Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:² preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.     

Immediate postgadolinium spoiled gradient-echo MRI for evaluating the abdominal aorta in the setting of abdominal MR examination

To assess the reproducibility and image quality of immediate postgadolinium chelate spoiled gradient-echo MRI in demonstrating disease of the abdominal aorta. All patients (27 patients: 21 men, 6 women) with substantial disease of the abdominal aorta, who underwent abdominal MR examinations at 1.5 T between 1991 and 1995, were entered in the study. Patients were referred for evaluation of suspected aortic disease (14 patients) or other abdominal diseases (13 patients). Three experienced investigators manually measured luminal and external aortic wall diameters and rated image quality, definition of inner and outer walls, extent of disease, and presence of other abdominal abnormalities, in an independent fashion. A cardiovascular surgeon then rated all studies to determine whether clinical management could be based on the MR findings alone. There was 98 to 99% agreement in measurements of luminal and external wall diameter between the three investigators. Overall image quality was rated as good in 77.8 to 88.9% of patients. A total of 31 additional nonaortic abdominal abnormalities were detected by all observers. The cardiovascular surgeon rated 25 of 27 studies as adequate to determine clinical management based on MR findings alone. Immediate postgadolinium spoiled gradient-echo MRI is a reproducible technique for the demonstration of abdominal aortic disease and possesses good image quality. Advantages of this technique include simultaneous evaluation of other nonvascular diseases of the abdomen, short examination time, and easy implementation as part of routine abdominal MRI scanning protocol.     

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.     

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.     

Cerebral accumulation of Tc-99m ethyl cysteinate dimer (ECD) in severe, transient hypothyroidism.

Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying 'noneuthyroid' individuals.     

Hereditary angioedema: A decade of management with stanozolol

Thirty-seven patients with hereditary angioedema, who, without therapy, had attacks of cutaneous angioedema, gastrointestinal colic, and/or upper respiratory symptoms at a frequency and severity sufficient to prompt treatment with an attenuated androgen, have been evaluated for the incidence of side effects and biochemical toxicity during various schedules leading to the minimal effective dose. Stanozolol was administered in a 2 mg daily dose, initially, and after the symptoms and signs were adequately controlled for 2 months at this dose or at 1 mg per day, the drug was administered every other day at 4 mg. Patients who responded adequately to this schedule were administered 2 or 1 mg every other day, and then the interval between doses was gradually increased to 1 week, after which the agent was stopped. Eighteen patients experienced adverse reactions to stanozolol while the minimal effective dose was attained. In each instance the side effect subsided with a reduction in dosage. The most common adverse reactions were biochemical evidence of hepatic dysfunction and, to a lesser extent, hirsutism and menstrual irregularities. Although 21 of 27 patients in an initial study of the minimal effective dose were maintained with daily therapy in 1980, by 1986 this group and 10 additional patients were distributed so that three patients were receiving daily maintenance, 18 were receiving alternate-day maintenance, and 16 patients were receiving no maintenance therapy [corrected]. Thus, stanozolol appears to be a safe and effective agent for management of hereditary angioedema when patients are continually monitored to define the minimal effective dose or the feasibility of stopping the drug.     

Comparative study of oral conditions in schoolchildren of Strasbourg, France, 1974–85

A representative sample of 1650 children randomly selected in the 6-15-yr-old schoolchild population of Strasbourg was examined by well-calibrated examiners. The prevalence of caries was determined with the DMFT, DMFS and dft indices using bitewing radiographs. Plaque, calculus and gingival indices were also determined. The results obtained were compared with the initial study of 1974 performed in Strasbourg using the same epidemiologic methods. Whereas no important variations were observed in caries prevalence of primary teeth, a significant reduction of caries activity was observed in DMFT and DMFS indices in all age groups. There was a reduction of these two indices of respectively 32% and 33% in the 12-yr-old children. The reduction was the most significant on approximal surface lesions. A statistically significant decrease of the calculus and gingival indices was also observed between 1974 and 1984. A less significant decrease was observed for the plaque index.