A new activity of N-cholinolytic drug benzohexonium.

We have found that N-cholinolytic drug benzohexonium produces a hypolipidemic effect: it reduces dyslipoproteinemia, fatty infiltration of the liver, and risk of atherosclerotic lesions.

Cross-linked hyaluronan used as augmentation substance for treatment of glottal insufficiency: safety aspects and vocal fold function.

OBJECTIVE: To examine safety aspects and vocal fold function after vocal fold augmentation with a cross-linked hyaluronan derivative (hylan B gel) as compared with bovine collagen. STUDY DESIGN; A prospective, randomized trial. METHODS: Eighty-three patients with glottal insufficiency were treated with injection augmentation with hylan B gel and bovine collagen and were examined at 1, 6, and 12 months after treatment. Seventy patients with unilateral vocal fold paresis (n = 35) or atrophy (n = 35) were randomly assigned to receive either hylan B gel (n = 47) or collagen (n = 23) injections into one vocal fold. Thirteen patients with glottal insufficiency caused by scar defects or paresis resulting from malignant disease were included in a nonrandomized group and were treated only with hylan B gel. Evaluations were made from patients' subjective ratings (visual analogue scales), digitized videostroboscopic measurements, phonetograms, maximum phonation time, and phonation quotients. RESULTS: Twelve months after injections, the patients' self-ratings were significantly improved for both the hylan B gel and the collagen groups. In addition, the videostroboscopic measurements showed significantly improved glottal closure for both groups. However, for the hylan B gel group, vibration amplitude and glottal area variations were preserved, and this group showed significantly less resorption at the injected vocal fold edge. Furthermore, maximum phonation time had increased significantly for the hylan B gel patients (collagen, nonsignificant). No serious adverse events were observed; three patients injected with hylan B gel had temporary inflammation at the injection site, which resolved without sequelae. CONCLUSIONS: The results showed that both hylan B gel and collagen can be safely used for injection treatment of glottal insufficiency. Both treatments resulted in significantly improved voice as rated by the patients. However, the patients treated with hylan B gel showed better vocal fold status and longer maximum phonation time at 12 months after treatment as compared with patients treated with collagen.

[Ganglionic blockers in abdominal surgery: facts and hypotheses. I. Benzohexonium and motor function of the gastrointestinal system in the early postoperative period]. / Ganglioblokatory v abdominal'noi khirurgii: fakty i gipotezy. Soobshchenie I. Benzogeksonii i motornaia funktsiia zheludochno-kishechnogo trakta v rannem posleoperatsionnom periode.

The method of registration of the intraluminal pressure was used to study the function of the stomach, small intestine and sigmoid colon under conditions of partial ganglionic blockade in the first days after truncal vagotomy and resection of the stomach. It was found that benzohexonium in doses 0.1-0.3 mg/kg failed to substantially decrease the frequency of early functional motor-evacuation disorders of the "operated" stomach, but the results of using N-cholinolytic was better after truncal vagotomy than after resection of the stomach. Benzohexonium in doses 0.1-0.2 mg/kg failed to considerably stimulate the motor function of the small intestine while the doses of 0.3-0.4 mg/kg resulted in a decrease of its contractile activity. No reliable changes in the qualitative and quantitative parameters of the sigmoid colon motor function were found against the background of ganglionic blockade. So, for prevention and correction of early postoperative motor-evacuation disorders of the gastrointestinal tract the ganglionic blockade with N-cholinolytics should not be taken as a method of choice or a variant of monotherapy.

[Ganglionic blockers in abdominal surgery: facts and hypotheses. 2.Clinical, pathophysiological and pharmacological aspects of ganglionic blocker use]. / Ganglioblokatory v abdominal'noi khirurgii: fakty i gipotezy. Soobshchenie 2. Klinicheskie, patofiziologicheskie i farmakologicheskie aspekty primeneniia ganglioblokatorov.

The authors discuss facts and hypotheses on the effects of benzohexonium upon the motor activity of the intestine and the significance of N-cholinolytics for prophylactics and treatment of postoperative pareses of the gastrointestinal tract. The ganglioblockers possess antistress effect, reduce the degree of pathological vegetative reactions and facilitate realization of the mechanisms of selfregulation of functions of the small and large intestine. Using benzohexonium during operation and in the first days after it makes the intestinal pareses less frequent. N-cholinolytics however do not have a considerable stimulating influence on the contracting activity of the gastrointestinal tract that accounts for their not high effectiveness in treatment of early functional motor evacuatory disorders. The points of action of gangliolytics, those at the level of the intestinal wall included, can not be considered to be completely established, as well as the mechanisms of their indirect effect. The ganglionic blockade should be considered as the basic method of prophylactics of the postoperative paresis of the intestine.

Cost implications of introducing an alternative treatment for patients with osteoarthritis of the knee in a managed care setting.

