Molecular hydrogen affords neuroprotection in a translational piglet model of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the major consequence of perinatal asphyxia (PA) in term neonates. Although the newborn piglet is an accepted large animal PA/HIE model, there is no consensus on PA-induction methodology to produce clinically relevant HIE. We aimed to create and to characterize a novel PA model faithfully reproducing all features of asphyxiation including severe hypercapnia resulting in HIE, and to test whether H2 is neuroprotective in this model. Piglets were anaesthetised, artificially ventilated, and intensively monitored (electroencephalography, core temperature, O2 saturation, arterial blood pressure and blood gases). Asphyxia (20 min) was induced by ventilation with a hypoxic-hypercapnic (6%O2 - 20%CO2) gas mixture. Asphyxia-induced changes in the cortical microcirculation were assessed with laser-speckle contrast imaging and analysis. Asphyxia was followed by reventilation with air or air containing hydrogen (2.1%H2, 4 hours). After 24 hours survival, the brains were harvested for neuropathology. Our PA model was characterized by the development of severe hypoxia (pO2 = 27 ± 4 mmHg), and combined acidosis (pH = 6.76 ± 0.04; pCO2 = 114 ± 11 mmHg; lactate = 12.12 ± 0.83 mmol/L), however, cortical ischemia did not develop during the stress. Severely depressed electroencephalography (EEG), and marked neuronal injury indicated the development of HIE. H2 was neuroprotective shown both by the enhanced recovery of EEG and by the significant preservation of neurons in the cerebral cortex, hippocampus, basal ganglia, and the thalamus. H2 appeared to reduce oxidative stress shown by attenuation of 8-hydroxy-2'-deoxyguanosine immunostaining. In summary, this new PA piglet model is able to induce moderate/severe HIE, and the efficacy of hydrogen post-treatment to preserve neuronal activity/function in this PA/HIE model suggests the feasibility of this safe and inexpensive approach in the treatment of asphyxiated babies.

Ischaemic postconditioning reduces serum and tubular TNF-α expression in ischaemic-reperfused kidney in healthy rats.

OBJECTIVE: We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic rats after renal ischaemia-reperfusion (IR) injury. We aimed to examine cytokine expression and apoptosis in tissue damage after revascularisation (TNF-α levels in serum and tissue). METHODS: Male Wistar rats (n = 32) were divided into four groups. The animals of normal feed groups (NF) were fed with normal rat chow and the cholesterol feed groups (CF) were fed with 1.5% cholesterol containing diet for 8 weeks. Anaesthetized rats underwent a 45-min cross-clamping in both kidney pedicles. Ischaemia was followed by 120-min reperfusion with or without PS protocol (group PS vs. IR). Postconditioning was induced by four intermittent periods of ischaemia-reperfusion of 15-s duration each. Serum cholesterol, triglyceride, urea and creatinine levels were determined. Proinflammation was characterized by the measurement of serum TNF-α. Tissue injury in kidney was determined by formaline-fixed, paraffin-embedded tissue sections. Tissue TNF-α levels were determined by immunohistochemistry. RESULTS: Significant elevation was observed in serum TNF-α level after IR injury in normal feed groups, which was reduced by PS. In CF group neither the elevation nor the postconditioning induced reduction were as significant as in the NF groups. In normal feed group PS caused a significant reduction in tissue TNF-α level which was significantly higher in CF. CONCLUSIONS: Ischaemic postconditioning proved to be an effective defense against IR in NF groups, but it was ineffective in CF groups in kidney tissue.

Effect of a glutathione S-transferase inhibitor on oxidative stress and ischemia-reperfusion-induced apoptotic signalling of cultured cardiomyocytes.

