Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

1 alpha(OH)D3 (ETALPHA) treatment and receptor studies in 16 patients with chronic and myeloproliferative disorders

10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily.     

Characterization of human mammary normal and neoplastic cells grown in culture

The paper presented here describes cultivation and characterization of human mammary normal (NMC) and neoplastic (BO) cells. Characteristics: growth rate, colony growth in soft agar, nuclear overlaps, induction of multinucleation by Cytochalasin B and transplantation in vivo were compared between NMC- and BO-cells. Normal (NMC) cells are characterized by a slow growth rate (cell doubling time less than 70 hours), no growth in soft agar, no induction of uncontrolled nuclear division and no development of tumors after transplantation of cells in nude mice in vivo. The two cell types do not differ with respect to the nuclear overlapping ratio. In contrast, neoplastic (BO) cells showed a lower doubling time (less than 20 hours), colony growth in soft agar (greater than 20 colonies/30,000 cells), induction of multinucleation by Cytochalasin B (greater than or equal to 3 nuclei/cell), and tumors in nude mice were observed. Both cell types were recommended as an in-vitro model for screening antineoplastic agents.     

Neurochemical dissociation of memory systems

The administration of scopolamine, an anticholinergic drug, reduced the ability to recall and recognize stimuli presented previously--abilities thought to require declarative memory. In contrast, measures of procedural memory were unaffected by scopolamine: performance on a serial reaction time task incorporating a repeating stimulus and response sequence showed no difference in acquisition and retention of the sequence after scopolamine or saline. These results suggest that the cholinergic system is required for declarative but not procedural memory.     

High-risk AML evidenced by a monoclonal antibody

A monoclonal antibody has been raised against a surface membrane antigen present on leukemic myeloblasts. In 52 consecutive patients with acute myeloid leukemia treated in a standardized fashion with intensive chemotherapy the immunologic subclass with respect to this antigen was correlated to the clinical outcome. We found the expression of this antigen to predict a poor prognosis, when measured as survival of CR-patients and as survival after 1st relapse.     

Profilometry, a method for the assessment of the therapeutic effectiveness of Kamillosan ointment

Experimentally induced toxic contact dermatitis was topically treated with 3 different ointments (Kamillosan ointment, Kamillosan ointment base. 0.1% hydrocortisone acetate). The structural changes of the epidermal surface were studied by means of profilometry. According to our results, Kamillosan ointment is remarkably superior to other reference products with regard to its soothing effect on human skin.     

Laparoscopic cholecystectomy in a patient with a biventricular cardiac assist device.

Evaluation and management of abdominal pathology in patients with ventricular assist devices is likely to become increasingly important as the utilization of these devices expands. Ventricular assist devices represent a class of intracorporeal or paracorporeal mechanical devices that augment cardiac output in patients with congestive heart failure. Patients with ventricular assist devices supporting both right and left ventricles (biventricular assist devices) are uniquely challenging to the general surgeon because these devices restrict direct access to the abdominal cavity and because of the perioperative implications of biventricular heart failure. We describe herein the first reported successful laparoscopic cholecystectomy in a patient with a paracorporeal biventricular assist device. Cholecystectomy was performed in this patient for acute cholecystitis that occurred while the patient was awaiting heart transplantation. Our results add weight to the small body of evidence that laparoscopy is well tolerated in ventricular assist devices patients. The unique aspects of the biventricular assist device patient make laparoscopic abdominal intervention particularly suitable in this patient population.     

Pyromania and enuresis. Multifactorial causes require multidimensional treatment concepts]

The abilities to control the voiding of the bladder and to act competently in dealing with fire are important factors of the normal development of children. Unfavourable conditional constellations in the socio-emotional, cognitive, or physical realm can cause developmental defects which manifest themselves in certain target symptoms, for instance Pyromania and Enuresis. The importance of multifactorial etiological models will be illustrated by a case report of a boy displaying symptoms of Pyromania and Enuresis nocturna. The analysis of the specific conditions of the case studied results in the appropriate multidimensional treatment concept.     

Preparation, characterization, therapeutic efficacy and toxicity of liposomes, containing the antitumour drug cis-dichlorodiamineplatinum(II)

Cis-dichlorodiamineplatinum(II) (cis-DDP) was encapsulated in reverse phase evaporation vesicles (REV, 0.6 mg cis-DDP/ml lipid solution) and multilayered liposomes (MLV, 0.3 mg cis-DDP/ml lipid solution) with different cholesterol content. The identity of cis-DDP in free and encapsulated form was checked by various techniques. Particle size, homogeneity of liposomes and distribution of cis-DDP in REVs were shown by electron microscopy. The examination of entrapped cis-DDP in REVs relating to buffer and serum stability, in vitro and in vivo antitumour activity and nephrotoxicity proved that all points are strongly influenced by the cholesterol (CH) content. Enclosed cis-DDP in phosphatidyl (PC)-REV has the same, and in PC: CH-REV, a lower effect in vitro and in vivo compared to treatment with the free drug. Irrespective of the application of tumour cells and substance (i.v., i.p.) in optimal therapeutic doses, an equal increase in life-span (ILS) was registered with the free drug and with PC-cis-DDP-REV, while cis-DDP in PC: CH-REV had a significantly reduced effectiveness. Liposomal encapsulation of cis-DDP also influenced body weight change and leucocyte counts. The blood urea nitrogen (BUN) level, as an indicator of renal toxicity, was only moderately increased after very high doses of cis-DDP (24 mg/kg) in PC: CH-REV.     

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.


Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation