Modulation of lnterleukin-2-Driven Proliferation of Human Large Granular Lymphocytes by Carbaryl, an Anticholinesterase Insecticide

Modulation of Interieukin-2-Driven Proliferation of Human LargeGranular Lymphocytes by Carbaryl, an Anticholinesterase Insecticide.Bavari, S., Casale, G. P., Gold, R. E., and Vitzthum, E. F.(1991). Fundam. Appl. Toxicol. 17,61-74. Studies in other laboratorieshave provided evidence that the interleukin-2 (IL2) signalingpathway in lymphocytes includes essential, serine proteases.Since the anticholinesterase (antiCHE) insecticides are potentserine hydrolase (esterase and protease) inhibitors, we assessedthe ability of carbaryl (CA, a widely used antiCHE insecticide)and a-naphthol (NA, a major metabolite of carbaryl) to modulateIL2-driven proliferation of large granular lymphocytes (LGL)purified from human peripheral blood. These cells express nearlyall of the natural killer (NK.) activity of human peripheralWood. NK cells are normal lymphocytes that respond to IL2 byproliferating and increasing their tumoricidal activity on aper cell basis. Cultures of purified LGL, initiated in the presenceof human recombinant IL2, were harvested on culture Day 4, thenproliferation was measured as [³H]thymidine incorporation. Whenadded only at the time cultures were initiated, CA inhibitedincorporation 10-32%, 35-53%, and 54-57% at 0.5, 5.0, and 50mm, respectively. In contrast, NA had no effect at 0.5 and 5.0mm, but was inhibitory (16-17%) at 50 mm. Reexposure to CA orNA, during the incorporation assay, had little effect on theobserved inhibition profiles. Chemically induced changes incell number during an 8-day culture period reflected the chemicallyinduced changes in [³H]thymidine incorporation. Neither CA norNA produced cell death. Quantitation of both CA and NA by HPLCindicated a rapid loss of CA (ca. 95% in 24 hr) and a much slowerloss of NA from the culture medium. CA inhibited human LGL proliferationat concentrations producing little or no inhibition of serumCHE, an indicator of exposure to antiCHE insecticides.     

Inhibition of Human Serum Complement Activity by Diisopropylfluorophosphate and Selected Anticholinesterase Insecticides

Inhibition of Human Serum Complement Activity by Diisopropylfluorophosphateand Selected Anticholinesterase Insecticides. CASALE, G. P.,BAVARI, S., AND CONNOLLY, J. J. (1989). Fundam. Appl. Toxicol.12, 460–468. Activation of the human complement (C') system,a major line of defense against infections, requires the participationof serine esterases. Since the widely used anticholinesteraseinsecticides inhibit serine esterases, the present study evaluatedpotencies of carbaryl, carbofuran, dichlorvos, and paraoxonto inhibit C' activities of a panel of normal human sera. C'-mediatedlysis of sheep red cells was measured with a modified assay(1) incorporating suboptimal concentrations of sensitizing antibodyand (2) exhibiting increased sensitivity to serine esteraseinhibitors. Test chemicals were added to diluted sera 2 hr priorto incorporation into C' reaction mixtures. Potencies to inhibitC' and serum cholinesterase (CHE) were compared to potenciesof diisopropylfluorophosphate (DFP), a potent serine esteraseinhibitor and a standard probe for C' esterases. At 0.5 to 3.0mM carbaryl, carbofuran, dichlorvos, and DFP produced a dose-dependentinhibition of lysis, whereas paraoxon was not inhibitory. Ona molar basis, carbalyl was three times more potent than DFP,and inhibited lysis 15–25 and 26–45% at 1.0 and3.0 mM respectively. Carbofuran, dichlorvos, and DFP were equipotent.Mean IC50's for inhibition of CHE (a marker for occupationalexposure to organophosphates and carbamates)by DFP, paraoxon,dichlorvos, carbofuran, and carbaryl were 1.0?l0^–8 4.1?l0^–8,1.0?l0^–7 3.3?l0^–6and 1.8?l0^–5M, respectively.Potencies of the insecticides to inhibit CHE did not predictabsolute or relative potencies to inhibit serum C' activity.     