OBJECTIVES: To illustrate the current cost of treating osteoarthritis (OA) of the knee and to demonstrate potential savings associated with the new treatment modality of viscosupplementation in a managed care setting. STUDY DESIGN: Pharmacoeconomic model with inputs obtained from peer-reviewed medical literature, clinical trial data, clinical expert opinion, and claims data. METHODS: A spreadsheet-based model was developed to define a treatment pathway for OA of the knee, illustrate the current costs of treating patients with the condition, and demonstrate the potential savings associated with introduction of Hylan G-F 20. A hypothetical cohort of patients categorized as having mild, moderate, or severe OA of the knee was followed over a 3-year time period. The analysis was conducted from the perspective of a managed care plan with a large Medicare population. RESULTS: The 3-year savings associated with adding 1 or more courses of Hylan G-F 20 therapy to the standard treatment pathway for OA of the knee was $8,810,771. The total savings per OA patient receiving Hylan G-F 20 was $4706. The number of total knee replacements (TKRs) avoided was 808. The model was highly sensitive to the durability of Hylan G-F 20; increasing and decreasing durability within a reasonable range resulted in 3-year savings of $9,131,879 and $2,012,082, respectively. CONCLUSIONS: Hylan G-F 20 has proven to be an effective treatment for patients with OA of the knee. Appropriate use of Hylan G-F 20 could delay the need for TKRs and generate savings in the managed care setting.

Injectable fillers for facial soft tissue enhancement.

Soft tissue augmentation materials have been advocated for correction of post-surgical or post-traumatic facial defects, as well as for age-related folds and wrinkles. While autogenous tissues may be the safest option, they require a second operative site. Animal-derived or synthetic materials have been advocated since the late 19th century, and have waxed and waned in popularity. In recent years, we have gained a better understanding of the physical events that occur when material is placed within or below the skin. With this knowledge, we stand at the threshold of a new era, where soft tissue fillers can be designed and customized to suit the individual patient. This article will review the major materials that have been or are now advocated for use as soft tissue fillers, and will detail their relative strengths and weaknesses in order to give the clinician a better perspective when considering a material for soft tissue augmentation.

The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.

The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.

[Postvagotomy diarrhea]. / Postvagotomicheskaia diareia.

Main pathogenic factors of postvagotomy diarrhea are considered. Among them are: rapid emptying of the stomach due to the draining operation and accelerated passage of chyme along the small intestine, development of a relative insufficiency of digestion and absorption, entrance of the hyperosmolar content into the colon. Diarrhea appears more often after truncal vagotomy, is paroxysmal, then in time regresses and is successfully treated with benzohexamethonium and diet. Surgical correction as the inversion of the segment of the small intestine or restoration of the pyloric sphincter is required in single cases with critical continuously recurring form of diarrhea.

Mechanisms of the putative cardioprotective effect of hexamethonium in anesthetized dogs given a large dose of bupivacaine.

BACKGROUND: Some reports suggest that activation of the autonomic nervous system by bupivacaine could participate in its cardiotoxicity. This is based in part on the fact that hexamethonium suppresses cardiac disturbances in anesthetized rabbits given small intracerebroventricular doses of bupivacaine. The aims of the current study were to determine, in anesthetized dogs, (1) whether the activation of the autonomic nervous system is deleterious after a large intravenous dose of bupivacaine and (2) whether the parasympathetic or sympathetic system is implicated in the bupivacaine-induced deleterious activation of the autonomic nervous system. METHODS: We used an electrophysiologic model in closed-chest dogs anesthetized with sodium pentobarbital. In group 1 (n = 6), dogs were given 4 mg/kg intravenous bupivacaine over 10 s. In group 2 (n = 6), dogs were given the same dose of bupivacaine 5 min after having received 0.2 mg/kg intravenous atropine sulfate. In group 3 (n = 9), dogs were pretreated with 10 mg/kg intravenous hexamethonium and then given bupivacaine 4 mg/kg. In addition, in group 3, the right atrium was paced at a basic cycle length of 400 ms to obtain a heart rate similar to that of group 1. RESULTS: Bupivacaine in group 1 induced significant bradycardia; lengthening of PR, atria-His, His-ventricle, and QTc intervals; and QRS widening. The first derivative of left ventricular pressure was significantly decreased, whereas left ventricular end-diastolic pressure was increased. Atropine pretreatment did not modify cardiac disturbances induced by bupivacaine. Hexamethonium pretreatment induced significantly less QRS widening and QTc lengthening than was seen in group 1 but worsened the bupivacaine effects on bradycardia, atria-His and PR intervals, mean aortic pressure, and first derivative of left ventricular pressure. Moreover, atrial pacing in group 3 induced alterations of QRS similar to those in group 1. CONCLUSIONS: Considering that marked slowing of ventricular conduction velocity (i.e., QRS widening) is known to facilitate reentrant ventricular arrhythmias, we conclude that (1) the activation of the autonomic nervous system by bupivacaine is not as deleterious as previously suggested; (2) the parasympathetic system is not markedly implicated in the worsening of direct bupivacaine cardiotoxicity; and (3) the sympathetic nervous system acts only by inducing a less marked bradycardia, which slows ventricular conduction velocity in a use-dependent manner, facilitating reentrant arrhythmias.

