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Background: Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis., Objectives: Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma., Animals: Ninety-seven client-owned dogs with naive or relapsed lymphoma and 23 healthy dogs., Methods: Prospective study. Serum TK1 activity measured by refined ELISA-based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4 weeks until relapse or last follow-up., Results: Serum TK1 activity was ≤20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n = 36) versus partial (PR, n = 29) response (P < .0001). Sensitivity (Se) and specificity (Sp) of sTK1 activity for detecting nonfully responders were 76% and 100%, respectively, with cutoff of 119.5 Du/L (AUC, 0.90; 95%-CI, 0.81-0.98; P < .0001). In dogs with CR, a 5-fold increase in sTK1 activity at a 4-week interval predicted relapse at the subsequent 4-week assessment with a Se 50% and Sp 94% (AUC, 0.72; 95%-CI, 0.55-0.90; P = .02). An increase of sTK1 activity (>2.7-fold value measured at clinical response) predicted relapse at subsequent 4-week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%-CI, 0.64-0.95; P = .004)., Conclusions and Clinical Importance: Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The clinical outcome of patients with severe primary and secondary mitral regurgitation (MR) and heart failure or significantly reduced left ventricular ejection fraction (LVEF) who underwent percutaneous mitral valve repair (pMVR) is yet not well known. This study compares midterm outcome of patients with severe left ventricular dysfunction (EF ≤30%) versus patients with slightly or moderately reduced or normal LVEF (EF >30%) after pMVR. One hundred thirty-six consecutive patients were enrolled: 42 patients displayed severe left ventricular dysfunction, group 1 (logistic EuroSCORE I 27.7 ± 21.8%; secondary MR in 37 patients), and 94 patients displayed slightly or moderately reduced or normal LVEF, group 2 (logistic EuroSCORE I 17 ± 18.2%; secondary MR in 21 patients). The primary efficacy endpoint was death of any cause, repeat mitral valve intervention, and/or New York Heart Association class ≥III, which was reached in 31% of patients in group 1 versus 40% in group 2 (p = 0.719) at a median follow-up of 371 days. MR, graded by transthoracic echocardiography, was reduced in both groups (p <0.001) and New York Heart Association class improved in each group (p <0.001), with no differences between groups (p >0.05). In conclusion, at midterm follow-up, the pMVR provided significant clinical benefits with comparable results achieved both in patients with significantly reduced and in patients with moderately reduced to normal LVEF. Thus, pMVR represents a feasible and effective treatment in high-risk patients who otherwise have limited therapeutic options and no safe option to reduce MR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found that DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions.

Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD gene. We detected large deletions of the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis. SSCP variants were detected in 22 probands and none in 60 X-chromosomes from normal individuals. Mutations were detected in all of the ALD probands. The mutations were distributed throughout the gene and did not correlate with phenotype. Approximately half were non-recurrent missense mutations of which 64% occurred in CpG dinucleotides. There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD.

To analyse spontaneous multichannel slow-wave MEG activity a tool was developed to extract focal abnormal activity with a higher spatial dipole density across time. The first version works on discrete volume units, the second version avoids a possible location error, works continuously and can be adjusted for individual slices three-dimensionally. The first version is used for screening and the second version is used to go into more detail. The dipole density plot (DDP) is not limited to single foci, nor to the single-dipole model; neither is it limited to the MEG. The DDP seems to be a valuable tool for detecting and locating lesions three-dimensionally within the brain.

Two recent studies have suggested the involvement of serum amyloid A (SAA) and P (APCS) genes in familial Mediterranean fever (MEF). To test the role of SAA and APCS in MEF and MEF-amyloidosis, we studied 17 informative families (15 Armenians, 2 non-Ashkenazi Jews) and 8 MEF patients with amyloidosis using a candidate gene approach. No evidence for any MEF-associated polymorphism was found in any of the 41 Armenian and Jewish MEF patients tested. Our family studies allowed us to rule out tight linkage between SAA and MEF (lod score = -2.16, theta less than or equal to 0.06). For APCS we found that the allele frequency in the MEF-amyloidosis patients was similar to that in 18 unrelated MEF patients without amyloidosis and their 33 healthy parents. Finally, we excluded close genetic linkage between APCS and MEF at 8.5 cM or less (lod score = -2.2).

