Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.     

Sirolimus allows renal recovery in lung and heart transplant recipients with chronic renal impairment.

BACKGROUND: Until recently, there has been no practical alternative to the use of calcineurin inhibitors (CIs) as primary immunosuppressants in lung transplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is a novel powerful immunosuppressant without renal toxicity, a common post-transplant problem associated with CI therapy. METHODS: SRL was used in 20 LTx and 5 HTx recipients >90 days post-transplant, where serious renal impairment was limiting CI dosing. Patients started on 2 to 5 mg/day orally at a median of 1,185 days post-transplant. Dosage adjustments were made according to trough levels, toxicity and perceived efficacy. With SRL initiation, 48% ceased CI therapy and the remainder decreased their dose substantively. RESULTS: After 30 days, 4 of 5 dialyzed patients ceased dialysis and 15 of 20 patients with an elevated serum creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. The direction of change in Cr at 30 days predicted longer term Cr. The starting Cr did not predict the 30-day or long-term value. There were two bouts of acute and one bout of chronic rejection. There were 35 infectious complications in 16 patients and 24 episodes of potential SRL-related toxicity in 17 patients. These events generally responded to dose reduction or temporary cessation and were level-related. Fifteen recipients presently remain on the drug. None of the 7 deaths could be directly related to toxicity. CONCLUSION: SRL is a useful alternative immunosuppressant, allowing significant CI withdrawal in transplant recipients with renal impairment. Whether the resulting improvement in Cr can be maintained in the long term probably depends on the balance between the extent of acute and chronic renal damage.     

Evolution and path models in human behavioral genetics

The evolutionary implications of the path-analysis model most often used in human behavior genetics are examined. With directional selection, a model of pure vertical environmental transmission does not respond in a fully adaptive fashion. Unless the coefficients of transmission are exactly 0.50, the population mean will not equilibrate at the selective optimum over time. If there is both genetic and vertical environmental transmission, then the population mean can equilibrate at the selective optimum. In the presence of genetic transmission, vertical environmental transmission increases population fitness and has a strong effect on the rapid movement of the mean toward the selective optimum. This raises the intriguing paradox of why empirical evidence suggests that vertical environmental transmission is usually small when it possesses such important fitness properties.This work was supported in part by Grant DA05131 from the National Institute on Drug Abuse.     

Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke.

We have previously shown that neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if administered before focal stroke. Here, we examined the therapeutic window and functional recovery after NRG-1 treatment in rats subjected to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Neuregulin-1 (2.5 ng/kg bolus, 1.25 ng/kg/min infusion) reduced infarct volume by 89.2%+/-41.9% (mean+/-s.d.; n=8; P<0.01) if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%+/-52.6%; n=7; P<0.01) and 12 h (57.0%+/-20.8%; n=8; P<0.01) after reperfusion. Neuregulin-1 administration also resulted in a significant improvement of functional neurologic outcome compared with vehicle-treated animals (32.1%+/-5.7%; n=9; P<0.01). The neuroprotective effect of the single administration of NRG-1 was seen as long as 2 weeks after treatment. Neurons labeled with the neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in the cortex, but the numbers were significantly reduced after NRG-1 treatment. These results indicate that NRG-1 is a potent neuroprotective compound with an extended therapeutic window that has practical therapeutic potential in treating individuals after ischemic brain injury.     

Light and electron microscopic and autoradiographic studies onN-methyl-N-amylnitrosamine-induced rat esophageal carcinogenesis

The purpose of this study was to investigate the histogenesis of experimental tumors in the rat esophagus. Thirty rats received 0.0015% N-methyl-N-amylnitrosamine (MNAN) in the drinking water for 12 weeks. Another 30 rats received tap water. All rats then received tap water until sacrifice. Rats from each group were sacrificed immediately after MNAN administration, four weeks after, and eight weeks after. One hour before sacrifice, [³H]TdR was injected by tail vein to label proliferating cells. The entire esophagus and stomach were removed and processed for light and electron microscopy and autoradiography. The overall frequency of esophageal tumors after MNAN was 83% and did not differ significantly among the three experimental groups. Tumors were primarily papillomas and squamous cell carcinomas and occurred with equal frequency in the upper, middle, and lower thirds of the esophagus. No tumors were found in the squamous-lined forestomach. Electron microscopy revealed abundant tonofilaments, free ribosomes, and mitochondria accompanied by vacuoles. By autoradiography, esophageal epithelial proliferation was markedly stimulated in nontumorous mucosa from all three experimental groups. We conclude that MNAN ingestion for 12 weeks reliably produces papillomas and squamous cell carcinomas throughout the rat esophagus, but not in the squamouslined forestomach, and that MNAN stimulated marked epithelial proliferation which is accompanied by thickening of the epithelium in nontumorus esophageal mucosa.     

Second neoplasms in survivors of childhood and adolescent cancer are often treatable.

PURPOSE: To estimate the incidence and types of second neoplasms in survivors of childhood and adolescent cancer, as well as the characteristics of those who developed second neoplasms. METHODS: Survivors who were under age 21 years at initial diagnosis, off therapy, and in remission for 2 years are referred to the Long Term Survivors' Clinic (LTSC) at Children's National Medical Center (CNMC). This review includes patients entered in the clinic database from January 1, 1997 to August 30, 2002. RESULTS: Twenty-three (2.3%) of 987 childhood cancer survivors followed in the LTSC had 26 (2.6%) second and third neoplasms. The mean age was 6.7 years at initial diagnosis, 20.3 years at diagnosis of the second neoplasm, and 20.5 years at diagnosis of the third neoplasm. Of 10 female and 13 male patients, 15 were white, six black, one Hispanic, and one Asian. All but two of the patients received radiation. Nineteen neoplasms, including seven thyroid carcinomas, six central nervous system tumors (three meningiomas), three basal cell carcinomas, two breast cancers, and one soft tissue sarcoma, occurred at sites within or contiguous to radiation sites. Five patients died, but the majority of neoplasms were treatable and most patients had good outcomes. CONCLUSION: Indefinite follow-up in a long-term survivors' clinic is indicated for adolescent and adult survivors of childhood cancer, with routine examination and screening for recurrence of the initial cancer as well as late effects, including second neoplasms.     

Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-na?ve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.     

Effect of Multiple Freeze-Thaw Cycles on Detection of Measles, Mumps, and Rubella Virus Antibodies

We investigated the effect of multiple freeze-thaw cycles on mumps, measles, and rubella virus serum antibody levels with whole-virus immunoglobulin G enzyme-linked immunoassays. Fresh serum samples from nine healthy adult volunteers were divided into six sets of five aliquots each. Samples were taken through a total of 10 freeze-thaw cycles and stored at 4°C until assayed. Each assay measurement was done in replicates of five, and the mean value was reported. After completing 10 freeze-thaw cycles, we found no clinically or statistically significant effect on measured antibody levels and found no discernible detrimental effect on the ability to measure these antibodies by enzyme-linked immunoassays.