Sotalol is a pure beta-adrenergic receptor antagonist. The present study was divided into a first and second therapy period. A total of 38 patients with atrial or ventricular arrhythmias were included in the first therapy period. After a drug-free period of approximately two months, 14 of the 38 patients entered the second therapy period and were given oral sotalol. During the two treatment periods, oral sotalol was given in doses ranging from 40 to 480 mg/day for 0.5 to 11 months in the first period and for four to nine months in the second period. Oral sotalol decreased or abolished arrhythmias in 92 per cent of the patients in the first therapy period and in all the patients in the second therapy period. Minor side effects occurred in two patients. Sotalol possesses a unique class III antiarrhythmic action. The electrophysiological profile is different from other beta-adrenergic blocking agents in that sotalol prolongs the duration of the intracellularly recorded action potential. This property may contribute to the antiarrhythmic efficacy demonstrated with sotalol.

Adult↗

PubMedDate not supplied

Altered steroidogenesis in whole-ovary and adrenal culture in cycling rats.

Cultures of minced, whole-ovary (whole-ovary culture) were used to determine if three selected chemicals altered steroidogenic profiles. First, phenolsulfonthalein (PST), when used in culture medium, was tested for its influence on in vitro steroidogenesis. Next, aminoglutethimide (AGTP; 0 or 150 mg/kg once) and di(2-ethylhexyl)phthalate (DEHP; 0 or 1500 mg/kg/day for 10 days) were administered in vivo to young adult cycling rats, and the ovaries and adrenals were removed and cultured for 1 h. Ovarian steroidogenic profiles of progesterone (P), testosterone (T), and estradiol (E) release into the medium were measured using radioimmunoassay techniques. PST in medium significantly decreased ovarian P production and altered T and E production so that the T/E ratio was significantly altered. Therefore, PST was excluded in the later studies. DEHP altered steroid profiles so that proestrus appeared to be delayed. AGTP decreased P and E production significantly, and T production was increased slightly in proestrus ovaries. These AGTP alterations in T and E resulted in a highly significant increase in the T/E ratio. Adrenals from the DEHP and AGTP experiments were also cultured for 1 h, and P was assayed in the medium. AGTP, but not DEHP, significantly increased the production of P in adrenals. Whole-ovary culture is recommended as an in vitro test for chemicals suspected of interfering with steroidogenesis in vivo. This test model should be placed strategically between in vivo studies of reproductive toxicity and complex in vitro mechanistic studies.

Adrenal Glands↗

PubMedDate not supplied

The use of cultured ovarian fragments to assess toxicant alterations in steroidogenesis in the Sprague-Dawley rat.

This study was conducted to determine the utility of using steroid production by cultured ovarian fragments to assess toxicant-induced alterations in ovarian steroidogenesis in Sprague-Dawley rats. To this end, serum steroid concentration and steroid production (progesterone (P4), testosterone (T), estradiol (E2)) by cultured ovarian fragments is described during a normal 4-day estrous cycle. This culture system was then used to profile the effects of aminoglutethimide shown to have two sites of steroidogenic inhibition, side chain cleavage enzyme and aromatase. LH, FSH, P4, and E2 concentrations in serum during the 4-day estrous cycle confirmed that described in the literature for untreated rats. All of the steroids measured had peak production levels during proestrus. The patterns of P4 and E2 production by the ovaries in an unstimulated culture mimics that seen in serum. Stimulation with hCG (100 mIU/mL) after the initial 1 h culture tends to even out the production of P4, while T production rises faster and peaks earlier. The pattern and levels of estradiol production in hCG-stimulated cultures are very similar to those in the unstimulated culture, both in pattern and in production levels. When cultured ovarian fragments from proestrous rats were treated in vitro with aminoglutethimide (1 to 16 microM), the pattern of steroid production that characterized the inhibitory effects were similar to those reported in the literature using isolated cell culture procedures. This pattern showed a rapid decrease in E2 production (IC50 of 2.43 microM), a concurrent rise in T production, and a decrease in P4 production (IC50 of 15.5 microM). This culture system is an appropriate system to rapidly assess toxicant effects on ovarian steroidogenesis following in vivo or in vitro exposure.

Aminoglutethimide↗

PubMedDate not supplied

A pill-a-month contraceptive.

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Biopsy↗

PubMedDate not supplied

Relationship between broiler chicken haematocrit-selected parents and their progeny, with regard to haematocrit, mortality from ascites and bodyweight.

