Molecular and macromolecular diffusion in human meniscus: relationships with tissue structure and composition.

OBJECTIVE: To date, the pathophysiology of the meniscus has not been fully elucidated. Due to the tissue's limited vascularization, nutrients and other molecular signals spread through the extracellular matrix via diffusion or convection (interstitial fluid flow). Understanding transport mechanisms is crucial to elucidating meniscal pathophysiology, and to designing treatments for repair and restoration of the tissue. Similar to other fibrocartilaginous structures, meniscal morphology and composition may affect its diffusive properties. The objective of this study was to investigate the role of solute size, and tissue structure and composition on molecular diffusion in meniscus tissue. DESIGN: Using a custom FRAP technique developed in our lab, we measured the direction-dependent diffusivity in human meniscus of six different molecular probes of size ranging from ∼300Da to 150,000Da. Diffusivity measurements were related to sample water content. SEM images were used to investigate collagen structure in relation to transport mechanisms. RESULTS: Diffusivity was anisotropic, being significantly faster in the direction parallel to collagen fibers when compared the orthogonal direction. This was likely due to the unique structural organization of the tissue presenting pores aligned with the fibers, as observed in SEM images. Diffusion coefficients decreased as the molecular size increased, following the Ogston model. No significant correlations were found among diffusion coefficients and water content of the tissue. CONCLUSIONS: This study provides new knowledge on the mechanisms of molecular transport in meniscal tissue. The reported results can be leveraged to further investigate tissue pathophysiology and to design treatments for tissue restoration or replacement.

Electric field effect on the contact angle for non-wetting drops.

A microscopic model is formulated concerning the electrowetting of an electrically conducting drop on a dielectric substrate. The interaction energy between the drop and substrate includes both van der Waals attractive forces and Born repulsive forces resulting in an equilibrium gap. An augmented Young-Laplace equation is derived and used as the basis for calculations of wetting phenomena both with and without an applied voltage. In the absence of an electric field, a well-defined Young's angle is established at a distance from the meniscus incipience that is less than 100 times the equilibrium gap. An expression for Young's angle is determined showing its dependence on material properties of the system. With an electric field applied, the meniscus angle changes continuously from the three-phase line (TPL), where it is near zero, until after a distance of at least ten times the thickness of the dielectric where the Lippmann angle is established. Therefore, the initial angle is not the Lippmann angle and care must be taken in the interpretation of measurements of an apparent contact angle.

Monocytes show immunoregulatory capacity on CD4+ T cells in a human in-vitro model of extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is a widely used immunomodulatory therapy for the treatment of various T cell-mediated disorders such as cutaneous T cell lymphoma (CTCL), graft-versus-host disease (GvHD) or systemic sclerosis. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP is not yet fully understood. Knowledge on the fate of CD14+ monocytes in the context of ECP is particularly limited and controversial. Here, we investigated the immunoregulatory function of ECP treated monocytes on T cells in an in-vitro ECP model. We show that ECP-treated monocytes significantly induce proinflammatory T cell types in co-cultured T cells, while anti-inflammatory T cells remain unaffected. Furthermore, we found significantly reduced proliferation rates of T cells after co-culture with ECP-treated monocytes. Both changes in interleukin secretion and proliferation were dependent on cell-contact between monocytes and T cells. Interestingly, blocking interactions of programmed death ligand 1 (PD-L1) to programmed death 1 (PD-1) in the in-vitro model led to a significant recovery of T cell proliferation. These results set the base for further studies on the mechanism of ECP, especially the regulatory role of ECP-treated monocytes.

High prevalence and functional effects of serum antineuronal antibodies in patients with gastrointestinal disorders.

