The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.

Removal of NAPL from columns by oxidation, sparging, surfactant and thermal treatment.

In this paper, four treatment techniques commonly applied to Volatile Organic Compounds (VOC) removal from soil are compared in column experiments with pure sand containing a residual Light Non-Aqueous Phase Liquid (L-NAPL) contamination. Oxidation is tested through the injection of Fenton reagent, with persulfate, and combined with sparging with the injection of ozone. Surfactant treatment was conducted at low flow rates with Tween®80. Sparging was conducted by air injection but at a low flow rate of 1 mL min-1. Finally several columns were thermally treated at a temperature of 80 °C. The results showed high removal (>90%) for all techniques used, although only thermal treatment on BTEX (Benzene, Toluene, Ethylbenzene and Xylenes) reached 100% efficiency. The main limiting factors of each technique were: (i) for oxidation, the solubility of the substance limited the removal; (ii) for surfactant both the solubility in the surfactant and the type of surfactant are important; (iii) for sparging, the main factors are contaminant vapor pressure and porous media grain size; (iv) for thermal treatment, the limitation arises from the contaminant vapor pressure and the medium hydraulic conductivity. A comparison with literature data shows that the results are consistent with most of the studies conducted on one technique.

Is profound hypothermia required for storage of cardiac allografts?

BACKGROUND: Improved methods of cardiac allograft protection are required to expand the pool of potentially available organs and to enhance the recovery of grafts subjected to prolonged ischemia. We have previously demonstrated that limited coronary perfusion provided by donor blood harvested at the time of organ procurement can improve both metabolic and functional recovery after transplantation. In this study we evaluated the hypothesis that limited coronary perfusion may enable prolonged cardiac storage while avoiding the potentially detrimental effects of profound hypothermia. METHODS: Fourteen orthotopic cardiac transplants were performed in female Yorkshire pigs by using donor blood perfusion during 5 hours of either tepid (25 degrees C) or cold (4 degrees C) storage. Assessments of myocardial metabolism and function were performed at baseline and after 45 minutes of normothermic (37 degrees C) reperfusion. RESULTS: Hearts protected with tepid perfusion displayed improved recovery of myocardial function (89% +/- 18% vs 63% +/- 25%, P =.05). Diastolic compliance was adversely affected in both groups after transplantation. Aerobic myocardial metabolism was better preserved in the tepid group. CONCLUSIONS: Profound hypothermia results in depressed myocardial metabolic and functional recovery after transplantation. Limited coronary perfusion with shed donor blood can permit cardiac allograft storage at tepid temperatures, resulting in improved myocardial performance.

Insertional inactivation of streptolysin S expression is associated with altered riboflavin metabolism in Streptococcus pyogenes.

Transposon Tn916 mutagenesis was used to create a mutant of Streptococcus pyogenes M type 3, designated ISS417, in which the ability to produce streptolysin S (SLS) and several other exoproteins was impaired. Concomitantly, the mutant became dependent upon riboflavin for growth and was able to grow in Todd Hewitt broth (THB) when supplemented with riboflavin or riboflavinrich yeast extract. The parent strain was apparently able to utilize THB-derived components as a substitute for riboflavin, while the mutant was not. Although the parent strain grew well in synthetic medium, it was unable to produce SLS, except when it was supplemented with a small amount of THB. Thus, a component of THB was able to "trigger" SLS formation in the parent strain. The mutant grew well in this medium, but was unable to produce SLS even when it was supplemented with THB. Southern hybridization analysis revealed that the ISS417 mutant harbours a single transposon insertion in its chromosome. Phage transduction experiments showed that the riboflavin dependency and the inability to make SLS phenotypes are co-transducible. The pleotrophic properties of the ISS417 mutant differ from those reported for insertional inactivation of the mga locus which regulates production of a number of surface proteins in S. pyogenes and the sar locus which regulates production of a number of exoproteins in Staphylococcus aureus. In view of the possibility that there exist a genetic linkage between the riboflavin biosynthetic pathway and expression of the oxygen-stable SLS, we hypothesize that SLS has a role in the growth economy of S. pyogenes.

Utility of thyroid function screening in adolescent psychiatric inpatients.

OBJECTIVE: Thyroid function abnormalities have been associated with psychiatric symptoms. This study examines the utility of thyroid screening among adolescent psychiatric inpatients. METHOD: A retrospective chart review of 196 first-time admissions to an adolescent psychiatric unit was conducted. Charts were screened for demographics, presence/absence of thyroid function testing, history of thyroid disease, medication/illicit substance use, and other factors of influence on thyroid testing. Thyroid test results were reviewed for abnormalities. RESULTS: Thyroid function testing was conducted in 150 of the 196 admissions. Fifty-two patients had abnormalities, most of which were isolated abnormalities of thyroxine (T4) or triiodothyronine uptake (T3U). Laboratory diagnosis of hyperthyroidism and mild hypothyroidism was met by two and eight patients, respectively; five had profiles that were normal upon subsequent testing 1 week later. None of the patients was symptomatic, and none required thyroid supplementation or antithyroid medications. Gender differences in T4 and T3U were noted, and age was positively correlated with T3U. CONCLUSIONS: Thyroid function tests may be spuriously abnormal in routine screening of newly admitted psychiatric patients. Routine thyroid screening among adolescent psychiatric inpatients is unwarranted except in patients who display physical signs or symptoms suggestive of thyroid disease.

