10 kHz spinal cord stimulation for the treatment of non-surgical refractory back pain: subanalysis of pooled data from two prospective studies.

Spinal cord stimulation at 10 kHz is a promising therapy for non-surgical refractory back pain; however, published data are currently limited. We present a subanalysis of prospectively collected clinical outcome data for non-surgical refractory back pain patients treated with 10 kHz spinal cord stimulation, from the independent cohorts of two previous studies (SENZA-RCT and SENZA-EU). Clinical outcomes were evaluated at pre-implantation (baseline), 3 months, 6 months and 12 months following 10 kHz spinal cord stimulator implantation. These included: pain relief; responder rate (≥ 50% pain relief from baseline); remission rate (VAS ≤ 3.0 cm); disability (Oswestry Disability Index(ODI)); and opioid use. At 3 months, average back pain decreased by 70% in the combined cohort (60% in the SENZA-RCT and 78% in the SENZA-EU cohorts). This was sustained at 12 months, with a 73% back pain responder rate and 68% remission rate in the combined cohort. Leg pain relief results were generally comparable to those for back pain relief. At 12 months, the combined cohort had an average decrease in ODI scores of 15.7% points from baseline and opioid use more than halved. In conclusion, 10 kHz spinal cord stimulation reduced pain, disability and opioid consumption in non-surgical refractory back pain subjects. Application of this therapy may improve the care of non-surgical refractory back pain patients and reduce their opioid consumption.

Central venous pressure during the post-anhepatic phase is not associated with early postoperative outcomes following orthotopic liver transplantation.

BACKGROUND: Fluid management during orthotopic liver transplantation poses unique challenges for the anesthesiologist. Maintenance of hypovolemia as indicated by low central venous pressure has been associated with reduced blood loss and improved outcomes in some studies, but with higher 30-day mortality and increased incidence of renal dysfunction in others. The primary aim was to evaluate the association of central venous pressure management after liver allograft reperfusion with immediate postoperative patient outcomes. METHODS: This was a retrospective investigation evaluating the intraoperative and postoperative records of 144 consecutive patients who underwent orthotopic liver transplantation at a single institution. RESULTS: We did not find any important association between central venous pressure management after graft reperfusion and postoperative patient outcomes. Specifically, these data do not support the hypothesis that maintenance of lower central venous pressure during the post-anhepatic phase of orthotopic liver transplantation is associated with improved immediate postoperative allograft function (except for a steeper decrease in post operative days 1-3 in 2 of the 3 liver function test: alanine aminotransferase and bilirubin) or overall patient survival, graft survival, composite graft/patient survival, intensive care length of stay, hospital length of stay or the occurrence of infections. CONCLUSION: Maintaining a lower central venous pressure during the post-anhepatic phase during orthotopic liver transplantation is not associated with any benefit in terms of immediate postoperative allograft function, graft survival or patient survival.

Radiofrequency ablation for chronic pain control.

With an increased knowledge of neural anatomy and technologic improvement, radiofrequency ablation (RFA) became an often-used technique for the pain control over an extended time period. Today, RFA is used safely for spinal pains of facet or discogenic origin, sympathetically maintained pain, and other pains of neural origin.

Anesthesia for kidney transplant surgery.

Organ viability associated with renal transplantation is a product of the managing of the donor patient, the allograft, and the recipient patient. Short- and long-term outcome is influenced by perioperative fluid and drug treatment, and the function and viability of the transplanted kidney seem to be optimized if graft perfusion is maximized through mild hypervolemia. At the same time, careful balancing of intraoperative fluids is necessary against cardiovascular problems frequently encountered in patients with uremia. Close intraoperative monitoring, optimization of intravascular fluid volume status to maximize kidney perfusion, and prompt correction of electrolyte disturbances (especially potassium) are key to short- and long-term success of renal transplants.

Complex regional pain syndrome type I in cancer patients.

Complex regional pain syndrome type I (CRPS-I) is infrequently associated with various malignancies, and may lead to severe pain in already debilitated patients. The causal relationship between CRPS-I and paraneoplastic syndrome, controversies in diagnosis and treatment, and new treatment modalities are presented.

