Electrical Cardioversion—Effectiveness of Quinidine Prophylaxis Following Countershock

Direct current countershock was given to 46 patients with chronic atrial fibrillation of diverse causes, with successful conversion in 87 per cent of them. Patients were observed while receiving quinidine prophylaxis, with serial determination of serum quinidine levels, for up to 22 months. Two quinidine preparations were employed, one a long-acting form, in various dosage regimens and both preparations were found to be effective prophylactic agents for maintaining reliable serum quinidine levels. Fifty per cent of patients remained in normal sinus rhythm at three months, 28 per cent at six months and 13 per cent at twelve months.     

The Relationship of Dosage Schedule to the Blood Level of Quinidine,Using All Available Quinidine Preparations

Blood quinidine levels obtained by single and multiple dosage schedules of all available quinidine preparations were ascertained. A maintenance blood level of 4 to 7 mg./l. of quinidine was considered a desirable range to prevent recurrence of auricular fibrillation in patients previously converted to sinus rhythm. Quinidine sulfate, quinidine gluconate, dihydroquinidine gluconate and quinidine polygalacturonate were given in dosage schedules of one tablet (equivalent to 200 mg. quinidine) every eight hours for four days, then two tablets every eight hours for three days. Blood quinidine levels were determined the same time each day. Schedules of two tablets of quinidine sulfate or quinidine gluconate every eight hours resulted in blood levels between 4 and 7 mg./l. Similar dosage schedules of the other preparations did not produce levels of this order, nor did quinidine polygalacturonate administered in a 12-hourly schedule. Serious respiratory arrest occurred in one case following quinidine sulfate. No other toxic reactions were noted in this study.     

DICUMAROL AND QUINIDINE IN THE AMBULATORY TREATMENT OF CHRONIC AURICULAR FIBRILLATION

Thirty-three patients with chronic auricular fibrillation were treated with digitalis and quinidine and in addition were given Dicumarol® to reduce the risk of embolism. In 21 of the patients the fibrillation was caused by rheumatic heart disease, and in 12 by arteriosclerosis or hypertension. Normal sinus rhythm was restored in 55 per cent of the 33 patients, in 67 per cent of those with arteriosclerosis or hypertension, and in 45 per cent of those with rheumatic heart disease. Embolism did not occur.     

Accumulation of histidine, 3-methylhistidine, and homocarnosine in the brains of protein-calorie deficient monkeys

Abstract— Seventeen monkeys (M. nemestrina and M. fascicularis) aged 10 months to about 5 yr were divided into two groups and fed either an adequate protein diet (20% casein) or a low-protein diet (2% casein). The diets were supplied to the animals in restricted amount (200 g/animal in two daily rations). In one experiment, the malnourished animals were initially fed a diet containiing 8 per cent protein and the protein content of the diet was gradually reduced over a period of 9 months, to 2 per cent. After about 3 months on the 2 per cent protein diet, the malnourished monkeys showed growth failure, severe anorexia, peri-ocular oedema, tremors of the head and limbs, atrophy of several visceral organs, fatty liver, hypoalbuminaemia, and depressed serum levels of many essential amino acids with an elevation of the ratio of non-essential to essential amino acids. These features are consistent with protein-calorie malnutrition. Examination of the brains revealed significant alterations in the levels of glycerophosphoethanolamine (—40 per cent), glutamic acid (—25 per cent), histidine (+230 per cent), homocamosine (+185 per cent), 3-methyl-histidine (+147 per cent), lysine (+55 per cent), phenylalanine (+33 per cent) and tyrosine (+26 per cent) in comparison to findings on the well-fed monkeys. The possible implications of elevated cerebral contents of homocarnosine in malnourished monkeys are discussed in the light of several reported human cases in whom neurological disorders are associated with increased histidine-containing dipeptides in the brain, CSF, blood and urine.     

MOLECULAR ASSOCIATION OF HEMOCYANIN PRODUCED BY X-RAYS AS OBSERVED IN THE ULTRACENTRIFUGE

1. When normal, monodisperse hemocyanin (60.5S) from Limulus Rolyphemus was irradiated in neutral buffer with x-rays, several new, more rapidly sedimenting ultracentrifugal components (86S, 107S, 122S) were produced, with a corresponding loss in the amount of the unaffected protein. The amount of the effect was roughly proportional to the amount of irradiation. 2. The new resolvable components apparently represented an association of the primary particles into aggregates of 2, 3, and 4 primary particles respectively. 3. The proportional amount of hemocyanin affected decreased almost to the vanishing point as the concentration of the protein was raised to high levels. 4. The absolute effect, i.e. the total number of particles affected in a given volume, increased with the concentration of hemocyanin, at least for concentrations below 15 per cent. 5. The presence of 33 per cent horse serum during irradiation inhibited the effect on the hemocyanin almost completely, with hemocyanin concentrations of both 0.8 and 14 per cent. 6. The presence of 2.8 per cent egg albumin during irradiation lowered the effect by about 70 per cent in the case of dilute preparations (0.8 per cent hemocyanin), but by only about 25 per cent in the case of 14 per cent solutions. 7. A lowering of the solution''s oxygen tension during irradiation enhanced the effect, almost doubling it in some cases. 8. The probable theoretical significance of these and other observations are discussed in the text.     

Interactions of quinidine and propranolol with mexiletine, encainide, flecainide and tocainide

Blood serum quinidine sulphate and propranolol levels have been measured in patients with cardiac arrhythmias treated simultaneously with mexiletine, flecainide, encainide and tocainide. It was found that mexiletine and encainide increase quinidine sulphate serum concentrations. Propranolol serum concentrations have been increased by mexiletine, encainide flecainide, and tocainide. Flecainide ant tocainide have not changed quinidine sulphate serum concentrations.     

Hypercholesteremia—Treatment with Cholestyramine,a Bile Acid Sequestering Resin

The results of administration of cholestyramine to 19 patients for periods of two to 21 months are reported.All patients consistently taking the drug obtained a significant reduction in the serum cholesterol. The average reduction was 26 per cent and the range was from 16 to 52 per cent.Cholestyramine acts as a bile acid sequestering resin, causing an increased loss of bile salts (cholates) in the stool. The drug acts by increasing the normal excretory pathway for cholesterol.     

Experiment to study some suspension media for the lyophilization of actinomycetes]

Viability and cultural properties of 59 actinomycetes and 17 bacteria lyophilized in polyvinylpyrrolidone (PVP), sodium glutamate, their combinations and horse serum were studied after storage for 2 years at a temperature of 4-10 degrees. A 5 per cent solution of sodium glutamate had a high protective effect on viability of the above organisms. The solution containing 3 per cent of sodium glutamate and 3 per cent of PVP was somewhat less effective. The cultures lyophilized in 5 per cent solution of sodium glutamate had the same viability levels as those lyophilized in horse serum, while the latter had better growth rates on their plating out on nutrient media. A 5 per cent solution of PVP had no advantages over sodium glutamate or horse serum with respect to preservation of the organism viability. No significant differences in the cultural properties: colour of the aerial and substrate mycelium and pigment production were noted in the actinomycetes lyophilized in various protective media and the analogous control cultures maintained by means of passages on fresh nutrient media.     

The results of the use of bleomycin and its analogs in the VAB-6 protocol in treating testicular tumors

Efficacy and toxicity of VAB-6 combinations with bleomycin, bleomycetin or peplomycin were studied in treatment of 77 patients with metastases of germ-cell tumors: testicle tumors in 71 patients and extragonadal tumors in 6 patients. After the chemotherapy complete regression was observed in 37 patients (48.7 per cent). In 44 patients (57.1 per cent) residual metastases after the chemotherapy were resected. The frequency of complete regression after using the VAB-6 combinations with bleomycin, bleomycetin and peplomycin amounted to 58.8, 61.5 and 47.1 per cent respectively. The treatment results depended on the disease extent. When the disease extent was minimal complete regression was observed in 87.5 per cent of the patients. The respective figures for the disease moderate and significant extents were 66.7 and 37.8 per cent. During the average observation period of 22.1 months (7-40 months) 39 patients survived and had no signs of the disease. The combinations markedly differed in their toxicity.     

A THERAPEUTIC REGIMEN FOR TUBERCULOUS MENINGITIS

The results of treatment of tuberculous meningitis in Highland Alameda County Hospital, since the advent of streptomycin, in 34 cases were: dead, 21 patients, or 61 per cent; alive, 10 patients, or 29 per cent. Three cases were excluded from the ultimate report due to inadequate follow-up. The mean survival time of the ten survivors at the time of report was 35 months, the longest being 74 months.The composite results of treatment elsewhere, as reported in the literature, have been: dead, 892, or 59 per cent; alive, 629, or 41 per cent.The pathogenesis of the disease and the effects of chemotherapy are discussed.A therapeutic regimen for tuberculous meningitis is presented, which has been used at Highland Hospital since INH became established as the most effective component in the combined chemotherapeutic attack on the disease.     

Viability of Bacillus popilliae after Lyophilization of Liquid Nitrogen Frozen Cells

The per cent viability of Bacillus popilliae after lyophilization of liquid nitrogen frozen cells was determined. Lyophilization of 9- to 12-hr cells which had been suspended in 5% sodium glutamate plus 0.5% gum tragacanth, frozen in liquid nitrogen vapor, and dried 4 to 5 hr with the ampoules exposed to room temperature resulted in survival of 64.6% of the original cells. After storage of these lyophilized preparations for 6 months at room temperature, 10.5% of the original cells were still viable.     

Serologic diagnosis of syphilis; the use of Treponema pallidum immobilization and immune adherence tests

TPI tests were carried out on 4,060 sera. Among 3,934 patients with reactive STS and no history of syphilis, 2,148 or 54.6 per cent had negative reaction to TPI tests, 1,695 or 43.1 per cent had positive reaction and 91 or 2.3 per cent had doubtful reaction. Two hundred and ninety-two or 73.0 per cent of 400 pregnant women with reaction to STS in the absence of a history of syphilis showed negative results by TPI test, 103 or 25.8 per cent had positive results and five or 1.2 per cent had doubtful reaction.Ninety-five or 75.4 per cent of 126 patients with a history of treated syphilis had positive reaction to TPI tests, 20 or 20.2 per cent had negative reaction and nine or 9.1 per cent had doubtful reaction.TPI and TPIA tests were done on 143 sera carefully selected for the study. Among 102 sera subjected to the TPI test, 46 or 100 per cent of these positive were also positive by TPIA tests, while 52 or 94.5 per cent of 55 TPI-negative sera were also nonreactive by TPIA test. One serum gave doubtful TPI test reaction and positive TPIA test reaction.     

SEROLOGIC DIAGNOSIS OF SYPHILIS—The Use of Treponema Pallidum Immobilization and Immune Adherence Tests

TPI tests were carried out on 4,060 sera. Among 3,934 patients with reactive STS and no history of syphilis, 2,148 or 54.6 per cent had negative reaction to TPI tests, 1,695 or 43.1 per cent had positive reaction and 91 or 2.3 per cent had doubtful reaction.Two hundred and ninety-two or 73.0 per cent of 400 pregnant women with reaction to STS in the absence of a history of syphilis showed negative results by TPI test, 103 or 25.8 per cent had positive results and five or 1.2 per cent had doubtful reaction.Ninety-five or 75.4 per cent of 126 patients with a history of treated syphilis had positive reaction to TPI tests, 20 or 20.2 per cent had negative reaction and nine or 9.1 per cent had doubtful reaction.TPI and TPIA tests were done on 143 sera carefully selected for the study. Among 102 sera subjected to the TPI test, 46 or 100 per cent of these positive were also positive by TPIA tests, while 52 or 94.5 per cent of 55 TPI-negative sera were also nonreactive by TPIA test. One serum gave doubtful TPI test reaction and positive TPIA test reaction.     

Carminomycin in drug combination in breast cancer and soft tissue sarcomas]

Thirteen patients with neglected mammary cancer were treated with karminomycin in combination with hexamethylmelamine. Twelve out of the 13 patients were previously subjected many times to cytostatic and hormonal therapy. A significant therapeutic effect was registered in 5 out the 13 patients (38 per cent), the total rate of the objective effect being 54 per cent. The remission period with a significant effect was 6 to 9 months. Fifteen patients with sarcoma metastases in the soft tissue were treated with karminomycin in combnation with methotrexate and cyclophosphane. A significant therapeutic effect was observed in 45 per cent of the cases with synovial sarcoma, hemangyopericitoma and leuomyosarcoma, the remission period being 4 to 12 months. The side effects of the above combinations were determined.     

