A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization

OBJECTIVE: This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization. METHODS: This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications. RESULTS: Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain. CONCLUSION: While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.     

Plasma serotonin in autism

Serotonin is necessary for normal fetal brain development. Administration of serotonin inhibitors to pregnant rats results in offspring with abnormal behaviors, brain morphology, and serotonin receptor numbers. Low maternal plasma serotonin may contribute to abnormal brain development in autism. In this study, plasma serotonin levels in autism mothers and control mothers of typically developing children were compared, and plasma serotonin levels in children with autism (n = 17) and their family members were measured. Plasma serotonin levels in autism mothers were significantly lower than in mothers of normal children (P = 0.002). Plasma serotonin levels correlated between autism mothers and their children, but differed between autistic children and their fathers (P = 0.028) and siblings (P = 0.063). Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.     

Dynamic magnetic resonance imaging for grading pelvic organ prolapse according to the international continence society classification: Which line should be used?

AIMS: To assess and compare the reliability of dynamic MRI to quantify pelvic organ prolapse (POP) according to the International Continence Society (ICS) using two different reference lines, and to determine which line gives the best concordance with clinical examination. METHODS: Forty-seven patients with genital prolapse underwent physical examination and dynamic MRI. Five nulliparous, symptom-free female volunteers underwent dynamic MRI as control subjects. Two distinct observers performed the MRI measurements of POP according to the ICS using two distinct reference lines: the mid-pubic line and a new one, the perineal line that provides a better match with the hymen plane. Measurements were repeated twice according to each line. The intra-class coefficient was used to estimate intra-observer and inter-observer reliability; the Altman and Bland plot was used to assess the agreement between MRI and clinical measurements. RESULTS: The intra-observer and inter-observer reliability of MRI measurements were in general excellent. Intra-class coefficients were better for the mid-pubic line than the perineal line. Although the MRI measurements correlate significantly with the physical measurements, the Altman and Bland plot shows an unacceptable magnitude of discrepancy between clinical and MRI examinations. CONCLUSIONS: Although dynamic MRI shows excellent inter- and intra-observer reliability, its agreement with clinical examination is poor whatever the line used.     

Lepidium meyenii （ Maca ） improved semen parameters in adult men

Aim: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24 - 44 years old. Methods: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment. Results: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treamaent. Increase of sperm count was not related to dose of Maca. Conclusion: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.     

Trans-Sinusal Frontal Approach for Olfactory Groove Meningiomas

The authors report on their experience with the trans-sinusal frontal approach in removing olfactory groove meningiomas. Six tumors were operated on by the trans-sinusal frontal approach, using a bicoronal incision; two tumors developed on one side, and there were four bilateral olfactosellar tumors. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked through a real subfrontal route along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stages of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, were removed along with the tumor. Tumor extensions toward the sella and the optic canals were removed without brain retraction, opening of the Sylvian fissure, or dissection of the carotid arteries. All patients made a good neurologic recovery; intellectual impairment disappeared within 1 month, and visual acuity normalized within 2 weeks. Olfactory nets were preserved on the contralateral side in unilateral tumors. The trans-sinusal frontal approach is technically easy and safe to achieve. Osteotomy and replacement of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, imageguided surgery allows precise deliniation of its limits and the free bone flap, including the calvarial outer layer, tangentially cut from one supraorbital canal to the other. The cosmetic result is perfect, as the normal contour of the forehead is maintained without any scar or visible burr hole. The trans-sinusal frontal approach gives access to the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoid processes. The trans-sinusal frontal approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas, whatever their size.     

Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use.

OBJECTIVE: Levosimendan is a promising new inotrope. We investigate the proper time for its infusion during or after open-heart surgery to avoid complications related with low-output syndrome and high dosage of inotropes. METHODS: Forty-five consecutive patients were randomised to receive levosimendan in addition to the conventional therapy, its infusion starting in the operating theatre (Group OT) or in the ICU (Group ICU) when low-output syndrome was certified and were consequently dependent on classical inotropic support and IABP. Levosimendan was infused at a rate of 0.1 microg/kg min without loading dose, the infusion being for at least 24h to a maximum 48 h. RESULTS: Levosimendan was well tolerated, with the simultaneous infusion of norepinephrine if required. Its efficacy was identical in both groups with improvement in the haemodynamic and functional status of patients (amelioration of stroke volume, cardiac index and mixed venous blood oxygen saturation, increase of left ventricular ejection fraction by echo study, de-escalation of traditional inotropes, subtraction of IABP and reduction in BNP plasma levels). The ICU stay and hospital stay were significantly decreased in patients of Group OT, compared to patients of Group ICU. Four patients died because of multiple organs dysfunction syndrome (MODS) due to sepsis (all patients of Group ICU). CONCLUSION: Levosimendan is a safe and efficient choice in the management of low-output syndrome during and after open-heart surgery. The shortening of hospitalisation and the trend for better outcome confirm its clear superiority when the infusion starts from the operating theatre.     

