[Vasopressin analogue injection as ultimate measure for counteracting severe catecholamine-refractory poisoning by several vasodilators taken with suicidal intent]. / Vasopressinanaloga als Ultima ratio bei einer schweren Intoxikation mit Vasodilatanzien.

HISTORY AND CLINICAL FINDINGS: A 78-year-old woman was admitted to the intensive care unit 9 hours after ingestion of 2 g of isosorbitmononitrate, 430 mg of amlodipine, 250 mg of benazepril and 600 mg of mirtazapin in suicidal intent. INVESTIGATIONS: Clinical findings and invasive monitoring showed signs of a hyperdynamic hemodynamic cardiovascular failure caused by toxic vasodilatation. TREATMENT AND COURSE: Despite of primary detoxication, intravenous volume infusion with calcium gluconate, glucagon and naloxone and administration (norepinephrine up to 2 micro g/kg/min) no hemodynamic stabilization was achieved. Only when the vasopressin-analogue argipressin was given peripheral vasodilatation was overcome and hemodynamic stabilization resulted. 10 hours after discontinuing argipressin and norepinephrine the patient developed a mesenteric ischemia, and she finally died on the third day after admission. CONCLUSION: In circulatory shock due to toxic vasodilatation the use of vasopressin analogue argipressin can be helpful as an ultima therapeutic measure in catecholamine refractory shock caused by vasodilatation. Attention must be paid to overwhelming vasoconstrictor effects resulting in mesenteric ischemia.

[Therapy of verapamil poisoning with noradrenaline and the phosphodiesterase inhibitor enoximone]. / Therapie der Verapamil-Intoxikation mit Noradrenalin und dem Phosphodiesterasehemmer Enoximon.

HISTORY: A 40 year old patient was transferred to the intensive care unit five hours after the ingestion of 2.4 g of verapamil. ADMISSION FINDINGS: Clinical investigation and invasive monitoring showed signs of cardiogenic shock. THERAPY: Despite primary detoxification and administration of calcium and norepinephrine no adequate cardiovascular stabilization could be achieved. Only when the phosphodiesterase inhibitor enoximone was added, an increase in myocardial inotropy and a stable cardiovascular state was achieved which was also due to the vasoconstrictory effect of norepinephrine overcoming vasodilatation induced by enoximone. CONCLUSION: Detoxification, calcium supplementation and catecholamines are established therapeutic measures. An additional therapy with phosphodiesterase inhibitors is a promising step in conquering predominant heart failure and hypotension.

B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene repertoire of B lymphocytes from germinal center-like foci in the synovial membrane indicates antigen selection.

The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM were stained for B and T lymphocytes. B cells were isolated from different areas of a focus. The rearranged VH genes were amplified by semi-nested polymerase chain reaction (PCR) using oligonucleotides specific for the six different VH families and heavy chain joining segments (JHs). PCR products were cloned and sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were potentially functional. Most of the rearranged genes were mutated (range, 1-15%). Thirty of 70 products had a mutational pattern typical for antigen selection. Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with data from healthy donors and patients with RA, while VH4 genes, in contrast to RA, were identified less frequently (10%) and VH5 genes were over-represented (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were shorter and more variable in length than in RA. Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

The B lymphocyte in rheumatoid arthritis: recirculation of B lymphocytes between different joints and blood.

In order to search for further evidence for a pathogenetic role of recirculating, antigen-driven B cell clones in rheumatoid arthritis (RA) rearranged VH genes were analysed for clonal relationship and somatic mutations from synovial tissue and peripheral blood of a patient with RA undergoing synovectomy of several finger joints. DNA was prepared from the synovial tissue of two finger joints and blood. PCR for the different VH families was performed with one specific oligonucleotide for each VH family and a mixture of JH-specific oligonucleotides. The PCR products were separated on a high resolution acrylamide gel differentiating one base pair difference of length. Transfer of the products onto a nylon membrane and hybridization with an oligonucleotide specific for the FR3 region revealed a polyclonal representation of rearranged VH1, VH3, VH4 and VH5 genes. The VH6 family, which is encoded by a single germline gene, was represented by few distinct bands, with some bands of identical height for both joints and blood. DNA from these bands of interest was eluted, reamplified by PCR, cloned and sequenced. Sequence analysis of 27 independent bacterial colonies allowed distribution of the different VH genes to seven B cell clones (A-G). Members of clone A were found in both joints and blood, clones B and C in one joint and blood, clone D in both joints, and clones E, F and G only in one joint. The VH regions were somatically mutated with characteristic patterns for the different clones. In conclusion, our findings confirm the systemic character of RA, because they show that not only expansion and affinity maturation of B cells occur in synovial membranes but antigen-specific B cells recirculate between different joints and blood.