Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy.

BACKGROUND & AIMS: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13 C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. METHODS: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation - defined as Child A6 (N = 22, 44%) or previous decompensation (N = 7, 14%) - or Child B cirrhosis (N = 21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12 weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. RESULTS: Aminopyrine breath test was available for all 50 patients at baseline. The 120' cumulative dose was directly associated at regression analysis only with albumin levels (P = .001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2 months (range 12.2-32.1 months). Lower Ʌ ABT - defined as changes of 120' cumulative dose from FUW12 to baseline - (HR 0.97, 95% CI 0.94-0.99; P = .02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P = .03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P < .001). CONCLUSIONS: In patients with advanced HCV cirrhosis who achieve SVR with DAA, Ʌ ABT assists in assessing the residual likelihood of liver-related events and deaths after viral cure.

Influence of COX-inhibiting analgesics on the platelet function of patients with subarachnoid hemorrhage.

BACKGROUND: Platelet function of patients with subarachnoid hemorrhage (SAH) may play an important part in both rebleeding and delayed cerebral ischemia, but little is known about aggregation pathways during the acute phase of stroke. Analgesics are used regularly in the first days after bleeding, and some can potentially inhibit the cyclooxygenase (COX) enzyme. We examined the platelet function of patients with SAH in order to describe their basal situation and determine whether the administration of intravenous nonsteroidal antiinflammatory drugs (NSAIDs) affected platelet aggregation. METHODS: Arachidonic acid (AA)-induced aggregation and the platelet function analyzer (PFA)-100 test with collagen/epinephrine cartridges were used to study a group of SAH patients that was treated with dexketoprofen and dipyrone and to compare them to patients that had received no analgesia. RESULTS: Ninety-six consecutive SAH patients prospectively enrolled in platelet studies. Twenty-seven patients were taking NSAIDs (10 on dexketoprofen and 17 on dipyrone), and there were 15 cases in the control group. AA-induced aggregation was 10% ± 3.2% for NSAIDs (mean ± standard error), specifically 17.2% ± 7% for dexketoprofen and 5.7% ± 1% for dipyrone. Aggregation in the control group was 72.4% ± 6% (P = .001). Both analgesics slowed the platelet plug formation during the PFA-100 test, with closure times of 237.2 ± 25 seconds for dexketoprofen and 198.4 ± 22 seconds for dipyrone and 138.1 ± 21 seconds in controls (P = .02). CONCLUSIONS: The administration of COX-inhibiting analgesics leads to an hypoaggregability state in the first days of SAH. Further insight into their impact on complications such as rebleeding and delayed cerebral ischemia is needed in order to optimize the headache treatment of SAH.

[Clinical trial on the effect of buphenine, aminophenazone and diphenylpyraline hydrochloride in treating the common cold in children of 6 to 24 months of age]. / Ensayo clínico sobre el efecto de la bufenina, aminofenazona y el clorhidrato de difenilpiralina en el tratamiento del resfriado común en niños de seis a 24 meses de edad.

INTRODUCTION: Acute respiratory infections are the second leading cause of morbidity in children under 18 years. Several drugs have been used with variable efficacy and safety, trying to reduce the associated symptoms and improve quality of life. OBJECTIVE: To evaluate the efficacy and safety of buphenine, aminophenazone and diphenylpyraline hydrochloride when compared with placebo for the control of symptoms associated with common cold in children 6-24 months of age. MATERIAL AND METHODS: Randomized clinical trial, double blind, placebo controlled, in 100 children < 24 months of any gender, with symptoms associated to common cold. They received the drug under study vs. placebo for seven days. Both groups received acetaminophen. The change on common cold related symptoms were evaluated. Statistic analysis was made with STATA 11.0 for Mac. RESULTS: Fifty-three children were randomized to study drug and forty-seven to placebo. Age of children in each group was similar (12.2 +/- 5.8 months vs. 12.7 +/- 5.8 months, p NS). There were significant differences between groups in relation to rhinorrea and sneezing resolution, with better results in Flumil group and no adverse events observed. CONCLUSIONS: The results in this study indicates that Flumil is a safe and effective drug for control of symptoms present in the common cold in children aged 6-24 months.

Analgesic activity of Enhydra fluctuans.

The methanol extract of Enhydra fluctuans, given orally at the dose of 250 and 500 mg/kg, was evaluated for its analgesic activity using the acetic acid induced writhing and the tail-flick methods. The extract showed promising activity in both tests.

[The activity of enzymes and free radical oxidation in acute and chronic fetal hypoxia in general anesthesia during cesarean section]. / Aktivnostta na enzimite i svobodno-radikalnoto okislenie pri ostra i khronichna khipoksiia na ploda v usloviiata na obshta anesteziia pri tsezarovo sechenie.

