Impact of MDR1 genetic polymorphisms on postoperative piritramide analgesia.

OBJECTIVES: The aim of prospective study was to evaluate the therapeutic efficacy of piritramide in patients after removal of parathyroid glands in relation to MDR1 genotype. In the treatment of moderate acute postoperative pain, piritramide plays a major role. It is difficult to predict its optimal therapeutic efficacy and tolerability in individual patients. METHODS: We compared the effect of piritramide in 56 patients after surgical removal of parathyroid glands in a prospective study. We evaluated pain intensity, pain difference and sum of pain difference (SPID) using visual analogue scale (VAS in mm) and adverse effects in the relationship with the MDR1 - polymorphism of G2677T/A. RESULTS: In the wild-type group (2677GG), there was maximal pain difference of 30.6 ± 24.9 and SPID of 209.33 ± 95.80 while in genotype 2677TT and 2677GT, the corresponding values were 19.5 ± 25.5 and 147.07 ± 91.38, respectively. In group of patients with wild type of 2677GG genotype, there was 80 % of responders with more than 50 % reduction in VAS as compared to baseline while in group with carriers of 2677T allele, there are only 39 % of responders present (χ² = 5. 83; p = 0.016). Furthermore, the total consumption of piritramide was lower in comparison with the variant-allele carrying group (p = 0.008). The total incidence of adverse drug reactions was observed in 40 % of patients with wild type of 2677GG genotype when compared to 83% in the group carrying the variant allele (χ² = 7.92; p = 0.005). Significantly more patients in the wild-type group were satisfied with postoperative pain treatment in comparison to the variant allele group (χ² = 6. 49; p = 0.0109). CONCLUSION: We observed a better analgesic effect of piritramide and a decreased incidence of side effects in the wild-type genotype (2677GG) group, when compared with variant-allele carrying patients (Tab. 2, Fig. 1, Ref. 7).

The effect of postoperative pain treatment on the incidence of anastomotic insufficiency after rectal and rectosigmoideal surgery.

The aim of prospective study was to evaluate the pain relief in the postoperative period and consumption of opioid and non-opioid analgesics as a risk factor of the anastomotic insufficiency after rectal and rectosigmoideal resection for carcinoma. Anastomotic insufficiency is one of the most feared and life threatening early complications. No articles about the effect of the response to opioid therapy in the postoperative period on the risk of this major clinical problem have been published. We compared the effect of opioid and non-opioid analgesics in 109 patients who underwent rectal and rectosigmoideal resection in a prospective study. We evaluated the appearance of anastomotic insufficiency and clinical conditions in the relationship with the pain relief in the postoperative period and consumption of opioid and non-opioid analgesics. The pain intensity and the consumption of analgesics were significantly increased in the group of nonresponders. The rate of PONV (postoperative nausea and vomiting) in the responders and nonresponders groups was 69% and 78%, respectively. However, the differences did not reach significant level. Other clinical conditions were not significantly different between the both groups, too. The difference in the incidence of anastomotic insufficiency between both groups was highly significant, 6% cases of anastomotic insufficiency in the responders group and 19% in nonresponders group (χ2 = 7.73; p=0.0054). Nonrespoders to opioid therapy and their high consumption of second-line analgesics is a high risk factor for anastomotic insufficiency.

Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms.

OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy. BACKGROUND: Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population. Available data provide controversial results regarding the analgesic efficacy of tramadol in subjects with different CYP2D6 genotypes. METHODS: Pain intensity was assessed using visual analogue scale at 2 and 24 hours after the knee arthroscopy in 156 patients. Polymorphisms CYP2D6*3,*4,*5,*6, and gene duplication and C3435T in MDR1 gene were analyzed by PCR - RFLP. RESULTS: Mean VAS2h value in the whole study group was 44.0 ± 16.5 mm. Mean pain difference, was lowest in the UM group and highest in the PM group. The pain difference varied significantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with significant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no significant differences among MDR1 subgroups with regards of pain difference. Mean tramadol consumption was 2.47 ± 1.17 mg/kg during the 24 h period. There were no significant differences in the drug consumption, reporting of adverse reactions, need for rescue analgesic medication or verbal description of pain among the CYP2D6 or MDR1 genotype subgroups. CONCLUSION: CYP2D6 plays a significant role in tramadol analgesic efficacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18).

Pupillometry in healthy volunteers as a biomarker of tramadol efficacy.

WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers. METHODS: Sixty-nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed. RESULTS AND DISCUSSION: Large interindividual variability was observed in the tramadol-induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P < 0·05) except for the reflex amplitude and constriction velocity. WHAT IS NEW AND CONCLUSION: The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.

