The Outcome of Monochorionic Diamniotic Twins Discordant at 11 to 13+6 Weeks' Gestation.

BACKGROUND: Monochorionic diamniotic (MCDA) twin pregnancies are associated with adverse perinatal outcome. Intertwin discordances at the time of nuchal translucency (NT) screening may have a value in the prediction of fetal loss or twin-to-twin transfusion syndrome. We aimed to determine the ability of intertwin NT and crown rump length (CRL) discordances among MCDA twins to predict adverse outcomes. MATERIAL AND METHODS: All MCDA twins with a documented routine ultrasound at 11 to 13+6 weeks' gestation, and known pregnancy outcome between August 2003 and August 2012 were included. Receiver operating characteristic curves were used to determine the ideal NT and CRL discordances cut-off points that maximized the ability to predict adverse outcome, which was defined as any of: death of one or both twins, twin-to-twin transfusion syndrome, or estimated fetal weight or birth weight discordances ≥25%. RESULTS: Of the 89 cases, 20 (22.5%) had at least one adverse outcome. NT discordance was more discriminatory of adverse outcome than was CRL discordance. The optimal values for predicting any adverse outcomes for NT were >23.7% and for CRL >3.5%. The positive predictive values for NT (52.4%) and CRL (29.8%) screening were relatively low; however, the lack of either NT or CRL discordances was more reassuring, with negative predictive values of 86.8% and 86.4%, respectively. CONCLUSIONS: NT discordance is more predictive for adverse fetal outcome in MCDA twins than CRL discordance. Neither NT nor CRL discordance are likely to modify the intensive monitoring required for these very high-risk pregnancies.

Comparative molecular analysis of ovine and bovine Streptococcus uberis isolates.

Streptococcus uberis causes clinical and subclinical mastitis in cattle and sheep, but it is unknown whether the composition of Strep. uberis populations differs between host species. To address this, we characterized a collection of bovine and ovine Strep. uberis isolates with shared geographical and temporal origins by means of an expanded multilocus sequence typing scheme. Among 14 ovine and 35 bovine isolates, 35 allelic profiles were detected. Each allelic profile was associated with a single host species and all but one were new to the multilocus sequence typing database. The median number of new alleles per isolate was higher for ovine isolates than for bovine isolates. None of the ovine isolates belonged to the global clonal complexes 5 or 143, which are commonly associated with bovine mastitis and which have a wide geographical distribution. Ovine isolates also differed from bovine isolates in carriage of plasminogen activator genes, with significantly higher prevalence of pauB in ovine isolates. Isolates that were negative for yqiL, one of the targets of multilocus sequence typing, were found among ovine and bovine isolates and were not associated with a specific sequence type or global clonal complex. One bovine isolate carried a gapC allele that was probably acquired through lateral gene transfer, most likely from Streptococcus salivarius. We conclude that ovine isolates are distinct from bovine isolates of Strep. uberis, and that recombination between isolates from different host species or bacterial species could contribute to changes in virulence gene profiles with relevance for vaccine development.

An evaluation using techniques to assess muscle and nerve regeneration of a flexible glass wrap in the repair of peripheral nerves.

In this study a flexible biodegradable wrap is compared with microsurgical epineurial suturing in the repair of cleanly divided peripheral nerves. Five groups of twelve sheep were used; one control group and four neurotmesis and repair groups. The four repair groups were; (1) Epineurial suture repair using a microscope and 9/0 polyamide; (2) Wrap secured by Tisseel glue; (3) Wrap secured by polycaprolactone glue; (4) Wrap secured by suturing. Regeneration of the median nerve was assessed by electromyography, nerve conduction studies, wet muscle mass measurements, and morphometry. The results suggested that nerve regeneration in the wrap+Tisseel glue group was as good as that in the epineurial repair group. The use of polycaprolactone glue is not recommended in nerve repair. Placement of the wrap was easy to learn and quick to carry out under direct vision. The wrap used in this study could prove to be a useful alternative to epineurial suturing to repair peripheral nerves and may have a particularly unique role in the developing world and battlefield.

Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer.

