How Can We Facilitate Spontaneous Termination of Ventricular Fibrillation and Prevent Sudden Cardiac Death? A Working Hypothesis

Spontaneous Ventricular Defibrillation. Ventricular fibrillation (VF) is one of the most life-threatening arrhythmias encountered in daily clinical practice. Its occurrence cannot be completely prevented by currently used antiarrhythmic drugs, and, in most instances, VF is sustained and leads lo the patient's death unless a successful DC defibrillation is applied. However, spontaneous reversion of VF to sinus rhythm has been observed in various animals and occasionally even in man. Hence, facilitation of self ventricular defibrillation must be explored as an alternative therapeutic approach. In experimental studies using several mammalian species, we have found that self ventricular defibrillation requires a good intercellular coupling and well synchronized electrical activity in the ventricles, which, in untreated animals, depend on their myocardial catecholamine content. It can then be hypothesized that any agent that elevates the catecholamine level during VF would facilitate spontaneous ventricular defibrillation, and drugs inhibiting extraneuronal catecholamine reuptake have indeed been shown to possess this ability. It is suggested that their effects are mediated by an increase in the intracellular cAMP level, and any compounds sharing this property could well prove efficacious in making VF transient and in reducing sudden cardiac death.     

Small cell carcinoma of the prostate with hypercalcemia

We present a case of small cell prostate carcinoma with hypercalcemia in a 75-year-old man. He was diagnosed as having stage T3bN1M0 adenocarcinoma of the prostate. His serum prostate-specific antigen level was reduced to below the normal range after a combination treatment of a luteinizing hormone-releasing hormone agonist and flutamide for prostate carcinoma. He subsequently experienced increasing fatigue, poor appetite, short time loss of consciousness and pain in his lower abdomen. His serum calcium level and carcinoembryonic antigen were increased. He died 5 months from the start of treatment. The autopsy revealed small cell carcinoma of the prostate and multiple metastasis of the lung, liver, pancreas, lymph nodes and spine.     

Repair of ileal conduit parastomal hernia by translocation of the stoma

We repaired a recurrent ileal conduit parastomal hernia, according to Kaufman's technique, by translocating the stoma to the opposite side of the abdominal wall without laparotomy. This procedure is a simple and less invasive treatment for large parastomal hernia.     

Studies on peptides

A decapeptide corresponding to the entire amino acid sequence of neurokinin A, a porcine spinal cord peptide, was synthesized in a conventional manner using protecting groups removable by 1 M TFMSA-thioanisole in TFA. The HS-CH₂CH₂CO group was introduced onto the synthetic neurokinin A by reaction of 3-(S-acetyl-thiopropionyl)-thiazolidine-2-thione, followed by deacetylation with hydroxylamine. 2,4-Dinitrophenyl-p-(β-nitrovinyl)-benzoate trapped the above HS-CH₂CH₂CO-neurokinin A derivative in acidic media, then BSA in basic media in nearly quantitative yield. A similar decapeptide, neurokinin B, was also synthesized and conjugated onto BSA using an alternative SH-introducing reagent, 3-(S-p-methoxybenzyl-thiopropionyl)-thiazolidine-2-thione, and the above heterobifunctional conjugating reagent.     

Synthesis of peptide inhibitors of human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase-like proteinase (ELP)

Stereoisomers of specific substrates for SFP and ELP, Suc-L-Tyr-L-Leu-L-Val-pNA and Suc-L-Ala-L-Tyr-L-Leu-L-Val-pNA, were synthesized by the conventional solution method. Suc-L-Tyr-D-Leu-D-Val-pNA was found to be an effective and specific inhibitor of SFP and ELP. Suc-L-Tyr-L-Leu-L-Val-Pipe and Suc-L-Tyr-D-Leu-D-Val-Pipe inhibited only SFP very slightly and showed no inhibitory effect on ELP. Both Dan-L-Tyr-L-Leu-L-Val-pNA and Dan-L-Tyr-D-Leu-D-Val-pNA exhibited an inhibitory effect on both SFP and ELP.     