Efectos del veneno de Buthus eupeus sobre la secreción gástrica / Effects of Buthus eupeus venom upon gastric secretion

La administración endovenosa del veneno del escorpión B. eupeus (a dosis de 0.25 mg/Kg) incrementa la secreción gastrica de acido y pepsinógeno en la rata, sin influenciar el volumen secretado. Ambas secreciones de acido y pepsinógeno fueron inhibidas por la atropina y la vagotomia. La secreción gastrica de ácido fue incrementada por el veneno de escorpion y este efecto fue disminuido por el tratamiento con cimetidina y hexamethonium. Los efectos del veneno de B. eupeus sobre la secreción gástrica de la rata son debidas a un efecto neurotoxico a nivel pre y postganglionar parasimpático

Hylan gel composition for percutaneous embolization.

Viscoelastic, pseudoplastic, radiopaque injectable hylan gel for percutaneous embolization was developed and evaluated by in vitro and in vivo tests. The embolization gel is composed of cross-linked hylan (hyaluronan, hyaluronate), tantalum, microcrystalline cellulose, hexamethonium chloride, and thrombin. Upon delivery through small-lumen catheters to the appropriate vascular site, the gel induces formation of a solid blood/gel coagulum. Results from animal studies (rat aorta, rabbit auricular artery) demonstrate that formation of complete and long-lasting arterial blockage is readily achievable without complications due to blood flow, partial vessel obstruction, uncontrolled polymerization, or movement of the gel or its components (specifically thrombin and hexamethonium chloride) into the circulation. Microscopic evaluation indicates that arterial occlusion initially occurs as a result of the injected gel and formed fibrin; at 7 weeks and beyond, arteries are occluded by injected gel, inflammatory cells and fibrosis (scar tissue).

Nicotine-induced tail-tremor and drug effects.

Tail-tremor induced by repeated and daily administration (0.5 mg/kg SC x 6 times/day) of nicotine as well as effects of various drugs on this response were investigated in Wistar strain male rats. Daily administration of nicotine in doses of 0.5 mg/kg SC caused tail-tremors to appear beginning on the 3rd day. Tail-tremor induced by the first injection of each day gradually increased with the daily injections, however, the heightened effect of this first injection at the beginning of each day decreased during the day upon repeated administration of 6 times/day at 2-hr intervals. Basically, tail-tremor appeared about 5 min after SC administration of nicotine and reached a peak approximately 7-9 min after injection, declining to zero afterwards. Different drugs showed various effects on this response. While mecamylamine (0.5 and 1.0 mg/kg IP) abolished nicotine-induced tail-tremor, arecoline (0.5 and 1.0 mg/kg IP), atropine (2.5 and 5.0 mg/kg IP), scopolamine (1.0 and 2.0 mg/kg IP) and hexamethonium (0.5 and 1.0 mg/kg IP) showed no such effects. Furthermore, physostigmine (0.1 mg/kg IP) actually potentiated this action. These results suggest that tail-tremor induced by nicotine may be mediated through central nicotine receptor system.

[Pharmacological analysis of morphofunctional changes in the adrenergic structures of the pancreas as affected by lesions of the endocrine and exocrine pancreas]. / Farmakologicheskii analiz morfofunktsional'nykh izmenenii adrenergicheskikh struktur podzheludochnoi zhelezy pri porazhenii ee éndo- i ékzokrinnogo otdela.

The adrenergic section of the vegetative pancreatic innervation has been examined, using morphological, histochemical and biochemical methods, during neurogenic injury, acute experimental pancreatitis and alloxan diabetes. It has been established that the development of those etiologically different processes was accompanied by catecholamine level reduction in the adrenergic structures of the pancreas which can be prevented by ganglioblockers. It is concluded that sympathetic nervous system participates in etiopathogenesis of a number of pancreatic diseases and that it is possible to prevent and treat them with sympathotropic agents.

[Physical therapy of hereditary neuropathies]. / K fizioterapii nasledstvennykh nevropatii.

In a series of 118 patients with the Charcot-Marie-Tooth neural amyotrophy the authors evaluated a comparative therapeutic efficacy of electrophoresis of benzohexamethonium and a new method of physiotherapy, namely, administration of ganglioblockers with the help of sinusoidal modulated currents. The results of the treatment were assessed from the time course of clinico-electrophysiologic parameters. The most marked positive course of the clinico-electrophysiological parameters was observed following electrophoresis of benzohexamethonium by sinusoid modulated current.