Neuroprotective, anesthetic, and cardiovascular effects of the NMDA antagonist, CNS 5161A, in isoflurane-anesthetized lambs.

BACKGROUND: N-methyl-d-aspartate (NMDA) receptor antagonists are neuroprotective in animal models of cerebral ischemia, but adverse cardiovascular and neurobehavioral effects have precluded their clinical use. The authors present the neuroprotective, anesthetic, and cardiovascular effects of a novel NMDA antagonist, CNS 5161A. METHODS: Lambs, 4.0-6.5 kg, were anesthetized with isoflurane, intubated, and ventilated and had thermodilution catheters placed in the pulmonary artery and 20-g catheters placed in the femoral artery. The minimum alveolar concentration (MAC) of isoflurane was determined using the "bracketing technique." CNS 5161A was given as a bolus and then as an infusion at three doses. Cardiovascular measurements were determined every 15 min. Other lambs (n = 25) were subjected to cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) for 120 min. Eighteen received CNS 5161A, and seven received saline vehicle. One hour after CPB, brains were perfusion-fixed and removed for in situ hybridization and immunohistochemistry analysis in half of the animals. The other half survived 48 h before their brains were examined for neuronal degeneration. RESULTS: Isoflurane at MAC significantly decreased blood pressure, heart rate, cardiac output, and systemic vascular resistance by 30-48% (n = 16; P < 0.05). CNS 5161A (n = 12) had no significant cardiovascular effects. All concentrations of CNS 5161A caused a significant reduction (21-29%) of the MAC of isoflurane (n = 12; P < 0.05). CNS 5161A, at serum concentrations greater than 25 ng/ml, completely inhibited c-fosmRNA and c-FOS protein expression in hippocampal neurons after 120 min of HCA, attenuated neuronal degeneration, and improved functional outcome by 47% (P < 0.05). CONCLUSIONS: CNS 5161A at neuroprotective concentrations before CPB-HCA significantly reduces the MAC of isoflurane without cardiovascular effects.

Small-dose dopamine increases epidural lidocaine requirements during peripheral vascular surgery in elderly patients.

UNLABELLED: We studied 20 patients over the age of 65 yr undergoing prolonged peripheral vascular surgery under continuous lidocaine epidural anesthesia, anticipating that the increased hepatic metabolism caused by small-dose IV dopamine would lower plasma lidocaine concentrations. Subjects were assigned (random, double-blinded) to receive either a placebo IV infusion or dopamine, 2 microg. kg(-1). min(-1) during and for 5 h after surgery. Five minutes after the IV infusion was started, 20 mL of 2% lidocaine was injected through the epidural catheter. One-half hour later, a continuous epidural infusion of 2% lidocaine at 10 mL/h was begun. The epidural infusion was temporarily decreased to 5 mL/h or 5 mL boluses were added to maintain a T8 analgesic level. Arterial blood samples were analyzed for plasma lidocaine concentrations regularly during and for 5 h after surgery. Plasma lidocaine concentrations increased continuously during the epidural infusion and, despite wide individual variation, were similar for the two groups throughout the observation period. During the observation period, the mean maximal plasma lidocaine concentration was 5.8 +/- 2.3 microg/mL in the control group and 5.7 +/- 1.2 microg/mL in the dopamine group. However, the mean hourly lidocaine requirement during surgery was significantly different, 242 +/- 72 mg/h for control and 312 +/- 60 mg/h for dopamine patients (P < 0.03). At the end of Hour 4, the last period when all 20 patients were still receiving the epidural lidocaine infusion, the total lidocaine requirement was significantly different, 1088 +/- 191 mg for the control group and 1228 +/- 168 mg for the dopamine group (P < 0.05). Despite very large total doses of epidural lidocaine (1650 +/- 740 mg, control patients, and 1940 +/- 400, dopamine patients) mean maximal plasma concentrations remained below 6 microg/mL, and no patient exhibited signs or symptoms of toxicity. We conclude that small-dose IV dopamine increased epidural lidocaine requirements, presumably as a consequence of increased metabolism. IMPLICATIONS: We tested dopamine, a drug that increases liver metabolism of the local anesthetic lidocaine to determine if it would prevent excessively large amounts of lidocaine in the blood during prolonged epidural anesthesia in elderly patients. Dopamine did not alter the blood levels of lidocaine, but it did increase the lidocaine dose requirement to maintain adequate epidural anesthesia.