The role of diclofenac and piritramide in the management of acute postoperative pain in hernioplasty.

OBJECTIVES: The aim of the study was to compare the effects of diclofenac and piritramide in acute postoperative pain after hernioplasty. BACKGROUND: In the treatment of moderate acute postoperative pain, non-steroidal anti-inflammatory drugs and opioids play the major role. The data on safety and effect of analgesia based on opioid and non-opioid drugs are still a controversial topic. METHODS: We compared the first-line treatment effects of diclofenac and piritramide in 105 patients after hernioplasty in a retrospective manner. The subsequent therapy combined piritramide with diclofenac. We evaluated the intensity of pain and its relief using a visual analogue scale (VAS). We also evaluated the necessity of application of other analgesics. RESULTS: One hour after the application of the first analgesic dose, we observed complete pain relief in 39.5% of patients treated with piritramide and in 19.4% of patients treated with diclofenac (chi2=5.17; p=0.02). After the use of piritramide, the pain relief (3.84 +/- 1.27 mm) was significantly higher than after diclofenac (3.34 +/- 0.77 mm). Another injection was needed in 76% and 54% of patients subjected to first-line treatment based on diclofenac and piritramide, respectively. CONCLUSION: We observed that the first-line analgesic treatment based on piritramide was more effective when compared to that based on diclofenac (Tab. 3, Ref. 3). Full Text in free PDF www.bmj.sk.

[The Bernard-Soulier syndrome. A hereditary functional and structural disorder of blood platelets]. / Bernarduv-Soulieruv syndrom. Hereditární funkcní a tvarove strukturální porucha krevních desticek.

BACKGROUND: The authors submit a clinical and laboratory description of a patient with Bernard-Soulier syndrome diagnosed in this country for the first time. The investigation comprises an analysis of haemostatic functions, selected structural indicators and the detailed morphology of thrombocytes. The analysis of defined inborn functional disorders of thrombocytes is a method for studying haemostatic mechanisms. METHODS AND RESULTS: In addition to standard haemostatic methods flow cytometry in used to assess the size of platelets, and using monoclonal antibodies against glycoproteins, their presence on the surface membrane is assessed. Thrombocytic glycoproteins are further analyzed using diagonal electrophoresis on sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE). The authors found medium thrombocytopaenia with the presence of giant thrombocytes which on elecronmicroscopic examination, with the occasional exception of endoplasmic membrane proliferation, do not display structural deviations. The assessed deviation of thrombocyte aggregation after ristocetin, suggesting a defect of the adhesive capacity of thrombocytes, is apparently due to reduction of the surface glycoprotein GPIb, proved by flow cytometry and SDS-PAGE. The drop of glycoprotein GPIb to 20% of normal values suggests a heterozygote type of disorder with a medium grade of haemorrhagic manifestations. CONCLUSIONS: This is the first case of Bernard-Soulier syndrome in the Czech literature. Its analysis provides evidence of the relationship of the adhesive function to the surface glycoprotein GPIb and confirm the effectiveness of the elaborated diagnostic methods.

Biochemical changes in sows after eleven or more farrowings.

The animals examined were 30 sows after eleven or more farrowings (pluriparous sows) and 26 primiparous sows. The pluriparous animals were 75.1 months old on the average and had farrowed an average of 13.23 litters. The mean age of the primiparous sows was 12.8 months. The blood sera of pluriparous sows had higher concentrations of total protein and urea and lower levels of 11-hydroxycorticosteroids (11-OHCS) and lower aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities than those of primiparous sows. The pluriparous sows showed mild hypoglycaemia and hypocholesterolaemia. When insulin was injected i.m. in the dose of 1 I.U. per kg body mass, a decrease in blood serum glucose, total protein and potassium levels was recorded 60 min later in both pluriparous and primiparous sows; a significant rise in 11-OHCS concentration occurred only in the primiparous sows. It was concluded that the response of the hypothalamo-pituitary-adrenal axis in pluriparous sows to an insulin load is reduced. Studies of pluriparous sows contribute to a better understanding of the ontogenetic development of pigs throughout their postnatal development.

[Heritability in the incidence of rudimentary teats in milk cows of the Bohemian spotted breed]. / Dedivost výskytu nadpocetných struku u dojnic ceského strakatého Plemene.