PURPOSE: Enhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated. PATIENTS AND METHODS: FUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN-a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography. RESULTS: The maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose-limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +/- 0.35 mumol/L to 1.85 +/- 0.48 mumol/L), elimination half-life (t1/2; mean, 9.7 +/- 4.3 minutes), area under the concentration-versus-time curve (AUC; range, 93 to 224 mumol/L x hours), total-body clearance (CI; range, 1,172 to 3,236 mL/min), or volume of distribution (range, 11.9 to 49.2 L) of FUra. Intrapatient data evaluation revealed a dose-independent effect of rIFN-a. The mean FUra Css after rIFN-a administration (1.31 mumol/L) was greater than that before rIFN-a administration (1.02 mumol/L, P < .0001). FUra Cl after rIFN-a administration was reduced by 20% to 35% compared with use of FUra alone (P < .0001). Patients with a greater than 20% decrease in FUra Cl had a fourfold greater incidence of diarrhea. CONCLUSION: rIFN-a reduces FUra Cl and, consequently, increases FUra-associated toxicity. Phase II studies of FUra and rIFN-a seem to be warranted.

Sorbsan calcium alginate fibre dressings in footcare.

This report outlines the successful application of Sorbsan-calcium alginate fibre dressings in footcare. This biomaterial has been found in clinical trials to have quite outstanding merit and can be used for sinus drainage and in the treatment of fissures, hypergranulation tissue, interdigital maceration, heloma molle and other lesions. Sorbsan bonds with and aids natural healing scabs and effects drainage of moist sites thus assisting in creating an environment conducive to the healing process. Similar promise has been demonstrated for this material in ongoing trials in hospitals in Sunderland where Sorbsan has been used effectively in the treatment of diabetic and trophic ulcers.

Wound treatment with Sorbsan--an alginate fibre dressing.

This highly absorbent, biodegradable dressing derived from seaweed can be successfully applied to cleanse a wide variety of secreting lesions. The high absorption of exudate is achieved via strong hydrophilic gel formation and this serves to control wound secretion levels and to minimize bacterial contamination. Alginate fibres trapped in a wound are readily biodegraded and do not have to be removed thus avoiding disturbance of granulation tissue formation. Additional features are odour remission, conformability and ready removal of tissue adherent material.

Controlled silver-releasing polymers and their potential for urinary tract infection control.

Calcium phosphate controlled release glass has been developed as a biocompatible vehicle for the sustained delivery of antibacterial silver ions. The solution rate in the presence of physiological fluids can be made constant over the design life of the product and one application in urinary tract infection control is outlined.

The metabolism of 16-fluoroestradiols in vivo: chemical strategies for restricting the oxidative biotransformations of an estrogen-receptor imaging agent.

16 alpha-Fluoro-17 beta-, 16 alpha-fluoro-17 alpha-, and 16 beta-fluoro-17 beta-[6,7-3H]estradiol were prepared from [6,7-3H]estrone via fluorination of 3,17-bis(tert-butyldimethylsilyloxy)-[6,7-3H]estratetraene with N-fluoropyridinium triflate and reduction of 16 alpha/beta-fluoro[6,7-3H]estrone with NaBH4. The three isomers were separated by silica-phase high-performance liquid chromatography. They were administered intravenously (4 mumol/kg to anaesthetized male rats. Their biliary metabolites (90-97% of dose over 6 h) were characterized by high performance liquid chromatography-mass spectrometry and compared with those of [6,7-3H]17 beta-estradiol. The four estrogens and their hydroxylated and methoxylated metabolites were excreted as glucuronides. C-16 fluorination blocked C-16 hydroxylated and also the dehydrogenation of the C-17 hydroxyl group. The 16 alpha-17 beta isomer was extensively glucuronylated at C(O)3 but also underwent aromatic hydroxylation and methoxylation before conjugation. Its C-17 epimer was subject to much greater aromatic hydroxylation but the catecholestrogen was O-methylated to a greater relative extent. The 16 beta-17 beta derivative underwent alicyclic as well as substantial aromatic hydroxylation and yielded numerous isomeric glucuronides of O-methylated catechols. Thus, the fluorine exerted complex effects (inhibitory and enhancing) on both localized (D-ring) and distal (A-ring) biotransformations of the estradiol molecule; the direction and magnitude of the effects being dependent upon the stereochemistry at C-16 and C-17. These findings provide structural guidelines for restricting the metabolism of tumor-imaging fluoroestrogens and thereby enhancing their delivery to the target tissue.

