The vincula; with particular reference to their vessels and nerves

The blood vessels and nerves of the vincula in the human hand were studied by anatomical dissection, serial histological section, and angiography. The segmental blood supply of the flexor tendon through the vincula was seen to come from constant branches of the digital vessels that pierce the fibrous sheath proximal to both the proximal and distal interphalangeal joints. These were traced with their accompanying nerves into the flexor tendons. Communication between the interosseous circulation and that of the tendons was demonstrated. The clinical implication of these findings and their application to tendon surgery are discussed.     

Giganto-cellular glioblastoma of the lumbosacral spinal cord

Summary A case of giganto-cellular glioblastoma multiforme occurring in the lumbosacral spinal cord is described.Supported in part by US Public Health Grant NS06239 from the National Institute of Neurological Diseases and Stroke     

Biochemische Aspekte der l-DOPA-Wirkung bei Parkinsonpatienten

Zusammenfassung Es wurde bei 19 Patienten mit Paralysis agitans die Wirkung einer Langzeitbehandlung mit 2500–5000 mg l-DOPA/die untersucht: a) mit Hilfe von klinischen Tests, b) durch Messung der Aminosäurezusammensetzung des Liquor cerebrospinalis. Krankheitsdauer und Ausprägung der Symptome waren verschieden. Der Beobachtungszeitraum betrug 3 Monate bis 2 Jahre.1. Bei 9 Patienten war vor Beginn der Behandlung mit l-DOPA die Aminosäurezusammensetzung im Liquor cerebrospinalis so verändert, wie es bei einer Parkinsonsymptomatik zu erwarten war: Die Konzentrationen von Glycin, Serin, Threonin, Cystein + Cystin und Methionin waren erhöht, die von Glutaminsäure vermindert. Diese Patienten sprachen auf eine Behandlung mit l-DOPA sehr gut bis gut an; das Aminosäurespektrum im Liquor cerebrospinalis normalisierte sich.2. Bei 5 Patienten wich vor Beginn der Behandlung mit l-DOPA die Aminosäurezusammensetzung des Liquors nur wenig vom normalen Durchschnitt ab, der Erfolg der l-DOPA-Therapie war nicht zufriedenstellend.3. Eine Normalisierung der Aminosäurewerte ohne wesentlichen Therapieerfolg wurde nicht beobachtet.4. Von 5 weiteren Patienten sprachen 4 auf l-DOPA gut an; eine Einordnung in die vorgenannten Gruppen erscheint aus verschiedenen Gründen nicht sinnvoll.Die Analyse der Liquoraminosäuren scheint somit eine Prognose zu erlauben, ob eine l-DOPA-Therapie sinnvoll ist oder nicht. Aus den vorgelegten Ergebnissen ist weiters zu folgern, daß das klinische Krankheitsbild Paralysis agitans keine einheitliche Krankheit ist, sondern sich einzelne Formen hinsichtlich der Störung des Stoffwechsels im ZNS voneinander unterscheiden.

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Biochemical aspects of the effect of l-DOPA in patients with Parkinson's disease

Summary We tested the effect of a prolonged l-DOPA therapy in 19 patients suffering from Parkinson's disease, by a) applying medical tests and b) measuring concentrations of free amino acids of cerebrospinal fluid. The period of observation ranged from 3 months up to two years, with doses from 2500 to 5000 mg l-DOPA per day.1. In 9 patients the pattern of free amino acids of CSF was altered according to what we are used to find in Parkinson's disease: the concentrations of glycine, serine, thereonine, cysteine + cystine as well as methionine were increased, that of glutamic acid decreased. The clinical success was very good along with a restoration to normal of the pathological amino acid pattern.2. In 5 patients the amino acid pattern was similar to that of normal controls. Clinically, these cases showed an unsatisfactory response to therapy, the amino acid pattern of CSF also remaining unchanged.3. In no case we did find a normalization of amino acid levels without an improvement of the clinical symptoms.4. Of another 5 patients 4 responded favourably to l-DOPA, one did not. These patients were not considered to belong to the above mentioned groups because of several complicating factors.The estimation of the pattern of free amino acids in CSF seems to be of prognostic value in yielding a biochemical parameter that seems to indicate whether or not a prolonged treatment with l-DOPA might be successful. Patients with a pathological pattern of CSF amino acids run a better chance of therapeutic improvement. We could not find any correlation between levels of amino acids in CSF and the duration of the disease or the severity of symptoms. We conclude that Parkinson's disease is not caused by a single type of disturbed cerebral metabolism.

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Abkürzungen AS Aminosäuren - Arg Arginin - Ala Alanin - Asp Asparaginsäure - Asp-NH₂ Asparagin - Cys Cystein + Cystin - l-DOPA l-Dihydroxyphenylalanin - Glu Glutaminsäure - Glu-NH₂ Glutamin - Gly Glycin - His Histidin - Ileu Isoleucin - Leu Leucin - Lys Lysin - Met Methionin - Phe Phenylalanin - Ser Serin - Thr Threonin - Tyr Tyrosin - Val Valin - ZNS Zentralnervensystem - BTS Brenztraubensäure - GOT Glutamat-Oxalacetat-Transaminase - GPT Glutamat-Pyruvat-Transaminase. Für das Forschungsstipendium, das uns die Durchführung dieser Arbeit ermöglichte, sind wir der Fa. Hoffmann-La Roche, Basel, zu Dank verpflichtet.     

Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis

Herein, we show that the hematopoietic-specific GEF VAV1 is ectopically expressed in primary pancreatic adenocarcinomas due to demethylation of the gene promoter. Interestingly, VAV1-positive tumors had a worse survival rate compared to VAV1-negative tumors. Surprisingly, even in the presence of oncogenic KRAS, VAV1 RNAi abrogates neoplastic cellular proliferation in vitro and in vivo, thus identifying Vav1 as a growth-stimulatory protein in this disease. Vav1 acts synergistically with the EGF receptor to stimulate pancreatic tumor cell proliferation. Mechanistically, the effects of Vav1 require its GEF activity and the activation of Rac1, PAK1, and NF-kappaB and involve cyclin D1 upregulation. Thus, the discovery of prooncogenic pathways regulated by Vav1 makes it an attractive target for therapeutic intervention.