Peripheral nerve war injuries.

OBJECTIVE: The purpose of this study is to evaluate peripheral nerve war injuries sustained during the war in southern Croatia and Bosnia and Herzegovina. PATIENTS AND METHODS: During the war in Croatia, 713 patients (99% male and 1% female) with wounds inflicted by firearms were examined at the Laboratory of Neurophysiology, University Hospital, Split. The patients, soldiers and civilians alike, ranged in age from 6 to 73 years (average, 28 years). All patients with firearm nerve war injuries underwent detection by electromyography and plurisegmental examination of the damaged peripheral nerve (neurography). The patients were examined and controlled on three occasions: within 2 months after wounding; up to 6 months after wounding; and more than 6 months after wounding. RESULTS: Single peripheral nerve lesions were present in 80% of the patients, and multiple peripheral nerve or plexus lesions were present in 20% of the patients. Peroneal and ulnar nerves were most often involved (20.9% and 19.8%, respectively). Associated massive injuries to the muscles, large blood vessels, or vital organs were present in 45% of the patients. Wounds were inflicted by shell fragments in 80% of the patients and by projectiles in 20% of the patients. CONCLUSION: According to our results, better recovery was achieved with conservative treatment and when physical therapy was initiated early with maximal patient cooperation. Electromyoneurographic findings were the most valid in the prognostic classification of war-inflicted peripheral nerve injuries.

Changes in the expression of voltage-gated K+ currents during development of human megakaryocytic cells.

We distinguished four distinct groups of megakaryocytic cells on the basis of their voltage-gated membrane currents. One group of 32 cells (15%), exhibited an inward rectifying current and had a diameter of 12 +/- 3.5 microm (mean +/- S.D.). A large group of 85 cells (39%) exhibited only a 'leakage-like' current and had a diameter of 15.8 +/- 3.7 microm. The other two groups of cells exhibited voltage-gated outward currents. One group consisted of 43 'I-type' cells (19%), with a diameter of 22.3 +/- 3.4 microm, for which the maximal outward current occurred for a voltage step from -60 to either 0 or +20 mV. For the last group of 60 'M-type' cells (27%), which had a diameter of 26.7 +/- 2.9 microm, the maximal outward current occurred for a voltage step from -60 to +80 mV, the largest voltage step used. The currents recorded in this study, from megakaryocytes having 'leakage-like' currents and 'I-type' currents, were indistinguishable from the voltage-gated currents of the megakaryocytes from myelogenous leukemia patients, in which voltage-gated currents were suppressed (Kapural, L., O'Rourke, F., Feinstein, M.B. and Fein, A. (1995) Blood 86, 1043), suggesting that the megakaryocytes from the myelogenous leukemia patients are a dedifferentiated or less mature form of megakaryocyte.

Suppression of the voltage-gated K+ current of human megakaryocytes by thrombin and prostacyclin.

We examined the effects of platelet activators and inhibitors of platelet function on the voltage-gated delayed rectifier K+ current of human megakaryocytes. We found that both the activators such as thrombin, the thrombin receptor peptide (TRP42-47) and ADP and the inhibitors such as prostacyclin suppressed the delayed rectifier current through two different mechanisms. The cAMP dependent protein kinase (A-kinase) inhibitor IP20 blocked the suppression of the delayed rectifier current by prostacyclin and failed to block the suppression by thrombin, TRP42-47 and ADP. The effects of IP20 suggest that the action of prostacyclin is mediated by A-kinase and the action of the three activators is not mediated by A-kinase. Pertussis toxin (PTX) an inhibitor of the inhibitory GTP-binding proteins (Gi) blocked the suppression of the delayed rectifier current by thrombin, TRP42-47 and ADP and failed to block the suppression by prostacyclin. The effects of PTX suggests that the action of the three activators is mediated by Gi or some other PTX-sensitive GTP-binding protein. We speculate that thrombin and other platelet activators that activate Gi may be suppressing the delayed rectifier current via a direct interaction of Gi or a subunit of it with the delayed rectifier potassium channel itself.

