Low-dose bupivacaine: a comparison of hypobaric and near isobaric solutions for arthroscopic surgery of the knee

The results of studies on the effect of volume, concentration or total dose of local anaesthetic on the spread of spinal anaesthesia are inconclusive. Most support the assumption that the total dosage is more important than the volume. We compared low-dose bupivacaine (6 mg) in 0.5% and 0.18% solutions as sole anaesthetic to achieve predominantly unilateral spinal anaesthesia for knee arthroscopy. Sixty patients were randomly allocated to two groups to receive either 1.2 ml 0.5% bupivacaine (6 mg) (n = 30) or 3.4 ml 0.18% hypobaric bupivacaine (6.1 mg) (n = 30). Drugs were administered at the L3-4 interspace with the patient in the lateral position. Patients remained in this position for 20 min before being turned supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale and compared between the operated and nonoperated sides. No significant changes were found in the spread or duration of sensory or motor block (p > 0.05). The haemodynamic changes were also similar between the groups. The same pinprick level of analgesia, degree of motor block and duration of spinal anaesthesia was obtained with bupivacaine (6 mg) in low (1.2 ml) or high (3.4 ml) volumes.     

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D₂ receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [¹²³I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D₂ receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=–0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D₂ receptors with SPET using [¹²³I]epidepride. Received 6 September and in revised form 21 October 1999     

Long-term effect of acetyl-L-carnitine on myocardial123I-MIBG uptake in patients with diabetes

Carnitine derivatives may have beneficial effects on cardiac and nerve function in patients with diabetes. The aim of this study was to investigate the effect of acetyl-L-carnitine (ALC) on myocardial sympathetic nervous function as measured with¹²³I-meta-iodobenzyl guanidine (MIBG) and single-photon emission tomography (SPET) in 19 patients with diabetes (placebo group,n=6; ALC group,n=13) at the beginning and at the end of a 1-year randomized, placebo-controlled, doubleblind trial. The coefficient of variation for the MIBG analysis was 4%. In patients who were given a placebo, global myocardial MIBG uptake deteriorated during the study (MIBG uptake 1-year follow-up/baseline, 0.86±0.05, mean±standard error of mean), whereas in patients treated with ALC, MIBG uptake did not change significantly (1-year follow-up/baseline, 1.07±0.08; p=0.03 between the groups). On the basis of these preliminary data, we conclude that long-term treatment with ALC may be of potential value in preventing the progressive loss of myocardial sympathetic nervous function in patients with diabetes. MIBG-SPET is a sensitive and thus valuable method in assessing the development of myocardial sympathetic nervous dysfunction.     

Fentanyl decreases β-CIT binding to the dopamine transporter

Evidence from animal studies suggest that centrally acting opiates increase synaptic dopamine (DA) concentration. However, the interaction between μ-opioid receptors and the DA system is unclear. We report here an effect of fentanyl on striatal [¹²³I]β-CIT binding to the DA transporter in a patient and in rats. A female patient underwent [¹²³I]β-CIT single-photon emission tomography (SPET) study after intrathecal injection of fentanyl for her back pain. After a 2-week drug-free period, the SPET study was repeated. In the experimental study, male Wistar rats were treated with fentanyl either acutely (50 μg/kg, i.p.) before imaging study or subacutely for 4 days (10 μg/kg, twice a day, i.p.). Brain planar imaging was performed at 3.5 hours after an intravenous injection of [¹²³I]β-CIT with gamma camera with a pinhole collimator. In a female patient, [¹²³I]β-CIT binding in the basal ganglia was decreased by 37% during fentanyl as compared to the binding after 2-week drug-free period. Similarly in rats, acute fentanyl treatment decreased [¹²³I]β-CIT binding to the striatum by 30% as compared to that of with the control rats. After subacute administration of fentanyl, no significant difference was observed compared to the control group. According to the present data, fentanyl decreases [¹²³I]β-CIT binding in the basal ganglia both in human and rats, suggesting that opiates possibly directly affect DA reuptake. Synapse 29:413–415, 1998. © 1998 Wiley-Liss, Inc.     

IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder

The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.Subject terms: Movement disorders, Disease genetics     

Predictors of quality-of-life after ileal pouch-anal anastomosis in patients with ulcerative colitis

Objectives: Predictors of the postoperative quality of life (QoL) following ileal pouch anal anastomosis (IPAA) have not been thoroughly investigated. This study was planned to assess the postoperative QoL following IPAA and to identify its predictors using the 15D instrument.