Effects of an Angiotensin II Antagonist on Reperfusion Arrhythmias in Dogs

Losartan, an angiotensin II receptor antagonist with no bradykinin potentiating property, provides the opportunity to study the consequences of blocking angiotensin II. The objective of this study was to evaluate the antiarrhythmic responses of reperfusion arrhythmia to hsartan in dogs. The effects of losartan on ventricular tachyarrhythmias induced during occlusion and reperfusion of the left anterior descending coronary artery were investigated in 30 dogs. The animals were randomized to receive either losartan (n = 15) or saline (n = 15). The VF inducing threshold was measured before occlusion and after reperfusion. Losartan (50 μg/kg per min) or saline was intravenously administered 5 minutes before occlusion and continued throughout the entire study period. The incidence of ventricular tachyarrhythmias during reperfusion was lower in the losartan group than in the control group (4/15 vs 6/15). There was no significant change in VF inducing threshold between the period before occlusion and during reperfusion in the losartan group (10.9 ± 5.7 vs 11.1 ± 5.7mA, P = NS), whereas there was a significant decrease in the control group (15.5 ± 4.4 vs 7.7 ± 3.9 mA, P < 0.01). Blockade of the angiotensin II receptor has beneficial effects on reperfusion arrhythmias.     

Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.     

Growth inhibition of leukaemic cells carrying the t(3;21) by the AML1/EVI-1 -specific antisense oligonucleotide

Summary. The t(3;21)(q26;q22) translocation is thought to play an important role in the acute phase transformation of CML. The formation of the AML1/EVI-1 fusion gene by the translocation leads to expression of the AML1/EVI-1 fusion protein. Here we demonstrate that the AML1/EVI-1 -specific antisense oligonucleotide markedly decreases the [H]thymidine incorporation and growth of leukaemic cells carrying the t(3;21) and the t(9;22), but not those of K562 cells. These results indicate that the AML1/EVI-1 fusion protein could contribute to proliferation of the t(3;21)-carrying leukaemic cells after entering the blastic crisis phase of CML.     

Amino acids and peptides. XVIII. Dipeptide formation during the synthesis of Z-Asp(OBzl)-OH

During the benzyloxycarbonylation of H-Asp(OBzl)-OH by the Schotten-Bauman reaction with benzyloxycarbonyl chloride in the presence of NaHCO₃ or Na₂CO₃, besides Z-Asp(OBzl)-OH, Z-Asp(OBzl)-Asp(OBzl)-OH was formed as side product, although the extent of the dipeptide formation differed depending on the base used (10% and 20% respectively). It was found that melting point, rotation value and Rf values upon thin-layer chromatography of Z-Asp(OBzl)-Asp(OBzl)-OH were quite similar to those of Z-Asp(OBzl)-OH.     

Common clonal origin of lymphocytes and plasma cells in splenic lymphoma with villous lymphocytes

In two-thirds of patients with splenic lymphoma with villous lymphocytes (SLVL) a small amount of M-protein can be detected in association with the presence of plasma cells in the peripheral blood (PB) and/or bone marrow (BM). However, it is not known whether lymphoma cells and plasma cells originate from the same clone. In this report we describe a case of SLVL which was characterized by the presence of marked monoclonal gammopathy (IgG-κ 90 g/l) and increased plasma cells in the BM. In an attempt to elucidate the origin of lymphoma cells and plasma cells, we performed morphological, cytogenetic and molecular studies on PB mononuclear cells (PBMNC) without plasma cells and BMMNC containing 10% plasma cells from this patient.
Immunofluorescence showed that lymphoma cells and plasma cells were positive for cytoplasmic γ heavy and κ light chains. Well-developed endoplasmic reticulum was observed in the cytoplasmic organelles of PBMNC using an electron microscope. The mean IgG concentration in the 3 d supernatant cultures of PBMNC was 374±24μg/l. More than 50% PBMNC differentiated into plasmacytoid cells in 6 d of liquid culture with IL-3 and IL-6. Analysis by two-colour FISH revealed that karyotypic abnormalities of monosomy X and trisomy 17 existed simultaneously in both lymphoma cells and plasma cells. JH gene rearranged bands from PBMNC and BMMNC by Southern blot hybridization were identical, whereas DNAs from PBMNC failed to hybridize with the Cμ probe.
These observations strongly suggest that lymphoma cells and plasma cells originate from the same clone, and that plasma cells, as well as lymphoma cells, which have undergone class switch recombination, could produce IgG type M-protein in this case.