Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Insulin-like growth factor-I (IGF-I) concentration in 150-kilodalton complexes containing human IGF-binding protein-3 (hIGFBP-3) after intravenous injection of adult rats with hIGFBP-3

After i.v. injection into adult rats, human insulin-like growth factor-binding protein-3 (hIGFBP-3) forms 150-kDa complexes with excess endogenous rat acid-labile subunit (ALS) within 2 min (Lewitt et al., 1993, Endocrinology 133:1797). Because their previous in vitro studies indicated that hIGFBP-3 only bound to ALS in the presence of IGF-I, and because little free IGF-I is present in plasma, the authors postulated that IGF-I had been mobilized to the circulation to saturate the 150-kDa hIGFBP-3 complexes. We examined this hypothesis by determining whether the hIGFBP-3 that appears in 150-kDa complexes 2 min after i.v. injection is accompanied by an increase in IGF-I. Within 2 min, some of the injected hIGFBP-3 (approximately 30% as much as endogenous intact rat IGFBP-3) is present in complexes that are cleared slowly from the circulation and presumed to be 150-kDa complexes. Gel filtration and immunoprecipitation studies performed on blood collected 2 min after injection confirmed that the injected hIGFBP-3 (46-82% as much as rat IGFBP-3) was associated with ALS in 150-kDa complexes. The formation of 150-kDa complexes containing hIGFBP-3 was not accompanied by a corresponding change in the IGF-I content (determined by RIA) of whole serum or 150-kDa serum fractions, suggesting that the hIGFBP-3 had rapidly associated with rALS in vivo without mobilizing IGF-I. Surprisingly, however, hIGFBP-3 was cleared much more rapidly from 150-kDa complexes formed after injection of hIGFBP-3 than after injection of hIGFBP-3:IGF-I complexes, suggesting that the complexes observed after hIGFBP-3 injection might not have formed in vivo. In fact, 150-kDa complexes formed to a similar extent when hIGFBP-3 was added ex vivo to blood collected from rats that had not received hIGFBP-3. We conclude that hIGFBP-3 can rapidly associate with rALS to form 150-kDa complexes in vivo without the mobilization of IGF-I. Because 150-kDa complexes also are formed ex vivo, however, we are unable to resolve whether the complexes that formed in vivo formed as binary or ternary complexes.     

Mechanism of the oxidation of 3,5,3',5'-tetramethylbenzidine by myeloperoxidase determined by transient- and steady-state kinetics

Earlier investigations of the oxidation of 3,5,3',5'-tetramethylbenzidine (TMB) using horseradish peroxidase and prostaglandin H-synthase have shown the formation of a cation free radical of TMB in equilibrium with a charge-transfer complex, consistent with either a two- or a one-electron initial oxidation. In this work, we exploited the distinct spectroscopic properties of myeloperoxidase and its oxidized intermediates, compounds I and II, to establish two successive one-electron oxidations of TMB. By employing stopped-flow techniques under transient-state and steady-state conditions, we also determined the rate constants for the elementary steps of the myeloperoxidase-catalyzed oxidation of TMB at pH 5.4 and 20 degrees C. The second-order rate constant for compound I formation from the reaction of native enzyme with H2O2 is 2.6 x 10(7) M-1 s-1. Compound I undergoes a one-electron reduction to compound II in the presence of TMB, and the rate constant for this reaction was determined to be (3.6 +/- 0.1) x 10(6) M-1 s-1. The spectral scans show that compound II accumulates in the steady state. The rate constant for compound II reduction to native enzyme by TMB obtained under steady-state conditions is (9.4 +/- 0.6) x 10(5) M-1 s-1. The results are applied to a new, more accurate assay for myeloperoxidase based upon the formation of the charge-transfer complex between TMB and its diimine final product.     