Materials and methods: A retrospective cohort study was conducted on IPAA-operated patients with ulcerative colitis in two Finnish tertiary hospitals during the period 1985–2014 (n?=?485). Medical records were examined to collect data on baseline, operative and postoperative characteristics. Patients were surveyed using the 15D-instrument to assess their postoperative QoL. Linear regression analyses and receiver operating characteristic curve were applied to identify the predictors of postoperative QoL.

Results and conclusions: Of all patients, 61.5% experienced worse postoperative QoL, with significantly lower QoL level than that of an age and sex-standardized general population in 12 dimensions of the 15D-instrument, with the highest mean difference QoL scores calculated for excretion, sexual activity and sleeping dimensions. Older age and preoperative hypertension were the only significant predictors of lower overall QoL (p?=?.003 and p?=?.03, respectively). A preoperative age of ≥35 years was the most valid predictor of lower postoperative QoL (Sensitivity?=?62.4% and Specificity?=?49.6%, p?=?.04). In conclusion, postoperative QoL is generally low using the 15D-instrument after IPAA. Worse postoperative QoL is predicted after the age of 35.     

Advanced pancreatic cancer- how to choose an adequate treatment option

The prognosis of pancreatic adenocarcinoma is poor, making it one of the leading causes of cancer-related death. The 5-year overall survival rate remains below 5% and little progress is made during the past decade. Only about 10%-20% of patients are eligible for curative-intent surgery and the majority end up having recurring disease even after radical surgery and postoperative adjuvant chemotherapy. Chemotherapy in metastatic disease is palliative at best, aiming at disease and symptom control and prolongation of life. Treatment always causes side effects, the degree of which varies from patient to patient, depending on the patient’s general condition, concomitant morbidities as well as on the chosen treatment modality. Why is pancreatic cancer so resistant to treatment? How to best help the patient to reach the set treatment goals?     

OX1 orexin/hypocretin receptor signaling through arachidonic acid and endocannabinoid release

We showed previously that OX(1) orexin receptor stimulation produced a strong (3)H overflow response from [(3)H]arachidonic acid (AA)-labeled cells. Here we addressed this issue with a novel set of tools and methods, to distinguish the enzyme pathways responsible for this response. CHO-K1 cells heterologously expressing human OX(1) receptors were used as a model system. By using selective pharmacological inhibitors, we showed that, in orexin-A-stimulated cells, the AA-derived radioactivity was released as two distinct components, i.e., free AA and the endocannabinoid 2-arachidonoyl glycerol (2-AG). Two orexin-activated enzymatic cascades are responsible for this response: cytosolic phospholipase A(2) (cPLA(2)) and diacylglycerol lipase; the former cascade is responsible for part of the AA release, whereas the latter is responsible for all of the 2-AG release and part of the AA release. Essentially only diacylglycerol released by phospholipase C but not by phospholipase D was implicated as a substrate for 2-AG production, although both phospholipases were strongly activated. The 2-AG released acted as a potent paracrine messenger through cannabinoid CB(1) receptors in an artificial cell-cell communication assay that was developed. The cPLA(2) cascade, in contrast, was involved in the activation of orexin receptor-operated Ca(2+) influx. 2-AG was also released upon OX(1) receptor stimulation in recombinant HEK-293 and neuro-2a cells. The results directly show, for the first time, that orexin receptors are able to generate potent endocannabinoid signals in addition to arachidonic acid signals, which may explain the proposed orexin-cannabinoid interactions (e.g., in neurons).     

Effects of DBS on auditory and somatosensory processing in Parkinson's disease

Motor symptoms of Parkinson's disease (PD) can be relieved by deep brain stimulation (DBS). The mechanism of action of DBS is largely unclear. Magnetoencephalography (MEG) studies on DBS patients have been unfeasible because of strong magnetic artifacts. An artifact suppression method known as spatiotemporal signal space separation (tSSS) has mainly overcome these difficulties. We wanted to clarify whether tSSS enables noninvasive measurement of the modulation of cortical activity caused by DBS. We have studied auditory and somatosensory‐evoked fields (AEFs and SEFs) of advanced PD patients with bilateral subthalamic nucleus (STN) DBS using MEG. AEFs were elicited by 1‐kHz tones and SEFs by electrical pulses to the median nerve with DBS on and off. Data could be successfully acquired and analyzed from 12 out of 16 measured patients. The motor symptoms were significantly relieved by DBS, which clearly enhanced the ipsilateral auditory N100m responses in the right hemisphere. Contralateral N100m responses and somatosensory P60m responses also had a tendency to increase when bilateral DBS was on. MEG with tSSS offers a novel and powerful tool to investigate DBS modulation of the evoked cortical activity in PD with high temporal and spatial resolution. The results suggest that STN‐DBS modulates auditory processing in advanced PD. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.