BLOOD LOSS DURING HYSTERECTOMY ASSOCIATED WITH THE USE OF TUBOCURARINE OR GALLAMINE

Patients undergoing hysterectomy were divided into two groups,one of which was given tubocurarine and the other gallaminetriethiodide as the muscle relaxant. In all other respects theanaesthetics were similar. During the course of operation thosepatients who were given gallamine showed significandy greaterblood losses. This difference did not appear to be related tothe surgeon performing the operation or to the duration of operation.It was concluded that the most likely cause was the higher heartrates, probably associated with higher cardiac outputs, in thegallamine group.     

Setting of Relatively Low Energy Outputs May Permit Implantation of a Nonthoracotomy Automatic Cardioverter Defibrillator System When High Energy Outputs Prove Ineffective

At intraoperative testing of defibrillation thresholds during implantation of internal Cardioverter defibrillators, standard step-down approaches of energy outputs are used. If relatively high energy outputs are not successful at defibrillating the heart, the electrodes are frequently reconfigured. When attempting implantation of a nonthoracotomy lead system, high defibrillation thresholds may warrant opening of the chest cavity to place one or more epicardial electrodes. A case is presented where a nonthoracotomy system was able to be implanted using relatively low energy outputs which were reproducibly successful at terminating ventricular fibrillation when higher energy outputs were unsuccessful. Mechanisms for this phenomenon and alternate recommendations for defibrillation testing are presented.     

THE YOUNG-DEES-LEADBETTER BLADDER NECK REPAIR FOR NEUROGENIC INCONTINENCE

PURPOSE: We review our experience with the Young-Dees-Leadbetter bladder neck repair among patients with neurogenic incontinence. MATERIALS AND METHODS: Between 1978 and 1997, 25 girls and 13 boys with a mean age of 10.5 years (range 5 to 25) underwent a standard Young-Dees-Leadbetter bladder neck repair for neurogenic incontinence. Of the 38 patients 26 had undergone prior urological surgery, including bladder neck surgery in 6 and bladder augmentation in 4. A primary Young-Dees-Leadbetter bladder neck repair was performed in 24 patients, a secondary Young-Dees-Leadbetter procedure in 6 and a primary Young-Dees-Leadbetter procedure with periurethral silicone sheath placement in 8. RESULTS: Of the 38 patients 30 (79%) are dry, 7 (18%) are partially dry and 1 remains incontinent. Total or partial dryness was achieved after the initial repair in 26 cases (68%), while 8 required an additional procedure and 3 required more than 2 procedures to achieve continence. All patients who underwent silicone sheath placement were initially dry but incontinence developed subsequently in 5 due to sheath erosion. Of the 38 patients 35 (92%) ultimately required bladder augmentation. CONCLUSIONS: The management of neurogenic incontinence remains difficult. Success with the Young-Dees-Leadbetter procedure in our experience nearly always requires augmentation cystoplasty. The majority of patients will achieve continence after the initial procedure, and persistent incontinence can frequently be cured with further bladder neck surgery.     

Tobacco smoking and risk of haematological malignancies in adults: a case–control study

A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute non-lymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose–response effect, and the variation in risk according to the histological subtype of the malignancy.     

APPENDICOVESICOSTOMY AND NEWER ALTERNATIVES FOR THE MITROFANOFF PROCEDURE: RESULTS IN THE LAST 100 PATIENTS AT RILEY CHILDREN′S HOSPITAL

PURPOSE: We present our experience using the various Mitrofanoff techniques to create a continent catheterizable stoma as an adjunct to continent urinary tract reconstruction in children and young adults. MATERIALS AND METHODS: Between 1990 and 1998 a Mitrofanoff procedure was performed at our institution in 55 male and 45 female patients with a mean age of 10.5 years. The etiology of incontinence was diverse but more than 90% of the patients had neurogenic bladder, the epispadias-exstrophy complex or a cloacal anomaly. Surgery included appendicovesicostomy in 57 cases, a Yang-Monti ileovesicostomy in 21, continent vesicostomy in 21 and formation of a tapered ileal segment as a catheterizable channel in 1. Simultaneously bladder augmentation was performed in 52 patients, bladder neck reconstruction was done in 48 and a Malone antegrade colonic enema stoma was constructed for fecal incontinence in 17. RESULTS: The abdominal stoma is continent in 98 of our 100 patients. Mean followup is 2 years (range 2 months to 8 years) with the longer followup in the appendicovesicostomy group. One patient with stomal incontinence who underwent revision is now dry. Postoperative complications requiring an additional procedure developed in 20 patients, including stomal stenosis in 12. Continent vesicostomy was most prone to stomal problems (6 of 21 patients, 29%). CONCLUSIONS: The Mitrofanoff procedure is a reliable technique for creating a continent catheterizable urinary stoma. Appendicovesicostomy continues to be our first option for this procedure, although we have also had good results with the Yang-Monti ileovesicostomy and continent vesicostomy. These newer options have allowed preservation of the appendix for the Malone antegrade colonic enema stoma procedure in patients with urinary and fecal incontinence.     

