Analgesic effects of piritramide in acute postoperative pain - comparison of intramuscular administration with patient-controlled intravenous analgesia and impact of OPRM1 and ABCB1 polymorphisms.

AIMS: The aim of this study was to compare the efficacy, consumption and safety after piritramide administered either intramuscularly (IM) on demand or via patient-controlled intravenous analgesia (PCA) and to examine the impact of OPRM1 and ABCB1 gene polymorphisms on the drug efficacy/safety in both regimens. METHODS: One hundred and four patients scheduled for elective inguinal hernioplasty received piritramide with PCA or IM for postoperative pain management. We evaluated piritramide consumption, pain intensity using visual analogue scale (VAS) and adverse effects. RESULTS: Median (IQR) piritramide consumption was 18.5 (13.5-31.2) and 15.0 (15.0-15.0) mg in the PCA and IM groups, respectively (P=0.0092). The respective values of area under the VAS2-16-time curve were 40 and 280 mm.h (P=0.0027). Opioid-induced adverse effects were more frequent in the PCA than in the IM group. Variant OPRM1 allele was associated with decreased pain relief, increased opioid consumption and increased incidence of adverse effects, while ABCB1 polymorphisms showed no impact on the observed parameters. CONCLUSIONS: We observed higher piritramide consumption, better pain relief and slightly worse safety profile in the PCA group compared with IM administration. Variant OPRM1 118G allele carriers required higher opioid dosing and suffered from more adverse effects, however, the differences between genotypes have been less pronounced in the PCA patients likely due to improved pain management via PCA.

Parathyroid Carcinoma in Patients that Have Undergone Surgery for Primary Hyperparathyroidism.

BACKGROUND/AIM: Parathyroid carcinoma is a rare clinical entity, which represents one of the main reasons, why surgery should be performed in specialized centres. Preoperatively, it is very difficult to distinguish between benign and malignant hyperparathyroidism. PATIENTS AND METHODS: During the years 1996-2016, we performed 2,220 operations in 2,075 patients with a diagnosis of primary hyperparathyroidism. RESULTS: Among these 2,220 operations, there were 16 operations for parathyroid carcinoma. These 16 operations, including reoperations, were performed in four patients. Two patients had no reoperation, but another 2 patients required 14 reoperations in total. Parathyroid carcinoma was described in 0.2% of all patients with a diagnosis of primary hyperparathyroidism. The number of operations was 0.73% of all operations of primary hyperparathyroidism in years 1996-2016. CONCLUSION: Prognosis of parathyroid carcinoma is quite favourable, patients evidence a long-term survival rate after the primary operation. However, every reoperation increases the number of possible complications, including recurrent laryngeal nerve injury.

Changes in the Pattern of Primary Hyperparathyroidism in Czech Republic.

Primary hyperparathyroidism (PHPT) is currently the most common endocrine disorder in Czech Republic after diabetes and thyroid diseases particularly in postmenopausal women. Over the past 40 years PHPT has changed from a rare severe disease of the bones and kidneys to common disease with hypertension, peptic ulcer, pancreatitis, easy fatigue and proximal muscle weakness. During 43 years we have examined one of the greatest groups of patients with PHPT. In the early 1970 the estimated incidence of PHPT in former Czechoslovakia was approximately 8 cases per 100 000 persons per year. Our data showed that the incidence of PHPT increased sharply to 24 cases per 100 000 persons per year in same community with the introduction of automated serum calcium and iPTH measurement. The disease is four times more frequent in women as in man. The ratio women to men did not changed since 1981. However the incidence of PHPT changed in Czech Republic from previous years, it develops around the fifth decade of life and is increasingly discovered with advancing age. The incidence of hypertension, diabetes mellitus, cholelithiasis, pancreatitis and peptic ulcer among patients with PHPT is higher as compared with the incidence of these diseases in the general population. However there are still patients suffering from bone and renal complication of PHPT. Removing the adenoma by an experienced surgeon is the first choice of treatment of patients with PHPT. The study offers valuable data on the actual state of hyperparathyroid patients in the Czech Republic.

Different effects of lobeline on neuronal and muscle nicotinic receptors.

Lobeline is a plant alkaloid known to interact with cholinergic system. The effect of lobeline on neuronal α3ß4 receptors expressed in COS cells and muscle embryonic αßγδ receptors naturally expressed in TE671 cells was studied using a patch-clamp technique. Our results show that lobeline inhibited responses to acetylcholine in human embryonic muscle nicotinic receptor in a pseudo-noncompetitive manner. The responses of rat neuronal α3ß4 receptors to a low concentration of acetylcholine were potentiated by a mixed occupation mechanism that corresponds to "competitive potentiation". This potentiation turned into voltage-dependent inhibition for α3ß4 receptors was activated by a high concentration of acetylcholine.

Dual effect of lobeline on α4ß2 rat neuronal nicotinic receptors.