Thrombolytic therapy in peripheral arterial occlusive disease: mechanisms of action and drugs available.

Catheter-directed thrombolytic therapy has become an important part of the treatment of patients with acute arterial and graft occlusion. The underlying pharmacologic principle is the activation of plasminogen, bound to fibrin within the thrombus. Guide-wire passage reliably predicts success of catheter-directed thrombolysis. The underlying disease process leading to thrombosis should be accurately identified and promptly corrected to reduce the probability of recurrent occlusion. Streptokinase (SK), urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) are the three agents used to treat peripheral arterial occlusive disease. The evolution from SK to UK and rt-PA and improvements in techniques and delivery systems have led to improved success rates and lower complication rates. Patient selection, basic technical considerations and overall results are discussed here. The currently available thrombolytic agents, as well as those being developed, are reviewed to provide background information for current and future applications.

Carboxyl terminus structural requirements for glycosyl-phosphatidylinositol anchor addition to cell surface proteins.

Glycosyl phosphatidylinositol (GPI)-anchored proteins contain in their COOH-terminal region a peptide segment that is thought to direct glycolipid addition. This signal has been shown to require a pair of small amino acids positioned 10-12 residues upstream of an hydrophobic C-terminal domain. We analysed the contribution of the region separating the anchor acceptor site and the C-terminal hydrophobic segment by introducing amino acid deletions and substitutions in the spacer element of the GPI-anchored Thy-1 glycoprotein. Deletions of 7 amino acids in this region, as well as the introduction of 2 charged residues, prevented the glycolipid addition to Thy-1, suggesting that the length and the primary sequence of the spacer domain are important determinants in the signal directing GPI anchor transfer onto a newly synthesized polypeptide. Furthermore, we tested these rules by creating a truncated form of the normally transmembranous Herpes simplex virus I glycoprotein D (gDI) and demonstrating that when its C-terminal region displays all the features of a GPI-anchored protein, it is able to direct glycolipid addition onto another cell surface molecule.

The 5' region of Tacaribe virus L RNA encodes a protein with a potential metal binding domain.

We have just completed the Tacaribe arenavirus (TV) genome structure by sequencing the 5' region of the L RNA. Analysis of the sequence has indicated the existence of an open reading frame (ORF) in the viral sense RNA encoding a 95 amino acid polypeptide. The first in phase AUG codon is in positions 70-72 from the 5' end of the viral RNA surrounded by a sequence favorable for the initiation of protein synthesis. The ORF ends at positions 355-357. The predicted polypeptide (P11) contains a cysteine-rich sequence bearing a remarkable similarity to the "zinc finger" sequences found in a number of proteins. We have recently reported that the 3' region of the TV L RNA encodes a polypeptide comprising 2210 amino acids in the viral-complementary sequence. This latter gene, i.e., the L gene, terminates at positions 442-440 from the 5' end of the viral RNA. The two genes encoded by the L RNA (L and P11) are in opposite strands of the RNA in sequences that do not overlap, but are separated by a noncoding intergenic region of 82 nucleotides. The nucleotide sequence of the intergenic region leads to the prediction of a strong secondary structure.

Effects of glutathione depletion on the cytotoxicity of agents toward a human colonic tumour cell line.

Levels of glutathione (GSH) in tumour tissue may be important in determining the clinical response to certain anticancer agents. Recent reports have suggested that D,L-buthionine-S,R-sulphoximine (BSO), a specific inhibitor of GSH synthesis, may be used to deplete tumour cell GSH and thus increase the therapeutic ratio of these agents. We have previously shown that 1-naphthol is a potential antitumour agent, and that its possible metabolite 1,4-naphthoquinone is thiol reactive and capable of redox cycling. It was therefore of interest to investigate the effect of pretreatment with BSO, on the toxicity of these agents, to tumour cells. For comparison we included three other cytotoxic agents, melphalan, helenalin and menadione, the toxicities of which are reported to be modulated by intracellular GSH. Depletion of GSH using BSO did not effect the toxicity of 1-naphthol, or 1,4-NQ but did produce slight potentiation of the cytotoxicities of menadione, helanalin and melphalan. The lack of effect of BSO on 1-naphthol and 1,4-NQ is not easily explained but if one also considers the modest potentiation of cytotoxicity+ achieved with the other agents studied, the potential use of BSO in combined chemotherapy is at best rather modest.

Pain characteristics and treatment in an outpatient cancer population.

Thirty of 100 consecutive outpatients at a comprehensive cancer center were assessed by their physicians as having pain due to cancer severe enough to require regular or narcotic medication. These 30 patients and their physicians then were approached with a semistructured questionnaire about pain characteristics and management. Pain severity correlated only with age older than 55 years. Patients tended to rate their pain as more severe than did their physicians, but believed that pain medications generally were effective. Side effects of pain medication and patient fears of dependence on medication appeared to be more important limiting factors in achieving complete pain relief from medication than undermedication by physicians. Both patients and physicians acknowledged a relationship between emotional state and pain, but there was a greater appreciation among patients than physicians of the usefulness of techniques such as relaxation and distraction in pain control.

