Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population.

Introduction: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers.

Comparing the Efficacy of Dorsal Root Ganglion Stimulation With Conventional Medical Management in Patients With Chronic Postsurgical Inguinal Pain: Post Hoc Analyzed Results of the SMASHING Study.

Objectives: Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment.

Study protocol: Effects of active versus passive recharge burst spinal cord stimulation on pain experience in persistent spinal pain syndrome type 2: a multicentre randomized trial (BURST-RAP study).

Background: Spinal cord stimulation (SCS) has shown to be an effective treatment for patients with persistent spinal pain syndrome type 2 (PSPS Type 2). The method used to deliver electrical charge in SCS is important. One such method is burst stimulation.

10 kHz Spinal Cord Stimulation for the Treatment of Failed Back Surgery Syndrome with Predominant Leg Pain: Results from a Prospective Study in Patients from the Dutch Healthcare System.

Introduction: Persistent back/and or leg pain is a common outcome after spinal surgery (otherwise known as failed back surgery syndrome [FBSS]). Studies have shown that spinal cord stimulation (SCS) at 10 kHz provides effective analgesia in FBSS patients with both back and leg pain symptoms and in those with predominant back pain. This study is the first to evaluate the therapy in FBSS patients with predominant leg pain.

Hemodynamic stability ensured by a low dose, low volume, unilateral hypobaric spinal block: modification of a technique.

We report the case of an 89-year-old female with a history of arterial hypertension, intermittent rapid atrial fibrillation and severe aortic valve stenosis, suffering from femoral neck fracture. Hyperbaric unilateral spinal anesthesia is a known technique to obtain stable hemodynamics combined with the possibility of continuous neurologic evaluation and preservation of cognitive functions. Because a hyperbaric unilateral technique can be very painful in case of traumatic hip fracture, a low dose, low volume, unilateral hypobaric spinal block may be an adequate alternative.

A multicenter, prospective, randomized, comparative evaluation of dual- versus triple-lumen catheters for hemodialysis and apheresis in 485 patients.

Background: The purpose of this study is to compare a new temporary triple-lumen catheter (TLC) for dialysis that has a third lumen devoted to fluid and medication administration or blood sampling with a marketed dual-lumen catheter (DLC).

Methods: Four hundred eighty-five patients referred for acute hemodialysis or apheresis were randomly assigned to either a TLC or DLC in a multicenter, prospective, randomized trial.

Results: Analysis of blood flow rates was completed on 464 patients (228 patients, DLC; 236 patients, TLC) with a total of 1,681 hemodialysis (808 treatments, DLC; 873 treatments, TLC) and 82 apheresis treatments (37 treatments, DLC; 45 treatments, TLC).

The role of renal sympathetic nerves in experimental chronic cyclosporine nephropathy.

Background: Sympathetic nervous system hyperactivity has been postulated to play a major role in the intense intrarenal vasospasm and hypertension provoked by cyclosporine. It has been argued that the denervated renal allograft may be partially protected from the tubulointerstitial fibrosis associated with chronic cyclosporine administration compared with innervated kidneys in extrarenal transplantation.

Methods: Utilizing a model of chronic cyclosporine nephropathy in which striped fibrosis develops in the uninephrectomized salt-depleted rat, the effect of renal denervation on renal structure and function was examined.

Cyclopentenyl cytosine inhibits cytidine triphosphate synthetase in paediatric acute non-lymphocytic leukaemia: a promising target for chemotherapy.

Cytidine triphosphate (CTP) synthetase is a key enzyme in the anabolic pathways of cytosine and uracil ribonucleotide metabolism. The enzyme catalyses the conversion of uridine triphosphate (UTP) into CTP, and has a high activity in various malignancies, which has led to the development of inhibitors of CTP synthetase for therapeutic purposes. We studied both CTP synthetase activity and ribonucleotide concentrations in leukaemic cells of 12 children suffering from acute non-lymphocytic leukaemia (ANLL), and performed incubation experiments with cyclopentenyl cytosine (CPEC), a nucleoside analogue that is capable of inhibiting CTP synthetase.

Adenocarcinoma of the colon metastasizing to the foot masquerading as osteomyelitis.

The authors report an unusual case of adenocarcinoma of the colon metastasizing to the foot. The initial diagnosis of osteomyelitis based on clinical, radiographic, and radionuclide uptake findings led to improper prolonged treatment, resulting in a major complication. A diagnostic biopsy of the involved bone is essential in any case in which the clinical diagnosis is uncertain.

Anuric renal failure from massive bilateral renal hematoma following extracorporeal shock wave lithotripsy.

We report a case of large bilateral perirenal and intrarenal hematoma formation leading to prolonged anuria in the absence of obstruction following extracorporeal shock wave lithotripsy. With conservative management, including the need for hemodialysis support, renal function gradually returned. A mechanism for this patient's anuric renal failure is postulated and caution is advised when considering simultaneous bilateral extracorporeal shock wave lithotripsy in patients with a potential risk of bleeding.

Determination of CTP synthetase activity in crude cell homogenates by a fast and sensitive non-radiochemical assay using anion-exchange high-performance liquid chromatography.

A non-radiochemical assay procedure for CTP synthetase was developed in which CTP is detected at 280 nm after separation with anion-exchange HPLC. A complete separation of all nucleoside triphosphates was achieved within 11 min and the minimum amount of CTP which could be accurately determined proved to be 5 pmol. Therefore, our assay procedure is ten-fold more sensitive compared to the frequently used radiochemical assays.

Hyperbaric oxygen enhances the effects of meta-iodobenzylguanidine (MIBG) on energy metabolism and lipid peroxidation in the human neuroblastoma cell line SK-N-BE(2C).

