Fixation of osteotomies using bioabsorbable screws in the canine femur

The purpose of this study was to compare the healing properties of femoral osteotomies fixed by bioabsorbable screws (20:80 polyglycolic copolylactic acid copolymer) to standard stainless steel screws of a similar design in a dog femoral model. Two osteotomies were used, the trephine osteotomy (10 mm diameter) in the metaphyseal lateral femoral condyle and in the femoral diaphysis, and a unilateral osteotomy in the lateral femoral condyle. Two months after the trephine osteotomies, the femurs that contained the polymer screws were not significantly different in mechanical strength from the femurs treated with the stainless steel screws, either in the diaphyseal or metaphyseal model. There was no histological difference in bone healing between the metallic and polymer screws for all periods (2, 9, and 17 months). There was no adverse inflammatory response to the polymeric or metallic screws. By month 17, the polymer screws were resorbed completely. All the diaphyseal screw tracks had healed with bone and areas of remodeling were evident in two specimens. For the femoral condyle osteotomy model at 2 months, the polymer screws were present and intact, and all osteotomies healed with no evidence of inflammation. By 9 months, only one specimen had polymeric material left in the screw track. At 15 months, the screw tracks still were present but no evidence of any polymer remained. The tracks were filled with fibrous and adipose connective tissue. All osteotomies stabilized with either bioabsorbable polymer screws or stainless steel screws did heal satisfactorily without any complications, inflammation, or osteolysis. The polyglycolic polylactic acid copolymer may have a clinical role as a bioabsorbable material without the concerns for the osteolysis, foreign body reaction, and sterile abscess formation that have occurred with bioabsorbable fixation methods in the past.     

Comparative rates of androgen production and metabolism in Caucasian and Chinese subjects

Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5 alpha-reductase activity with a resultant decrease in prostate tissue dihydrotestosterone levels and clinically apparent prostate cancer. An alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide and androsterone glucuronide levels might reflect reduced production of androgenic ketosteroid precursors as a result of genetic or environmental factors. The present study examined 5 alpha-reductase activity, androgenic ketosteroid precursors, and the influence of genetic and environmental/dietary factors in groups of Chinese and Caucasian men. We found no significant differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China, and Caucasians living in Pennsylvania. To enhance the sensitivity of detection, we used an isotopic kinetic method to directly measure 5 alpha-reductase activity and found no difference in testosterone to dihydrotestosterone conversion ratios between groups. Then, addressing the alternative hypothesis, we found that the Caucasian subjects excreted significantly higher levels of individual and total androgenic ketosteroids than did their Chinese counterparts. To distinguish genetic from environmental/dietary factors as a cause of these differences, we compared Chinese men living in Pennsylvania and a similar group living in Beijing, China. We detected a reduction in testosterone production rates and total plasma testosterone and sex hormone-binding levels, but not in testosterone MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing Pennsylvania Chinese with their Caucasian counterparts, we detected no significant differences in total testosterone, free and weakly bound testosterone, sex hormone-binding globulin levels, and testosterone production rates. Taken together, these studies suggest that environmental/dietary, but not genetic, factors influence androgen production and explain the differences between Caucasian and Chinese men.     

The effects of 5-HT1A receptor agonists, 5-HT1A receptor antagonists and their interaction on the fear-potentiated startle response

Time-resolved small-angle X-ray scattering (TR-SAXS) was used to monitor the structural changes that occur upon the binding of the natural substrates to a mutant version of the allosteric enzyme aspartate transcarbamoylase from Escherichia coli, in which the creation of a critical link stabilizing the R state of the enzyme is hindered. Previously, SAXS experiments at equilibrium showed that the structures of the unligated mutant enzyme and the mutant enzyme saturated with a bisubstrate analog are indistinguishable from the T and R state structures, respectively, of the wild-type enzyme (Tauc et al., Protein Sci. 3:1998-2004, 1994). However, as opposed to the wild-type enzyme, the combination of one substrate, carbamoyl phosphate, and succinate, an analog of aspartate, did not convert the mutant enzyme into the R state. By using TR-SAXS we have been able to study the transient steady-state during catalysis using the natural substrates rather than the nonreactive substrate analogs. The steady-state in the presence of saturating amount of substrates is a mixture of 60% T and 40% R structures, which is further converted entirely to R in the additional presence of ATP. These results provide a structural explanation for the reduced cooperativity observed with the mutant enzyme as well as for the stimulation by ATP at saturating concentrations of substrates. They also illustrate the crucial role played by domain motions and quaternary-structure changes for both the homotropic and heterotropic aspects of allostery.     

Kinins and thrombolysis

The effect of sho-saiko-to on the concentration of acid soluble glycoprotein in serum and on the granuloma formation in carrageenin cotton pellet-induced rats was investigated. As a result, a significant negative correlation between the concentration of acid soluble glycoprotein and granuloma weight was observed. Furthermore, both the concentration of acid soluble glycoprotein and the inhibition rate of the granuloma formation were significantly higher in the sho-saiko-to group than in the control group. These results suggest that acid soluble glycoprotein plays an important role in promoting the anti-inflammatory effect of sho-saiko-to.     

Role of neutrophil-endothelial cell adhesion in inflammatory disorders

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.     

Doctors who perform operations. A study on in-hospital surgery in four diverse geographic areas (second of two parts)

To facilitate manpower planning in the surgical field, a study was c onducted into the work loads of surgeons in various specialities in 4 different geographical areas. Surgeons in group practice and surgeons who were Board-certified specialists carried a statistically significant larger work load of surgery. The certified surgeons performed more and more complex operations. The mean operative work load increased steeply with age, reaching a maximum at 40-44 years, and fell linearly after that age. Approximately 18 years following medical school graduation were needed for a surgeon to achieve his maximum work load. The geographic factor had no appreciable effect on work loads. Tables which broke down frequencies for each major type of operation for each type of surgical specialist indicated that even commonplace operations were not frequent events on the average for any individual surgeon. It is concluded from the study that work loads are relatively low due to excessive supply of surgeons. This is of concern because there is some doubt about maintenance of surgical skills by those doctors who perform infrequent operations. The widest variation in practice was evident between ophthalmologists and thoracic surgeons, indicating that manpower planning in this field would have to be done on a specialty-by-specialty basis. 3 plans for redistributing the operative work load and reducing the number of specialist surgeons are considered.