Long-term antiarrhythmic therapy with acetylprocainamide

Nineteen patients whose arrhythmias were initially suppressed with acetylprocainamide underwent long-term treatment with this drug. Eleven patients were still taking the drug at the end of 12 months. Drug withdrawal with substitution of a placebo caused an increase in ventricular premature beats. Thus, suppression of ventricular premature beats persisted for 1 year. The eight withdrawals from the study were due to death during the year (n = 6) or recurrence of arrhythmias. The deaths occurred in patients who were in New York Heart Association functional class II (one patient), III (three patients) and IV (two patients). Ventricular performance, assessed from systolic time intervals, improved with drug therapy and declined during drug withdrawal. Symptomatic effects were common, with seven patients requiring a reduction in dosage or discontinuation of therapy. Three patients treated for 3 years continued to show drug suppression of ventricular premature beats compared with the level during placebo substitution. Small amounts of procainamide were present in all patients because of in vivo deacetylation of acetylprocainamide. Many patients with good initial responses to this drug had recurrent arrhythmias during long-term therapy. For this reason, the usefulness of acetylprocainamide as an antiarrhythmic drug appears to be limited.     

A new observation in the clinical spectrums of erythroleukemia. A report of 46 cases.

Erythroleukemia is a disease manifested by an abnormal proliferation of erythroid and myeloid precursors, generally consisting of a primary erythroid phase (chronic erythemic myelosis), a transition phase involving erythroid and myeloid precursors (erythroleukemia) and, finally, the purely myeloblastic (acute myeloblastic leukemia) phase. The experience at Memorial Sloan-Kettering Cancer Center is reported. Presenting signs and symptoms are consistent with prior reports. The chemotherapy results in the past have been poor; because of the poor results, chemotherapy is started only if one of the following criteria are present: (1) frequent transfusion requirements; (2) rapidly increasing peripheral white blood cell count or percentage of leukemic blast forms; (3) frequent recurrent infectious and/or hemorrhagic complications. A hitherto unrecognized association of erythroleukemia and symptomatic rheumatic disease and numerous immunologic abberations are reported. The symptoms related to this rheumatic disorder do not seem to be relieved by therapy directed at the leukemic process, but rather by the use of simple anti-inflammatory agents.     

Analysis of T cell subsets in cancer patients treated with interferon

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.     

Renal handling of low molecular weight proteins

The renal filtration, absorption and final disposal of lysozyme (lysozyme—mol wt 14,000), insulin and growth hormone were studied to gain a better quantitative understanding of the fundamental variables involved in the renal handling of low molecular weight proteins. The glomerular barrier offers little hindrance to the filtration of lysozyme, the glomerular sieving coefficient being 0.8 ± 0.1 (SD). The intrarenal route by which injected lysozyme accumulates in the kidney is via filtration and subsequent absorption (uptake) by renal tubular cells. Uptake or adsorption from the peritubular side is negligible compared to luminal uptake. Renal clearance and renal titration experiments in the intact dog and in the isolated perfused rat kidney showed that the lysozyme absorption process can be best characterized as a high capacity, low affinity transport system which is directly or indirectly dependent on energy input. The final disposal of absorbed ¹²⁵I-lysozyme, ¹²⁵I-insulin and ¹²⁵I-growth hormone was studied in the isolated perfused rat kidney by measuring the radioactivity released from the kidney to the perfusate and analyzing the nature of the released product by gel chromatography. The rate of release of radioactivity as well as its nature was dependent on the molecular species of the absorbed protein. The rate of release was higher for ¹²⁵I-insulin and ¹²⁵I-growth hormone and lower for ¹²⁵I-lysozyme. Lysozyme absorbed from the luminal side was released to the perfusate both as intact protein molecules and as catabolic products, whereas absorbed ¹²⁵I-insulin was almost entirely released to the perfusate as catabolic products. It is concluded that low molecular weight proteins are extensively filtered by the kidney, absorbed from the luminal side by renal tubular cells and released back to the circulation either as intact molecules or as catabolic products (amino acids and polypeptides). This process contributes in an important way to the plasma turnover of low molecular weight proteins including peptides and protein hormones.     

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.     

Prognostic factors in advanced colorectal carcinoma: Importance of lactic dehydrogenase level,performance status,and white blood cell count

In 220 patients with advanced colorectal carcinoma, objective tumor response to chemotherapy and survival were related to the following parameters: age, sex, performance status, time interval from diagnosis to metastases, initial site of metastases, and initial white blood cell count, lactic dehydrogenase, alkaline phosphatase, and carcinoembryonic antigen levels. Each variable was first evaluated separately. By conventional statistical methods, none of the variables significantly predicted response, although the following parameters significantly (p < 0.01) predicted survival: Patients with an initially normal level of lactic dehydrogenase versus those with an abnormal level of lactic dehydrogenase had median survivals of 16 and 7.0 months, respectively; normal versus abnormal carcinoembryonic antigen levels, 23 and 9.2 months, respectively; white blood cell count of less than 10,000 versus greater than 10,000 cells/mm³, 11 and 7.0 months, respectively; performance status of greater than 70 versus less than 60,11 and 6.6 months, respectively; and lung versus liver metastases, 12 and 8.0 months, respectively. By studying the variables together with multivariate analysis, we found that the most important variables in predicting response were the lactic dehydrogenase level and the white blood cell count. In predicting survival, the most important variables were the lactic dehydrogenase level, performance status, and lung involvement. We recommend that future randomized therapeutic trials for advanced colorectal carcinoma should delineate and perhaps stratify for the lactic dehydrogenase level, performance status, white blood cell count, and/or the presence of lung involvement.     

Virilizing luteoma of pregnancy. Report of a case with measurements of testosterone and testosterone binding in plasma

Virilizing luteoma of pregnancy with maternal and fetal virilization is reported in a 19 year old woman. Antepartum steroid determinations in the mother revealed an elevated urinary 17-ketosteroid excretion and markedly increased plasma testosterone levels. The percentage binding of testosterone in plasma was lower than expected for normal pregnancy. Surgical removal of the tumor resulted in complete regression of the signs of virilization in the mother and partial regression of the clitoral hypertrophy in the infant. These changes were associated with a return of the biochemical findings to normal.     

Iodine and lithium-induced hypothyroidism. Documentation of synergism

Signs and symptoms of hypothyroidism were noted in a patient receiving lithium carbonate for 2 years as prophylaxis against recurrence of mania and depression. When lithium therapy was stopped, the hypothyroidism resolved; but it recurred with the administration of potassium iodide. When potassium iodide therapy was discontinued, the patient became euthyroid. In a second patient chemical evidence of hypothyroidism (fall in circulating thyroid hormone levels, elevation of serum thyrotropin) was noted after he had received 3 weeks of lithium therapy. With the addition of potassium iodide, laboratory evidence of hypothyroidism became more pronounced, and clinical signs of hypothyroidism developed. All abnormalities resolved promptly following the withdrawal of lithium and iodine. These observations suggest that lithium and iodine can act synergistically to produce hypothyroidism and that the combined use of these agents should be avoided.     

Role of circulatory congestion in the cardiorespiratory failure of obesity.

