No correlation between number of MRI-evident lesions in cerebrum and the soleus stretch reflex in multiple sclerosis patients

The aim of the study was to investigate if the stretch reflex of the soleus muscle was useful in quantifying upper motor neuron lesions. The soleus stretch reflex was recorded in 10 healthy subjects and 20 patients with active relapsing-remitting multiple sclerosis and correlated to the number of MRI lesions in cerebrum and clinical scores (expanded disability status scale and regional functional scoring system). The short latency stretch reflex was elicited by rotating the left ankle joint 4 degrees with a rise time in the interval of 40-640 ms. The amplitude of the stretch was larger in multiple sclerosis patients being 88.5 microV in patients and 12.8 microV in controls, P = 0.007. The sensitivity of the stretch reflex expressed as the slope of the best linear fit was increased in MS patients to 2.6 microVs/degree compared with 0.6 microVs/degree (0.1-2.2) in controls, P = 0.009. There was no correlation between amplitude of the stretch reflex and number of MRI lesions (r = -0.03). In conclusion, the soleus stretch reflex might be useful to quantify spasticity but is not useful in detecting dysfunction of upper motor neurons in MS.     

Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.     

The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity

BACKGROUND: A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major (moderate to severe) depression by the patients' self-reported symptoms. This Major Depression Inventory (MDI) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items. METHODS: The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index of validity for the clinician's DSM-IV and ICD-10 diagnosis of major (moderate to severe) depression. The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms. RESULTS: The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92. The specificity varied between 0.82 and 0.86. When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic. LIMITATIONS: The sample of subjects was limited. Patients with psychotic depression were not included. CONCLUSION: The MDI was found to have a sensitivity and specificity which is acceptable. The questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score.     

Clinical outcome after surgery on schwannomas in the extremities

BACKGROUND Schwannoma is a benign, encapsulated and slowly growing tumor originating from Schwann cells and is rarely seen in the peripheral nerve system. Typical symptoms are soreness, radiating pain and sensory loss combined with a soft tissue mass.AIM To evaluate pre-and postoperative symptoms in patients operated for schwannomas in the extremities and investigate the rate of malignant transformation.METHODS In this single center retrospective study design, all patients who had surgery for a benign schwannoma in the extremities from May 1997 to January 2018 were included. The location of the tumor in the extremities was divided into five groups; forearm, arm, shoulder, thigh and leg including foot. The locations of the tumor in the nerves were also categorized as either; proximal, distal, minor or major nerve. During the pre-and postoperative clinical evaluation, symptoms were classified as paresthesia, local pain, radiating pain, swelling, impairment of mobility/strength and asymptomatic tumors that were found incidentally(with magnetic resonance imaging). The patients were evaluated after surgery using the following categories: Asymptomatic or symptomatic patients(radiating and/or local pain) and those with complications. The follow up period was from the time of surgery until last examination of the particular physician. Multivariate logistic regression analysis was performed to identify independent prognostic factors for postoperative significant symptoms at follow-up.RESULTS We identified 858 cases from the institutional pathology register. We excluded cases with duplicate diagnoses(n = 407), pathology not including schwannomas(n = 157), lesions involving the torso, spine and neck(n = 150) leaving 144 patients for further analysis. In this group 99 patients underwent surgery and there were five complications recorded: 2 infections(treated with antibiotics) and 3 nerve palsies(2 involving the radial nerve and one involving the median nerve) that recovered spontaneously. At the end of follow-up, 1.4 mo(range 0.5-76) postoperatively, we recorded a post-operative decrease in clinical symptoms: Local pain 76%(6/25), radiating pain 97%(2/45), swelling 20%(8/10). Symptoms of paresthesia increased by 2.8%(37/36) and there was no change in motor weakness before and after surgery 1%(1/1). Multivariate analysis showed that tumors located within minor nerves had a significantly higher prevalence of postoperative symptoms compared with tumors in major nerves(odds ratio: 2.63; confidence intervals: 1.22-6.42, P = 0.029). One patient with schwannoma diagnosed by needle biopsy was diagnosed to have malignant transformation diagnosed in the surgically removed tumor. No local recurrences were reported.CONCLUSION Surgery of schwannomas can be conducted with low risk of postoperative complications, acceptable decrease in clinical symptoms and risk of malignant transformation is low.     

Bromazepam in generalized anxiety

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits –0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as at least good in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.General practice The following general practitioners are gratefully acknowledged for their excellent co-operation: K. Andreasen (Grenaa), T. Andreasen (Helsingoer), C. Bjerre-Christensen (Viby J), J. Brix (Aabenraa), N.B. Caning (Stokkemarke), N. Christensen (Odense), P. Dehn-Jensen (Lyngby), J. Eggert (Langebaek), H. Fuglsang-Damgaard (Havndal), I. Fraemohs (Allingaabro), J. Gylling (Nykoebing Sjaelland), E. Halkjaer-Soerensen (Roedding), B. Hansson (Frederiksvaerk), C. Hauge (Espergaerde), S. Hede (Aalborg), G. Jensen (Copenhagen S), T. Knudsen (Arden), P. Kofod (Vejle), K. Kraen (Varde), V. Lade (Hjoerring), S. Mehlsen (Auning), J. Meyer-Christensen (Hobro), R. Michael (Langebaek), J. Munch (Oersted), L. Moeller-Hansen (Alleroed), U. Moeller (Graasten), K. Nielsen (Malling), S. Kjaerem Nielsen (Copenhagen), P.V. Nielsen (Odense), J. Peulicke (Espergaerde), O. Ravn (Roedding), C.U. Rosenberg (Aarhus), J. Rude (Goerlev), S. Spangsberg (Holbaek), H. Soegaard (Oelgod), O. Tang (Hoersholm)     