Synthesis and physicochemical properties of the furan dicarboxylic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, an inhibitor of plasma protein binding in uraemia.

The furan dicarboxylic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-propyl FPA) accumulates in the plasma of patients with chronic renal failure and is a major contributor to the drug binding defect of uraemic plasma. This acid has also been implicated in several other aspects of the uraemic syndrome: anaemia, irregularities of thyroid function, neurological symptoms and inhibition of active tubular secretion. The acid is not commercially available and its synthesis, starting with Meldrum's acid and methyl succinyl chloride, is described. The pKa values were measured by titration and values of 3.2 and 3.6 respectively were assigned to the carboxylic acid groups attached directly to the ring at position 3 and at position 2 (on the side-chain). The partition coefficient (log P) between hydrochloric acid and octanol was 1.2 and the distribution coefficient (log D; octanol-phosphate buffer pH 7.4) was -0.59. The pKa values and the degree of hydrophobic character of 5-propyl FPA are consistent with those of other protein-bound acids which undergo active tubular secretion by the kidney and this substance may serve as an endogenous marker for the effects of drugs and disease on this process.

Homicide in Alabama: an analysis of urban, suburban and rural murders in the Deep South.

Eleven hundred forty-four (1144) homicides occurring in Alabama, U.S.A. during a 2-year period are presented and analyzed according to the demographic parameters of the victims, location in urban, suburban, or rural community, type of homicide based on a medical examiner's classification, presence of drugs, weapon employed and other factors. Urban dwellers, Blacks and males are found to be at high risk. Alcohol is much more prevalent than other drugs in homicide victims. Although the handgun is the weapon most commonly used throughout the state, in the rural regions the longgun is used almost as often. The difficulty of making valid comparisons with other homicide studies is discussed and the establishment of a uniform classification of homicides urged.

Activated carbon for haemoperfusion.

Some features of activated carbon are consisted and the grades of the adsorbent used in haemoperfusion are examined. Aspects of the activation process and the properties of the resultant carbons are discussed.

Biodegradable controlled release glass in the repair of peripheral nerve injuries.

The experiments in this paper were concerned with the recovery of function and ease of application of an entubulation technique using a biodegradable, controlled release glass tube (CRG) for the repair of a transected peripheral nerve. The peroneal nerves of 15 New Zealand White rabbits were repaired with either a CRG tube filled with freeze-thawed muscle, or a conventional freeze thawed muscle graft (FTMG). These were compared with controls in which a CRG was used to enclose the cut ends of a nerve separated by a 1 cm gap. Electrophysiological and morphometric assessment was carried out 6 months after repair. No statistical difference was found in any test between the FTMG and the CRG tube filled with freeze thawed muscle. The CRG tube and 1 cm gap produced inferior levels of recovery of function when compared with the other two repair groups.

Peripheral nerve repair by means of a flexible biodegradable glass fibre wrap: a comparison with microsurgical epineurial repair.

In this study, a new technique for the repair of divided peripheral nerves using a flexible controlled-release glass wrap is described and its successful use is reported. Corglaes is a biodegradable and biocompatible glass which, when used as a solid glass tube form as a nerve conduit, allows nerve regeneration. It is now produced as a flexible, porous wrap (CRG-wrap). In this study, the CRG-wrap was used to repair divided median nerves in the upper forelimb of sheep. The wrap was secured in place around the divided nerve ends using fibrin glue or 6/0 polyglactin sutures. Microsurgical epineurial suturing was used to repair the same injury in another group. Twelve sheep were used in each group. A control group of sheep, on which no operations had been carried out, was also examined. The outcome of each repair was assessed at 7 months by measuring transcutaneous stimulated jitter (TSJ), maximum conduction velocity (CVmax), wet muscle mass and morphometric measurements. Testing was carried out on the limb that had been operated upon and the normal contralateral forelimb. The ratio of the measurements taken in the operated and the normal limb (the right and left forelimbs in the control group) was used when carrying out statistical analyses on the results. The mean and variance of the ratios of each of the measured variables in the three repair groups were similar suggesting that nerve regeneration had occurred to a similar degree in all the repair groups (analyses were carried out using one-way ANOVA and Scheffé's test, with statistical significance assumed at p<0.05). The repair of peripheral nerves using the CRG-wrap is easy to learn, quicker and cheaper than microsurgical epineurial suturing, and can be carried out by any surgeon with basic surgical skills. It was concluded that CRG-wrap is a useful alternative to microsurgical epineurial suturing for the repair of peripheral nerves.

