Improvement of Decreased Critical Flicker Frequency (CFF) in Headache Patients With Drug Abuse After Successful Withdrawal

A considerable proportion of headache patients fulfill the criteria of "drug abuse" (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis.
The present study deals with the question whether this impairment of vigilance and continuous performance is reversible. Forty-eight headache patients with drug abuse were investigated three times by means of CFF analysis: immediately before (A), immediately after (B), and 3 weeks after having finished (C) inpatient drug withdrawal.
Immediately after withdrawal, a significant decrease of headache intensity was observed. The CFF values, however, remained unchanged at a depressed level, probably due to withdrawal medication and the initial sedative side effects of thymoleptic agents (given as prophylaxis).
Three weeks after withdrawal, however, the CFF values were significantly improved, and were now within a range not far from the normal values known from a healthy general population. Thus, even after many years of drug abuse, headache patients have a good chance to improve their vigilance and continuous performance and to reach normal or close to normal levels.     

Recombinant allergen fragments as candidate preparations for allergen immunotherapy

Background: Lately, renewed interest has arisen in the new forms of allergen immunotherapy because they may offer alternatives for drug treatment. Objective: The purpose of this study was to develop a well-characterized preparation of the main respiratory cow dander allergen, Bos d 2, with attenuated allergenic activity. Methods: The immunologic characteristics of Bos d 2 preparations were studied by indirect IgE ELISA, ELISA inhibition, Western blotting, histamine release, skin prick tests, and the proliferation tests of allergen-specific T-cell clones. Results: The complete recombinant Bos d 2 was observed to bind effectively, IgE of cow-allergic patients in indirect ELISA. In other experiments, the IgE-binding capacity of recombinant Bos d 2 proved to be lower compared with native Bos d 2. When the two overlapping recombinant fragments of Bos d 2 (corresponding amino acids 1-131 and 81-172, respectively) covering the whole molecule were compared with the complete recombinant Bos d 2 with several methods, only a low level of residual reactivity was observed. For example, recombinant fragments could not bind antibody at all in ELISA inhibition tests retaining, however, some reactivity in skin prick tests. In contrast, the fragments were able to stimulate vigorously Bos d 2-specific T-cell clones. Conclusion: The approach we have taken may offer a simple and reproducible way to produce hypoallergenic preparations for immunotherapy, circumventing simultaneously some of the problems of other experimental methods such as individual T-cell epitope recognition in peptide-based immunotherapy. (J Allergy Clin Immunol 1997;100:721-7.)     

Langzeit-Prognose von Patienten mit juvenilem Insult

Zusammenfassung Bei 57 von 70 Patienten, die vor dem 40. Lebensjahr erstmals zerebrale Durchblutungsstörungen auf ischämischer Basis erlitten hatten, wurde der weitere Verlauf über durchschnittlich 84 Monate verfolgt. Innerhalb von 48 Monaten nach dem initialen Ereignis kam es bei 22 von 51 Patienten (43,1%) mit Spontanverlauf zu weiteren Manifestationen (Rezidivquote fur Patienten mit transitorischischämischen Attacken 78,6%, für Patienten mit prolongierten reversiblen Defekten 33,3%, für Patienten mit kompletten Schlaganfällen 28,6%), wobei 31,5% aller Patienten schon innerhalb des ersten Jahres neuerliche zerebrale Durchblutungsstörungen erlitten, die meisten sogar innerhalb der ersten wenigen Monate.Trotz der wesentlich höheren Rezidivrate waren Patienten mit initialen passageren zerebralen Durchblutungsstörungen am Ende des Beobachtungszeitraums (BZR) in sozialer Hinsicht weniger beeinträchtigt als Patienten mit kompletten Schlaganfällen als Erstmanifestation. 78,4% aller Patienten waren am Ende des BZR voll arbeitsfähig.Bei 72,2% der patienten mit neuerlichen zerebralen Durchblutungsstörungen war das Herdgeschehen einem anderen als dem urspriinglich betroffenen Gefäßgebiet zuzuordnen.Patienten mit arterieller Hypertonic im BZR halten eine etwas ungünstigere Langzeitprognose, während Nikotinkonsum wie auch relatives Körpergewicht auf den Schweregrad der sozialen Beeinträchtigung keinen Einfluß hatte.Trotz der eher günstigen Langzeitprognose weisen unsere Ergebnisse — besonders im Hinblick auf die hohe Rezidivquote innerhalb der ersten Monate nach der initialen Attacke — auf die Notwendigkeit einer unverzüglichen umfassenden diagnostischen Abklärung und Einleitung einer individuellen Therapie bei Patienten mit juvenilem Insult hin.     