Diazepam prevents progression of kindled alcohol withdrawal behaviour

The purpose of the present experiment was to study the kindling hypothesis of alcohol withdrawal stating that exposure to repeated episodes of alcohol withdrawal results in an increased severity of subsequent withdrawal reactions. Two groups of male Wistar rats were subjected to 13 episodes of 2 days severe alcohol intoxication and 5 days alcohol withdrawal. Animals in the control group (n=80) developed clinical withdrawal signs following each intoxication episode. In the diazepam group (n=80) the withdrawal reactions during episodes 1–9 were blocked by intraperitoneal diazepam administration (0–30 mg/kg) 8, 11 and 15 h into withdrawal. During episode 10–13 diazepam treatment was terminated and convulsive withdrawal behaviour was observed 9–15 h after last alcohol dose. The probability of seizure activity during these four withdrawal episodes was calculated as 0.239 and 0.066 in the control and the diazepam groups, respectively. Based on Monte Carlo simulation techniques, this difference was found to be statistically significant (P<0.05). No differences in the non-convulsive alcohol withdrawal symptoms tremor, hyperactivity and rigidity were detected between controls and diazepam animals after diazepam treatment. It was concluded that the increased convulsive behaviour in the control group was caused by cumulated kindling-like cerebral alterations during the previous repeated alcohol withdrawal phases.     

Spontaneous retroperitoneal hematoma: our experience

We report 15 cases of spontaneous retroperitoneal haematoma. The etiology and the diagnostic and therapeutic procedures were evaluated. The haematoma source was the adrenal gland in 4 patients and the causes were pheochromocytoma (1), adenoma (1), myelolipoma (1) and idiopathic (1). In 10 patients the source was the kidney and the causes were angiomyolipoma rupture (6), renal cell carcinoma (3) and ureteral calculi (1). In the remaining case, the haematoma was produced by fibrinolytic and anticoagulant therapy in a patient with acute myocardial infarction. The imaging diagnostic techniques employed were abdominal ultrasonography and CT scan, which allowed the diagnosis of haematoma and showed his size and extension in all the cases. With these two techniques, and with the retrograde pyelography in one patient, we obtained the etiologic diagnosis in 12 of the 15 cases. Surgical treatment was performed in 12 patients (adrenalectomy in 2, simple nephrectomy in 3, radical nephrectomy in 5 and partial nephrectomy in 2).     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

A simple procedure for quantification of neurite outgrowth based on stereological principles

The molecular mechanisms controlling formation and remodelling of neuronal extensions are of considerable interest for the understanding of neuronal development and plasticity. Determination of neurite outgrowth in cell culture is a widely used approach to investigate these phenomena. This is generally done by a time consuming tracing of individual neurites and their branches. We have used stereological principles to determine the length of neurites. The total neuritic length per cell was estimated by counting the number of intersections between neurites and test lines of an unbiased counting frame superimposed on images of cell cultures obtained by conventional computer-assisted microscopy. The absolute length, L, of neurites per cell was subsequently estimated from the number of neurite intersections, I, per cell by means of the equation L=(πd/2)I describing the relationship between the number of neurite intersections and the vertical distance, d, between the test lines used. When measuring neurite outgrowth from PC12 cells and primary hippocampal neurons, data obtained by counting neuritic intersections correlated statistically significantly with data obtained using a conventional tracing technique. However, information was acquired more efficiently using the stereological approach. Thus, using the described set-up, the stereological procedure was approximately five times less time consuming than the conventional method based on neurite tracing. The study shows that stereological estimation of neuritic length provides a precise and efficient method for the study of neurite outgrowth in cultures of primary neurons and cell lines.     

Clinimetrics and Clinical Psychometrics: Macro- and Micro-Analysis

Background: Clinimetrics was introduced three decades ago to specify the domain of clinical markers in clinical medicine (indexes or rating scales). In this perspective, clinical validity is the platform for selecting the various indexes or rating scales (macro-analysis). Psychometric validation of these indexes or rating scales is the measuring aspect (micro-analysis). Methods: Clinical judgment analysis by experienced psychiatrists is included in the macro-analysis and the item response theory models are especially preferred in the micro-analysis when using the total score as a sufficient statistic. Results: Clinical assessment tools covering severity of illness scales, prognostic measures, issues of co-morbidity, longitudinal assessments, recovery, stressors, lifestyle, psychological well-being, and illness behavior have been identified. Conclusion: The constructive dialogue in clinimetrics between clinical judgment and psychometric validation procedures is outlined for generating developments of clinical practice in psychiatry.