Medullary carcinoma of the thyroid in the multiple mucosal neuromas syndrome

The clinical features of the multiple mucosal neuromas (MMN) syndrome permit the recognition of these patients and their potential development of the associated medullary thyroid carcinoma (MTC). The distinctive physical appearance caused by the mucosal neuromas, the Marfanoid habitus and, occasionally, the positive family history aid in establishing the diagnosis. Neurogangliomas are frequently present in the gastrointestinal tract of these patients who may have megacolon, constipation and diarrhea. The third instance of the MMN syndrome is reported in the newborn as intestinal obstruction. It is suggested that the syndrome be considered in the differential diagnosis of Hirschsprung's disease and bowel obstruction in the neonate. Serum calcitonin measurements following stimulation by calcium or pentagastrin infusion reliably detect incipient MTC and may be used to select those MMN patients requiring thyroid surgery. Recognition of patients with the MMN syndrome and subsequent calcitonin screening and early surgical intervention will significantly reduce the chance of their developing terminal MTC. All MMN patients with mucosal neuromas or intestinal neurogangliomas should have such evaluations at least yearly. Relatives who are at risk for inheriting this dominant disease should be similarly evaluated, regardless of their normal appearance.     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

Interstitial radiation therapy for hepatic metastases: sonographic guidance for applicator placement

A new technique is reported for the treatment of hepatic metastases using sonography-directed percutaneous placement of a 14-gauge needle applicator and a high-intensity "remote afterloading" iridium-192 (Ir-192) source for interstitial radiation therapy. The results with six patients show that the procedure is easily performed, patient tolerance is good, and there is minimal disruption of the patient's lifestyle. Hospitalizations have been less than 24 hr. Partial response or stable disease in the liver was observed in all six patients. Tumoricidal doses up to 5000 rad (cGy) in a single treatment with durations from 7 to 41 min were achieved in small volumes (less than 25 cm3) with no clinically significant toxicity on follow-up evaluations from 2-6 months. The technique appears to ablate discrete metastatic tumor deposits in the liver.     

Crystalluria in marathon runners

Summary Epidemiological evidence suggests that marathon runners have a higher incidence of renal stone formation than occurs in the general population. Since crystalluria and stone disease are thought to be related, we subjected urine samples from a group of marathon runners to particle counting and sizing in a Coulter Counter equipped with a population accessory unit. The volume-size distribution curves so obtained were bimodal with one peak occurring in the 2–5 m diameter range and a second in the 15–32 m diameter range—a pattern that is remarkably similar to the distributions reported for recurrent idiopathic stone formers and distinctly different to those recorded for control subjects. Analyses by scanning electron microscopy and X-ray powder diffraction revealed other features which are regarded as typical of stone formers' crystalluria. These physicochemical data indicate that marathon runners may be at increased risk of urinary stone formation.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

An ethological analysis of the effects of chlordiazepoxide and bretazenil (Ro 16-6028) in the murine elevated plus-maze

The effects of chlordiazepoxide (2.5-15.0mg/kg), a full benzodiazepine receptor agonist, and bretazenil (5.0-30.0mg/kg), a partial benzodiazepine receptor agonist, were examined in the murine elevated plus-maze paradigm. Behaviours recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. Results show that chlordiazepoxide (10-15mg/kg) and bretazenil (5-30mg/kg) not only decreased traditional indices of anxiety but also reduced risk assessment behaviours such as head-dipping and stretch attend postures from secure areas of the maze. Both compounds produced these effects without adversely affecting general activity levels. While traditional indices of anxiety did not clearly discriminate between the two compounds, some differences were apparent on the ethological measures. The dose-response curves for bretazenil were generally shallower than those for chlordiazepoxide, confirming its partial agonist profile. Together, these data support the view that benzodiazepine receptor partial agonists may have utility in the management of human anxiety disorders.     

Perceptions of practice problems encountered by family physicians, pediatricians, and orthopedic surgeons

Information about physicians' practice problems was solicited through a structured questionnaire mailed to a group of family physicians, pediatricians, and orthopedic surgeons. Overall, a lack of personal time was the major concern across the three groups of physicians. Comparisons among the three types of physicians revealed two patterns: Family physicians reported more concerns in the "interpersonal" dimension, whereas orthopedic surgeons had more concerns in the "legal-economic" dimension. These patterns of differences persisted with two variables controlled: gender and time period in which they completed their residency program. These findings indicate that physicians' concerns in their practice vary among the specialties, and they imply that the changed economy and reimbursement system might have more impact on one than the other. Thus the effectiveness of residency training and continuing education might be improved by emphasizing the specialty-related problems in practice.