Pharmacologic Therapy of Atrial Flutter

Pharmacologic Therapy of Atrial Flutter. Atrial flutter is a relatively rare but nonetheless important arrhythmia. Its mechanism and anatomy have been defined as right atrial macroreentry. It responds to treatment with a variety of antiarrhythmic agents but, in general, drug efficacy for acute termination is low. The addition of pacing to drug therapy markedly improves the success rate for restoration of sinus rhythm. Useful antiarrhythmic agents include amiodarone, sotalol, disopyramide, flecainide, and propafenone, but definitive efficacy studies have not been performed. The risk of provoking 1:1 AV conduction and a marked increase in ventricular response rate is always present. AV nodal blocking drugs (digoxin and verapamil) probably offer protection from this unwanted effect, but the prevalence of 1:1 conduction and the efficacy of AV nodal blockade remain to be established. When drug management fails, there is a place for radiofrequency ablation. Little is known about the thromboembolic risk of atrial flutter. As a consequence, the role of prophylactic anticoagulation is uncertain. Current interest in atrial flutter will ensure that these and other clinical questions are answered in the near future.     

Linkage relationships between the three phosphoglucomutase loci PGM1, PGM2 and PGM3

1. Phosphoglucomutase phenotypes have been studied in several generations of the family of an individual heterozygous at each of the three loci, PGM₁, PGM₂, and PGM₃. 2. PGM₁ and PGM₂ phenotypes were determined using red cells. Fibroblasts grown in tissue culture were used for PGM₃ phenotyping. 3. The family results support the genetical hypothesis based on the analysis of dizygotic twin pairs that the PGM₃ isozyme patterns found in the placenta are determined by two alleles, PGM¹₃ and PGM²₃. 4. Locus PGM₃ is not closely linked to locus PGM₂ 5. The data also support the previous findings that locus PGM₁ is not closely linked to PGM₂ or PGM₃.     

HLA Sharing and Fertility in Hutterite Couples: Evidence for Prenatal Selection Against Compatible Fetuses

ABSTRACT: Antigenic differences between mother and fetus (i.e., blood group incompatibilities) were traditionally considered deleterious for viviparous reproduction. Recently, evidence has accumulated suggesting that maternal response to paternally derived fetal antigens, paradoxically, may facilitate maintenance of pregnancy. Thus, fetuses whose paternally derived antigens do not differ from maternal antigens (i.e., histocompatible pregnancies) may be at a selective disadvantage during pregnancy. Parents sharing histocompatibility antigens (i.e., HLA) may produce compatible fetuses and show overall reduced fertility. Indeed, increased HLA sharing has been reported in some couples experiencing repetitive spontaneous abortion. However, the effects of HLA sharing in couples not selected because of previous pregnancy losses have not been assessed. To elucidate the reproductive effects of maternal-fetal histocompatibility, we initiated prospective population-based studies of parental HLA sharing and reproductive outcome in the Hutterites, a population isolate that lives communally and proscribes contraception. The relationship between HLA-A, -B, and -DR sharing and reproductive outcome was examined in 111 Hutterite couples. Intervals from marriage to each birth were no longer among couples sharing antigens; differences were significant at the second birth and remained significant through the sixth birth (P < .05). When the effects of sharing at individual loci were examined, HLA-DR was the only individual locus that was a significant predictor of birth interval length (P = .025). Completed family sizes were 6.5 and 9.0 among couples sharing and not sharing HLA-DR, respectively (P = .082, 2-tailed). However, recognized fetal loss rates did not differ among couples sharing and not sharing antigens. We interpret these results as evidence for reduced fertility among some Hutterite couples sharing HLA, as a result of maternal-fetal compatibility for HLA-DR, per se, or alleles at an undefined, HLA-DR-linked locus. Our data further suggest that longer intervals associated with HLA-DR sharing may result from losses occurring early in gestation, before Hutterites would recognize pregnancy.     

Acute, Pharmacokinetic, and Subchronic Toxicological Sudies of 2,4-Dichlorophenoxyacetic Acid

