Citations

OBJECTIVE—The aim of this trial was to evaluate the effects of α-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND METHODS—In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients’ global assessment of efficacy. RESULTS—Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (≥50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients’ global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo. CONCLUSIONS—Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

This case study describes the use of intensive exposure and response prevention (ERP) for the treatment of pediatric obsessive-compulsive disorder (OCD). The adolescent described in this report lives a long distance from treatment providers with expertise in managing severe OCD symptoms. Thus, he has to travel out of town for effective therapy. The treatment program results in substantial immediate benefits. However, gradual relapse is noted once treatment is over and the patient returns to his home environment. Obstacles to the accessibility of ERP for pediatric OCD, conducting successful treatment, and generalizing and maintaining gains are discussed with the aim of drawing attention to, and facilitating the prevention of, these difficulties. Suggestions for addressing the shortcomings highlighted by this case are presented.

Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 ± 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (−0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.

Abstract Purpose: Rituximab is a chimeric antibody that induces B-cell apoptosis and recruits immune effector cells to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic responses by T cells and natural killer cells. This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL). Experimental Design: Fifty-eight patients with histologically confirmed relapsed B-cell NHL were randomized to receive concurrent treatment with rituximab and IL-12 (arm A) or rituximab with subsequent treatment with IL-12 after documented nonresponse or progression after rituximab (arm B). Treatment consisted of 375 mg/m2 rituximab on days 1, 8, 15, and 22 and 300 ng/kg IL-12 given s.c. twice weekly starting on day 2 for arm A or upon progression for arm B. Results: The overall response rate was 37% (11 of 30) in arm A and 52% (13 of 25) in arm B. All of the responses seen in arm B occurred while patients received rituximab, and no responses occurred during treatment with subsequent IL-12. The median duration of response was 16 months for arm A and 12 months for arm B. Biopsy specimens were serially obtained in a subset of patients and showed that changes in gene expression were different when cells from the peripheral blood were compared with cells from lymph node biopsies. Conclusions: The concomitant use of IL-12 and rituximab had modest disease activity in patients with B-cell NHL, but the sequential administration of IL-12 after rituximab did not result in additional clinical responses.