Platelet scintigraphy in cerebrovascular diseases

The benefit of platelet scintigraphy using 99mTc-phytate as a method to detect atherosclerotic lesions in extracranial neck vessels was tested on 143 patients. 29 patients had an abnormal scan of the neck vessels. The scintigraphic results were critically evaluated, taking clinical observations and the angiograms performed on 88 patients into consideration. Platelet scintigraphy can be useful as an additional examination in some patients. Generally, however, the value and reliability of platelet scintigraphy must be seen as insufficient, making further prospective studies with histological examinations imperative.     

Tick-borne encephalitis in the Saarland and the Rhineland-Palatinate

Summary The Saarland and the Rhineland-Palatinate are not considered endemic regions for tick-borne encephalitis (TBE), and patients in this region have not been routinely advised to undergo vaccination or serologic testing for TBE. In 1994, a significantly increased incidence of TBE cases was noted in the neighbouring state of Baden-Württemberg. In the same year, the first TBE acquired in the Saarland was diagnosed. To investigate the infection risk for TBE in the Saarland and Rhineland-Palatinate, the records of 2,123 serologic tests for TBE collected since 1989 were systematically examined. In addition, 904 frozen sera of patients displaying inflammatory changes in the cerebrospinal fluid (CSF) were analyzed. IgG and IgM antibodies against TBE virus were found in 15 patients, four of which were verified clinically and serologically as TBE. One of these four cases was certainly and another was probably acquired in the Saarland. Three other patients displayed serologic signs of a TBE virus contact. The results of this study suggest that the occurrence of single cases in the Saarland has to be considered, but the risk is very small.

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Zeckenencephalitis im Saarland und in Rheinland-Pfalz

Zusammenfassung Das Saarland und Rheinland-Pfalz gelten nicht als Frühsommer-Meningoenzephalitis (FSME)-Endemiegebiete. Daher wurde in dieser Region nicht zu einer Impfung gegen FSME geraten und es wurde auch nur selten serologisch auf diese Krankheit untersucht. 1994 wurde in Baden-Württemberg eine deutliche Zunahme der Erkrankungsfälle registriert. Ferner wurde in diesem Jahr die erste im Saarland erworbene FSME dokumentiert. Zur Klärung der Frage, wie hoch das Infektionsrisiko für TBE im Saarland und Rheinland-Pfalz ist, wurden seit 1989 durchgeführte 2123 serologische FSME-Untersuchungen aufgearbeitet und 904 tiefgefrorene Seren von Patienten mit entzündlichen Liquorveränderungen serologisch nachuntersucht. Bei insgesamt 15 Patienten fanden wir IgG- und IgM-Antikörper gegen den Erreger der FSME. 4 Fälle wurden klinisch und serologisch als FSME gesichert, wobei eine Erkrankung sicher und eine weitere wahrscheinlich im Saarland erworben wurden. Bei drei weiteren Patienten fanden wir serologische Hinweise auf einen FSME-Virus Kontakt. Die Untersuchungsergebnisse legen den Verdacht nahe, daß im Saarland mit vereinzelten Erkrankungsfällen gerechnet werden muß. Das Infektionsrisiko ist jedoch sehr gering.

     

The molecular significance of amyloid β-peptide for Alzheimer's disease

Alzheimer's disease is the most common form of dementia. Although the majority of the cases occur sporadically, in some rare cases Alzheimer's disease is genetically inherited. Pathologically, Alzheimer's disease is characterized by the accumulation of senile plaques within the extracellular space of brain regions known to be important for intellectual functions. In addition to senile plaques, deposits of identical biochemical composition are found in the walls of meningeal and cerebral blood vessels. Senile plaques are surrounded by degenerating neurons indicating a toxic interference of amyloid plaques with neurons. The major component of senile plaques is the 4 kDa amyloid β-peptide. This peptide has been shown to exhibit neurotoxic properties when added to cultured neurons, or injected into rat brains. Amyloid β-peptide is derived from a high molecular weight precursor, the β-amyloid precursor protein, by proteolytic processing. Mutations responsible for the early onset of Alzheimer's disease in some families are found within the gene coding for the β-amyloid precursor protein. These mutations strongly influence the generation of amyloid β-peptide resulting in a significant overproduction of the peptide or the generation of elongated forms which are known to aggregate and precipitate much faster. Moreover, mutations found in other genes known to cause early onset of Alzheimer's disease have been shown to interfere directly with the production or precipitation of amyloid β-peptide.     

Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators

N-sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of Abeta42 and an increase of Abeta38. The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the e-site.     

Influence of temperature on isometric contraction and passive muscular tension in paramyotonia congenita (Eulenburg)

Four patients without symptoms of episodic hyperkalemic weakness from two families with paramyotonia congenita (Eulenburg) are described. 1. Maximum voluntary muscle contraction of the upper and lower arm was studied under isometric conditions at different temperatures. If the temperature was lowered stepwise, distinct paresis occured at 32--31 degrees C which increased with the amount of muscular effort. The upper arm muscles, however, developed weakness gradually after cooling. 2. During cooling of the resting muscle, the EMG showed dense spontaneous activity of the fibrillary type, which decreased again at about 30 degrees C. It can be assumed that in paramyotonia congenita cooling produces muscle cell membrane depolarization which at a critical level causes the firing of action potentials and finally muscular paresis. 3. Increasing muscular stiffness can be interpreted as abnormally slow muscular relaxation after isometric contraction. In the forearm muscles the time to 3/4 relaxation after cooling was about six times normal, in the upper arm muscles only two times normal. As an additional parameter the mechanical resistance to passive stretching of a muscle has been studied. This passive muscular tension increased simultaneously with the onset of weakness. 4. The close relation between weakness and stiffness suggest that both symptoms are caused by the same basic defect which is probably located in the sarcolemma. It is suggested that a defect of the sodium channel causes a cooling-dependent increase in sodium conductance. Raised intracellular sodium causes in the first place membrane depolarization, and in the second place depression of calcium reuptake through competition by sodium for calcium binding sites. This would explain muscle stiffness and delayed relaxation as well.     

Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.