Oxidative stress and ischemia-reperfusion (I/R) injury are crucial in the pathogenesis of cardiovascular diseases. The antioxidant glutathione S-transferase (GST) is responsible for the high-capacity metabolic inactivation of electrophilic compounds and toxic substrates. The main objective of the present study was to examine the effect of GST inhibition (with the administration of ethacrynic acid [EA]) on the viability and apoptosis of cardiomyocytes when these cells are exposed to various stress components of I/R and mitogen-activated protein kinase (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase [ERK]) inhibitors. The primary culture of neonatal rat cardiomyocytes was divided into six experimental groups: control group of cells (group 1), cells exposed to H(2)O(2) (group 2), I/R (group 3), I/R and EA (group 4), H(2)O(2) coupled with EA (group 5), and EA alone (group 6). The viability of cardiomyocytes was determined using a colorimetric MTT assay. The apoptosis ratio was evaluated via fluorescein isothiocyanate-labelled annexin V and propidium iodide staining. c-Jun N-terminal kinase, p38, Akt/protein kinase B and ERK/p42-p44 transcription factors were monitored with flow cytometry. c-Jun N-terminal kinase activation increased due to GST inhibition during I/R. EA administration led to a significant increase in p38 activation following both H(2)O(2) treatment and I/R. ERK phosphorylation increased when GST was exposed to I/R. A pronounced decrease in Akt phosphorylation was observed when cells were cotreated with EA and H(2)O(2). GST plays an important role as a regulator of mitogen-activated protein kinase pathways in I/R injury.

[Acute arterial occlusions of the upper extremities--clinical data]. / Akútne uzávery tepien horných koncatín--nás klinický materiál.

The authors describe 30 cases of acute arterial occlusions of upper extremity during the last 10 years (1992-2001) in a group of 27 patients. In 27 cases the occlusions were caused by embolism and in 3 cases by acute thrombosis. In the group were 12 men and 18 women. The embolus was the most frequently located in brachial artery (cubital)--17 times (63%). In one case we were forced to perform amputation of left upper extremity for gangrene. Authors accentuate that early and adequate treatment lead to salvage of extremity in 80-100%.

[Results of surgical treatment of gastric cancer]. / Nase výsledky chirurgickej liecby rakoviny zalúdka.

The authors retrospectively analyse a group (1991-2000) of 129 patients with malignancies of the stomach operated at the Surgical Department of The District Hospital in Lucenec. The operated patients were: males 83 (64%), females 46 (36%), mean age--63.4 years. Elective operations were performed in 78.2% and acute operations in 21.8%. We were able to make resections in 90 (69.8%) patients and palliative operations in 39 (30.2%) patients. On the basis of histologic examinations-adenocarcinomas dominated (120 patients--93%). The postoperative mortality was 4.65% and five-year survival 12%.

[Simultaneous bezoars in the stomach, ileum and cecum causing acute ileus in a 30-year-old imbecile--case report]. / Súcasný bezoár zalúdka, ilea a céka u 30rocného imbecila pod obrazom akútneho ilea--kazuistika.

Bezoars are concretions of foreign materials in the stomach, small intestine or bowel in people or animals, which impair GIT motility or cause intestinal obstruction. The authors describe an interesting case report of a 30-year-old imbecile with manifestation of simultaneous bezoar of stomach, ileum and caecum and its operative treatment. They describe a short characteristics of this clinical unit, which is reported in the literature only in a few case reports.

[Personal experience with laparoscopic cholecystectomy in acute cholecystitis]. / Nase skúsenosti s laparoskopickou cholecystektómiou pre akútnu cholecystitídu.

Authors refer about their experiences with operations of acute cholecystitis by laparoscopy. They have evaluated retrospectively 1600 cases of laparoscopic cholecystectomies (LCHE) realized in the period from 1994 to 2000. In 302 (18.8%) cases was realized laparoscopic cholecystectomy for acute cholecystitis, which was confirmed by histopathological finding. During the mentioned period a total number of laparoscopic cholecystectomies for acute cholecystitis (n = 302) rise a number of classical cholecystectomies for the same diagnosis (n = 227). Very important role by authors take early dispatching a patient to a department of surgery and early estimation the diagnosis with consecutive laparoscopic treatment. Rates of peroperation, postoperation complications and reoperations in laparoscopic surgery of acute cholecystitis is comparable with elective laparoscopic cholecystectomy.

