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.

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.

Efficacy and toxicity of drug combinations in treatment of physostigmine toxicosis.

Atropine, in combination with 1 of 6 other drugs, was tested in mice for the ability to prevent death by an otherwise lethal dose of the cholinesterase inhibitor, physostigmine. The atropine dose (4 mg/kg, i.p.) was kept constant, while the dose of the other drug in the pair was tested in 5 geometrically spaced doses, ranging down to 1/16 of the maximum dose (which caused no gross behavioral signs). Atropine alone saved 20% of the mice. The combination of atropine and benactyzine saved 100% of the mice at all 5 doses of benactyzine; similar complete protection was afforded by the combination of atropine and the largest dose of an oxime, TMB4 (15 mg/kg). Over 80% survivals were achieved with the larger doses of atropine combinations involving hexamethonium, mecamylamine, and diazepam. No enhanced protection occurred with atropine combinations with the oxime, 2-PAM. The toxicity of the effective combinations, when used in high doses without physostigmine challenge, revealed that deaths occurred over a narrow range of doses of all combinations except atropine/diazepam. An additive toxic effect of atropine was suggested with its combinations with TMB4, mecamylamine, and diazepam, whereas no additive toxicity occurred with combinations involving hexamethonium or benactyzine (i.e., the LD50 of the combinations was about the same as for hexamethonium or benzactyzine alone). The combinations with the best therapeutic safety ratio were with diazepam (no deaths at a dose 10 times that which saved 100% of mice) and benactyzine (no deaths at a more than 50-fold dose).

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.

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.

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.

The digital circulation in congestive heart failure.

Congestive heart failure (CHF) is a complex clinical entity which is still little understood pathophysiologically. Unless it is in the intractable state it responds well to therapy. It has been known for many years that the peripheral circulation can be dramatically altered when CHF is progressively and rapidly developing and worsening. As compensation develops, these changes gradually return to normal. We have long been studying the digital circulation of patients with CHF and have been impressed with the changes in the behavior of the peripheral blood vessels in these patients.

Porphyria in relation to surgery and anaesthesia.

A review is presented of the more recent biochemical findings in the hepatic porphyrias. The clinical aspects of acute porphyria are re-emphasized and illustrated with a case history. In particular the differentiation between porphyria and surgical causes of abdominal pain is stressed. The anaesthetic management is discussed and details of diagnostic and screening tests are given.

[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.

[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis]. / Primenenie preparatov simpatoliticheskog deistviia dlia profilaktiki i lecheniia posleoperatsionnykh parezov kishechnika

For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications.

[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.

[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.

[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.