Slow rhythmic activity (SRA) in the frequency range from 2.5 to 5.0 cps was studied in 20 subjects (Ss) in order to examine its effect upon sensorimotor reactions and its possible relationship to psychological findings. With monopolar EEG derivations, maximal power density of SRA is found in frontal regions, whereas bipolar leads reveal maximum occurrence of SRA over posterior areas. Reaction times (RT) to visual and auditory stimuli increase significantly during the occurrence of SRA; the amount of this prolongation (ca. 74 ms) is independent of stimulus modality but significantly correlates with SRA frequency: the lower the frequency, the higher the RT increment. In psychological tests, most Ss with SRA displayed disturbances of emotionality as well as 'pathological' values in the subscales hysteria, hypochondria, psychasthenia, and paranoia, but none of our Ss was diagnosed as psychotic. There is a high correlation between the SRA frequency and the extent of psychological deviations: Ss with low SRA frequency values are more likely to reveal psychological disturbances than Ss with high SRA frequency. The possible origin and physiological impact of SRA is discussed and the desirability of further neurophysiological studies is emphasized.

This is a report, based on a one year's stay at the hospital of the Gondar College of Medical Sciences (PDR Ethiopia), on the usage of traditional therapeutic practices as described by patients of the neurologic-psychiatric department in their histories. More frequently than others, psychotic patients, patients suffering from headache, and patients complaining of fits had used traditional treatments before seeking medical help.

The efficacy of electrical stimulation on a chronically denervated muscle depends on stimulus parameters, which have an important influence on the development of atrophy. Stimulus frequency and/or total activity are particularly responsible for the development of some histological, biochemical and contractile features. The present study in 18 rabbits deals with a recently developed electrical stimulus, which had proved effective in maintaining muscle force following denervation. This current has (1) unusual long bidirectional rectangular impulses (20 ms) and (2) a frequency of 25 Hz, which is between the frequencies of fast- and slow-firing motor units. Electrical stimulation began 28 (in one animal 53) days after total motor and sensory denervation of the right hindleg, and was continued until the end of the experiment, up to 205 days. To mimic a therapeutic regimen, which should be agreeable to patients, daily treatment times were kept to a minimum (2 x 6 min), and surface electrodes were used. Morphometric evaluation of the fast flexor digitorum sublimis muscle showed that such electrical stimulation was able to preserve fibre diameter at a level of 72-86% of the initial values for several months, while unstimulated fibres showed the usual atrophy with a decrease of diameters below 40% of normal. The stimulation induced a "hybrid" fibre type with properties of a slow muscle (rich in mitochondria in NADH-dependent tetrazolium reductase staining and electron microscopy) as well as of a fast-twitch muscle (fibre type IIb in myofibrillar ATPase stainings).

Soon after Cerletti had introduced electroconvulsive treatment into psychiatric therapy in 1938, electroencephalographic examinations were made during and after ECT. Based on the majority of the results gained it was supposed that intensity and persistence of EEG changes after electroconvulsive shocks depend on number and frequency of single shocks. However, our investigations on 49 patients of the Psychiatric Clinic of Karl-Marx-University, Leipzig, show that intensity and persistence of post-therapeutic EEG deviations after ECT reveal no statistically significant correlation with number and frequency of electroconvulsive shocks used. Unilateral accentuations occurred exclusively after unilateral treatment (alone or combined with bilateral technique) among our subjects.

Six persons showing what is called slow posterior activity (4/s rhythm) in the electroencephalogram were reexamined after a period of five years. Sensorimotor reaction times were recorded in addition to the electroencephalogram which was analyzed for the frequency of LPA and for the degree of stability of time dependence. The frequency and distinctness of LPA were found to be stable after five years (r = 0.09 and 0.82, respectively; p less than 0.001), whereas the alpha rhythmus of the subjects had undergone considerable changes (r = 0.34; p greater than 0.05). The extension of reaction times to be observed under the influence of LPA was also seen to remain constant (r = 0.79; p less than 0.05). Accordingly, LPA proved an extremely stable characteristic which did not show any substantial variations in the course of five years.

The results of the studies carried out in four carriers of characteristics are presented under localistic aspects proceeding from the different local distribution of rhythmized activity around 4/s with unipopular and bipolar lead technique. A hypothesis of the origin of the activity is presented which would be in agreement with its distribution characteristics and reactivity.