BACKGROUND: Antineuronal antibodies can be associated with both gastrointestinal (GI) and brain disorders. For example, antibodies against the potassium channel subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central nervous system (CNS) and myenteric plexus and cause encephalitis, commonly preceded by severe unspecific GI symptoms. We therefore investigated the prevalence of antineuronal antibodies indicative of treatable autoimmune CNS etiologies in GI patients. METHODS: Serum samples of 107 patients (Crohn's disease n = 42, ulcerative colitis n = 16, irritable bowel syndrome n = 13, others n = 36) and 44 healthy controls were screened for anti-DPPX and further antineuronal antibodies using immunofluorescence on rat brain and intestine and cell-based assays. Functional effects of high-titer reactive sera were assessed in organ bath and Ussing chamber experiments and compared to non-reactive patient sera. KEY RESULTS: Twenty-one of 107 patients (19.6%) had antibodies against the enteric nervous system, and 22 (20.6%) had anti-CNS antibodies, thus significantly exceeding frequencies in healthy controls (4.5% each). Screening on cell-based assays excluded established antienteric antibodies. Antibody-positive sera were not associated with motility effects in organ bath experiments. However, they induced significant, tetrodotoxin (TTX)-insensitive secretion in Ussing chambers compared to antibody-negative sera. CONCLUSIONS & INFERENCES: Antineuronal antibodies were significantly more frequent in GI patients and associated with functional effects on bowel secretion. Future studies will determine whether such antibodies indicate patients who might benefit from additional antibody-directed therapies. However, well-characterized encephalitis-related autoantibodies such as against DPPX were not detected, underlining their rarity in routine cohorts.

[Efficacy, tolerability, and safety of cannabinoids in gastroenterology: A systematic review]. / Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden in der Gastroenterologie : Eine systematische Übersichtsarbeit.

BACKGROUND: The medical use of cannabis is discussed in gastroenterology for inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and chronic pancreatitis. MATERIALS AND METHODS: A systematic literature search until March 2015 was performed in the databases Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org , and clinicaltrials.gov. Randomized controlled trials (RCT) investigating herbal cannabis and/or pharmaceutical cannabinoids in IBD, IBS, or chronic pancreatitis with a study duration of ≥ 4 weeks and a sample size of at least n = 10 per study arm were identified. Clinical outcomes comprised efficacy (pain, nausea, appetite/weight, diarrhea, health-related quality of life, and remission rates for IBD), tolerability (drop-out rate due to side effects), and safety (severe side effects). Methodology quality of RCTs was evaluated with the Cochrane Risk of Bias Tool. RESULTS: Only one RCT treating 21 patients with Crohn's disease and herbal cannabis was identified. The study revealed no significant differences of remission rate because of low statistical power. However, there was a clear tendency for less abdominal pain and improved appetite with medical cannabis. The methodological risk of the study was high. Furthermore, results of two RCTs investigating synthetic cannabis in IBD and chronic pancreatitis, respectively, have not yet been released. No RCT for IBS was found. Several case reports described cannabis-induced acute pancreatitis. CONCLUSIONS: Cannabis may be useful for symptom relief in Crohn's disease such as pain, nausea, and loss of appetite. However, studies with high methodological quality, sufficient sample size, and study duration are mandatory to determine potential therapeutic effects and risks of cannabis in gastroenterology. Currently, use of tetrahydrocannabinol to alleviate symptoms such as pain and appetite loss in Crohn's disease should only be considered in individual patients after failure of established medical therapies and only after careful risk-benefit assessment.

Predictivity of Early Depressive Symptoms for Post-Stroke Depression.

