Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum

The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats.     

Brief report: imitation effects on children with autism

Twenty children with autism (mean age, 5 years) were recruited for the study from a school for children with autism. The children were randomly assigned to an imitation (n = 10) or contingently responsive (n = 10) interaction group based on a stratification table for gender and developmental and chronological age. The sessions consisted of four phases, with each phase lasting 3 minutes. In the first phase, the child walked into a room that was furnished with a sofa, a table, chairs, and two sets of identical toys. An adult was in the room sitting very still like a statue (first still-face condition). In the second phase, the adult either imitated the child or was contingently responsive to the child. In the third phase, the adult sat still again (second still-face condition), and in the fourth phase, the adult engaged in a spontaneous interaction. During the third phase (the second still-face condition), the children in the imitation group spent less time in gross motor activity and more time touching the adult, as if attempting to initiate an interaction. The contingency condition appeared to be a more effective way to facilitate a distal social behavior (attention), whereas the imitative condition was a more effective way to facilitate a proximal social behavior (touching).     

Triptans induce vasoconstriction of human arteries and veins from the thoracic wall

A common side effect of migraine treatment with triptans is chest symptoms. The origin of these symptoms is not known. The aim of the present study was to examine the vasocontractile effect of triptans in human arteries and veins from the thoracic wall and in coronary artery bypass grafts. In vitro pharmacology experiments showed that the 5-hydroxytryptamine (5-HT) type 1B and 1D receptor agonists, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan, induced vasoconstriction in the thoracic blood vessels from 38% to 57% of the patients. 5-carboxamidotryptamine (5-CT) and sumatriptan elicited a vasoconstriction that was antagonized by the 5-HT1B receptor antagonist SB224289, whereas the 5-HT1D receptor antagonist BRL115572 had no effect. 5-HT induced a contraction that was inhibited by the 5-HT2A receptor antagonist ketanserin. 5-HT2A, 5-HT1B, and 5-HT1D receptor mRNA levels were detected by real-time PCR in all blood vessels studied. In conclusion, triptans induce vasoconstriction in arteries and veins from the thoracic wall, most likely by activation of 5-HT1B receptors. This response could be observed in only 38% to 57% of the patients, which may provide an explanation for why a similar number of patients experience chest symptoms as a side effect of migraine treatment with triptans.     

Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat

Low dietary magnesium (Mg) may be a risk factor for osteoporosis. In animals, severe Mg deficiency (0.04% of nutrient requirement [NR]) results in bone loss. We have also found that a more moderate dietary Mg restriction (10% of NR) also resulted in loss of bone. We now report the effect of Mg intake of 25% NR on bone and mineral metabolism in the rat. Serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured at 2, 4, and 6 months in control and Mg-deficient animals. Femurs and tibias were collected for mineral content, micro-computerized tomography, histomorphometry, and immunocytochemical localization. Profound Mg deficiency developed as assessed by marked hypomagnesemia and 27% reduction in bone Mg content. Serum calcium was not significantly different between groups. Mg depletion resulted in a significantly lower serum PTH concentrations. Serum 1,25(OH)2-vitamin D was also significantly lower. No difference was noted in markers of bone turnover. Histomorphometry and micro-computerized tomography demonstrated decreased bone volume and trabecular thickness. No difference was observed for osteoclast or osteoblast number. Inflammatory cytokines may contribute to bone loss. We found that immunocytochemical localization of TNFalpha in osteoclasts was increased 138-150%. This increase in TNFalpha may be due to increased substance P as it was found to be elevated from 179% to 432%. These data demonstrate that Mg intake of 25% NR in the rat causes lower bone mass which may be related to increased release of substance P and TNFalpha.     

Altered postural control during the luteal phase in women with premenstrual symptoms

The purpose of this study was to investigate postural control in women with and without premenstrual symptoms (PMS) in three hormonally verified phases of the menstrual cycle. Thirty-two women were recruited to participate in the study and 25 of these women were included in the results. Menstrual cycle phases were determined by sex hormone analyses in serum and LH detection in urine. A prospective rating of PMS was used to divide the subjects into two groups: one with PMS (cyclic) and one without (non-cyclic). For measurement of postural control, subjects stood on a force platform (AMTI) in two-legged stance (eyes open and closed) and one-legged stance (eyes open and closed). There were no significant differences in the two-legged stance between the phases of the menstrual cycle or between groups. In one-legged stance with eyes open, there was a significant increase in postural displacement in the mid-luteal phase in the cyclic group, but no differences were detected between phases in the non-cyclic group. These findings may be related to the previously reported increased injury rate and psychomotor slowing in the luteal phase in women with PMS.     

