Apraxia in deep cerebral lesions.

In a series of 50 patients with cerebrovascular lesions (demonstrated with CT scan), seven patients had lesions located in the basal ganglia and/or thalamus. All these seven patients were apractic. Ideomotor apraxia was present in all patients; five also had constructional apraxia, and one had bucco-facial apraxia. None of the patients had utilisation apraxia. These observations indicated that apraxia is not only a "high cerebral (cortical) function", but may depend also on the integrity of subcortical circuits and structures.     

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.     

Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu In vivo model of human multiple myeloma.

Interleukin-6 (IL-6) protects multiple myeloma cells against apoptosis induced by glucocorticoids. Here, we investigated whether inhibition of the IL-6 signaling pathway by the IL-6 receptor superantagonist Sant7 enhances the in vivo antitumor effects of dexamethasone on the IL-6-dependent multiple myeloma cell line INA-6. For this purpose, we used a novel murine model of human multiple myeloma in which IL-6-dependent INA-6 multiple myeloma cells were directly injected into human bone marrow implants in severe combined immunodeficient (SCID) mice (SCID-hu). The effect of in vivo drug treatments on multiple myeloma cell growth was monitored by serial determinations of serum levels of soluble IL-6 receptor (shuIL-6R), which is released by INA-6 cells and served as a marker of tumor growth. In SCID-hu mice engrafted with INA-6 cells, treatment with either Sant7 or dexamethasone alone did not induce significant reduction in serum shuIL-6R levels. In contrast, the combination of Sant7 with dexamethasone resulted in a synergistic reduction in serum shuIL-6R levels after 6 consecutive days of treatment. Gene expression profiling of INA-6 cells showed down-regulation of proliferation/maintenance and cell cycle control genes, as well as up-regulation of apoptotic genes in multiple myeloma cells triggered by Sant7 and dexamethasone combination. In vitro colony assays showed inhibition of myeloid and erythroid colonies from normal human CD34(+) progenitors in response to dexamethasone, whereas Sant7 neither inhibited colony growth nor potentiated the inhibitory effect of dexamethasone. Taken together, these results indicate that inhibition of IL-6 signaling by Sant7 significantly potentiates the therapeutic action of dexamethasone against multiple myeloma cells, providing the preclinical rationale for clinical trials of Sant7 in combination with dexamethasone to improve patient outcome in multiple myeloma.     

Endovascular treatment versus intravenous thrombolysis alone in isolated M2 occlusion: a meta-analysis

Neurological Sciences - Optimal reperfusion strategies for M2 occlusion are still uncertain, with previous studies questioning benefit of mechanical thrombectomy (MT) over intravenous thrombolysis...     

Acute and chronic efficacy of felodipine in congestive heart failure

In 13 patients with congestive heart failure we tested the acute hemodynamic effects of 5 vs. 10 mg felodipine tablets, in a double-blind, cross-over study. One hour after felodipine 5 mg, echocardiographic ejection fraction (%), cardiac index (thermodilution-ml/min/m2), and pulmonary wedge pressure (mm Hg) significantly changed (from 21 +/- 2 to 26 +/- 2, 2350 +/- 150 to 2790 +/- 160, 24 +/- 4 to 17 +/- 4) while they remained steady after felodipine 10 mg. The greatest stroke index increases were associated with felodipine 5 mg in 12 patients and 10 mg in 1 patient. Therefore we evaluated (open study) the long-term (2 months- 1 year) clinical and hemodynamic efficacy following the treatment with the acutely most effective dose (twice daily). After 2 months ejection fraction, cardiac index and pulmonary wedge pressure were respectively 24 +/- 2, 2550 +/- 150, and 18 +/- 4 (12 hours after the last drug administration, n = 11, P less than 0.02 from baseline). These parameters further increased one to two hours after the following administration of felodipine. Clinical improvement (reduction of 1 functional class, according to the New York Heart Association) was observed in 8/13 patients. These 8 patients participated to the one year follow-up. In 5 patients follow-up was interrupted because of acute cardiovascular events. However, before study interruption (5 patients) or ending (3 patients) clinical status did not worsen and ejection fraction remained higher than in the pretreatment period. Therefore, low dose felodipine might be used in the treatment of congestive heart failure.     

Spironolactone improves lung diffusion in chronic heart failure.

AIMS: To evaluate whether anti-aldosteronic treatment influences lung diffusion (DLCO) in chronic heart failure (HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLCO abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. METHODS AND RESULTS: Thirty stable chronic HF patients, with reduced DLCO (<80% of predicted), were randomly assigned to active treatment (25 mg spironolactone daily) or placebo in addition to conventional anti-failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLCO and membrane diffusing capacity (DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLCO due to an increase of DM (DLCO: 18.3+/-3.9 vs. 19.9+/-5.5 mL/min/mmHg; DM: 28.1+/-7.7 vs. 33.3+/-8.6 mL/min/mmHg) and peak oxygen consumption (peak VO2 16.8+/-1.9 vs.18.6+/-2.2 mL/min/kg). Increments of DLCO and peak VO2 were linearly related (R=0.849, P<0.001). CONCLUSION: These data show a positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti-aldosteronic drugs improve HF clinical condition and prognosis.     

In vitro activity of human immunodeficiency virus protease inhibitors against Pneumocystis carinii

Since 1996, the introduction of protease inhibitors (PIs) has led to a dramatic decrease of human immunodeficiency virus-related Pneumocystis carinii pneumonia. This effect is clearly due, in large part, to the induction of immune reconstitution by highly active antiretroviral therapy (HAART). However, it is conceivable that PIs had other beneficial effects, including direct activity against Pneumocystis. In this study, the occurrence of specific aspartyl proteases in Pneumocystis is described. These protease targets seemed to be affected in vitro by antiretroviral PIs. These data suggest intriguing implications for the possible antipneumocystis benefit of receiving indinavir, ritonavir, nelfinavir, or saquinavir during HAART.