Fully implantable distraction nail for the treatment of shortening deformity and bone defect. Spectrum of indications

Since the first clinical experiences with the fully implantable programmable distraction nail nearly ten years ago, the system has been improved in Munich and meanwhile used in 26 patients. During the first 10 cases there has been highest interest in the reliability of the system, while in the following the expansion of indications was more important. At the thigh a good indication beside shortening is the combination of shortening and axis deviation, even if the center of deviation is located near to the knee joint in the supracondylar area. According to preoperative planing the deformity correction can be done acutely while the lengthening procedure follows postoperatively automatically at night-time. If the stabilization with an intramedullary nail is possible, large bone defects can be treated by bone transport using this system also. The fully implantable intramedullary nail has proved its variable functions in cases of large bone defects combined with shortening of the femur. The system is able to perform the bone transport at first and the lengthening procedure automatically without any further operation thereafter.     

Lesion pattern in patients with multiple sclerosis and depression

To assess if a specific lesion pattern or changes of the basal limbic system as seen in primary depression and depression associated with neurodegenerative disorders might be identified in depressive multiple sclerosis (MS) patients, we submitted 78 MS patients to a MRI examination consisting of a quantitative measurement of lesions and of hyperintense signals from the pontomesencephalic midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a transcranial ultrasound examination rating its echogenicity semiquantitatively and a standardized neurological, neuropsychiatric and neuropsychological assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for depression. Depressed MS patients had a significantly larger temporal lesion load than non-depressed MS patients, especially on the right side. A trend of difference was detected for lesions of the right parietal lobe, the right frontal lobe, the cerebellum and the total lesion load. Neither hyperintense signals or relaxometry nor echogenicity of the region at the level of the pontomesencephalic midline were significantly different between the groups. We conclude that depression in MS patients is not associated with an alteration of the basal limbic system at the brainstem as seen in Parkinson's disease or unipolar depression but with an increased lesion load of the projection areas of the basal limbic system.     

Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activation and refractory maps

Isochronal maps of ventricular activation were analyzed in dogs 3-5 days after ligation of the left anterior descending coronary artery utilizing a 64-channel multiplexer. Isochronal maps of the effective refractory period were determined from 62 epicardial sites and correlated with the activation maps. The ischemia occurring in the surviving epicardial layer prolonged refractoriness in a spatially nonuniform manner. The resulting pattern of refractoriness on the epicardial surface resembled concentric rings of isorefractoriness which increased in duration from the normal zone to the center of the ischemic zone. The formation of an arc of functional unidirectional conduction block occurred along the gradient of refractoriness and the exact location of the arc depended on the S1-S2 interval. When a short S1-S2 failed to induce reentry, fewer adjacent sites with sufficiently disparate refractoriness formed a smaller arc of block. A subsequent S3 encountered further nonuniformly shortened refractoriness (normal areas had shortened refractoriness greater than ischemic areas) and the arc of block was lengthened. This required a longer time for the wavefront to circulate around the arc. When it then reached the distal side of the arc, refractoriness had expired proximal to the arc and reentry occurred. Similarly, nonuniform shortening of refractoriness explained why one reentrant beat may or may not produce successive reentrant beats. Therefore, the spatial pattern of refractoriness forms the substrate for the arc of unidirectional conduction block that is fundamental to the development of ventricular reentry in this experimental model.     

No influence of brain-derived neurotrophic factor (BDNF) polymorphisms on treatment response in a naturalistic sample of patients with major depression

The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD) remains to be elucidated. Recent post hoc analyses indicated a potential association of three polymorphisms in the BDNF gene with worse treatment outcome in patients with the subtype of melancholic depression. We aimed at replicating these findings in a German naturalistic multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265 (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy controls. We applied univariate tests and logistic regression models stratifying for depression subtype and gender. The three polymorphisms were not associated with MDD as diagnosis. Further, no associations were found in univariate tests. With logistic regression, we only found a tendency towards an association of the rs6265 (Val66Met) polymorphism with overall response to treatment (response rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment outcome stratified for subtypes of depression did not differ significantly between the investigated polymorphisms or using haplotype analyses. However, results showed a tendency towards significance. At this stage, we cannot support an influence of these three polymorphisms. Further studies in larger patient samples to increase sample sizes of subgroups are warranted.     

A sertoli cell-specific knockout of connexin43 prevents initiation of spermatogenesis

The predominant testicular gap junctional protein connexin43 (cx43) is located between neighboring Sertoli cells (SCs) and between SCs and germ cells. It is assumed to be involved in testicular development, cell differentiation, initiation, and maintenance of spermatogenesis with alterations of its expression being correlated with various testicular disorders. Because total disruption of the cx43 gene leads to perinatal death, we generated a conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system, which lacks the cx43 gene solely in SCs (SCCx43KO), to evaluate the SC-specific functions of cx43 on spermatogenesis in vivo. Adult SCCx43KO(-/-) mice showed normal testis descent and development of the urogenital tract, but testis size and weight were drastically lower compared with heterozygous and wild-type littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant reduction in the number of spermatogonia but increased SC numbers/tubule with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and in intratubular SC clusters. Our data demonstrate for the first time that cx43 expression in SCs is an absolute requirement for normal testicular development and spermatogenesis.