Haemodynamic effects of verapamil administration after large doses of fentanyl in man.

Thirteen patients with good left ventricular function undergoing coronary artery revascularization were studied to determine the cardiovascular effects of verapamil, 75-150 micrograms X kg-1, after a large dose (100 micrograms X kg-1) of fentanyl, with pancuronium for muscle relaxation. The patients were continued on their usual cardiovascular medications until the time of surgery, which included nitrates, beta adrenergic blockers, and nifedipine. Anaesthesia with fentanyl was associated with decreases in mean arterial blood pressure, systemic vascular resistance, left ventricular stroke work index, and circulating catecholamine levels. Mean values were not further changed by verapamil, but individual patients had additional modest decreases in blood pressure and systemic vascular resistance. Cardiac index, however, was well maintained. Plasma catecholamines remained depressed after verapamil under the study condition. Thus, in patients with good left ventricular function, clinically relevant doses of verapamil were well tolerated even in the presence of an anaesthetic that included large doses of fentanyl, with suppression of circulating catecholamine levels.

Impairment of the chick's grip and balance by streptomycin. A preliminary study.

Chicks were injected daily with streptomycin (400 or 1,200 mg/kg). Damage to the vestibular apparatus was accompanied by steadily impaired abilities of chicks to tighten their grips as evidenced by reduced torque and by slippage of their feet on the perch. As compensation, intoxicated chicks adjusted their footing with cautious, deliberate movements. They always stood erectly and stiffly on the perch; they were unable to roost. They also experienced difficulties in balancing. While symptoms were qualitatively similar at both dosages, their onset came earlier and with greater severity at 1,200 mg/kg. Control chicks steadily increased their torque and displayed normal balance during the course of the experiment.

Transcutaneous nerve stimulation: its significance and applications in podiatry.

In summation, the neuranatomy and neurophysiology of pain have been presented. Three of the classical theories of pain transmission were also discussed, these being the specificity, pattern, and gate control theories. The gate control theory postulates that stimulation of large diameter sensory nerve fibers blocks pain sensation at the level of the substantia gelatinosa in the dorsal horn of the spinal cord. This theory is used as the basic explanation for the function of the TNS, a device that can control pain by stimulation of the skin through surface electrodes. TNS stimulation appears to be most efficacious when the electrodes are placed either directly over or just proximal to the painful region. Podiatric application appears to lend itself quite naturally to TNS therapy. Several surgical and nonsurgical cases were presented where TNS therapy was employed and in this preliminary study approximately a 63% improvement in pain state was shown. We believe this modality is useful for patients who should limit their intake of analgesic medications, whether they are medically compromised, allergic to various pain medication, or simply are highly intolerant to pain. TNS is also useful in patients who do not respond well to the more traditional and conventional podiatric treatments. Our study illustrates TNS to be efficacious in pain states of a surgical, chronic or acute nature and even pain secondary to systemic disease. It should be noted that TNS is not curative, per se, but is a useful adjunct in the therapeutic regime. This form of therapy, although not without hazard, is relatively safe and easy to use, and although it is not the answer to all pain states, it is highly recommended when applicable.

A benzo[alpha]pyrene-7,8-dihydrodiol-9,10-epoxide is the major metabolite involved in the binding of benzo[alpha]pyrene to DNA in isolated viable rat hepatocytes.

Benzo[alpha]pyrene is metabolised by isolated viable hepatocytes from both untreated and 3-methylcholanthrene pretreated rats to reactive metabolites which covalently bind to DNA. The DNA from the hepatocytes was isolated, purified and enzymically hydrolysed to deoxyribonucleosides. The hydrocarbon-deoxyribonucleoside products after initial separation, on small columns of Sephadex LH-20, from unhydrolysed DNA, oligonucleotides and free bases, were resolved by high pressure liquid chromatography (HPLC). The qualitative nature of the adducts found in both control and pretreated cells was virtually identical; however pretreatment with 3-methylcholanthrene resulted in a quantitatively higher level of binding. The major hydrocarbon-deoxyribonucleoside adduct, found in hepatocytes co-chromatographed with that obtained following reaction of the diol-epoxide, (+/-) 7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene with DNA. Small amounts of other adducts were also present including a more polar product which co-chromatographed with the major hydrocarbon-deoxyribonucleoside adduct formed following microsomal activation of 9-hydroxybenzo[alpha]-pyrene and subsequent binding to DNA. In contrast to the results with hepatocytes, when microsomes were used to metabolically activate benzo[alpha]-pyrene, the major DNA bound-product co-chromatographed with the more polar adduct formed upon further metabolism of 9-hydroxybenzo[alpha]pyrene. These results illustrate that great caution must be exercised in the extrapolation of results obtained from short-term mutagenesis test systems, utilising microsomes, to in vivo carcinogenicity studies.