[Dental treatment of handicapped children under general anesthesia]. / Fogyatékos gyermekek fogászati kezelése általános érzéstelenítésben.

Complex dental treatment of a 15-year-old mentally retarded boy was presented by the authors. Oral surgical, restorative dental, and prosthetic intervention (upper and lower bridge) was done partly with intravenous narcotic agent (Propofol) and partly under intubation narcosis.

A new route, jet injection for anesthetic induction in children. IV. Midazolam plasma levels.

The jet injector route for midazolam was used in 40 children 1 - 6 years of age undergoing various short duration surgical procedures. A randomly selected dose of 100, 150, and 200 microg/kg was given by a jet injector and compared to 80 microg/kg by conventional i.m. injection with syringe and needle to induce sedation/anesthesia. Because of clinical limitations, plasma midazolam levels were measured for only up to 32 min post-injection. Peak levels were 70.4, 105.8, 157.3, and 135.5 ng/ml in the corresponding groups. Plasma levels reached their peak faster after 200 microg/kg jet injection than after 80microg/kg i.m. midazolam. Furthermore, midazolam plasma levels were sustained longer after 200 microg/kg by jet injection. Larger doses of midazolam are required by jet injection than by i.m. injection. Individual subjects showed considerable variability in plasma levels of midazolam by both methods of administration, although jet injection was more convenient and less traumatic.

A new route, jet injection for anesthetic induction in children--III. Ketamine pharmacokinetic studies.

The jet injector route for ketamine was used on 30 children 1-6 years of age undergoing various surgical procedures. A randomly selected dose of 2.5, 3.5, or 6.0 mg/kg of ketamine was given to induce anesthesia. Peak plasma ketamine levels did not follow a simple arithmetic increment related to dose. Dosage based on mg/m2 body surface area or mg/kg body weight provided similar blood levels of ketamine. The beta-phase t1/2 of ketamine in these children was shorter than that found in adults. Considerable individual variability was observed in both the plasma levels to a given dose of jet-injected ketamine and in the beta-phase t1/2. The ketamine beta-t1/2s were not dose related.

Investigation of effect of lesser curvature seromyotomy of the stomach in animal experiments.

The effectiveness of seromyotomy of the lesser curvature of the stomach--the simplified version of proximal selective vagotomy--was investigated in eleven dogs. Decreased acid secretion was proved with congo red test and pH measuring by glass electrode. No significant damage to the motor function of the stomach was found with scintigraphy. Histological examinations revealed neurofibre degeneration peripherally to the seromyotomy line after peripheral vagotomy and vacuolar degeneration in the ganglion cells and amputation neuromas in the seromyotomy line.

[New possibility in inguino-femoral hernia repair: laparoscopic herniaplasty]. / Uj lehetóség az inguino-femoralis sérvek rekonstrukciójában: a laparoscopos hernioplastica.

The development of minimally invasive surgery brought up the challenge: to repair the frequent inguino-femoral hernias laparoscopically. The authors performed 65 laparoscopic hernioplasties in one year: "transabdominal preperitoneal" technique was used in 61 cases und "intraperitoneal onlay mesh" in 4 cases. Fifty-three patients were operated on, 12 of them had bilateral hernias. Recurrent hernia was the indication in 22 patients (34%). The average operating time was 102 and 144 minutes in the unilateral and the bilateral cases, respectively. There was no wound infection, or general complication. Spontaneously dissolving seroma/hematoma of the spermatic cord was noticed and detected by ultrasound in 5 patients (7.7%). The neuralgia caused by the irritation of the nerves of the region in 4 patients (6.1%) disappeared without sequels after treatment with vitamins B. The 2 early recurrences (3.2%), considered to be caused by technical inexperience, these patients were treated successfully with the "intraperitoneal onlay mesh" technique. In the authors' opinion there are definite advantages of laparoscopic hernioplasty, namely the minimal postoperative pain, early mobilization, shorter hospital stay and early restoration of full physical activity (in 1-2 weeks) as well as the known disadvantages of this technique (narcosis, longer operative time, intraperitoneal procedure, higher costs).