Contraceptive use and efficacy in a genetically counseled population

Abstract

This paper reports contraceptive use and efficacy rates among 648 married women aged 15 to 44 who had received genetic counseling six months previously. Over half (53.5 per cent) of the counseled population were using non‐surgical contraception; 20 per cent were pregnant or postpartum; 10 per cent were seeking to become pregnant; 11 per cent were sterilized. Only 4.5 per cent were neither using contraceptives nor seeking to become pregnant. Women who were certain about their reproductive intentions after counseling utilized contraceptives effectively, with only two pregnancies at six months among those seeking to delay wanted pregnancies and only one pregnancy among those seeking to prevent pregnancy. This represents six‐month contraceptive failure rates of 4.3 and 2.1 per cent respectively for the two groups, rates similar to those with comparable intentions in the U. S. population at large. A distinguishing characteristic of the genetically counseled group was that 32 per cent of contraceptive users reported that their reproductive intentions were uncertain after counseling. The six‐month pregnancy rate in this uncertain group was 10 per cent.     

Trophoblastic Tumors of the Uterus—Problems of Methotrexate Therapy

Nineteen patients with trophoblastic tumors of the uterus were evaluated at the University of California San Francisco Medical Center. Eight patients, admitted before 1956, did not receive chemotherapy; the mortality rate was 87.5 per cent. Ten of the remaining 11 patients were given intermittent, intensive Methotrexate therapy; actinomycin D and vincristine were used in treating two patients in whom resistance to Methotrexate developed. The mortality was 10 per cent. Toxicity was a prominent factor but was completely reversible when chemotherapy was stopped.None of the patients showed recurrent disease during follow-up evaluation eight months to five years and eight months after therapy was completed.It is postulated that continuing chemotherapy four to six months after the chorionic gonadotropin titer becomes negative decreases recurrent disease.     

Trophoblastic tumors of the uterus-problems of methotrexate therapy

Nineteen patients with trophoblastic tumors of the uterus were evaluated at the University of California San Francisco Medical Center. Eight patients, admitted before 1956, did not receive chemotherapy; the mortality rate was 87.5 per cent. Ten of the remaining 11 patients were given intermittent, intensive Methotrexate therapy; actinomycin D and vincristine were used in treating two patients in whom resistance to Methotrexate developed. The mortality was 10 per cent. Toxicity was a prominent factor but was completely reversible when chemotherapy was stopped.None of the patients showed recurrent disease during follow-up evaluation eight months to five years and eight months after therapy was completed.It is postulated that continuing chemotherapy four to six months after the chorionic gonadotropin titer becomes negative decreases recurrent disease.     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

LIPID COMPOSITION OF GLIAL CELLS ISOLATED FROM BOVINE WHITE MATTER

Abstract— —Glial cells were isolated from bovine white matter by differential centrifugation with'Ficoll'and their lipid composition was analysed. The preparations contained 20.8 per cent lipid and 792 per cent protein. The major lipid components were cholesterol, ethanolamine glycerophosphatides (EGP), cerebroside and serine glycerophosphatides (SGP). Sphingomyelin, cerebroside sulphate and inositol glycerophosphatide were present in lower proportions. EGP contained the largest proportion of aldehydes (17 per cent) and SGP contained 12 per cent. Choline glycerophosphatides contained only a trace of aldehyde. No gangliosides were present in the filial cell preparations.     

Quantitative method for determining variamycin]

A quantitative spectrophotmetric method for the assay of variamycin in commercial samples was developed. It was based on the measurement of the optical density of variamycin solutions in 0.01 N hydrochloric acid at a UV spectrum wave length of 412 nm. A method of thin-layer chromatography for a semi-quantitative estimation of tetraside, the main admixture of variamycin was devised. On storage for 18 months the content of variamycin in the preparations did not change as compared to that at the moment of the drug manufacturing and the amount of tetraside in 18 months did not exceed 2 per cent.