Percutaneous radiologic drainage of pancreatic abscesses

OBJECTIVE: The purpose of our study was to review and report the patient selection, techniques, and results of percutaneous drainage of pancreatic abscesses by retrospective review. MATERIALS AND METHODS: Fifty-nine patients (46 men and 13 women) with a mean age of 44 years old had 80 pancreatic abscesses that were drained percutaneously under radiologic guidance (CT, n = 77; sonography, n = 2; and fluoroscopy, n = 1). Abscesses had a wide spectrum of causes, with alcoholic pancreatitis being most common, trauma second most common, and gallstones third. Ten patients had undergone surgery for pancreatic necrosis or abscess. Patients with pancreatic pseudocysts, necrosis, or acute fluid collections were excluded from this study. RESULTS: Of the 59 patients, 51 (86%) were cured with percutaneous drainage and antibiotic therapy. Of the patients who were not cured with percutaneous drainage, seven required surgery and one underwent repeat percutaneous drainage. In the 59 patients, complications included non-life-threatening bleeding in three patients. Ten of 59 patients (17%) had fistulas that spontaneously formed into the gastrointestinal tract. The duration of catheterization ranged from 4 to 119 days, with a mean duration of 33 days. The rate of mortality at 30 days after completion of percutaneous drainage was 8% (5 of 59). CONCLUSION: Percutaneous drainage was an effective therapy for this defined group of patients with pancreatic abscesses. Factors leading to the relatively high success rate described in this study likely included selection of patients; catheters of adequate size, number, and location; careful follow-up with appropriate catheter manipulations; and an integrated, cooperative approach whereby surgeons were willing to permit drainage to effect its benefits, rather than operating prematurely.     

Norepinephrine release in the human forearm: effects of epinephrine

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.     

Phosphorus-31 magnetic resonance brain spectroscopy of children at risk for a substance use disorder: preliminary results

The purpose of this exploratory investigation was to evaluate the heuristic potential of 31P magnetic resonance spectroscopy (MRS) in elucidating a neurobiologic component of the liability for a substance use disorder (SUD). We investigated 31P MRS spectra employing chemical shift imaging (CSI) derived from four distinct anatomic brain locations (i.e. frontal, occipital, right parietal, left parietal) in three groups of peripubertal children who are hypothesized to be at increasing levels of familial SUD risk. Specifically, we studied children with a positive paternal family history of SUD and a disruptive behavior disorder (DBD) diagnosis (SUD+/DBD+; n = 10), in contrast, to those with a positive paternal SUD history in the absence of other psychopathology (SUD+/DBD-; n = 13) and matched control children from normal families (SUD-/DBD-; n = 13). In addition, we examined neurocognitive tests of our subjects to determine any associations between cognitive capacities with regional 31P MRS spectra. The highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of phosphodiesters confined to the right parietal voxel. This right parietal phosphodiester proportion correlated only with the Information Scale score on a standard intelligence test for children. This suggested a relationship between general learning ability and motivation for academic achievement and right parietal physiology in the highest-risk sample. Variations in synaptic pruning could account for this observation.     

Retinal dystrophy in long chain 3-hydroxy-acyl-coA dehydrogenase deficiency

We report a case of Bellini duct carcinoma of the left kidney with invasive growth pattern. A 39-year-old man was admitted to our hospital with the chief complaint of gross hematuria. Ultrasonography showed left renal swelling but normal reniform configuration of the kidney was maintained. Computed tomography demonstrated a low density tumor infiltrating into the renal cortex and with tumor extension into the renal vein. Renal angiography revealed a hypovascular tumor. We suspected a left renal cell carcinoma with tumor extension into the left renal vein, and performed radical nephrectomy. Macroscopically, the resected kidney had a normal outer contour. The tumor with infiltrative growth pattern existed in renal medulla. Histopathologic examination revealed a papillary adenocarcinoma originated in Bellini duct (pT3bN2M0). The patient underwent systemic chemotherapy (M-VAC). This case showed invasive growth pattern, which were different from the usual renal cell carcinoma and Bellini duct carcinoma.     

7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)