OBJECTIVES: Depression is a frequent complication after stroke. However, little is known about the predictive value of early self-reported depressive symptoms (DS) for later development of post-stroke depression (PSD) 6 months after discharge. DESIGN: Using a prospective longitudinal design, we investigated the prevalence of DS and examined their predictive value for depressive disorders 6 months after stroke while statistically controlling major established PSD risk factors. SETTING AND PARTICIPANTS: During inpatient rehabilitation, 96 stroke patients were screened for DS. After 6 months, 71 patients were attainable for a follow-up. MEASUREMENTS: DS was assessed using the 15-item Geriatric Depression Scale (GDS-15). At follow-up a telephone interview that included the Structured Clinical Interview for Psychiatric Disorders (SCID), which is based on DSM-IV criteria, and the GDS-15 was conducted. Patients with major depression (MD) at the follow-up were considered to have PSD. RESULTS: Regression analyses were conducted to examine the influence of early DS on PSD after 6 months while controlling for age, premorbid depression, and functional and cognitive impairments. The percentage of patients who scored above the GDS-15 cut-off for clinically relevant DS increased significantly, from 37% to 44%, after 6 months. According to the SCID, 27% of stroke patients fulfilled the criteria for MD, and another 16% fulfilled those for minor depression. Logistic regression showed that DS at baseline significantly predicted PSD at follow-up (odds ratio: 1.43; 95% CI: 1.15-1.8). CONCLUSION: Self-reported DS during inpatient rehabilitation are predictive for PSD 6 months after discharge. Assessment of early DS contributes to identifying stroke patients at risk for PSD, thereby facilitating prevention and treatment.

High frequency of intrathecal immunoglobulin synthesis in epilepsy so far classified cryptogenic.

BACKGROUND AND PURPOSE: The influence of the immune system on seizures and epileptogenesis has been increasingly considered, in particular the role of autoantibodies. In this study, we aimed to determine the frequency of intrathecal antibody synthesis in the cerebrospinal fluid (CSF) compartment of patients with epilepsy. METHODS: In a retrospective cohort study trial in a university hospital neurology department, 164 well-characterized patients with different etiologies of seizures and epilepsies, and 77 control patients were included. RESULTS: CSF-specific immunoglobulin (IgG, IgM and IgA) synthesis was significantly (P < 0.0001) more frequent in patients with epilepsy (34.1%) compared with age- and sex-matched controls (2.6%). The highest incidence of intrathecal Ig synthesis was detected in patients with encephalitis-related acute symptomatic seizures (86.7%), but also in patients with focal epilepsy so far classified cryptogenic (45.2%). Antibody synthesis was not related to the number of CSF white blood cells. CONCLUSIONS: Humoral immune activation in the CSF compartment was detected in one-third of patients with epilepsy, besides acute symptomatic seizures particularly frequent in cryptogenic epilepsy--an etiology so far defined as not having a detectable cause. Systematic prospective clinical and experimental trials are required to identify antigenic targets and select appropriate patients for which immunotherapy might offer new causal therapeutic options.

Differences in alloimmune response between elderly and young mice.

OBJECTIVE: The upper age of renal transplant recipients is rising on the transplant wait list. Age-dependent immune responsiveness to new antigens has not been thoroughly studied. This study used a mouse model of alloantibody response to neoalloantigen to study age-related differences. METHODS: Transgenic huCD20-C57BL/6 mice were immunized intraperitoneally with BALB/c splenocytes (2.5 × 10(7)) at baseline and 1 month. Plasma samples were collected at baseline and 1 and 2 months after inoculation, frozen, and tested in a batch run (n = 22). Samples were tested by flow cytometric crossmatch for alloantibody with 2-fold serial dilution from neat to 1:640 using BALB/c splenocytes as targets. The sum of the median fluorescence intensity of the tested sample was calculated after subtracting that of an autologous serum control. Elderly mice (ELD; 42-103 weeks) at inoculation were compared with younger mice (YOU; 11-15 weeks). Statistical analysis was performed with 2-sample t test. RESULTS: Mean age (weeks) between the groups was significantly different (ELD 69.3 ± 9.6 vs YOU 13.4 ± 1.4; P < .001). There was no difference in alloantibody between groups at baseline (ELD 0.7 ± 3.1 vs YOU 0.6 ± 0.4; P = .93). There was a higher alloantibody response at 1 month for YOU (52.9 ± 31.78) compared with ELD (5.12 ± 8.18). There was a greater difference after the 2 month (YOU 109.38 ± 66.43 vs ELD 21.97 ± 27.14; P < .0024). CONCLUSIONS: There was a difference in response to new alloantigen in this animal model. Older animals had significantly decreased responses to new alloantigen stimulation 1 month after inoculation and even more profound decreases at 2 months compared with young animals. This model may be used to study differences in immune refractoriness to antigen signaling. It may be important to adapt clinical immunosuppression in the aged population to possible decreased responses to immune stimulation.