Ischemic preconditioning specifically restores complexes I and II activities of the mitochondrial respiratory chain in ischemic skeletal muscle

OBJECTIVE: Defective mitochondrial function has been reported in patients presenting with peripheral arterial disease, suggesting it might be an important underlying mechanism responsible for increased morbidity and mortality. We therefore determined the effects of prolonged ischemia on energetic skeletal muscle and investigated whether ischemic preconditioning might improve impaired electron transport chain and oxidative phosphorylation in ischemic skeletal muscle. METHODS: Thirty rats were divided in three groups: the control group (sham, n = 9) underwent 5 hours of general anesthesia without any ischemia, the ischemia-reperfusion (IR) group (n = 11) underwent 5 hours ischemia induced by a rubber band tourniquet applied on the left root of the hind limb, and in the third group, preconditioning (PC group, n = 10) was performed just before IR and consisted of three cycles of 10 minutes of ischemia, followed by 10 minutes reperfusion. Maximal oxidative capacities (V(max)) of the gastrocnemius muscle and complexes I, II, and IV of the mitochondrial respiratory chain were determined using glutamate-malate (V(max)), succinate (V(s)), and N, N, N,'N'-tetramethyl-p-phenylenediamine dihydrochloride ascorbate as substrates. RESULTS: Physiologic characteristics were similar in the three groups. Ischemia reduced V(max) by 43% (4.5 +/- 0.4 vs 7.9 +/- 0.5 micromol O(2)/(min x g dry weight), P < .01) and V(s) by 55% (2.9 +/- 0.3 vs 6.3 +/- 0.4 micromol O(2)/min/g dry weight; P < .01) in the IR and sham groups, respectively, and impairments of mitochondrial complexes I and II activities were evident. Of interest was that preconditioning prevented ischemia-induced mitochondrial dysfunction. Both V(max) and V(s) were significantly higher in the PC rats than in IR rats (+32% and +41%, respectively; P < .05), and were not different from sham values. CONCLUSIONS: Ischemic preconditioning counteracted ischemia-induced impairments of mitochondrial complexes I and II. These data support that ischemic preconditioning might be an interesting approach to reduce muscular injuries in the setting of ischemic vascular diseases.     

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.     

Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR

Atypical lipomatous tumor/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by the amplification of MDM2 and CDK4 genes. To evaluate the accuracy of fluorescence in situ hybridization (FISH) analysis in the differential diagnosis of adipose tissue tumors, we investigated MDM2-CDK4 status by FISH, real-time polymerase chain reaction (PCR) [quantitative PCR (Q-PCR)] and immunohistochemistry (IHC) in a series of 200 adipose tumors. First, we evaluated MDM2-CDK4 amplification and expression in a series of 94 well-defined adipose tissue tumors. Results showed that FISH was interpretable in 45 of 50 cases (90%), and was more specific and sensitive than Q-PCR and IHC. We then used the same techniques as complementary diagnostic tools in a series of 106 adipose and soft tissue tumors of unclear diagnosis to distinguish between (i) lipomas and atypical lipomatous tumor/well-differentiated liposarcomas, (ii) malignant undifferentiated tumors and dedifferentiated liposarcomas, and (iii) a variety of benign tumors and liposarcomas. Our results indicate that although helpful, IHC alone is often insufficient to solve diagnostic problems. FISH and Q-PCR methods gave concordant results and were equally informative in most cases. However, the proportion of noninterpretable cases was slightly higher with FISH than with Q-PCR. When tumor cells represented a minor component of the tumor tissue, such as with inflammatory tumors, FISH was more powerful than Q-PCR by allowing visualization of individual cells. In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone.