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Initial and long-term outpatient experience with lorcainide for suppression of malignant and potentially malignant ventricular arrhythmias.

There is a need for effective, well-tolerated antiarrhythmic agents, particularly those effective by both intravenous and oral routes. Lorcainide, a new antiarrhythmic drug with such properties, was given long-term orally to 24 patients controlled initially with intravenous therapy--19 with frequent (greater than 1/min) complex premature ventricular complexes (PVCs) on a baseline 24-hour Holter monitor and five with ongoing sustained ventricular tachycardia (VT) or frequent paroxysmal sustained VT, for a mean of 13 months (range 0.03 to 39.4 months). Long-term lorcainide was given in divided doses of 200 to 800 mg/day (median 260, mean 269 +/- 90 mg/day). Response to long-term lorcainide therapy was assessed at a mean of both 26 days and 12.2 months. Frequency of PVCs on baseline averaged 13,490/24 hours (median 10,578, range 2,115 to 61,716); couplets averaged 309/24 hours (median 166, range 0 to 5,686), and runs averaged 33/24 hours (median 30, range 0 to 2,951). Median frequency of PVCs decreased by 94% (p much less than 0.001) and 97% (p less than 0.01) at the first and second lorcainide efficacy assessments, respectively. Couplets decreased by a median of 99% (p much less than 0.001) and 100% (p less than 0.005) at the first and second assessments, respectively. Runs were suppressed by a median of 100% at both evaluations (p much less than 0.001). Only three (16%) of the patients with complex PVCs failed to respond to therapy. No recurrence during lorcainide has been noted in the five patients with ongoing sustained VT or recurrent episodes of VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Inhibition of farnesyl transferases from malignant and non-malignant cultured human lymphocytes by prenyl substrate analogues.

Cytosolic prenyl transferases from two human lymphoid tissue-derived cell lines, IM-9 and Molt-4 cells, are shown to isoprenylate recombinant p21H-ras. Isoprenylation was inhibited by an N-acetylated pentapeptide (N-Ac-Lys-Cys-Val-Leu-Ser), c,t-farnesyl diphosphate, c,t,t-geranylgeranyl diphosphate, t,t,t-geranylgeranyl diphosphate and a photolabile farnesyl diphosphate analogue. c,t-Farnesyl and t,t,t-geranylgeranyl monophosphates were also effective inhibitors of the Molt-4 enzyme but not the IM-9 enzyme.

Alkyl and Aryl Transferases↗

Alpha-fetoprotein-like activity in sera from patients with malignant and non-malignant disease and healthy individuals.

A new method, radio-crossed immunoelectrophoresis, demonstrates alpha-fetoprotein (AFP) in sera with a sensitivity of 1 mug/1. By this method AFP with alpha mobility was not found in sera from healthy individuals, patients with chronic active hepatitis and cirrhosis, primary biliary cirrhosis, secondary liver cancer and cystic fibrosis. In some of the sera, AFP was elevated when measured by conventional radioimmunoassay method and the sera contained an AFP-like substance with gamma mobility when analyzed by radio-crossed immunoelectrophoresis. The nature of this gamma substance is still obscure and needs further investigation.

Cystic Fibrosis↗

Catalogue of Epstein-Barr virus (EBV) receptors on human malignant and non-malignant hematopoietic cell lines.

Epstein-Barr virus (EBV) can induce a broad spectrum of hematological diseases, especially in immune deficient patients. We assayed for receptor for EBV (EBVR) using fluoresceinated viral particles on 44 human hematopoietic cell lines derived from patients with T, B, and non-T, non-B acute lymphocytic leukemia (ALL), non-lymphoid leukemia, Burkitt lymphoma, myeloma and several unique lines we and others have recently developed. All 31 EBV nuclear-associated antigen (EBNA) negative cell lines were of neoplastic origin. Seven of 13 EBNA-positive cell lines were of normal cell origin. Four of 25 non-B (surface immunoglobulin negative) EBNA-negative neoplastic cell lines were EBVR-positive. Three of six EBNA-negative B-cell (surface immunoglobulin positive) lines were EBVR-positive. Nine of 13 EBNA-positive Burkitt and non-Burkitt cell lines strongly expressed EBVR. Four EBNA-positive Burkitt lymphoma cell lines exhibited EBVR only to a limited degree. Studies of the cell lines for EBVR, complement receptors (CR) and surface immunoglobulin (SIg) revealed that presence of SIg does not obligate the presence of EBVR. Functional EBVR accompanied SIg among EBNA-negative cell lines. SIg-negative cell lines can possess EBVR. Fourteen of 16 EBVR-positive lines were also positive for CR. The EBVR assay is a useful tool for assessing the potential role of EBV in the induction of hematopoietic disorders.

Antigens, Surface↗

Blood levels of reduced and oxidized glutathione in malignant and non-malignant human colorectal lesions.

Glutathione blood levels were determined in colorectal cancer patients (n = 10), patients with adenomatous colorectal polyps (n = 8), and healthy subjects (control group; n = 10). Mean GSH level (micrograms/ml) was significantly higher in cancer patients [515.4 +/- 76.1 (S.D.)] than in those with polyps [407.7 +/- 90.5 (S.D.), P less than 0.05] and the control group [360.9 +/- 67.9 (S.D.), P less than 0.001]. Statistically significant lower GSSG blood level were observed in cancer patients when compared to the other groups. The highest mean blood GSH/GSSG ratio (log transformed) was observed in cancer patients [2.17 +/- 0.108 (S.D.)] and the lowest in healthy subjects [1.88 +/- 0.032 (S.D.)]. All between-group differences in the GSH/GSSG ratio were statistically significant. These findings suggest that glutathione blood levels as well as GSH/GSSG ratio may have applicability as a guide for following the activity of colorectal diseases.

Adult↗

Argyrophilic nucleolar organizer regions (AgNORs) in inflammatory pre-malignant and malignant lesions of the uterine cervix.

Nuclear organizer regions (NORs) code for ribosomal RNA and are associated with non-histone nucleoproteins, which can be identified by silver staining (AgNORs). AgNORs have been correlated to proliferative activity of tumors and hence may be prognosis-related. The present study evaluates AgNOR counts in inflammatory lesions of the uterine cervix, cervical intra-epithelial neoplasia, and invasive cervical squamous carcinoma. Significant variation in AgNOR counts were observed between the three study groups, with invasive carcinoma showing maximum counts. Further, a highly significant positive correlation was observed between AgNOR counts and tumor progression. These results therefore suggest that AgNOR counts may be of significance in the evaluation of cervical carcinogenesis and could elaborate histopathological diagnosis of cervical lesions.

Carcinoma, Squamous Cell↗