The effect of lobeline on rat α4ß2 nicotinic receptors expressed in COS cells was studied using the patch-clamp technique. Currents were recorded in whole-cell mode 2-4 days after cell transfection by plasmids coding the α4ß2 combination of receptor subunits. In cells sensitive to acetylcholine, the application of lobeline evoked minor responses (up to 2% of maximal acetylcholine response). When acetylcholine was applied to the background of an already running application of lobeline, acetylcholine responses were inhibited in a concentration- and time dependent manner. However, when lobeline was applied simultaneously with acetylcholine without any prepulse or during an already running application of acetylcholine, the acetylcholine responses were potentiated up to 300-600% of that of the control. The site of lobeline action overlaps with the cholinergic site, as was proven by the partially protective effect of (+)-tubocurarine. Thus, lobeline can apparently desensitize receptors when applied alone (inhibition) whereas its binding to a second agonist site with the first one already occupied by acetylcholine leads to channel opening (potentiation).

The influence of orthognathic surgery on ventilation during sleep.

Orthognathic surgery has varying effects on respiratory parameters. The authors undertook a prospective study of patients requiring mandibular advancement, mandibular setback and maxillary Le Fort I advancement, and surgically assisted rapid maxillary expansion (SARME). Breathing parameters were monitored in a sleep laboratory the night before the operation and in a mean of 9.5 months after the operation. In patients treated with mandibular advancement, the respiratory disturbance index (RDI), oxygen desaturation index (ODI), and number of obstructive apnoeas (OAs) improved significantly. In patients treated with mandibular setback and maxillary Le Fort I advancement, the RDI, ODI, index of flow limitations (IFL), number of obstructive hypopnoeas (OHs), OA, and oxygen saturation deteriorated. In contrast, patients treated with SARME improved only mildly. These results indicate that bimaxillary surgery for Class III malocclusion increased upper airway resistance, probably because of a more dorsal positioning of the base of the tongue, representing an iatrogenic obstructive sleep apnoea (OSA). A young person would probably be able to balance such a decline in respiratory function using different adaptative mechanisms. Mandibular advancement significantly improved respiratory parameters during sleep. The possible effect of orthognathic surgery on the upper airways should be incorporated into the treatment plan.

Potassium-selective microelectrode revealed difference in threshold potassium concentration for cortical spreading depression in female and male rat brain.

It has been found with potassium-selective microelectrodes that the threshold extracellular concentration of potassium [K(+)](e) for eliciting fast spreading depression from the site of administration 1.5mm away is 80% lower in the rat female cortex (8.0 ± 0.6 mM) than in the male cortex (14.4 ± 0.4mM). The rate of the first slow phase of [K(+)](e) rise before reaching the threshold and speed of SD propagation were similar for both sexes as well as the rise of the second active fast phase of the [K(+)](e) increase. Lower [K(+)](e) threshold in females can facilitate the rapid K(+) release from the nerve tissue cells that may cause a cerebrovascular vasodilatation and the attack of migraine pain.

Surgical treatment of primary hyperparathyroidism in children: report of 10 cases.

Primary hyperparathyroidism in children is very rare. It is caused by overproduction of parathormone by a pathologically changed parathyroid gland. We carried out a retrospective study in 10 patients (age 10-17 years) who had surgical treatment between 1996 and 2007. The main signs of primary hyperparathyroidism were urolithiasis, nephrolithiasis, nephrocalcinosis and bone resorption, as well as non-specific signs such as fatigue, torpidness and muscle weakness. Patients were examined using sonography, MIBI-scintigraphy, CT and MRI. Calcium was measured before and after surgery; parathormone was monitored postoperatively. Surgery was curative in nine patients; reoperation was necessary in one patient because an ectopic parathyroid gland was not detected during the primary operation. Other major complications were not observed. Removal of pathologically changed parathyroid glands offers definitive and safe treatment of primary hyperparathyroidism in children. Special care should be taken if an ectopic parathyroid gland is suspected.

Dependence of miniature endplate current on kinetic parameters of acetylcholine receptors activation: a model study.

Mathematical modeling was applied to study the dependence of miniature endplate current (MEPC) amplitude and temporal parameters on the values of the rate constants of acetylcholine binding to receptors (k+) when cholinesterase was either active or inactive. The simulation was performed under two different sets of parameters describing acetylcholine receptor activation--one with high and another with low probability (Pohigh and Polow) of receptor transition into the open state after double ligand binding. The dependence of model MEPC amplitudes, rise times, and decay times on k+ differs for set Polow and set Pohigh. The main outcome is that for set Pohigh, the rise time is significantly longer at low values of k+ because of the prolongation of ACh diffusion time to the receptor. For the set Polow, the rise time is shorter at low values of k+, which can be explained by the small probability of AChR forward isomerization after ACh binding and faster MEPC's peak formation.