Subthalamic nucleus deep brain stimulation in primary cervical dystonia.

OBJECTIVES: The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies. METHODS: In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patient's preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured. RESULTS: STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation. CONCLUSIONS: This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.

In vitro monitoring of in vivo development of human anti-thymoglobulin antibodies by ELISA.

Thymoglobulin (rATG), polyclonal immunoglobulin, is prepared from rabbits immunized with human thymocytes. It is effective in prevention and treatment of renal allograft rejection. Human antibodies against antilymphocyte preparations can reduce efficacy by accelerating drug clearance or by inducing serum sickness. We developed an enzyme-linked immunosorbent assay (ELISA) to study posttreatment development of anti-rATG. In an Institutional Review Board-approved trial, we tested 101 allograft recipients for anti-rATG antibodies. Patients received rATG intravenously at 1.25 to 2.0 mg/kg/d for 2 to 14 days. Serum samples were obtained pretreatment and at weeks 1, 2, 4, 6, and months 3 and 6 post-rATG. ELISA plates were coated with rATG (10 microg/mL). Samples were diluted 1:100 and tested in quadruplicate. Positive samples were titrated. Horseradish peroxidase-conjugated (HRPO) affinity-purified goat anti-human immunoglobulin G (H&L) antibody reacted with bound human antibody. A chromagenic substrate for HRPO was added and optical density (OD, 490 nm) was read. An OD of twice the negative control was considered positive. Mean ODs of negative and positive controls were 0.113 +/- 0.030 and 1.042 +/- 0.196, respectively. Ten patients had detectable anti-rATG before rATG administration (1:100). Thirty-five of 101 patients (35%) developed anti-rATG antibody. Patients showed an initial positive anti-rATG antibody from days 8 to 59 after infusion and titers from 1:100 to 1:4000. In spite of rATG's postulated anti-B-cell activity, this study confirms that rATG induces sensitization at a frequency and titer seen with other xenogeneic antilymphocyte antibodies. Formation of such antixenoantibodies can have a negative impact on treatment response and hence warrant monitoring.

FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity.

The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.

[Suicide attempt with high-dose ecstasy]. / Suizidale hochdosierte Ecstasy-Einnahme.

The case of a 16-year-old female patient is reported, who has taken in 30 tablets of Ecstasy in a suicide attempt. Initially were seen a tachycardia,hyperdynamic circulation, dehydration, leg-myocloni in the awake excited female patient. For prophylaxis of aspiration general anaesthesia and intubation with following gastric lavage were performed. During the intensive care treatment the high blood pressure persisted, although general anaesthesia and anti-hypertensive therapy was continued. After extubation the neurologic status of the patient was normal. Emergency physicians see more and more often Ecstasy-intoxications. Signs of an acute intoxication with Ecstasy are a sympathomimetic reaction with tachycardia,hypertonic blood pressure and cardiac arrhythmia as well as fever, respiratory and renal insufficiency, rhabdomyolysis, cerebral edema and convulsion. A specific antidote does not exist; the symptomatic therapy consists of airway management, hemodynamic stabilisation, primary drug-elimination and, in case of need, application of betablockers and relaxants.

High cervical spinal cord stimulation (CSCS) increases regional cerebral blood flow after induced subarachnoid haemorrhage in rats.