A new route, jet-injection for anesthetic induction in children - II. ketamine dose-range finding studies.

Ketamine (K) i.m. has been widely used for anesthetic induction in small children in the last decades, if mask induction has failed. In many instances, however, physical restraint was required. In order to eliminate the pain of i.m. injection and to prevent the psychological and physical trauma associated with restraint, we evaluated the utility of jet-injection (j.i.) of K for anesthetic induction in a dose-range finding study. Thirty children (age 1-6 years), whose parents gave a valid consent approved by the IRB and were scheduled for minor surgeries, were randomized into 3 equal groups: A/ketamine 6.0 mg/kg j.i., B/ketamine 3.5 mg/kg j.i., C/ketamine 2.5 mg/kg j.i. As a drying agent atropine 20 microg/kg was also given i.v. The onset of full amnesic/sedative effect of K, the scoring of sedation and emotional state, the ease of placement of the i.v. catheter, the speed of recovery by Aldrete scores, and the time for safe discharge were evaluated. Although no demographic differences were observed among the groups the duration of surgery and anesthesia were longer in the B group (41 and 49 min) than in the A or C groups. The onset of sedation was significantly (p < 0.05) faster in group A (174 sec) than in group B (312 sec) or C (303 sec). However, no significant difference was observed in the onset of complete sedation among the groups. The sedation index was the lowest representing the best sedation in group A (4.2) while in group B and C were somewhat higher (4.6 and 4.4). There were no differences in the ease of i.v. cannulation among the groups. Recovery from anesthesia was the slowest in group A, although the differences among the 3 groups did not reach statistical significance. The mean discharge times ranged from 10-13 min with no differences among the groups. Laryngospasm occurred in 4:10 in group A and 1:10 in groups B and C. Evidently the high dose of K, 6.0 mg/kg caused a proneness to laryngospasm. Since no additional benefit was derived from this high dose, the lower doses (3.0 mg/kg) of K may be sufficient for routine use. None of the children experienced unpleasant recall or pain for the injection or the whole procedure. This new route of anesthetic induction with the jet-injector utilizing K may provide pain-free and stress-free induction as compared to its i.m. injection. This technique also prevents transmission of infection and is [correction of and cost] cost effective since simultaneous and/or sequential injection can be given from a single vial of K.

[Jet injection, a new method for the induction of anesthesia in children]. / Uj módszer az anaesthesia bevezetésére gyermekekben oltópisztollyal.

In order to shorten anaesthesia induction and to avoid pain of the intramuscular injection, we evaluated the efficacy and safety of midazolam given by a jet-injector, utilized solely for mass inoculations until now. Premedication with midazolam with the jet-injector, indeed, proved to be effective, rapid and safe in children. The best results were found in two groups receiving 150-200 microgram/kg midazolam. Within 5 minutes, it was easy to cannulate a vein in children injected by the jet-injector, whereas the effect of intramuscular injection developed slowly, within 7 minutes. In the latter group, cannulation of the vein was more difficult than in the other groups. The separation from the parents and anaesthetic induction were greatly facilitated by midazolam given by the jet-injector. Amnesia was present not only for anaesthetic induction but also for the injection. Recovery was not more prolonged in those premedicated with midazolam with the jet-injector than with midazolam administered by other routes: oral, rectal or nasal. The children induced with the aid of jet-injector had no unpleasant recall based on interviews with the patients and parents.

A new route, jet-injection for anesthetic induction in children: I. Midazolam dose-range finding studies.

In order to assure rapid anesthetic induction in children and to prevent the psychological and physical trauma associated with restraint during mask induction or intramuscular injection, we evaluated the utility of a jet-injector and the effectiveness of midazolam for anesthetic co-induction in a dose-range finding study. Forty children (age: 1-6 yrs), whose parents gave a valid consent approved by the Institutional Review Board (IRB) and who underwent minor surgery, were randomized into four equal groups: A. midazolam 100 micrograms/kg by jet-injection (JI); B. midazolam 150 micrograms/kg JI; C. midazolam 200 micrograms/kg JI; D. midazolam 80 micrograms/kg i.m by conventional syringe-needle. As a drying agent, atropine 20 micrograms/kg JI or i.m. was also added to the midazolam solution. The onset and full sedative effect of midazolam, the scoring of sedation and emotional state, the ease of placement of the intravenous catheter, the speed of recovery by Aldrete-scores and the time for safe discharge were evaluated. No demographic differences were observed among the four groups with similar mean duration of surgery and anesthesia. The mean sedation score was reduced in Group C the most, less in the B, A and D groups. The onset of sedation ranged from 3-5 min in groups A, B or C as compared to 5-9 min in D. Ideal conditions for the start of i.v. catheter were best achieved in group C (8:8) and B (8:10) in contrast to groups A (2:10) and D (0:10). Whereas no i.v. start was difficult in B and C, 6:10 were difficult in D and A. None of the children in the three JI groups (A, B and C) experienced unpleasant recall or pain from the injection during the whole procedure. Response to verbal stimuli recovered in 3 min after the end of anesthesia and the children were discharged 8-9 minutes afterward. None of the children needed a longer than 15-minute interval to reach an Aldrete score of 10. No differences among the groups were observed as to the time of recovery or discharge. This new route of midazolam administration with the jet-injector allows pain-free and stress-free induction of anaesthesia after rapid placement of an intravenous catheter and prevents the transmission of infections.

A new method to repair inguino-femoral hernias: laparoscopic hernioplasty.

The development of minimally invasive surgery has accepted the challenge by having tried to repair inguino-femoral hernias laparoscopically. The authors performed 65 laparoscopic hernioplasties in one year. "Transabdominal preperitoneal" technique was applied in 61 cases and "intraperitoneal onlay mesh" in 4 cases. Fifty-three patients were operated, 12 of them had bilateral hernias. Recurrent hernia was the indication in 22 patients (34%). The average operating time was 102 and 144 minutes in the unilateral and the bilateral cases, respectively. There was neither wound infection, nor general complication. Spontaneously dissolving seroma/haematoma of the spermatic cord was noticed (detected by ultrasound) in 5 patients (7.7%). The neuralgia caused by the irritation of the nerves of the region in 4 patients (6.1%) disappeared without sequels after treatment with vitamins B. The 2 early recurrences (3.2%) were considered to be caused by technical unexperience; the affected patients were treated successfully with the "intraperitoneal onlay mesh" technique. It is emphasized that laparoscopic hernioplasty has definite advantages, namely minimal postoperative pain, early mobilization, short hospital stay and early restoration of full physical activity (in 1 to 2 weeks). On the other hand, general anaesthesia and intraperitoneal invasion are required and the operation consumes much time and cost.

[The effect of lesser curve seromyotomy of the stomach in animal experiments]. / A gyomron végzett kisgörbületi seromyotomia hatásának vizsgálata állatkísérletekben.

The authors investigated the efficiency of the seromyotomy of the lesser curvature of the stomach in 11 dogs. Reduction of the acid production was verified by glass electrode pH measuring of the gastric mucosa. Scintigraphic examination showed that the operation did not damage the motor function (motility) of the stomach. The fact of peripheral vagotomy was established by histological examination: degeneration of nerve fibres was detected on the peripheral side of the line of the seromyotomy, vacuolar degeneration was found in the cells of parasympathetic ganglions, and amputation neurinomas were shown in the line of the seromyotomy.