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San Diego, CA, United States

Smith R.C.,Nathan Kline Institute for Psychiatric Research | Smith R.C.,Kirby Forensic Psychiatric Center | Jin H.,New York University | Jin H.,Northwestern University | And 10 more authors.
Schizophrenia Research | Year: 2013

Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120. mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3. month treatment with Pioglitazone (30-45. mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. Results: In the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3. month values also showed significant (P < .05) decreases in fasting insulin, 2. h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients. © 2012 Elsevier B.V. Source

Kim Y.S.,San Diego VA Health Care System | Kim Y.S.,Seoul National University | Weinstein M.,San Diego VA Health Care System | Weinstein M.,Seoul National University | And 5 more authors.
Diseases of the Colon and Rectum | Year: 2013

BACKGROUND: Anal sphincter complex muscles, the internal anal sphincter, external anal sphincter, and puborectalis muscles, play an important role in the anal continence mechanism. Patients with symptoms of fecal incontinence have weak anal sphincter complex muscles; however, their length-tension properties and relationship to anatomical disruption have never been studied. OBJECTIVE: This study aimed to assess the anatomy of the anal sphincter complex muscles with the use of a 3-dimensional ultrasound imaging system and to determine the relationship between the anatomical defects and the length-tension property of external anal sphincter and puborectalis muscles in women with incontinence symptoms and in control subjects. DESIGN: Severity of anal sphincter muscle damage was determined by static and dynamic 3-dimensional ultrasound imaging. The length-tension property was determined by anal and vaginal pressure with the use of custom-designed probes. PATIENTS: Forty-four asymptomatic controls and 24 incontinent patients participated in this study. MAIN OUTCOME MEASURES: The anatomical defects and length-tension dysfunction of anal sphincter complex muscles in patients with fecal incontinence were evaluated. RESULTS: The prevalence of injury to sphincter muscles is significantly greater in the incontinent patients than in the controls. Eighty-five percent of patients but only 9% controls reveal damage to ≥2 of the 3 muscles of the anal sphincter complex. Anal and vaginal squeeze pressures increased with the increase in the probe size (lengthtension curve) in the majority of controls. In patients, the increase in anal and vaginal squeeze pressures was either significantly smaller than in controls or it decreased with the increasing probe size (abnormal length-tension). LIMITATIONS: We studied patients with severe symptoms. Whether our findings are applicable to patients with mild to moderate symptoms remains to be determined. CONCLUSIONS: The length-tension property of the external anal sphincter and puborectalis muscles is significantly impaired in incontinent patients. Our findings have therapeutic implications for the treatment of anal incontinence. © The ASCRS 2013. Source

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