Cadmium Mobilization by Monoaralkyl- and Monoalkyl Esters of meso-2,3-Dimercaptosuccinic Acid and by a Dithiocarbamate

Syntheses and relative cadmium mobilizing properties are described for three new monoaralkyl esters (HOOCCH(SH)CH(SH)COOR, where R = phenylethyl ((CH₂)₂C₆H₅), MPhEDMS; R = 3-phenylpropyl ((CH₂)₃C₆H₅), MPhPDMS; and R = 2-phenoxyethyl ((CH₂)₂OC₆H₅), MPhOEDMS) of meso-2,3-dimercaptusuccinic acid. These were prepared by the reaction of the corresponding alcohol with meso-2,3-dimercaptosuccinic acid (DMSA) in aqueous HCl. When administered intraperitoneally to cadmium-loaded mice at 0.50 mmol/kg/day for four consecutive days, all induced significant reductions in the whole body cadmium levels. MPhEDMS, 60%; MPhPDMS, 66%; and MPhOEDMS, 58% in comparison with control levels. At the same dosage monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and a dithiocarbamate, sodium N-benzyl-4-O-(β-D-galactopyranosyl)-d -glucamine-N-carbodithioate (BLDTC) induced reductions of 65% and 57%, respectively. Hepatic and renal cadmium were also depleted significantly, while brain cadmium levels were unchanged. These compounds induced a significant reduction in the cadmium levels of the spleen, and one, MPhOEDMS, produced a 10% decrease in pancreatic cadmium. The manner in which the later injections removed smaller fractions of the total body cadmium is consistent with a bodily distribution of these compounds by which they are concentrated primarily in the kidneys and the liver, with much smaller amounts reaching other organs. It is proposed that these compounds enter renal and hepatic cells through an anion transport system.     

In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads

The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament, function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterioi tibial loads ranging from 22 to 110 N at knee flexion angles of 0–90°. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 ± 7.3 N under 22 N of anterior tibial load applied at 90° of knee flexion to 110.6 ± 14.8 N under 110 N of applied load at 15° of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45°, reaching a maximum of 75.2 ± 18.3 N at 15° of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60° and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.     

Consistent stress profiles in mothers of children with autism

The present study extends the area of research on stress in parents of autistic children. In this study we used the Questionnaire on Resources and Stress (Holroyd, 1987) to compare the stress profiles across mothers (a) who lived in different cultural and geographic environments; (b) who had children of different ages; and (c) who had children with different functioning levels. Results showed a characteristic profile that was highly consistent across each of these subgroups. Major differences from the normative data occurred on scales measuring stress associated with dependency and management, cognitive impairment, limits on family opportunity, and life-span care. Results suggest the importance of developing treatment programs aimed at reducing stress in specific areas in families with autistic children.Orchard Mental Health CenterThis research was supported by U.S. Department of Education, NIDRR Cooperative Agreement No. G0087C0234 (Koegel and Dunlap), by U.S. Public Health Service Research Grants MH28210 (Koegel) and MH39434 (Schreibman) from the National Institute of Mental Health, by Grant No. G008530082 from the U.S. Department of Education, Handicapped Children's Early Education Program (Dunlap), and by Fogarty Senior International Fellowship 1 FOB TWO 1374-01 (Schreibman) from the Fogarty International Center of the National Institutes of Health. The authors acknowledge the contributions of Prof. Dr. med. Hedwig Amorosa, and Dorle Staniczek, Soz. Pad. of the Max Planck Institute for Psychiatry, Munich, West Germany, and express particular appreciation to Prof. Dr. med. D. Ploog, Director of the Institute.     

Physiotherapy rehabilitation of the smile after long-term facial nerve palsy using video self-modeling and implementation intentions.

OBJECTIVE: To improve smiling after long-term facial nerve palsy (FNP). Physiotherapy rehabilitation of an adapted (more symmetrical) smile was investigated in FNP subjects 1 year post-onset, using video self-modeling (video replay of only best adapted smiles) and implementation intentions (preplanning adapted smiles for specific situations). STUDY DESIGN AND SETTING: Prospective, blinded clinical trial. Facial-Nerve-Palsy Clinic. RESULTS: After video self-modeling: 1) reaction time (RT) to initiation of adapted smiles became 224 ms faster whereas RT for everyday (asymmetrical) smiles became 153 ms slower; 2) adapted smiles were completed 544 ms faster; 3) adapted smiles had higher overall quality, movement control, and symmetry ratings; and 4) Facial Disability Index scores also improved. Implementation intentions after video self-modeling ensured transfer of adapted smile to everyday situations. CONCLUSION: Following intervention the smile improved, with significant changes in availability, execution speed, and quality. SIGNIFICANCE: This study supports these rehabilitation techniques to maximize quality of smiling following FNP. EBM rating: B-2b.     