Ciliated metaplasia in a patient of Mediterranean origin with gastric adenoma.

We report here the first case of ciliated gastric metaplasia in a Croatian patient. This is also the first case of ciliated metaplasia reported in a patient of Mediterranean descent. Cilia were found in slightly cystically dilated gastric glands underneath a gastric adenoma with severe dysplasia. They were visualized by desmin immunohistochemical stain. Cells that presented with cilia were columnar cells, some of them with vacuolization of the cytoplasm. This case report shows that ciliated metaplasia occurs in patients of Southern European origin.

Splenic-gonadal fusion of the continuous type in an adult female.

The first case of a continuous type splenic-gonadal fusion in an adult female is described. This extremely rare anomaly occurs more often in the male where the abnormality may be associated with skeletal abnormalities or cryptorchidism. The few cases of splenic-gonadal fusion in the female previously described were found mainly in infants. The present case of splenic-gonadal fusion occurred as a duct, approximately 10 cm long, extending from the inferior pole of the spleen to a junction in the left ovarian suspensory ligament. The superior two-thirds of this tubular structure consisted of splenic tissue, while the caudal one-third of the duct was composed of fat and fibrous tissue. In addition, two blood vessels, an artery and a vein, were present throughout the entire length of duct, and were located extracapsullary to the spleen in the cranial portion of this anomaly. The patient had no associated malformations in contrast to the majority of patients with continuous-type splenic-gonadal fusions.

Suppression of the delayed rectifier type of voltage gated K+ outward current in megakaryocytes from patients with myelogenous leukemias.

In normal human megakaryocytes, we identified a delayed rectifier type of voltage-gated outward K+ current (DRK). In two human megakaryoblastic tumor cell lines (DAMI, CHRF-288-11) and the human erythroleukemia cell line (HEL) the DRK current was not detected. To determine if the absence of the DRK current in the tumor cells is the result of the underlying malignant state, we examined megakaryocytes from myelogenous leukemia patients. In 24 of 29 megakaryocytes from the myelogenous leukemia patients, the DRK current was greatly suppressed, whereas in the remaining 5 megakaryocytes a normal large amplitude DRK current was present. We had the opportunity to reexamine megakaryocytes from a patient with acute promyelocytic leukemia (M3), after chemotherapy. Whereas the DRK current was suppressed before treatment, the current reappeared after chemotherapy. Exposure to the adenylate cyclase activator, forskolin, caused the appearance of a voltage-gated outward current in the megakaryocytes of patients with acute myelogenous leukemia. This finding suggests either that the channels underlying the DRK current are present but somehow suppressed in megakaryocytes from these patients or that forskolin induces a different voltage-gated outward current. We suggest that the megakaryocytes from the myelogenous leukemia patients with suppressed DRK current are abnormal, whereas the others may be normal megakaryocytes. The suppression of the DRK current may be a contributory factor to the dysregulation of thrombopoiesis (Zittoun et al: Semin Hop Paris 44:183, 1968 and Rabellino et al: Blood 63:615, 1984) in myelogenous leukemias.

Speed of action of various muscle relaxants at the neuromuscular junction binding vs. buffering hypothesis.

The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. The onset and recovery time constants of inhibition of brief acetylcholine pulses, caused by long pulses of relaxants for all of the muscle relaxants, were inversely related to apparent dissociation constants (KD values), that ranged from 4.56 microM (gallamine) to 0.11 microM (doxacurium). The kinetics showed only modest temperature dependence (Q10 values of 1/time constant of offset were typically < 1.4). Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)