The effects of high cervical spinal cord stimulation (cSCS) on regional cerebral blood flow (rCBF) were investigated after experimentally induced subarachnoid haemorrhage (SAH) in rats by the means of (99m)Tc-HMPAO. The experiments were carried out on a total of 24 Wistar rats, divided in three groups [group I: control without SAH, group II: SAH, group III: SAH and cSCS]. (99m)Tc-HMPAO was administered intravenously (group II/group III) 48 hours after induction of SAH. In group III, (99m)Tc-HMPAO was given after 3 hours of cSCS. All animals were sacrificed 30 minutes after application on (99m)Tc-HMPAO. Radioactivities were determined in blood, cerebrum and cerebellum. The ratio cerebrum/blood and cerebellum/blood was calculated to ascertain "extraction rate" in the sample differentially. The following mean values were calculated for the cerebellum/blood ratio: Group I: 1.06, SD: 0.21; Group II: 0.66, SD: 0.21; Group III: 1.00, SD: 0.37. Comparing the mean values a highly significant difference could be found between group II and III (p = 0.007) and between group I and II (p = 0.0019), respectively. Calculations of the cerebrum/blood ratio revealed similar results. After SAH cSCS enhances cerebral and cerebellar blood flow in rats. Possibly, cSCD constitutes a new therapeutic approach in the treatment of disturbed regional cerebral blood flow after SAH.

Gastric versus duodenal feeding in patients with neurological disease: a pilot study.

Both gastric and duodenal feeding tubes are used to provide enteral nutrition. Most studies comparing the two methods have focused primarily on rates of complications, rather than on nutritional outcomes, and show no difference in complications between the two methods. It is not clear which feeding route provides the best nutritional outcomes. The primary purpose of this randomized clinical pilot study was to compare the percentage of recommended calories and protein received by patients with neurological disease being fed enterally via gastric or duodenal feeding tubes. Secondary aims were to compare the following between groups: physiological effects of feeding, reasons for delay in feeding, volume of feeding residual, number of feeding tubes replaced, cost of feeding, and number and types of complications. A convenience sample of 25 neuro intensive care unit patients was randomly assigned to gastric or duodenal feeding. Enteral feeding was ordered by using a standardized prescription formula and provided by the nursing staff. Serum albumin and prealbumin levels were measured at baseline, day 3, and day 10. Nitrogen balance was measured on day 10. Enteral feeding data were collected daily. No significant differences were found between gastric and duodenal groups in nutritional outcomes, including percentage of recommended calories and protein received, physiological effects of feeding, reasons for delay in feeding, feeding residual, number of feeding tubes replaced, cost of feeding, and number and types of complications. Neither group achieved mean recommended caloric or protein intake during the 10 days of the study. Further research is needed to address how recommended nutrients can be provided enterally in a more timely and complete manner in critically ill NICU patients.

Effects of electrical stimulation of the Gasserian ganglion on regional cerebral blood flow after induced subarachnoid hemorrhage in pigs evaluated by 99mTc-HMPAO-SPECT.

It could be demonstrated that cervical spinal cord stimulation increases cerebral blood flow. The effects of electrical stimulation of the trigeminal ganglion in the acute phase of SAH in pigs were investigated. The experiments were carried out on 11 domestic pigs divided in two groups (group I: SAH [n = 5]; group II: SAH and trigeminal stimulation [n = 6]). In all animals a native SPECT was performed. The Gasserian ganglion was exposed for inserting the stimulation electrode. SAH was induced by injecting 10 ml autologous blood through a catheter placed in the suprasellar cistern. 30 minutes after SAH-induction electrical stimulation was started for two hours in group II (2.8-4.5 V, 50 Hz, 300 microseconds). 99mTc-HMPAO (400-540 MBq) was injected intravenously 110 minutes later. In group I 99mTc-HMPAO was applied after the same time interval. 80 minutes later SPECT was performed. Data were processed to calculate the uptake of radioactivity (%/kg tissue weight). The mean values were calculated for the different groups: native animal examination (%/kg tissue weight): 0.6343; group I: 0.468; group II: 0.6533. Comparing the mean values a highly significant difference between group I and group II (p < 0.01) and between native examination and group I (p < 0.01) could be found. No statistical significance could be detected on comparing the left/right-ratio in any ROI. The electrical stimulation of the Gasserian ganglion leads to a significantly increased uptake of 99mTc-HMPAO after induced SAH. Maybe the stimulation of the Gasserian ganglion constitutes a new therapeutic modality treating disturbed rCBF after SAH.