In this paper we report the effects of the combination of MIBG (a structural analogue of norepinephrine, used in its radio iodinated form for the diagnosis and therapy of neuroblastoma) and hyperbaric oxygen on the human neuroblastoma cell line SK-N-BE(2c). Exposure of the neuroblastoma cells to hyperbaric oxygen conditions enhanced the effects of MIBG on cell proliferation, lipid peroxidation and energy metabolism of the cell line. Cell proliferation and energy metabolism were further decreased and lipid peroxidation further increased.

Meta-iodobenzylguanidine (MIBG) inhibits malate and succinate driven mitochondrial ATP synthesis in the human neuroblastoma cell line SK-N-BE(2c).

In this paper, we report on our studies of the effects of MIBG, a structural analogue of norepinephrine, on SK-N-BE(2c) cells. In micromolar concentrations, MIBG caused almost complete inhibition of the proliferation of SK-N-BE(2c) cells. In intact SK-N-BE(2c) cells, addition of MIBG led to a decrease of the ATP to ADP ratio.

Experimental nephrotoxicity, hepatotoxicity and pharmacokinetics of cyclosporin G versus cyclosporin A.

Cyclosporin G (CsG) is an analogue of cyclosporin A (CsA) with strong immunosuppressive activity. We compared these two drugs in a rat model in which salt depletion promotes irreversible renal interstitial fibrosis with renal dysfunction in animals given CsA for three weeks. When both drugs were given in the same dosage on a weight basis (15 mg/kg/day, subcutaneously), CsA blood levels were higher than CsG (3305 vs.

A fast and novel assay of CTP synthetase. Evidence for hysteretic properties of the mammalian enzyme.

A novel assay of CTP synthetase was developed which allows the processing of large numbers of samples. The amount of glutamate produced by CTP synthetase was determined with glutamate dehydrogenase and the NAD analogue acetyl-pyridine-adenine dinucleotide was used to shift the initial unfavourable equilibrium towards the formation of a-ketoglutarate. The amount of glutamate determined with the assay was comparable to that of CTP.

Nephrotoxicity of immunosuppressive drugs.

Drugs used to modify the immune response in solid organ transplantation or autoimmune disease may cause dose-related nephrotoxicity. Cyclosporine, FK506, cyclosporine G, and rapamycin have all been studied experimentally and to a more limited extent in patients. This paper summarizes this literature using data from clinically relevant animal models.

Nephrotoxicity of immunosuppressive drugs.

Acute and chronic nephrotoxicity frequently limits the therapeutic benefits of immunosuppressive therapy for transplant and autoimmune indications. The clinical aspects, pathophysiology, and relevant pharmacology of current and future immunosuppressive drugs are reviewed in this paper. Insights gained from experimental models of chronic nephrotoxicity associated with tubulointerstitial fibrosis are presented.

Surgical management of painful polycystic kidneys.

In patients with symptomatic PKD who have failed medical management, surgical intervention is a reasonable option, providing long-term pain relief in the majority of patients. Individuals for whom this approach is indicated are usually narcotic dependent or disabled by pain. Cyst decompression surgery does not appear to significantly retard or arrest progressive renal insufficiency.

Dissociation of glomerular filtration rate from tubulointerstitial fibrosis in experimental chronic cyclosporine nephropathy: role of sodium intake.

In addition to its well-recognized ability to provoke acute renal dysfunction by promoting intense renal vasoconstriction, cyclosporine produces a chronic tubulointerstitial nephropathy characterized by striped interstitial fibrosis in humans. With a model of chronic cyclosporine nephropathy in which striped fibrosis develops in the uninephrectomized salt-depleted rat, the relationship between renal functional impairment and structural changes was studied during cyclosporine treatment and after its withdrawal in order to ascertain the natural history of this lesion. Groups of uninephrectomized rats maintained on a salt-depleted (-NaCl) or salt-replete (+NaCl) diet were treated with cyclosporine, 15 mg/kg per day, or vehicle by sc injection.

Clinical management of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common systemic genetic disease which comprises 8 to 10% of patients treated by dialysis and transplantation. Breakthroughs in molecular genetics and cell biology have led to new insights into cyst formation and growth. Until the specific genetic defects are identified, the management of this disorder will necessarily be empiric.

Production of less chronic nephrotoxicity by cyclosporine G than cyclosporine A in a low-salt rat model.

Chronic tubulointerstitial nephropathy during long-term cyclosporine A (CsA) use has led to a search for equally effective but safer analogues. In this study we evaluated one of these analogues, cyclosporine G (CsG), in a rat model of chronic cyclosporine nephrotoxicity. CsG has immunosuppressive effects equivalent to CsA when dosed on a weight basis.

Application of simple chromatographic methods for the diagnosis of defects in pyrimidine degradation.

Recent findings suggest that inborn errors of pyrimidine catabolism are less rare than generally assumed. We propose a complete set of diagnostic methods for these disorders, suitable for the clinical chemistry laboratory, and present relevant reference data. Applications of thin-layer chromatography, high-performance liquid chromatography, and conventional cation-exchange amino acid analysis lead to detection of various defects in pyrimidine degradation, including the recently described deficiencies of dihydropyrimidine dehydrogenase and dihydropyrimidinase.

Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement, culminating in renal insufficiency in over one half of affected individuals. The highly variable onset and clinical course of ADPKD may be due to factors extrinsic to the genetically defined renal cysts. In this study, cyst fluid samples from 12 nonazotemic and 18 azotemic ADPKD subjects were examined for in vitro biologic activity that promotes cellular proliferation and the secretion of fluid by renal epithelial monolayers, two pathogenetic mechanisms that have critical roles in the formation and the rate of expansion of renal cysts.