The set of 2,230 dairy cows was studied for genotype influence on the occurrence of rudimentary teats in the dairy cows of Bohemian Spotted breed. In the studied population 57.62% cows had rudimentary teats. Out of this percentage, 45.23% of animals had only one small teat, 50.43% cows had two small teats and 4.34% had more than two rudimentary teats. The estimation of rudimentary teat heritability was carried out by the method of daughter regression to dams in 185 pairs. The calculated heritability coefficient was medium high (h2 = 0.56 +/- 0.15). As found out further, the dams having rudimentary teats had by 20% higher proportion of daughters with rudimentary teats than the dams without rudimentary teats. This relationship is statistically highly significant. The interrelationship between the dams and daughters as to the occurrence of one or two rudimentary teats was statistically insignificant. By means of the analysis of variance in the groups of half-sisters after 49 sires (the average number of animals per group amounted to 45), the intracorrelation coefficient was determined and used for the calculation of the heritability coefficient h2 = 0.26 +/- 0.07.

[Economic significance of the prevention of losses caused by blood-sucking diptera in grazing dairy cows]. / Ekonomický význam prevence ztrát pusobených dvoukrídlým krev sajícím hmyzem u pasených dojnic.

It was was demonstrated in an experiment that the blood-sucking dipterous insects adversely affected the efficiency of cows on pasture; these cows showed a significantly decreased milk yield and milk fat percentage. The experiment was conducted in South Bohemia at Chlum u Trebone where seven species of gnats occurred in considerable abundancy, including the largest populations of Aedes sticticus (Meig.), Ae. cinereus Meig., Ae. vexans Meig. and Ae. punctor Kirby, which represented more than 80% of all gnats, and where gad-flies lived at the same time, represented by 18 species of five genera, chief among which were the species Tabanus bromius (L.) and T. maculicornis (Zett.), forming over 60% of all gad-flies. The experiment with 25 control dairy cows of the Bohemian Spotted breed lasted 62 days (July, August 1977). Diethyltoluamide in a 10% water emulsion was used as repellent with which cows were sprayed (with a special spraying apparatus) in 48h intervals. In the experimental (sprayed) cows, compared with the untreated control cows, milk yield per head per day increased by 6.23%, i. e. 43.56 kg milk, and butterfat percentage increased by 11,81%, representing 3.62 kg per head per day. In conversion to fat-corrected milk (milk with a constant 4% fat content), milk yield increased by 9.69%. In conversion to values per 1000 cows on pasture the net value of milk increased by 709.41 Kcs per day. The return rate of the money expended is 1.31 crowns. The results were statistically significant to highly significant.

[Biochemical and hematological changes in sows during estrus]. / Biochemické a hematologické zmeny u prasnic v údobí ríje.

After the second and fourth parturition of piglets, ten clinically healthy sows, weaned on the second day of life, were subjected to examination two to three days before heat, during heat (defined by typical changes on the outer genitals and immobilization in the presence of a boar) and two days after insemination. During the morning hours, four hours after the last feeding, blood was taken from V. cava cranialis. Seventeen parameters were determined in whole blood and in the blood serum. In the period of oestrus, compared with the period two to three days before this period and two days after insemination, a marked increase was observed in the concentration of the serum levels of 11-hydroxycorticosteroids, iron, and in the activity of alanine aminotransferase. The activity of aspartate aminotransferase was increased in heat only in comparison with the period of the two days after insemination. The concentration of haemaglobin in whole blood was significantly increased in comparison with the period before oestrus and after insemination. Further, in the heat period -- as compared with the time before it -- a considerable drop was observed in the content of inorganic phosphorus and vitamin A. The possible mechanism of the occurrence of other changes is discussed.

[Effect of hypodermyiasis in cattle on milk-production indicators in 1st-calvers]. / Vliv hypodermatózy skotu na produkcní ukazatele mléka u prvotelek.

We investigated the effect of hypodermosis on the quantitative and some qualitative indicators of milk from 20 experimental and 18 control first-calvers of the Pinzgau cattle breed. The experiment took place at two experimental localities in mountainous pastures of the Central-Slovakian region. In the experimental animals, treated with Hypocid, the production of milk per dairy cow increased on an average by 115.98 kg, i.e. 24.83%, over the experimental period of 61 days (May, June) with an average invasion intensity of 5.94 larvas in control animals. Milk fat production increased on an average by 7.20 kg, i.e. 34.97%. Production recalculated to FCM milk amounted on an average to 31.61%. The profitability of treating hypodermosis with the Hypocid preparation is expressed by the average savings of 0.40 Kcs per litre of milk per day.

[Elimination of testosterone and androstendione in the urine of boars in relation to the incretory function of the testes]. / Vylucování testosteronu a androstendionu mocí kancu ve vztahu k inkrecní funkci varlat.

