Pseudosickling of hemoglobin Setif

Hemoglobin Setif produces pseudosickling of red cells in vitro; the nature of the process and the conditions that "trigger" it are unknown. Studies of red cells, hemolysates, purified hemoglobin solutions, and artificial mixtures of Hb A and Setif suggest that pseudosickling is produced by intracellular crystallization of insoluble hemoglobin. Increased tonicity of the suspending medium accentuates the process, probably by causing a rise in intracellular hemoglobin concentration. If precipitates from A/Setif mixtures are analyzed, they always contain Hb A, suggesting an unusual mechanism for the process. Despite the fact that osmolality in the renal medulla is similar to that which produces pseudosickling in vitro, carriers do not have renal dysfunction of the type found in patients with sickle cell disease.     

The Development of a Predictive Method for the Estimation of Flux Through Polydimethylsiloxane Membranes. IV. Application to a Series of Substituted Quinolines

The steady-state flux of 33 substituted quinoline derivatives was determined in polydimethylsiloxane membranes using isopropyl alcohol as the receiver solvent. These diffusants constituted a diverse group of compounds possessing a wide range of hydrophobic, steric, and electronic characteristics. Various parameters representing these physicochemical properties such as cyclohexane–water fragmental constants, molar refractivity, Hammett's constants, intramolecular hydrogen bonding ability, melting point, and mole fraction solubility were employed to develop empirical models capable of relating the rate of diffusion to these characteristics of either the substituent on the quinoline ring or the compound itself.     

Complement activation mediates intestinal injury after resuscitation from hemorrhagic shock

BACKGROUND: Endothelial cell injury after hemorrhage and resuscitation (HEM/RES) might contribute to intestinal hypoperfusion and mucosal ischemia. Our recent work suggests that the injury might be the result of complement activation. We hypothesized that HEM/RES causes complement-mediated endothelial cell dysfunction in the small intestine. METHODS: Male Sprague-Dawley rats (195-230 g) were anesthetized and HEM to 50% of baseline mean arterial pressure for 60 minutes. Just before RES, animals received either soluble complement receptor-1 (sCR1, 15 mg/kg) to inhibit complement activation or saline vehicle. Resuscitation was with shed blood and an equal volume of saline. Two hours after RES, the small bowel was harvested to evaluate intestinal nitric oxide synthase activity (NOS), neutrophil influx, histology, and oxidant injury. RESULTS: HEM/RES induced tissue injury, increased neutrophil influx, and reduced NOS activity by 50% (vs. SHAM), all of which were completely prevented by sCR1 administration. There were no observed differences in oxidant injury between the groups. CONCLUSION: Histologic tissue injury, increased neutrophil influx, and impaired NOS activity after HEM/RES were all prevented by complement inhibition. Direct oxidant injury did not seem to be a major contributor to these alterations. Complement inhibition after HEM might ameliorate reperfusion injury in the small intestine by protecting the endothelial cell, reducing neutrophil influx and preserving NOS function.     

Effect of instructions on isokinetic trunk strength testing variability, reliability, absolute value, and predictive validity.

Although isokinetic strength testing has been in use for more than two decades, and numerous studies have addressed isokinetic performance of the lumbar spine, the effect of instructions on isokinetic trunk strength has not been studied. In a sample of 30 healthy women, this study examined the effect of "high-demand" instructions on lumbar strength performance. High-demand instructions were found to have a substantial positive effect on performance variability, reliability, absolute magnitude, and validity. Under these conditions, isokinetic trunk strength was found to be predictive of performance in a frequent lifting-lowering task.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation

BACKGROUND: Altered intestinal blood flow during systemic inflammation leads to organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We hypothesized that separate mechanisms are active in the large resistance and small mucosal microvessels to account for this dichotomy. METHODS: Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours after a single inoculation of bacterium or 24 hours after a second inoculation (ie, 72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10(-9) to 10(-5) mol/L) in resistance (A(1)) and premucosal (A(3)) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from dose response curves for each animal. RESULTS: Vasodilator sensitivity to acetylcholine in A(1) arterioles was significantly decreased at 24 hours, and these changes persisted up to 72 hours after a single bacterial inoculation. There was no change in the dilator sensitivity of A(3) arterioles after a single inoculation. When there was a challenge with a second bacterial inoculation, there was a reversal of the A(1) dilator response and an increase in A(3) sensitivity. CONCLUSIONS: An initial septic event results in a decrease in dilator reactivity in the resistance A1 arterioles that persists for at least 72 hours. A sustained septic challenge results in increased dilator reactivity in both A(1) and A(3) vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic approach to preservation of intestinal blood flow will be necessary.     

Screening for complement deficiency in bacterial meningitis

Seventy-seven children with bacterial meningitis were screened for complement deficiency. Both the classical and the alternate pathways were normal in 75 patients. Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis. Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway.