Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

Comparison of local and general anesthesia in tension-free (Lichtenstein) hernioplasty: a prospective randomized trial

To compare pulmonary effects, postoperative pain and fatigue, morbidity, patient satisfaction, and cost of different anesthetic techniques for inguinal hernia repair, 50 patients were randomized to local and general anesthesia groups (LA and GA). All patients received the same premedications and the same postoperative analgesic regimen. The standardized postoperative analgesic, intramuscular pyroxicam 20 mg, was given to all patients in the recovery room and an additional 20 mg on the same day was given as requested by each patient. Pulmonary function studies and arterial blood gas analysis were performed 1 h prior to the operation and at the postoperative 8th and 24th hours. All patients underwent Lichtenstein's tension-free hernioplasty. Postoperative pain and fatigue were registered 8 h and 24 h after the operation. A questionnaire was filled out by the patients, and they were asked to give grades for the general comfort of the anesthesia and the surgical procedure (1=worst, 10=best). Postoperative pulmonary function tests were significantly poorer in the GA group both on 8th- and 24th-hour measurements (P<0.05). Patients who underwent LA had significantly lower PCO₂ and higher PO₂ at the postoperative 8th hour (P<0.05). Mean postoperative pain and fatigue scores revealed a significant difference in favor of local anesthesia at only the 8th hour (P<0.05). There were two complications, one in each group (a hematoma in LA and a urinary retention in GA). Patient satisfaction grades were not different in the two groups. We conclude that LA in inguinal hernia repair does not adversely affect pulmonary functions, patients feel less pain, and patient satisfaction is comparable to that with GA. Electronic Publication     

Serum iron levels in schizophrenic patients with or without akathisia.

The pathophysiology of akathisia still remains controversial. Iron deficiency was proposed to be an important factor in the development of akathisia. In the present study, it was aimed to compare levels of serum iron and linked variables in chronic akathisic (n=30), and non-akathisic patients (n=30) with schizophrenia and healthy controls (n=30) because of the controversy in the association of iron and akathisia. The Barnes Akathisia Scale for akathisia and Simpson-Angus Rating Scale for extrapyramidal side effects were used. Serum iron and linked variables and hematological profile of the patients and control subjects were determined. Serum iron levels were significantly lower both in akathisic and non-akathisic groups compared to the control group (P<0.001). Moreover, akathisic patients had significantly lower iron levels than non-akathisic patients (P<0.05). Total iron binding capacity was significantly higher in patients with akathisia compared to the control group (P<0.01). Although non-akathisic patients had a mild increase in total iron binding capacity, it was not statistically significant compared to the control group (P>0.05). Ferritin levels were determined to be significantly lower in both groups compared to the control group (P<0.01). In addition, there was a significant difference in ferritin levels between the patients with and without akathisia (P<0.05). In conclusion, our results support the hypothesis that an association between akathisia and iron metabolism exists.     

Formulation and in Vitro-in Vivo Evaluation of Sustained-Release Lithium Carbonate Tablets

The release of lithium carbonate incorporated into polymethylmethacrylate, poly vinyl chloride, hy-drogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.     

Multicenter Randomized Comparison of Xenon and Isoflurane on Left Ventricular Function in Patients Undergoing Elective Surgery

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane.

Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography.

Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon.     

Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis

The presence of certain defects in both cellular and humoral immunity after thermal injury has been established. Likewise, the translocation of enteric bacteria to the mesenteric lymph nodes and to distant organs has also been observed following serious thermal injury. The effects of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa, and cecal bacterial content were investigated in a rat model of burn wound sepsis in which albino Wistar rats were scalded over 30% of their bodies, after which the lesions were infected by 1×10⁸ colony-forming units (cfu)Pseudomonas aeruginosa. The control group was treated with 5% dextrose solution subcutaneously starting 2 days preburn, while the treatment group received 100μg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were killed to examine the bowel and culture of the mesenteric lymph nodes (MLN), livers, and spleens. No significant differences were observed between the groups regarding the cecal bacterial content and small bowel; however, a difference was seen in the ratio of translocation in the MLN liver and spleen and quantitative MLN cultures. Based on these findings, G-CSF was thus found to be significantly effective in reducing bacterial translocation due to burn wound sepsis.     

Evaluation of prosthetic mesh closure in semiopen-abdomen patients

Abstract Background. To avoid the adverse consequences of abdominal compartment syndrome and to reduce the high mortality the celiotomy wound in patients with abdominal sepsis was closed without tension using prosthetic mesh. This produces a semiopen situation that permits staged reinterventions together with the functional reconstitution of the continuity of the abdominal wall. Material and Methods. Twenty-five patients with intra-abdominal sepsis of various causes were evaluated retrospectively to assess the results of semiopen management of the septic abdomen and reoperations on demand in severe peritonitis. All of the patients were in a state of neglected peritonitis, and had at least one failing organ system. The Mannheim Peritonitis Index (MPI) scoring system was used for stratification of abdominal sepsis. Results. The mean MPI score of 25 patients was 24, ranging 10 to 33. Eight (32%) patients were reexplored (MPI=21). There were overall 9 (36%) complications in patients with mean MPI score of 23. Six (24%) mesh-related complications (infection and enterocutaneous fistulas) developed (MPI=19). The mean MPI score of patients without complications was 24. Four (16%) patients died with index MPI score of 26 due to fulminant hepatitis, myocardial infarction, and multiple organ failure. The admission period averaged 63 days. Conclusions. In 25 critically ill patients with abdominal sepsis the mortality was lower than expected, relative to heterogeneous data from the literature; also, major complications occurred less frequently although the mean MPI score was high. The authors conclude that this approach is a reliable contribution to the complex treatment of these patients. Electronic Publication     

Low-dose erythropoietin is effective and safe in children on continuous ambulatory peritoneal dialysis

Hypertension is one of the most important complications of erythropoietin (rHuEPO) therapy in dialysis patients. In this study, the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [BP] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis (CAPD). Patients were randomized to receive rHuEPO 50 U/kg, either once a week (group 1, 50 U/kg per week) or three times a week (group 2, 150 U/kg per week). At the beginning of the study, 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy. In group 1, the hematocrit increased gradually and significantly from 18.98%±1.79% to 30.1%±1.62% after 6 months, while in group 2 it rapidly increased from 19.53%±1.86% to 32.4%±1.11% after 3 months. A significant increase in the mean arterial BP was observed in group 2. Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group. None of the patients in group 1 required a change in antihypertensive medication. We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD, and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension. Received December 11, 1995; received in revised form September 16, 1996; accepted September 19, 1996     

Percutaneous radiofrequency rhizotomy of lumbar spinal facets: The results of 46 cases

The results of percutaneous radiofrequency rhizotomy of lumbar spinal facets in 46 patients followed at least three months (mean 15 months) are reported and compared with those reported previously. Satisfactory pain relief three months after the procedure was achieved in 36.4 percent of patients without operations and in 41.7 percent of patients with operations other than fusion.No patient had previously undergone fusion.Treatment of low-back pain by using radio-frequency thermocoagulation of spinal facets is a simple, safe, and well-tolerated procedure. It can be used to relief of pain in spite of decreasing rates of success within the follow-up period.