The single-dose oral LD₅₀ values in Fischer 344 rats for technical-grade2,4-dichlorophenoxyacetic acid (2,4-D), es ters, and salts rangedfrom 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylaminesalt in males). The LDH values for the acid, esters, or salts,when expressed as acid equivalents, were consistent which suggeststhat the acute toxicity was due to 2,4-D per se. Acute dermalLD₅₀ values in rabbits for the acid, esters, and salts weregreater than 2000 mg/kg. Overall, these results indicate thatthe acute oral and dermal toxicity of 2,4-D are low. Pharmacokineticswere evaluated in male Fischer 344 rats given single oral dosesof 10, 25, 50, 100, or ISO mg 2,4- [¹⁴CJD/kg The amount of 2,4-Din the plasma, kidney, and urine 6 hr postdosing indicated thatthe urinary elimination of 2,4-D was saturated in male ratsgiven oral doses in excess of 50 mg/ kg. Subchronic dietarystudies in male and female Fischer 344 rats used dose levelsof 0, 15, 60, 100, or 150 mg/kg/thy of purified or technical-grade2,4-D acid for 13 weeks. Body weight gains were decreased forboth sexes at the higher dose levels of purified and technical-grade2,4-D acid. Kidney weights were increased in all treated malerats and in females given the higher three dose levels of purified2,4-D. Treatment-related cytoplasmic alterations were presentin the renal proximal tubules of most rats given 60mg/kg/thyand higher of purified or technical-grade 2,4- D; a few femalesgiven 15 mg/kg/thy also had slight alterations in the cytoplasmof the proximal tubules. A dose-related degenerative changewas identified in the descending proximal renal tubules of allmale rats given the highest three dose levels of either testmaterial and some given 15 mg/kg/thy. Dose levels of 100 or150 mg/kg/thy of either compound for both sexes produced minimalswelling and increased staining homogeneity in the liver cellsand were associated with a slight elevation of liver weightand serum glutamic pyruvic transaminase activity. Higher doselevels of technical-grade and purified 2,4-D decreased totalserum tetraiodothyronine levels in female rats, however, themorphology of the thyroid gland was normal. The no-observed-effectlevel (NOEL) was less than 15 mg/kg/day for both purified andtechnical-grade 2,4-D acid.     

SPERM CHROMOSOME ANEUPLOIDY AS RELATED TO MALE FACTOR INFERTILITY AND SOME ULTRASTRUCTURE DEFECTS

Some men have elevated levels of sperm chromosome aneuploidy. In this study, we have evaluated and summarized sperm aneuploidy rates in male infertility patients and control groups. The mean aneuploidy rate for five chromosomes (X, Y, 13, 18, 21) was 1.2 ± 0.1 for fertile controls, 1.4 ± 0.1 for a general population control group, and 5.8 ± 1.14 for the patients. When the patients were classified by the type of male factor infertility, the total aneuploidy rate was 2.6 ± 0.3 in men with moderately diminished semen quality (n = 7), 4.0 ± 0.3 patients with severe teratoasthenooligozoospermia, and 15.9 ± 3.8 for men with rare ultrastructure defects such as round head only syndrome or severe tail agenesis. Some infertility patients have a severely elevated level of sperm chromosome aneuploidy, which may contribute to infertility or diminish the likelihood of a successful outcome from IVF/ICSI. The severity of sperm chromosome aneuploidy appears to be proportional to the severity of abnormal semen quality: in particular, abnormal morphology. The high rates of aneuploidy in patients with severe ultrastructure defects suggest that caution should be employed in counseling those patients prior to IVF/ICSI.     

The Involvement of General Practitioners in the Care of Patients with Human Immunodeficiency Virus Infection: Current practice and Future Implications

The objective was to determine the current use of their generalpractitioner (GP) by patients with human immunodeficiency virus(HIV) infection and whether such patients would be interestedin having ‘shared care’ between a specialist HIVclinic and their GP. A questionnaire was administered to 203HIV-positive men attending the HIV outpatient clinic of a centralLondon teaching hospital. The main outcome measures were patientcharacteristics, numbers of patients registered with a GP, numbersof patients with a GP aware of their diagnosis, contacts withthe GP in the last year and level of interest and shared care.Eighty-five per cent of patients were registered with a GP ofwhom 67% knew of the diagnosis. Those diagnosed for more than2 years were significantly more likely to have an informed GP.A total of 73% of those registered had visited their GP in theprevious year although only 27% had visited for an HIV-relatedproblem. Only 19% had a GP actively involved in their HIV care.In all 51% of the patients indicated an interest in having sharedcare between the clinic and their GP. A high proportion of HIVpatients are registered with and attend a GP although they rarelyconsult for HIV-related problems. A significant proportion ofpatients expressed interest in having shared care suggestingthat there is the potential for increased GP involvement inthe care of patients with HIV infection.     

Critical review of nutrition assessment tools to measure malnutrition in chronic kidney disease

The use of the Subjective Global Assessment (SGA) and similar clinical tools for nutrition assessment is integral in the nutritional management of chronic kidney disease (CKD) patients. The present paper is a critical review of the quality of studies introducing and validating SGA‐based tools in CKD. In the CKD literature, clinical, predictive and criterion validity were investigated by a number of studies. Common limitations identified include the use of questionable statistical methods, difference in prevalence of malnutrition based on tool or administrator (i.e. dietitan, nephrologist or nurse) and use of inadequate reference tests to establish true nutrition status. The SGA appears to have the best diagnostic evidence to adequately detect the presence of abnormal nutrition status and prognostic evidence to predict poor outcome. Modified scored versions may improve clinician’s ability to detect degree of malnutrition; however, the present review indicates more work is required. Tools based on the original SGA claiming validity in CKD and potentially other clinical areas should be approached with caution. Critical evaluation of study design, reference tests and statistical methods is recommended before implementing new tools in practice.