The following study dwells on a basic problem in obstetrics anaesthesia. It shows a present view of the in NLA and ataractics having effect on free radical oxygenation process in mother-fetus system in Cesarean section. 101 pregnant women have been studied as the values of FROq serum antioxygenase activityq serum enzymes activity in women blood and in blood of umbilical cord have been compared.

A device for automatic measurement of writhing and its application to the assessment of analgesic agents.

A device was developed for automatically measuring writhing in mice so as to be applied to the assessment of analgesic agents. The device was composed of a specially designed container equipped with a detector, namely, a mechanoelectro transducer for writhing. The detector was made up of units of a string, two plates, and two strain gauges. In the unit, each end of the string was connected to either of the plates to which either of the strain gauges was attached. The change in tension of the string due to writhing was converted into the mechanical strain of the plates and then the resistance change of the strain gauges. The resistance change was amplified by a Wheatstone bridge circuit that was connected to a differential amplifier, a high-pass filter, comparator(s), and a monostable multivibrator to obtain the electrical signal for writhing. Using this device, writhing was continuously measured, and evaluation of various types of analgesic agents was performed. The result suggests that this device has sufficient accuracy both for the detection of writhing and the evaluation of analgesics. It has the advantage of automatic measurement of writhing in contrast to the conventional visual observation method.

[Efficacy and tolerance of a local application of phenazone and chlorhydrate lidocaine (Otipax) in infants and children with congestive otitis]. / Efficacité et tolérance d'une application locale de phénazone et de chlorhydrate de lidocaïne (Otipax) dans les otites congestives du nourrisson et de l'enfant.

The efficacy and safety of ear drops containing phenazone and lidocaine hydrochloride (Otipax) for the treatment of congestive myringitis were evaluated in 18 infants and children aged 1 to 10 years. Relief of pain was evident 5 minutes after instillation and significant after 15 to 30 minutes. Serial photographs of the tympanic membrane demonstrated prompt improvement of inflammation. Congestion was significantly reduced after five minutes and overall ear drum color was significantly improved after 15 to 30 minutes. No adverse effects were recorded. These data suggest that Otipax is effective and safe for the treatment of painful congestive myringitis in infants and children.

[The expediency of optimizing lipid peroxidation in treating complicated forms of myocardial infarct healing]. / O tselesoobraznosti optimizatsii perekisnogo okisleniia lipidov v lechenii oslozhnennykh form zazhivleniia infarkta miokarda.

Experiments on 36 dogs revealed a relationship of inhibition and stimulation of lipid peroxidation (LPO) and reactivity of myocardial infarction (MI) concerning outcomes of healing. It is shown that in complicated IM it is necessary to optimize LPO turning its dynamics to uncomplicated disease forms. In hyperreactive MI it is judicious to use antioxidants while in hyporeactive LPO stimulation is indicated using ultraviolet radiation of the blood.

[Effect of propyphenazone on drug biotransformation in the liver. A comparison with phenylbutazone using the aminopyrine breath test]. / Zum Einfluss von Propyphenazon auf die Arzneimittelbiotransformation in der Leber. Eine Vergleichsstudie mit Phenylbutazon unter Verwendung des Aminopyrin-Atemtestes.

By means of the aminopyrine breath analysis the influence of phenylbutazone, propyphenazone and of the combination preparation Wofapyrin "new" on the aminopyrine-N-demethylation, a hepatic microsomal performance of biotransformation in patients with diseases of the rheumatic circle of forms was examined. The enzyme-inducing effect of phenylbutazone known from literature could be confirmed. On the other hand despite a relatively highly dosed one-week treatment propyphenazone did not lead to changes of the demethylation capacity of the liver in the majority of the patients. In individual cases increases of the capacity are possible. In general, however, the doses of propyphenazone usual in the practice for the treatment of acute feverish infections no disturbing effects of induction or inhibition on the metabolic liver functions represented by the amino-N-demethylation are to be expected. The enzyme-inducing effect of Wofapyrin "new" is to be ascribed to the phenyl-butazone component.

Analgesic efficacy and tolerability of diflunisal in oral surgery.

A double-blind, completely randomized study was carried out on 169 patients to compare the analgesic efficacy and tolerability of diflunisal with that of Veralgin after surgical removal of impacted third molars. One group received 1000 mg diflunisal (Donobid, MSD) 2 h preoperatively and then 500 mg twice daily for 2.5 days, and the other group Veralgin (aminophenazon. 286 mg, barbital. 114 mg, aethylmorph. hydrochlorid. 20 mg, Orion), a fixed combination widely used in Finland, 1 tablet twice daily beginning 2 h prior to operation. Visual analogue scales were used to estimate pain. Diflunisal was found to be superior in relieving pain in the early postoperative period, the associated frequency of adverse clinical experiences was lower and the final evaluation of analgesic efficacy by both the patients and the investigators, was in its favour. The study confirms that postoperative pain after third molar surgery can be controlled well without the use of mainly centrally acting combination analgesics.

Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

[Hypokalemic periodic paralysis provoked by "Ambene"]. / Hypokaliämische periodische Lähmung provoziert durch "Ambene".

The case of a 42-year-old man is reported, who on four occasions developed a hypokalaemic periodic paralysis after an intramuscular injection of "Ambene". The detailed examination of this patient shows, that it is the primary, autosomal dominant inherited form of hypokalaemic periodic paralysis, and not the secondary form, which is caused by a renal or gastrointestinal loss of potassium. Clinical and electrophysiological, as well as histopathological and electron microscopic findings are presented, showing the typical vacuolar myopathy with submicroscopic tubular structures. In the literature there is evidence for an increased sensitivity of the muscle membrane to insulin with an increased potassium-shift inside the cell in hypokalaemic periodic paralysis. "Ambene" is a combination, which contains amongst other substances dexamethasone and the local anaesthetic drug lidocain. In the present case the paresis was possibly caused by a combined effect of dexamethasone with a consequent hyperglycaemia and lidocain with a change in the excitability of the muscle membrane. The pathophysiological mechanism of hypokalaemic periodic paralysis is discussed in terms of the release by the combination of these two drugs. It has not previously been reported that "Ambene" can provoke a hypokalaemic periodic paralysis. This is a severe side effect because of the resulting cardiac and respiratory problems.

Comparison of paracetamol and aminophenazone plus diazepam suppositories for anxiety and pain relief after tonsillectomy in children.

The anxiety and pain-relieving effect of paracetamol 10 mg/kg or a combination of aminophenazone 4 mg/kg and diazepam 0.2 mg/kg suppositories was studied in 82 children after tonsillectomy in a double-blind study. Both suppositories were studied after halothane or enflurane anaesthesia. At 30 min after administration of coded suppositories, 88-90% of the children in various groups needed extra analgesics, and received pethidine 0.5 mg/kg i.v. Thereafter, the anxiety and pain relief was satisfactory in all groups. There was no significant difference between the effects caused by the drugs. No bleeding occurred from the operation site in any of the study groups. The results suggest that both paracetamol and a combination of aminophenazone and diazepam in the doses used here were weak analgesics for throat pain after tonsillectomy in children during the early postoperative period.

[Mechanism of formation of blocking factors and method of antiblocking immunotherapy in malignant tumors]. / O mekhanizme obrazovaniia blokiruiushchikh faktorov i metode antiblokiruiushchei immunoterapil zlokachestvennykh opukholei.

A hypothesis on blocking factor formation in carcinogenesis is discussed. Destabilisation of cell membranes and increased levels of proteolytic enzymes in tumor tissue are considered to be the trigger mechanism. Protease level in large bowel tumor was found to be higher than in normal tissue. Plasminogen level in cancer patients was significantly higher than in healthy subjects. Application of different experimental schemes of treatment with membrane-stabilizing drugs and an inhibitor of protease was followed by antitumor and antiblocking effects. Sorption of rheumatoid factor and immune complexes from plasma led to a decrease in the blocking activity of plasma in vitro. In cases of rectal cancer, plasmapheresis was followed by tumor regression and a fall in immune complex concentration.

[Formalin-induced minor tremor response as an indicator of pain].

Formalin which was said to produce prolonged pain and inflammation was injected subcutaneously into the back of guinea pigs, and minor tremor pain response (MTP-response) was measured using the MT-pick up, integrator and digital volt meter. The MTP-response curve showed a biphasic pattern. Immediately after injection, the MTP-response curve showed a significant peak which lasted for about 2 min (the first phase) and subsequently dipped rapidly, and after 5 min, it began to rise slowly again and had a peak at 30 min (the second phase). Morphine (6 mg/kg, s.c.) inhibited completely the first and second phases. Levallorphan (1.2 mg/kg), however, reversed the inhibitory effect of morphine at the first phase, but not at the second phase. Aspirin (200 mg/kg, i.p.), aminopyrine (100 mg/kg, s.c.) and pentazocine (5 mg-10 mg/kg, s.c.) inhibited significantly the formalin-induced MTP-response at both phases. Pyridinol carbamate (200 mg/kg, i.p.) and hydrocortisone (25 mg/kg, i.p.) had no effect on the MTP-response at the first phase, but inhibited it at the second phase. There was a parallelism between the time course of the vascular permeability induced by formalin and that of the second phase of MTP-response. From these results, it is suggested that the first phase of MTP-response is derived from the direct effect of formalin on free nerve endings, while the second phase is derived from the inflammation. Since two kinds of pain features were differentiated in this method, the relationships with so-called "immediate pain" and "delayed pain" were discussed. Furthermore, this method can be utilized to assess pain and the action of analgesics objectively and quantitatively.