Catecholaminergic polymorphic ventricular tachycardia: successful emergency treatment with intravenous propranolol

Catecholaminergic polymorphic ventricular tachycardia (VT) is a rare arrhythmogenic disorder, which may cause sudden death and whose relationships with mutations in cardiac ryanodine receptor gene have been recently established. The present article reports a catecholaminergic polymorphic VT case of a 9-year-old girl, without any previous history of syncope, who has been found unconscious while playing and referred comatose to pediatric intensive care unit. The electrocardiogram pattern showed runs of bidirectional and polymorphic VT degenerating into ventricular fibrillation, without QT interval abnormalities. Various attempts of cardioversion, lidocaine, and magnesium sulfate intravenous infusions were only partially effective. Owing to catecholaminergic polymorphic VT highly suggesting electrocardiogram pattern, intravenous propranolol was administered, achieving immediate VT interruption. Long-term nadolol therapy effectively prevented further arrhythmias, with no relapses up to 10 months later; a good neurologic recovery was also obtained. Genetic evaluation revealed in this patient-but not in relatives-a mutation in ryanodine receptor gene on chromosome 1.     

Effects of vacuum-assisted closure on central hemodynamics in a sternotomy wound model

Several authors have reported promising results with vacuum-assisted closure therapy in poststernotomy mediastinitis. The aim of this study was to investigate the hemodynamic outcome following the application of six negative pressures on an open sternotomy wound. Six 70-kg pigs underwent median sternotomy followed by vacuum-assisted closure therapy. Six negative pressures (-50, -75, -100, -125, -150, and -175mmHg) were applied to each pig for 30min each while hemodynamic parameters were measured. An increase in cardiac output was observed at -75mmHg when compared to the other five pressures: -50mmHg (P<0.05; CI 0.12-1.13l/min), -100mmHg (P<0.001; CI 0.34-1.32l/min), -125mmHg (P<0.001; CI 0.51-1.52l/min), -150mmHg (P<0.001; CI 0.50-1.47l/min), and -175mmHg (P<0.05; CI 0.13-1.17l/min). A decrease in systemic vascular resistance was observed at -75mmHg when compared to -125mmHg (P<0.01; CI 108-552dyn.s/cm(5)) and -150mmHg (P<0.01; CI 90-543dyn.s/cm(5)), but not compared to the other pressures. No change (P=ns) was observed in heart frequency, mean arterial pressure or central venous pressure. Our data demonstrates that vacuum-assisted closure therapy of -50 to -175mmHg does not impair the central hemodynamics in a porcine sternotomy model.     

Bone loss induced by dietary magnesium reduction to 10% of the nutrient requirement in rats is associated with increased release of substance P and tumor necrosis factor-alpha