Augmentative treatment of chronic deafferentation pain syndromes after peripheral nerve lesions.

Deafferentation pain syndromes developing after peripheral nerve lesions are difficult to treat. According to the follow-up (mean: 39.5 months) of 6 patients suffering from causalgic pain we will present our method of augmentative therapy in chronic neuropathic pain caused by peripheral nerve lesions, i.e., peripheral nerve stimulation (PNS), spinal cord stimulation (SCS) and chronic intrathecal opioid infusion. None of the patients showed intraoperative or follow-up complications. Evaluated by visual analogue scales all patients reported a good to excellent pain relief (75-100%). (1) Regarding the favourable long-term results of PNS, this method should be considered in cases of mononeuropathic pain syndromes. (2) Neuropathic pain syndromes which are not assignable to a singular nerve lesion, can often be managed effectively by SCS. (3) In contrast to the widespread opinion, deafferentation pain syndromes of central or peripheral origin can be treated satisfactorily by intrathecal opiate administration.

[The sacral perineural system--are there radiological criteria for an indication for surgery? First results and literature survey]. / Sakrale Perineuralzysten--gibt es radiologische Kriterien für eine Operationsindikation? Eigene Ergebnisse und Literaturübersicht.

PURPOSE: To establish recommendations for diagnostic imaging of cystic lesions of the sacral region and to evaluate for potential predictors of therapeutic outcome. METHODS: Conventional imaging of the lumbar spine, conventional CT, myelography, post myelo-CT and MRI were performed in 7 symptomatic [corrected] patients. All patients underwent operative decompression and histological examination. The radiographic examinations were reevaluated retrospectively and correlated with the postoperative outcome. RESULTS: In one patient the differential diagnosis of a neurinoma could not be excluded with CT and CT-myelography alone. In all 7 patients MRI provided a definite diagnosis and a precise presentation of the cyst extension. A complete postoperative remission of symptoms was noticed in 4, a partial remission in three cases. The correlation of cyst extension, cyst shape, and the communication with the subarachnoid space did not provide predictive information concerning operative outcome. CONCLUSION: MR can be used as the sole imaging tool for demonstration of cystic lesions. Relevant disadvantages in comparison to myelography and myelo-CT were not evident. No imaging modality could predict the value of surgical intervention.

Steady-state plasma kinetics of slow-release propafenone, its two isomers and its main metabolites.

Steady-state plasma kinetics of propafenone (CAS 54063-53-5), the S- and R-enantiomers, and the two main metabolites were investigated in a double-blind, placebo-controlled dose-finding study using a slow-release formulation of propafenone at three different dose regimens (2 x 225 mg, 2 x 325 mg, and 2 x 425 mg). The study included a total of 24 patients (18 m, 6 f) with symptomatic ventricular arrhythmia. Since statistically valuable data was limited by a considerable portion of undetectable plasma concentrations among patients having received verum, kinetics could be followed up only in a group of 14 patients (10 m, 4 f) over a period of 12 h under steady state conditions. All patients were phenotyped prior to the study by measuring the ratio of sparteine/dehydrosparteine and three poor metabolizers were identified. A detailed description of the analytical methods used is given. With the low dose, a mean plasma level of 87 +/- 16 ng propafenone per ml plasma was obtained, with the medium dose a level of 243 +/- 34 ng/ml and with the higher dose 334 +/- 71 ng/ml were reached. All three doses of the slow-release preparation resulted in a smoothened and thus therapeutically favorable plasma concentration curve, independently from phenotype. With regard to the two propafenone enantiomers, a preferential clearance of the R-form (S/R = 2.08 +/- 0.19) could be confirmed without observing a change in the S/R ratio with time.