12 and 24 months after surgery was calculated. Acute kidney injury (AKI) was defined a as a?>?25% reduction in eGFR.

Results

There were no statistically significant differences between the clamping techniques in terms of postoperative 1–3 days, 12 and 24 months eGFR change percentage and risk of progression to chronic kidney disease (CKD). No significant difference in short- and long-term renal functions was found between the minimally invasive or open AO and AV clamping subgroups at any time point. In multivariate analysis, the R.E.N.A.L score (AO group p?=?0.026, AV group p?<?0.001) and preoperative eGFR (AO group p?<?0.001, AV group p?=?0.010) were strong predictors of the acute kidney injury in both groups. Older age (AO group p?=?0.045, AV group p?=?0.010) and preoperative eGFR (AO group p?=?0.008, AV group p?=?0.002) were significantly associated with CKD progression at 2-year follow-up in both groups.

Conclusion

AV clamping does not adversely affect postoperative renal function compared to AO clamping. Preoperative patient- and tumor-related factors are more important for renal function regardless of the clamping technique.

     

Benign leiomyoma with multiple metastases to vertebrae and calvarium: An index case with comprehensive review of endocrine targets

Neurosurgical Review - “Benign” metastatic leiomyomas (BML) are indolently growing metastatic tumors which mostly associate with uterine leiomyomas in women in reproductive ages. The...     

Somatostatin infusion withdrawal in the diagnosis of childhood growth hormone deficiency

OBJECTIVE: An evaluation of growth hormone (GH) testing for GH deficiency (GHD) in childhood is confounded by the lack of a world-wide consensus on the definition of GHD. Although a single GH test remains the most powerful biochemical tool in the evaluation of a child with growth failure, the test remains far from ideal. Withdrawal of somatostatin (SS) infusion is followed by a rebound rise of GH thought to be mediated by endogenous GH-releasing hormone (GHRH) function. This study was designed to compare the GH response to 90 min SS infusion in children with normal GH secretion versus children with GH deficiency. METHODS: Ten children with GHD and 10 healthy controls (NC) have been evaluated for GH response to somatostatin infusion withdrawal (SSIW) and compared with response of two provocative tests, glucagon plus propranolol test and L-Dopa test. All children received constant infusion of somatostatin for 90 min (3 microg/kg per h, Stilamin, Serono, Aubonne, Switzerland). In order to determine GH, blood samples were obtained 90 min before the SS infusion and 0, 15, 30, 45, 60, 75, and 90 min after the cessation of infusion. RESULTS: Growth hormone peak levels with SSIW were significantly lower in GH deficient children than in healthy children (2.5 +/- 1.2 ng/dL, vs 21.9 +/- 5.3 ng/dL, respectively, P < 0.01). No adverse effects were observed during or after somatostatin infusion. CONCLUSION: In the present study, SSIW elicited a significant GH rise in healthy children but not in children with GH deficiency. Although further controlled studies using more data are necessary to expand these findings, the results suggested that children with GH deficiency can be reliably discriminated from healthy children by SSIW.     

Role of early EEG and neuroimaging in determination of prognosis in children with complex febrile seizure

BACKGROUND: The present study investigates the role of early use of EEG in children with no known neuropathology prior to the first CFS, and the contribution made by computed tomography (CT) and magnetic resonance imaging (MRI) to treatment and prognosis. METHODS: Over a period of 7 years, the authors evaluated 159 children (age range: 2 months-5 years) who were being treated for CFS at Haydarpasa Numune Training and Research Hospital, Pediatrics Clinic, Istanbul, Turkey, and who had no previously known neurological disorder. Patients who presented with febrile seizure were determined to have CFS if they fulfilled the following criteria: <3 months of age when seizure occurred, duration of seizure >/=15 min, more than one seizure occurred during a single episode of illness, or focal seizures and postictal neurological deficit was found. EEG was performed on all patients. CT was performed on the patients who had postictal neurologic deficit or focal seizures. Cranial MRI was performed on patients who had focal findings in their EEGs. RESULTS: Electroencephalogram abnormality was found in 71 cases; 51 of these were diagnosed with epilepsy during follow up. Six of the 16 cases whose EEGs were abnormal between days 2 and 6 were diagnosed with epilepsy. Twenty of the 30 cases whose EEGs were abnormal between days 7 and 10 were diagnosed with epilepsy. All 25 cases who had abnormal EEGs after day 11 were diagnosed with epilepsy. CT was performed for 36 patients, of which five were found to have pathological changes. Pathological changes were detected in two of the nine patients who had cranial MRI. Patients who received CT or MRI were all diagnosed with epilepsy during follow up. CONCLUSION: The results suggest that if neurological examination of CFS patients are normal after their clinical status has stabilised, EEG should be performed after 7 days at the earliest, however for the most accurate diagnosis EEG should be performed 10 days after CFS. The most important predictor for neuroimaging was found to be detection of postictal neurologic deficit. MRI had no advantages over CT in first treating CFS in the emergency unit.