Dietary Mg intake has been linked to osteoporosis. Previous studies have demonstrated that severe Mg deficiency [0.04% of nutrient requirement (NR)] results in osteoporosis in rodent models. We assessed the effects of more moderate dietary Mg restriction (10% of NR) on bone and mineral metabolism over a 6-mo experimental period in rats. At 2, 4 and 6 mo, serum Mg, Ca, parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D, alkaline phosphatase, osteocalcin and urine pyridinoline were measured. Femurs and tibiae were collected for measurement of mineral content, microcomputerized tomography, histomorphometry, and immunocytochemical localization. By 2 mo, profound Mg deficiency had developed as assessed by marked hypomagnesemia and up to a 51% reduction in bone Mg content. These features continued through 6 mo of study. Serum Ca was slightly but significantly higher in Mg-deficient rats than in controls at all time points. At 2 mo, serum PTH was elevated in Mg-deficient rats but was significantly decreased at 6 mo in contrast to control rats in which PTH rose. Serum 1,25-dihydroxy-vitamin D was significantly lower than in controls at 4 and 6 mo. A significant fall in both serum alkaline phosphatase and osteocalcin suggested decreased osteoblast activity. Histomorphometry demonstrated decreased bone volume and trabecular thickness. This was confirmed by microcomputerized tomography analysis, which also showed that trabecular volume, thickness and number were significantly lower in Mg-deficient rats. Increased bone resorption was suggested by an increase in osteoclast number over time compared with controls as well as surface of bone covered by osteoclasts and eroded surface, but there was no difference in osteoblast numbers. The increased bone resorption may be due to an increase in TNF-alpha because immunocytochemical localization of TNF-alpha in osteoclasts was 199% greater than in controls at 2 mo, 75% at 4 mo and 194% at 6 mo. The difference in TNF-alpha may be due to substance P, which was 250% greater than in controls in mononuclear cells at 2 mo and 266% at 4 mo. These data demonstrated that a Mg intake of 10% of NR in rats causes bone loss that may be secondary to the increased release of substance P and TNF-alpha.     

Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients

The axillary sentinel lymph node biopsy (SLNB) has gained increasing popularity as a novel surgical approach for staging patients with breast carcinoma and for guiding the choice of adjuvant therapy with minimal morbidity. Patients with negative SLNB represent a subset of breast carcinoma patients with definitely better prognosis, because their pN0 status is based on a very thorough examination of the sentinel lymph nodes (SLNs), with a very low risk of missing even small micrometastatic deposits, as compared with routine examination of the 20 or 30 lymph nodes obtained by the traditional axillary clearing. The histopathologic examination of the SLNs may be performed after fixation and embedding in paraffin, or intraoperatively on frozen sections. Whatever is the preferred tracing technique and surgical procedure, the histopathologic examination of each SLN must be particularly accurate, to avoid a false-negative diagnosis. Unfortunately, because of the lack of standardised guidelines or protocols for SLN examination, different institutions still adopt their own working protocols, which differ substantially in the number of sections cut and examined, in the cutting intervals (ranging from 50 to more than 250 microm), and in the more or less extensive use of immunohistochemical assays for the detection of micrometastatic disease. Herein, a very stringent protocol for the examination of the axillary SLN is reported, which is applied either to frozen SLN for the intraoperative diagnosis, and to fixed and embedded SLN as well.     

CardioSEAL/STARflex versus Amplatzer devices for percutaneous closure of small to moderate (up to 18 mm) atrial septal defects

Background

The Amplatzer septal occluder (ASO) allows the percutaneous closure of small to very large atrial septal defects (ASDs). The CardioSEAL/STARflex (CS/SF) can be used only for closure of small to moderate ASDs (stretch size up to 18 mm). These 2 devices are widely used in clinical practice. Therefore, a comparison of their use in the closure of small to moderate ASDs is needed.

Methods

From December 1996 to September 2002, 274 consecutive patients (mean age 20.3 ± 17 years) underwent percutaneous closure of small to moderate ostium secundum ASDs. The CS/SF device was used in 121 patients, and the ASO was used in 153.

Results

There were no differences in age, sex ratio, or pulmonary/systemic flow ratio. Stretch size of the defect was higher in the ASO group (13.6 ± 3.5 mm vs 15.5 ± 3.2 mm, P < .001). Procedure time and fluoroscopy time were shorter in patients treated with the ASO (61 ± 21 vs 75 ± 32 min, P < .0003, and 11.6 ± 9 vs 23.8 ± 17.4 min, P < .0001, respectively). Residual shunt at procedure and discharge was significantly more frequent in the CS/SF group (P < .0001). There were no differences in the complication rate for the 2 groups (CS/SF 4/121 vs ASO 6/153). Length of follow-up was longer in the CS/SF group (24 ± 14 vs 16 ± 9 months, P = .0001). Residual shunting was significantly more frequent in the CS/SF group during follow-up, while closure rate reached 100% after 1 month in ASO group.

Conclusions

The 2 devices are clinically safe and effective in ASD closure. However, percutaneous closure of small to moderate ASDs with ASO is quicker and provides an higher rate of complete occlusion.