Polyvinylidene fluoride monofilament sutures: can they be used safely for long-term anastomoses in the thoracic aorta?

Polyvinylidene fluoride (PVDF) represents an attractive alternative to polypropylene as a monofilament vascular suture because of its satisfactory physicochemical properties, it ease of handling, and its good biocompatibility. However, the polymer's ability to remain mechanically and chemically stable when exposed to a mild hydrolytic environment over the long term has yet to be demonstrated. One in vitro study involved the comparison of the long-term relative resistance of PVDF and polypropylene sutures to hydrolysis for a period of 9 years. The PVDF suture showed major molecular rearrangements from the original ratio of three crystalline structures to the single beta crystalline phase. The observation of some surface oxidation and water inhibition did not significantly modify the tensile strength of the PVDF suture, which retained 92.5% of its original value. In contrast, the polypropylene sample did not undergo any recrystallization but was associated with more oxidation byproducts and more water molecules near the surface, which contributed to a 46.6% loss in initial tensile strength. An in vivo study confirmed that PVDF sutures are biocompatible and are able to maintain satisfactory biostability when used to anastomose thoracic aortic allografts for a period of 6 months in the dog. The cellular reaction of fresh allografts as well as the control autografts to PVDF sutures was minimal. In other allografts that had been preserved in a supplemented medium for 1 week prior to implantation, the PVDF sutures healed satisfactorily with the formation of neocollagen and few macrophages surrounding the monofilament. No evidence of instability at the allograft-host artery junction was observed, confirming that the PVDF sutures were able to ensure a secure anastomosis in the thoracic aorta. PVDF sutures have demonstrated superior long-term biostability in vitro and minimal tissue response in vivo. These are two essential requirements when evaluating the use of a suture for vascular surgery in general and thoracic aortic surgery in particular.     

Raloxifene and estrogen: comparative bone-remodeling kinetics

The pattern of changes in human bone remodeling produced by raloxifene (60 mg/day) was compared to that of estrogen (given as hormone replacement therapy) in 33 early postmenopausal women randomly assigned to raloxifene, estrogen, or no treatment. Remodeling was measured using calcium tracer kinetic methods employed under a constant diet and full metabolic balance conditions. Studies were performed at baseline and, to detect both early and late remodeling changes, at 4 and 31 weeks of treatment. Both raloxifene and estrogen produced a significant positive calcium balance shift at each treatment measurement point: +74 and +60 mg/day at 4 weeks, and +60 and +91 mg/day at 31 weeks for raloxifene and estrogen, respectively. Externally, this balance change was due to a highly significant fall in the urinary calcium level and marginal improvement in calcium absorption efficiency. Internally, bone resorption was significantly reduced at both measurement points: -64 and -60 mg/day at 4 weeks, and -82 and -162 mg/day at 31 weeks for raloxifene and estrogen, respectively. Bone formation was not significantly affected by either agent at 4 weeks; at 31 weeks, formation was reduced by estrogen, but not by raloxifene. Thus, at 4 weeks, the general pattern of remodeling change was identical for the two agents. At 31 weeks, remodeling suppression was greater for estrogen than for raloxifene; however, remodeling balance was the same for the two agents. We conclude that raloxifene and estrogen affect the bone remodeling apparatus similarly, and that raloxifene, therefore, is acting on bone as an estrogen agonist.     

RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.     

Unfolding mechanism of rubredoxin from Pyrococcus furiosus

As part of our studies on the structural and dynamic properties of hyperthermostable proteins, we have investigated the unfolding pathways of the small iron-sulfur protein rubredoxin from Pyrococcus furiosus (RdPf) at pH 2. Unfolding has been initiated by temperature jump, triggered by manual mixing of a concentrated protein solution into a thermally preequilibrated buffer. The process has been followed in real time by absorption, tryptophan fluorescence emission, and far-UV circular dichroism. Unlike the case of the mesophilic rubredoxin from Clostridium pasteurianum (RdCp), RdPf displays a complex unfolding kinetics, pointing to the formation of at least three intermediates. All of the steps, including the one involving metal ion release, are extremely slow. However, hydrophobic core relaxation--not Fe3+ loss--is rate-determining for RdPf unfolding. This clearly rules out the fact that Fe3+ is solely responsible for the kinetic stability of RdPf. Results have been discussed in terms of sequential vs parallel pathways, and the possible role of irreversible phenomena has been taken into consideration. Aggregation does not appear to play a significant role in the observed kinetic complexities. According to a proposed sequential mechanism, partial release of secondary structure elements precedes iron loss, which is then followed by further loss of beta-sheet content and, finally, by hydrophobic relaxation. Although the main features of the RdPf unfolding mechanism remain substantially unchanged over the experimentally accessible temperature range, final hydrophobic relaxation gets faster, relative to the other events, as the temperature is decreased. A qualitative assessment of the unfolding activation parameters suggests that this arises from the very low activation energies (Ea) that characterize this step.     

Persistence of porcine reproductive and respiratory syndrome virus in intensive farrow-to-finish pig herds

We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal subjects to determine the relationship between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size. We examined (1) the root mean square voltage (RMS10-40, microV), (2) the integration (A10-40, microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05) were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was significantly longer in patients with anterior RMI patients than in patients with inferior RMI. The A30 was correlated with the ejection fraction and total creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively, p < 0.001). These results suggest that the A30 may be an important predictor of ventricular dysfunction and infarct size in patients with RMI.     

Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids

The purpose of this study was to analyze our results of surgical treatment of arthrogryposis of the elbow and to compare our tendon transfer results using range of motion (ROM) criteria versus functional use criteria. Eighteen tendon transfers for elbow flexion in 14 children with arthrogryposis with an average follow-up period of 4 years (range, 1-14 years) and 6 elbow capsulotomies with triceps lengthening in 6 children with arthrogryposis with an average follow-up period of 5 years (range, 2-9 years) were evaluated. Each child was assessed by a questionnaire regarding functional use of the upper extremity, physical examination of ROM and strength, and a videotaped activities of daily living evaluation. Tendon transfer results were classified and compared using 2 methods of evaluation: postoperative strength and ROM and effective functional use of the tendon transfer to perform activities of daily living. The 6 elbow capsulotomies improved from an average preoperative arc of 17 degrees of motion (average extension, -2 degrees; average flexion, 19 degrees) to an average final follow-up arc of 67 degrees (average extension, -25 degrees; average flexion, 92 degrees). The 18 tendon transfers evaluated by strength and ROM criteria showed 9 triceps to biceps transfers in 9 arms (7 good, 1 fair, and 1 poor), 5 pectoralis to biceps transfers in 4 arms (1 good, 3 fair, and 1 poor), and 4 latissimus dorsi to biceps transfers in 3 arms (2 good and 2 fair). Evaluation by functional use criteria gave the same result in 13 transfers and downgraded the result in 5; the downgraded results were due to resultant flexion contracture or limited functional use because the transfer was in the nondominant arm. Based on this review, optimal surgical candidates for tendon transfer are children older than 4 years, who have full passive ROM of the elbow in the dominant arm, and at least grade 4 strength of the muscle to be transferred.