Brain asymmetry,immunity, handedness

The principle of symmetry-asymmetry is widely presented in the structural and functional organization of the nonliving and living nature. One of the most complex manifestations of this principle is the left-right asymmetry of the human brain. The present review summarizes previous and contemporary literary data regarding the role of brain asymmetry in neuroimmunomodulation. Some handedness-related peculiarities are outlined additionally. Brain asymmetry is considered to be imprinted in the formation and regulation of the individual’s responses and relationships at an immunological level with the external and internal environment. The assumptions that the hemispheres modulate immune response in an asymmetric manner have been confirmed in experiments on animals. Some authors assume that the right hemisphere plays an indirect role in neuroimmunomodulation, controlling and suppressing the left hemispheric inductive signals.     

Disease susceptibility genes for autism

Autism is a complex neurodevelopmental disorder characterized by impairment in social interaction accompanied by a delay or lack of language, restricted interests, stereotyped behavior, and repetitive movement. Genetic predisposition to autism is evident from family and twin studies, and heritability in idiopathic autism is estimated at over 90%. Frequency of the disorder is approximately 1:2000 with a male to female ratio of 4:1. Affected individuals look normal at birth, and the symptoms manifest at the first 2-3 years of life. The spectrum of clinical symptoms and the severity of the disorder are variable even among siblings. Family studies and several genome-wide linkage analyses support the hypothesis of complex inheritance with involvement of as many as 10-100 genes of moderate effect. Identification of genes responsible for the phenotype would help to understand the molecular mechanisms of the disorder. Several genes have been proposed to play a role in susceptibility to autism, and this paper will overview those genes and their potential role in the disorder.     

Aicardi syndrome: epilepsy surgery as a palliative treatment option for selected patients and pathological findings

The optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo‐pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1–3 isolated spasms per day. Case 2 had a right fronto‐parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.     

Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station.

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.     

Treatment of End-Stage Renal Disease in Central and Eastern Europe: Overview of Current Status and Future Needs

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990–1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RTT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.     

The possible role of nuclear imaging in assessment of the cardiac resynchronization therapy effectiveness in patients with moderate heart failure

Background

The aim of the study was to elucidate the role of nuclear medicine imaging in the selection of candidates for cardiac resynchronization therapy (CRT) and in the evaluation of CRT effectiveness

Methods

We studied 28 patients (19 male and 9 female) with dilated cardiomyopathy (DCM) and heart failure (HF). Before implantation of CRT device, all patients underwent SPECT with ^99mTc-MIBI at rest to evaluate the myocardial perfusion, ¹²³I-BMIPP to evaluate the myocardial metabolism, and gated cardiac blood-pool SPECT (GBPS) to assess the myocardial contractile function. Following CRT, all patients were examined with 99mTc-MIBI SPECT and GBPS 12 ± 3 months after the intervention.

Results

All patients after CRT were divided into three groups. The first group included 10 patients with LVEF increased by more than 10 % (hyperresponders), the 2nd group included 11 patients with an increase in EF of more than 5 % but less than 10 % (responders) and third group consisted of 7 males whose LVEF remained unchanged or worsened compared with pre-operative values (nonresponders). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (EF, EDV, ESV, SV), intra- and interventricular dyssynchrony, as well as in the midsize of perfusion defects. Following long-term CRT, we found increase in LVEF and decrease in average size of perfusion defects in groups of hyperresponders and responders (p < 0.05). Results of SPECT with ¹²³I-BMIPP, performed prior to CRT, showed that nonresponders had more pronounced disturbance of myocardial metabolism compared with the group of hyperresponders (20 vs. 14.7 %, p < 0.05).

Conclusion

The radionuclide methods can be used as possible indicators in the evaluation effectiveness and selection of candidates on the CRT.     

Arteriovenous fistula for long-term venous access for boys with hemophilia

OBJECTIVES: Hemophilia is a sex-linked condition affecting about 1 of every 5000 males in the United States. The management of children with hemophilia can be improved with regular intravenous infusion of factor VIII or IX, thus preventing crippling and sometimes fatal hemorrhage. Maintaining this vital intravenous access is often hampered by gradual loss of superficial veins or repeated central catheter sepsis and thrombosis. This study reviewed an experience with arteriovenous fistula in selected hemophilia patients with limited venous access. METHODS: Consecutive patients operated on between October 2000 and July 2006 for venous access with the creation of an arteriovenous fistula were reviewed. They were selected because of repeated problems with other venous access. Patency, ease of use, duplex scan derived brachial artery diameter, and arm length were assessed. RESULTS: During a 69-month period, 10 arteriovenous fistulas (five brachial artery-basilic vein fistulas, 5 brachial artery-cephalic vein fistulas) were created for nine patients. The patients were a median age of 5.5 years (range, 1 to 27 years), and all were <13 except the 27-year-old patient. There were no postoperative hematomas requiring evacuation. One arteriovenous fistula failed to mature and was redone in the opposite arm, which subsequently occluded after 13 months. Of the mature fistulas, patency was 100% at 1 year, 80% (4/5) at 3 years, and 75% (3/4) at 4 years, with mean follow-up of 22 months. Brachial artery diameter increased in the involved arm by a ratio of 1.95 (range, 1.51 to 2.5) compared with the opposite arm. Arm length disparity was increased by 0.5 cm (range, 0.8 to 1.5 cm) in the involved arm. All fistulas allowed good access at home by a care provider. CONCLUSIONS: For hemophilia patients with compromised venous access, arteriovenous fistulas provide good early patency. Brachial artery diameter and arm length require continued follow-up.     

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.