Does Preoperative Platelet Function Predict Bleeding in Patients Undergoing Off Pump Coronary Artery Bypass Surgery?

Objective

We sought to examine the relationship between preoperative platelet function and perioperative bleeding in patients undergoing CABG.

Background

There are many ways to measure platelet aggregability. Little is known about their correlations with one another, or with bleeding.

Methods

We prospectively studied 50 patients undergoing a first isolated off‐pump CABG. Thirty‐four were exposed to a thienopyridine prior to surgery; 16 were not. Preoperative platelet function was measured by VerifyNow®, TEG®, AggreGuide?, Plateletworks®, vasodilator‐stimulated phosphoprotein (VASP) phosphorylation, and light transmission aggregometry. Bleeding was assessed 2 ways: drop from pre‐ to nadir postoperative hematocrit, and chest tube drainage. Correlation coefficients were calculated using Spearman's rank‐order correlation.

Results

Mean age was 62 years. Patient characteristics and surgical details were similar between the thienopyridine‐exposed and non‐exposed patients. The correlation coefficients between the 4 point‐of‐care platelet function measurements and hematocrit change ranged from ?0.2274 to 0.2882. Only Plateletworks® correlated with drop in hematocrit (r = 0.2882, P = 0.0470). The correlation coefficients between each of the 4 point‐of‐care platelet function tests and the chest tube drainage were also poor, ranging from ?0.3073 to 0.2272. Both AggreGuide? (r = ?0.3073, P = 0.0317) and VASP (r = ?0.3187, P = 0.0272) were weakly but significantly correlated with chest tube drainage. The correlation among the 4 point‐of‐care platelet function measurements was poor, with coefficients ranging from ?0.2504 to 0.1968.

Conclusions

We observed little correlation among 4 platelet function tests, and between those assays and perioperative bleeding defined 2 different ways. Whether any of these assays should be used to guide decision making in individual patients is unclear. (J Interven Cardiol 2015;28:223–232)

     

A LONG CONTINENT ILEOVESICOSTOMY USING A SINGLE PIECE OF BOWEL

PURPOSE: In 1981 Mitrofanoff presented a procedure to create a continent urinary stoma for intermittent catheterization. Since then, several other methods have been introduced, including the Yang-Monti ileovesicostomy. The length of these ileovesicostomies is limited by the circumference of the bowel segment used, which is inadequate in some cases. We developed a procedure to double the length of the Yang-Monti ileovesicostomy using a single section of bowel. MATERIALS AND METHODS: A 3.5 cm. section of ileum is isolated on its mesentery. The bowel is divided into 2 segments for 80% of its circumference, leaving the bowel intact over the mesentery. Each ring of bowel is then divided adjacent to the mesentery but on opposite sides, allowing the bowel to be unfolded and reconfigured in a single long strip that may then be tubularized. The blood supply to the tube is excellent and it is in the center of the reconfigured ileum. The ends may be trimmed or widely spatulated as necessary. RESULTS: We have performed this procedure in 8 patients. The resulting ileovesicostomy created from a 3.5 cm. section ofileum is 10 to 14 cm. long and accepts a 12F catheter. A larger tube may be created from a longer piece of ileum. All patients are dry and they perform catheterization easily. CONCLUSIONS: This form of ileovesicostomy allows the creation of a long bowel tube that is easily catheterized. The longer length of the tube increases application of the continent stoma principle to more patients and enables reconstruction to be performed with optimal placement and without tension.