Dysbaric osteonecrosis in divers and caisson workers. An animal model

Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.     

Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumors

Specimens from 25 consecutive patients undergoing lung resection for peripheral carcinoid tumor were examined for evidence of neuroendocrine cell hyperplasia and associated obliterative bronchiolitis. Where available, the CT scans (n = 11) were reviewed for evidence of multiple tumors, and pulmonary function data (n = 16) were reviewed for evidence of airflow obstruction. Nineteen of the 25 patients (76%) had neuroendocrine cell hyperplasia in addition to the dominant carcinoid tumor. Eight patients (32%) had lesions of obliterative bronchiolitis associated with foci of neuroendocrine cell hyperplasia, and two of these patients had asymptomatic airflow obstruction that could not be related to smoking or other lung disease. We conclude that multicentric neuroendocrine cell proliferation is common in patients with peripheral carcinoid tumor of the lung. Associated bronchiolar fibrosis occurs in a high proportion of such patients, but it is usually asymptomatic.     

Interaction versus independence of startle-modification processes in the rat

The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.     

Hepatitis B surface antigen carrier state in neonates. Prophylaxis with large doses of conventional immune human serum globulin

Acute type B viral hepatitis developed near the term of pregnancy in seven women. All had signs of acute hepatitis at delivery, and hepatitis B surface antigenemia persisted two to four weeks after delivery. Two milliliters of conventional immune human serum globulin was administered to the neonates within a week of birth, after preexisting type B viral hepatitis infection was excluded. The antibody against hepatitis B surface antigen (anti-HBs) content of two of the administered batches of immune human serum globulin was 1:32 and 1:64. None of the babies became hepatitis B surface antigen carriers, and anti-HBs developed without obvious clinical hepatitis in one baby. Conventional immune human serum globulin in larger doses may be a relatively safe and effective prophylaxis against the development of hepatitis B surface antigen carrier state even if the anti-HBs content in the administered dose is relatively small.     

Cytochalasin B inhibits actin-related gelation of HeLa cell extracts

When the 100,000 g supernatant fraction (extract) of HeLa cells lysed in a buffer containing sucrose, ATP, DTE, EGTA, imidazole, and Triton X-100 is incubated at 25 degrees C, it gels, and actin and a HMWP are progressively enriched in the extract and in gel isolated from extract. CB (greater than or equal to 0.25 muM) inhibits gelation and specifically lowers the concentrations of actin and the HMWP in the fraction which sediments at 100,000 g after incubation. These results indicate that actin and HMWP are partly disaggregated by cytochalasin treatment, and thus that their aggregation is related gelation. Inasmuch as previous results showed that actin is present and HMWP is enriched in the plasma membrane fraction of HeLa cells, the results also point to a possible relation between plasma membrane-associated gel and in vivo effects of CB.     

Chemotactic and bactericidal capacities of human newborn monocytes

We evaluated the chemotactic and bactericidal capacities of human cord blood monocytes, and the ability of cord lymphocytes and sera to generate chemotactic (LDCF) and opsonic factors for monocytes. Our results suggest that the intrinsic locomotive capacity, and the receptor system for LDCF, are adequately developed in the newborn monocyte. Moreover, newborn lymphocytes appear to produce adequate amounts of LDCF, capable of attracting adult monocytes. Poor chemotaxis was observed only when cord monocytes were exposed to supernatants of cord lymphocytes, which suggests that both contribute to this abnormal response. An inhibitory factor for which only cord monosensitivity of monocytes and strength of chemotactic factor between adults and newborns would explain these results. Bactericidal capactiy of cord monocytes against Escherichia coli K-12 opsonized by either cord or adult serum was comparable to that of adult monocytes.     

Cholinergic sites in skeletal muscle. II. Interaction of an agonist and two antagonists with the acetylcholine site

The equilibrium interactions of alpha-bungarotoxin, d-tubocurarine, and carbamylcholine with junctional and extrajunctional skeletal muscle acetylcholine receptors were examined. d-Tubocurarine is a competitive inhibitor of the bindings of alpha-bungarotoxin to the acetylcholine receptor. No substantive difference was observed in the association of d-tubocurarine with the junctional and extrajunctional receptors. In contrast, the carbamylcholine inhibition of toxin binding is not competitive. The data indicate that either the single set of alpha-bungarotoxin and d-tubocurarine bindings sites contains two subsets of carbamylcholine sites or that the carbamylcholine binds in a cooperative manner to a single set of sites. In addition, the affinity of carbamylcholine for extrajunctional receptors may be higher than the affinity for junctional receptors.     

Femorotibial bypass in the elderly for revascularization of the severely ischemic lower extremity

In the elderly, revascularization of a severely ischemic lower extremity with occlusion of both femoral and popliteal arteries often can be achieved by surgical construction of a distal bypass to the tibial or peroneal arteries. An aggressive diagnostic and therapeutic approach is necessary, in an attempt to prevent recourse to primary amputation. Femoroperoneal or femorotibial bypass can be performed safely and is recommended in elderly patients with advanced ischemia of a lower extremity with absolute indications for surgical intervention, e.g., gangrene, gangrenous ulceration or rest pain. A significant number of limbs can be salvaged by this method. Although the mortality rate in the older age groups is predictably higher, the overall rate for this operation compares favorably with that for primary amputation.