The role of circulatory congestion in the cardiorespiratory dysfunction of massive obesity was investigated in 18 patients. They were hypervolemic and had increased cardiac outputs proportionate to their weight. The average resting left ventricular filling pressure was within the upper limits of normal, but it increased to abnormally high levels with increased venous return of passive leg raising, and further during exercise. The elevations in pressure were associated with high resting central blood volumes which increased significantly with exertion. These findings are consistent with reduced distensibility of the central circulation in these congested patients. Weight reduction was accompanied by a decrease in central blood volumes and restoration of a normal left ventricular response in three of four patients and a return toward normal in one. The improvement in ventricular function with relief of edema and dyspnea. In 14 patients with normal or only minimal alveolar hypoventilation, there were no significant transpulmonary diastolic pressure gradients despite a marked increase in left ventricular end-diastolic pressures. One patient, after regaining weight, subsequently had an abnormal gas exchange and an increased pulmonary vascular resistance. He and two others with severe alveolar hypoventilation demonstrated cor pulmonale on a background of left ventricular dysfunction and congestion of the circulation. Two other patients, the least obese of the group, had hypoventilation and cor pulmonale with normal left ventricular pressures. Hypervolemia and a hyperdynamic state are common features of the obese patients. High cardiac output is maintained despite marked circulatory congestion which may result in generalized anasarca and increased ventricular filling pressures. This clinical syndrome may be present in obese patients without intrinsic heart disease and may be reversible with weight reduction. The central circulatory congestion may contribute to the development of the alveolar hypoventilation syndrome in certain obese patients.     

Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.     

Exercise left ventriculography utilizing intravenous digital angiography

Exercise left ventriculography has been shown to be a sensitive and specific tool for the detection of coronary artery disease. At the present time, such studies require radionuclide-base methods. Computer-based techniques recently have been shown to provide high resolution images of the left ventricle when the levophase of an intravenous injection of radiopaque contrast medium is imaged with fluoroscopy. To evaluate the possible efficacy of using "intravenous digital subtraction left ventriculograms" in exercise ventriculography, such ventriculograms were performed at rest and during maximal supine bicycle exercise in 31 patients. Studies that could be analyzed were obtained in 29 patients. In 21 patients with coronary artery disease, ejection fraction was 58% at rest and 45% with exercise (p less than 0.001 vs. rest). In contrast, in seven patients with no coronary artery disease, ejection fraction was 65% at rest and 69% with exercise (difference not significant). In a subgroup of 8 patients with "severe" coronary obstruction, the change in ejection fraction from rest to exercise was -18%, while in the remaining 13 patients with less severe disease, it was -9% (p less than 0.001). All patients with coronary artery disease manifested new or worsening segmental wall abnormality with exercise, compared with two of seven patients without coronary disease (p less than 0.01). Sixteen patients underwent rest and exercise radionuclide cineangiography in addition to digital subtraction angiography. There was a strong correlation between the two techniques for ejection fraction at rest (r = 0.78, p less than 0.001), ejection fraction and with exercise (r = 0.83, p less than 0.001) and change in ejection fraction from rest to exercise (r = 0.88, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Eosinophilia,elevated immunoglobulin E level and chronic enteritis due to intestinal helminthiasis

Recurrent urticaria, abdominal pain, peripheral eosinophilia, hyperimmunoglobulin E and small bowel abnormalities on roentgenograms prompted evaluation of a 36 year old man for intestinal parasitism. Evidence for helminthiasis as the cause of his symptoms included changing antibody titers to helminth antigens and a dramatic response to therapy. Helminth larvae or eggs were not recovered. Diagnosis of strongyloidiasis, the most likely cause of the illness, is discussed.     

Fever and pulmonary thromboembolism.

Fever patterns associated with pulmonary thromboembolism have not been well characterized. Upon review of 35 consecutive patients with angiographically documented pulmonary emboli, fever was present in 24 patients; and in 20, it was attributed solely to pulmonary thromboembolism. Analysis of these cases indicates that high fever (temperature greater than 39 degrees C) due to pulmonary thromboembolism may occur early, and low-grade fever may continue for a week or more. Fever persisting beyond six days, however, especially with temperatures over 38.5 degrees C, should not be ascribed to pulmonary thromboembolism unless other causes have been carefully excluded. If the clinical setting and patient's findings are consistent with pulmonary thromboembolism, one should not be deterred from presumptively making this diagnosis and initiating therapy because of the presence of high fever.