The elimination of testosterone and androstendion in the urine was tested in six sexually mature boars. The administration of chorionic gonadotropin to intact animals resulted in a marked, statistically significant, rise of the amounts of excreted testosterone and, in part of the cases, androstendion. The responses were individual. Bilateral orchidectomy caused a statistically highly significant decrease of the elimination of both steroids under study without pronounced adrenocortical compensation. The administration of the adrenocorticotropic hormone to castrated boars did not exert any significant influence on the excretion of the substances studied. The use of chorionic gonadotropin given to the castrated boars did not produce any significant changes in the elimination of hormones. It has been inferred that testosterone as well as androstendion in the urine of boars are almost exclusively of testicular origin and that the response of the values of both steroids to the administration of chorionic gonadotropin is specific after testicular incretion. The discussion concerns the importance of these findings for the evaluation of the incretion reserve of the testes and for the diagnosis of incretion hypogonadism in boars.

[Therapy of hypodermyiasis in heifers from the economic point of view]. / Terapie hypodermatózy jalovic z ekonomického hlediska.

The test set of animals consisted of sixty one- to two-year-old heifers of the Slovak Spotted and Pinzgau breeds kept at three sites. The Hypocid preparation (containing 40% trichlorphon) in the dose of 15 ml per 100 kg of live weight was applied to these cows by the lavage method in the sacrolumbar region of the spine in 1973. Another group, consisting of 58 heifers, was left untreated as controls. In the experimental period extending over 158, 150 and 120 days at different sites (143 days on an average), weight gains and the health condition of the experimental and control animals were checked in monthly intervals. The average extensity of invasion in the control heifers was 79.31% and the intensity of invasion was 14.58%. The extenseffectiveness of Hypocid (EE) was 97.90% and the intenseffectiveness of the preparation (IE) was 99.99%. The results prove a negative effect of hypodermatosis on the weight gains of untreated heifers and high profitability of the therapy: after subtraction of the costs of therapy the savings were 1.74, 3.88 and 2.25 crowns per kg gain per day (2.62 crowns on an average). The veterinary measures gave the following savings per each crown expended: 2,243.55; 3,066.85 and 922.83 crowns (depending on site).

[Persistence of oxytetracycline residues in the organism of calves treated with Oxymykoin Spofa inj. ad us.vet]. / Persistence reziduí oxytetracyklinu v organismu telat lécených prípravkem Oxymykoin Spofa inj. ad us. vet

By means of two biological diffusion methods an oxytetracycline (OTC) content was determined in the tissues of nine calves treated with a single i. m. OTC dose in the quantity of 15 kg-1 body mass. The preparation used for the treatment was Oxymykoin Spofa inj. ad us. vet. For the testing 2 collection strains -- B. cereus var. mycoides (ATCC 11778) and B. subtilis (ATCC 6633) were employed. The method using spore suspensions of the above strains was more sensitive. OTC was quantitatively determined in the samples by reading the standard curves. By evaluation of the two methods the following results were obtained: 5 to 10 days post injection all calves were positive. 15 days after the administration one out of 3 calves was positive. 20 days following the injection both calves were negative. The most frequent residue occurrence was recorded at the injection site, then in the kidney and liver. Spleen lung and bone marrow were completely without any finding. Maximum concentrations were found in the samples from the injection sites and kidney. In the other organs and muscles (noninjection sites) many times lower concentrations were found. Culinary and technological treatment of positive meat and liver samples revealed that already 15 minutes' boiling destroyed the microbiologically active OTC residues; on the contrary, after roasting OTC inactivation in the samples was not that univocal. Freezing and salting are utterly insufficient for OTC inactivation. A preslaughter withdrawal time of 20 days is recommended for the preparation tested.

[Effect of various factors on the electric conductivity of mixed milk]. / Vliv nekterých faktoru na elektrickou vodivost smesného mléka

The authors evaluated the method of the determination of the electric conductivity of purchased milk for the estimation of the hygienic aspects of milk quality and for mass diagnosis of the inflammatory diseases of dairy cow mammary glands. The variability coefficient of duplicates varied from 1.37 to 3.09%. The study of the dependence of milk conductivity measurement on milk temperature revealed a statistically highly significant positive correlation between the values of these two factors. In the temperature range from 30 degrees C to 35 degrees C the coefficients of correlation ranged from 0.951 to 0.996. Furthermore, interference caused by milk acidity was examined during a five-day incubation of samples at 25 degrees C. A statistically significant difference was observed from the third hour of incubation (P less than 0.05) and a statistically highly significant difference from the fourth hour of incubation (P less than 0.01). The evaluation of the diagnostic value of the method of the measurement of electric conductivity in purchased milk revealed a positive correlation to the content of chloride ions (r = 0.69) and to the number of the cellular elements of milk (r = 0.33).