51 patients with rheumatoid arthritis and high rheumatoid factors (mean titres 928) underwent examination for the demonstration of an extraarticular organ manifestation within the scope of the cooperation between the Department of Medicine of the Karl-Marx-University Leipzig and the Institute for Rheumatology of the Academy of Medical Sciences of the USSR in Moscow. The frequency of nodous rheumatism (about 60%) is comparable with the frequency of polyneuropathy. In 20% of the patients a systemic muscle atrophy, a hepatomegaly as well as a Raynaud-syndrome were stated. By means of skin biopsy in 28% perivascular infiltrates were found. Altogether in 6 patients (12%) a participation of the lungs and the pleura, respectively, could be proved. Only rarely a clinically manifest heart disease caused by the rheu-we we found an pericardial effusions in 3 cases. In systemic manifestation, such as myositis, participation of the eyes or vasculitis of the digital arteries with necrosis, were only sporadically to be established. Among 22 patients we found an pericardial effusions in 3 cases. In systemic manifestation in most cases increased parameters of activity were found. From the practical point of view apart from increased titers of the rheumatoid titres and circulating immune complexes (C1q-BT) increased concentrations of the C-reactive protein are prognostically significant. The presence of high rheumatoid factor titres alone as well as the isolated presence of rheumatic nodes must not always be connected with an unfavourable prognosis. When severe extraarticular manifestations are present a possibly early, intensive occasionally extracorporeal treatment is indicated.

Electroencephalographic examinations of eighteen patients with spinocerebellar ataxias and of thirteen normal sibs of four of the subjects are reported. The authors frequently observed low levels of potential and a tendency toward slackening in basic activity, which is in agreement with data presented in the literature; theta-delta inclusions in the temporal regions were found especially in cases of cerebellar ataxia. Examinations of the sib frequently showed low-potential curves. However, the use of electroencephalography for the purpose of identifying, in the case of hereditary ataxia, latently diseased sibs for heterozygous individuals does not seem possible.

Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue.

A case of pattern-sensitive epilepsy is reported which is characterized in that the pattern is formed from images of human faces with clearly recognizable eyes. Similarities to previously reported cases of pattern-sensitive epilepsy as well as dissimilarities from those cases are discussed.

Ever since it was introduced, electric convulsion therapy (ECT) has been a subject of reports presenting spectacular successes and alarming side effects. The appearance of psychopharmaceutic therapy made ECT appear completely superfluous and, therefore, dispensable. However, this conclusion proved to be premature: ECT retained its defined justification. We therefore counter Breggin's polemic allegation that "Electric convulsions are no therapy" with our own experience that "Electric convulsions are therapy" and proceed to justify our opinion. After a detailed description of the origins of the criticisms voiced against ECT, its risks and side effects are discussed from the clinical and cerebro-electrical standpoint and compared with the risks and side effects of other forms of psychiatric somatotherapy. Severe and irrepairable damage by ECT can now be avoided and; in fact, has never been observed among our patients. It must also be pointed out that, far from excluding each other, ECT and psycho- or social therapy are often complementary or even mutually necessary.

The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm). The results suggest that the immunosuppression caused by OPL in BALB/cByJ mice was primarily due to TCDD, that the non-TCDD components of OPL diminished the TCDD immunotoxicity in the DBA/2J strain, and that the thymic atrophy and hepatomegaly were caused primarily by the non-TCDD components of the OPL.

The influence in 8 of our patients with ophthalmic migraine of photic driving with sine-like flashing lights on EEG background activity was checked and the visually evoked potentials following the application of diffused simple light stimuli were analyzed using the recovery cycle technique. The results indicate a slightly increased tonic activity of the structures of the mesencephalic formatio reticularis, such as may be produced by slight functional disturbances. Some vegetative secondary symptoms of migraine attacks and some of the changes in EEG observed in patients with ophthalmic migraine are explicable by such an abnormality.

The results of electroencephalographic and familial studies of 31 Wilson's disease patients coming from 26 kindreds are presented. Prior to treatment, 8 patients showed pathological conditions, while 9 and 11 patients showed borderline and normal conditions, respectively, it having not been possible to determine electroencephalographic conditions characteristic of Wilson's disease and find any relationships between the intensity of E.E.G. changes and the clinical picture and stage of development of the disease, respectively. Under penicillamine treatment, there was observed a tendency toward normalization of pathological conditions rather than deterioration of normal E.E.G. findings. So far as familial studies are concerned, the authors report the results obtained for 9 fathers, 19 mothers, and 24 siblings from a total of 21 kindreds; what is remarkable in this connection is the comparatively small percentage of normal E.E.G. findings for healthy siblings. It was only in one single kindred that it was possible to observe similarities between E.E.G. variations of individual family members.