Reflections on the role of carbon haemoadsorption in therapeutic medicine.

The selection of Norit RBX-1-activated carbon granules for blood detoxification by haemoadsorption is outlined. Synthetic polymer membranes have been coated on to this carbon by a specially developed process and perfusion devices prepared from these materials have been evaluated in animal models of acute poisoning and liver failure. Clinical application of carbon haemoadsorption has been explored in acute poisoning, liver failure and uraemia. The experience to date would suggest that carbon will have to be augmented by other adsorbent species before life support systems based principally on haemoadsorption become a reality especially in the treatment of uraemia and in liver failure. A secondary role as a temporary adjunct to dialysis has been established for carbon haemoperfusion in the treatment of uraemic pericarditis and is under further investigation in the treatment of pruritus, pigmentation and neuropathy.

Banked blood microfiltration. II. Dacron-wool microfilter.

It is well established that debris tends to accumulate in banked blood, the amount of debris increasing with storage time. If such a blood is transfused to a patient, it will be filtered by the capillary network of the lungs and could cause various intensities of microemboli. These can be prevented by microfiltration--the Swank IL200 transfusion filter made of Dacron wool is perfectly suitable. It removes more than 70% of the debris 29-100 mum size from four blood units and its efficiency for particle removal is greatly increased by lactate priming.

Catecholestrogens as mediators of carcinogenesis: correlation of aromatic hydroxylation of estradiol and its fluorinated analogs with tumor induction in Syrian hamsters.

17 beta-Estradiol is known to induce kidney tumors in male Syrian hamsters when administered chronically, whereas 4-fluoroestradiol does so only after an extended induction period and 2-fluoroestradiol is not carcinogenic; both fluorinated analogs are hormonally active. Because C-4 and C-2 hydroxylations are, respectively, minor and major routes of estrogen metabolism in vivo, these observations suggest mediation of tumorigenesis by catecholestrogen metabolites. However, the analogs were reported to undergo oxidative defluorination in vitro. We have determined the metabolic fates of estradiol, 2-fluoroestradiol, and 4-fluoroestradiol in male hamsters. [6,7-3H]Estradiol was principally C-2 hydroxylated when given intravenously at either 0.1 mumol/kg or 50 mumol/kg; 2-hydroxyestradiol was eliminated in bile and urine, largely as a glucuronide, without undergoing extensive deactivation via O-methylation. Alicyclic alcohol metabolites were minor products. [6,7-3H]2-Fluoroestradiol underwent either glucuronylation or sequential dehydrogenation and alicyclic hydroxylation followed by glucuronylation but neither oxidative defluorination nor compensatory C-4 hydroxylation. [6,7-3H]4-Fluoroestradiol was also considerably dehydrogenated to the keto form and glucuronylated. Nevertheless, only 4-fluoroestradiol yielded appreciable quantities of C-2 hydroxylated metabolite at the lower dose; methylation was an insignificant pathway. No defluorinated products were observed. Dehydrogenation of both analogs and alicyclic hydroxylation of the 2-fluoroestrone metabolite were less extensive at the higher dose; all of the polar metabolites of 2-fluoroestradiol in bile, although not those in urine, declined to trace amounts. C-2 hydroxylation of 4-fluoroestradiol was greater at this dose. Thus, the rank order of catechol formation from estradiol and its fluoro analogs observed in vivo, unlike that found in microsomal incubations, was consistent with the hypothesis that catechols mediate estrogen-dependent renal carcinogenesis in hamsters.