Effect of 6-hydroxydopamine lesions of the amygdala on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement

Bilateral six-hydroxydopamine (6-OHDA) lesions were placed in the amygdala of rats self-administering cocaine (1.5 mg/kg per injection i.v.) under a progressive ratio schedule of reinforcement. Post-lesion access to three doses of cocaine (1.5, 0.75 and 0.37 mg/kg per injection i.v.) revealed a lesion effect only at the highest dose. At this dose, the lesion caused a significant increase in breaking point. No change in the breaking point was produced at the lower two doses. The biochemical results show a significant reduction in dopamine and DOPAC levels within the amygdala and an increase in dopamine within the NACC. In contrast, noradrenaline and serotonin (5-HT) levels were unaffected by the lesion in any of the dissected areas. These results demonstrate that no specific effect on cocaine reinforcement was produced by 6-OHDA lesions of the amygdala. The possibility that the lesion may have attenuated the anxiogenic qualities of the high dose of cocaine is discussed.     

The correction of BMD measurements for bone strontium content.

Strontium ranelate (SR) is a new oral treatment for osteoporosis associated with large increases in bone mineral density (BMD) compared with alternative therapies such as bisphosphonates. Much of the BMD increase during SR treatment is a physical effect caused by the increased attenuation of X-rays due to the accumulation of strontium in bone tissue. The aim of this study was to assess the contribution made by bone strontium content (BSC) to the overall BMD increase by evaluating the percentage F of the BMD change explained by the physical presence of strontium in bone. A value of F less than 100% would provide evidence of the anabolic effect of SR as an additional factor contributing to the overall BMD increase. Studies of mixtures of strontium hydroxyapatite (SrHA) and calcium hydroxyapatite (CaHA) scanned on a variety of dual-energy X-ray absorptiometry (DXA) systems show that a 1% molar ratio of SrHA/(CaHA+SrHA) causes a 10% overestimation of BMD. The correction of spine BMD measurements for the physical effects of strontium depends on knowledge of 2 further factors: (1) bone biopsy measurements of iliac crest BSC and (2) the ratio R of BSC at the DXA site to BSC at the iliac crest measured in animal studies. We used clinical trial data and values of R(spine) measured in studies of monkeys and beagle dogs to determine values of F(spine) for 1, 2, and 3 yr treatment with SR. Based on the average value of R(spine) approximately 0.7 for male and female monkeys, we found values for F(spine) approximately 75-80% for 1, 2, and 3 yr of treatment. Using the value of R(spine) approximately 1.0 from the beagle study gave values of F(spine) approximately 100%. Although values of F(spine) as low as 40% are possible, we conclude that the most likely figure is 75% or greater. However, it is apparent that there are large uncertainties in the correction of BMD results for the effect of bone strontium and that the most important of these is the inference of BSC values at DXA scan sites from measurements of iliac crest bone biopsy specimens.     

Bilateral Mid-Diaphyseal Femoral Stress Fractures in the Elderly

Abstract Background: Osteoporosis is characterized by low bone density and poor bone mineralization. Mid-diaphyseal stress (insufficiency) fractures of the femur caused by osteoporosis are rare. The symptoms of these lesions are vague and confusing. The physician must be alert to the possibility of femoral shaft stress fractures when evaluating an elderly patient complaining of back, hip or leg pain. Case Study: A 72-year-old osteoporotic female patient with bilateral mid-diaphyseal stress fractures of the femur is reported. The diagnosis of femoral shaft stress fracture in the elderly is very difficult when based on physical findings and plain radiography only. A magnetic resonance imaging (MRI) scan or nuclear scintigraphy is necessary for early diagnosis. In the described case, the patient had an excellent result after surgical treatment with intramedullary nails. Conclusion: MRI or nuclear scintigraphy must be obtained to exclude the possibility of femoral shaft stress fractures in the elderly. In the absence of contraindications, surgery is the best solution for this kind of lesion.