A previous work of this group demonstrated that the relative haematocrit value of broilers is inherited and may serve as an indicator to susceptibility to the ascites syndrome in cold-stressed broilers. In this study, a full-pedigreed population was produced from male and female grandparent breeding stock that was selected by haematocrit and by normal selection parameters. Matings were made between low (L), medium (M) and high (H) haematocrit parents: L x L, M x M, and H x H. In their progeny, both before and after cold exposure, there was a statistically linear relationship between actual haematocrit and their H, M and L grouping (P<0.0001); heritability of the haematocrit was high (0.46-0.81). Both the low haematocrit parent and progeny groups showed an increased bodyweight. Exposure of the progeny from all the parental groups to an ascites-predisposing cold environment caused similar losses from ascites in the progeny of all three groups. Although this finding was not the same as in the previous trial where the H haematocrit group was associated with high ascites mortality, it is hypothesized that other factors, such as arterial blood saturation with oxygen, interacted in these birds at genetic or environmental levels.

Animals↗

PubMedDate not supplied

Iron supplementation after femoral head replacement for patients with normal iron stores.

OBJECTIVE: To assess the efficacy of oral iron therapy in the recovery of patients' hemoglobin levels after major surgery. DESIGN: Randomized controlled trial. SETTING: Private orthopedic practice confined to one large community hospital. PATIENTS: One hundred seventy consecutive elderly patients undergoing hip surgery; 75 failed to meet entry hematologic or medical criteria; 95 were randomized, with 16 withdrawn because of complications. INTERVENTION: Thirty-seven patients received ferrous sulfate orally four times a day for the duration of their hospitalization. Forty-two patients who received no iron supplement served as the control group. MAIN OUTCOME MEASURES: Changes in hemoglobin levels and reticulocyte counts over the 2- to 3-week follow-up period. RESULTS: There was no significant difference in mean hemoglobin levels between the treatment and control groups (95% confidence interval [CI] for difference of -6.6 to 5.4 g/L). Corrected reticulocyte fractions increased equally in both groups (95% CI for difference of -9 x 10(3) to 2 x 10(-3). The study was designed to detect a difference in mean hemoglobin levels of 8.5 g/L or greater or a difference in mean reticulocyte fraction of 10 x 10(-3) between the two groups with a power of 0.80 at the .05 (two-sided) level of significance. CONCLUSION: The administration of oral iron supplements to elderly, healthy orthopedic patients postoperatively did not hasten the recovery of hemoglobin levels, provided adequate tissue iron stores were present.

Administration, Oral↗

PubMedDate not supplied

Controlled early feed restriction as a potential means of reducing the incidence of ascites in broilers.

Male broiler chicks were grown at cold temperatures to enhance susceptibility to the ascites syndrome. Various feeding regimens were used to determine whether they could influence mortality due to ascites. It was found that a precisely controlled early feed-restriction regimen at the age of 6 to 11 days significantly reduced mortality from all causes and mortality due to ascites, while maintaining optimum body weight and feed conversion at marketing age.

Animal Feed↗

PubMedDate not supplied

Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies.

Idarubicin is a new derivative of Daunorubicin which was found to be more potent and more active than Daunorubicin and Doxorubicin in several experimental leukemias. Its antileukemic activity in preclinical models prompted the introduction of Idarubicin into clinical studies. As a single agent, Idarubicin produced complete remission in 20% and 30% of patients with heavily pretreated pediatric and adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. Idarubicin combined with Cytarabine and/or other antileukemic agents produced complete remissions in 46% of patients with refractory or relapsed AML and in 58% of patients with refractory or relapsed ALL (adult and pediatric). Subsequently, Idarubicin has been employed in untreated AML patients in combination with Cytarabine and/or Etoposide, producing complete remissions in more than 80% of patients. In ALL patients the drug has been used in combination with Vincristine, Cytarabine and Prednisone, producing complete remissions in 82% of patients. Recently, Idarubicin has been utilized in combination with intermediate doses of Cytarabine in refractory or relapsed ALL and AML, and 70% of patients achieved complete remission. Preliminary results of ongoing prospective randomized studies in untreated adult AML seem indicate that Idarubicin is at least equivalent, if not superior to Daunorubicin. The antileukemic activity of Idarubicin given orally as single agent, or in combination with other drugs, has been shown in AML and myelodysplastic syndromes. The toxicity of Idarubicin includes mild nausea and vomiting, alopecia and liver dysfunction. Ongoing randomized trials comparing Idarubicin to Daunorubicin should provide more information about the potential cardiotoxicity of this drug.

Animals↗

PubMedDate not supplied

Acute fatal hyperaluminemic encephalopathy in undialyzed and recently dialyzed uremic patients.

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Aged↗