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Biomedical subjects

J C Rutledge

Publications and source records attributed to J C Rutledge.

At least 73 records · Page 4Linked to original sources
PubMed1988

Mutagen-induced fetal anomalies and death following treatment of females within hours after mating.

In an earlier study (Generoso et al., 1987), it was observed that the mutagen, ethylene oxide (EtO), produced remarkable increases in the incidence of developmental abnormalities and death of fetuses when early zygotic stages were exposed. This is a major finding in experimental induction of embryopathy, implicating genetic damage to the zygotes as the likely cause. In the subsequent study reported here, 3 other mutagens--ethyl methanesulfonate (EMS), ethyl nitrosourea (ENU), and triethylene melamine (TEM), were studied for embryopathic effects following exposure of dictyate oocytes, prefertilization oviducal eggs and sperm, early pronuclear zygotes, zygotes undergoing pronuclear DNA synthesis, and two-cell embryos. All 4 mutagens produced developmental abnormalities among living fetuses following exposure of early pronuclear zygotes (the only stage studied for this endpoint in this report). With respect to stage specificity and gestational timing of death of conceptuses, EMS and EtO on one hand and ENU and TEM on the other, are very similar to one another. EMS, like EtO, produced a high incidence of midgestation and late fetal deaths only in prefertilization oviducal eggs and sperm and in early pronuclear eggs. In contrast, ENU and TEM produced high losses of conceptuses in all postmating stages studied but death occurred primarily prior to or around the time of implantation. Thus, the frequency of induction and the expression of embryopathy, which ranged from early embryonic preimplantation and late fetal deaths to subtle fetal anomalies, are dependent upon the stage exposed and the mutagen used.

Abnormalities, Drug-Induced↗
PubMed1988

Aldosterone reverses potassium-induced food aversions in adrenalectomized rats.

Young adult male rats were individually housed and given a standard ration (66 ml) of a liquid diet (Nutrament) each day. The animals were divided into 7 groups: five groups were bilaterally adrenalectomized (ADX) and given one of 5 doses of aldosterone and/or dexamethasone by continuous, osmotic minipump infusions. The remaining two groups served as intact and sham operated controls. Each of the seven groups were subdivided into 3 dietary groups: a basal potassium dietary group, a moderately potassium-supplemented dietary group, and a highly potassium-supplemented dietary group. All rats with intact adrenals as well as those ADX rats given basal or 10 X basal aldosterone treatment consumed all of their allotted 66 ml of diet each day, independent of the level of potassium supplementation. ADX rats given little or no aldosterone treatment that were given access to the moderately or highly supplemented diets became anorexic, eating little or none of the diet. These data are discussed with reference to the factors controlling the intake of ADX rats.

Adrenal Glands↗
PubMed1987

Exposure of female mice to ethylene oxide within hours after mating leads to fetal malformation and death.

When previously mated female mice were exposed to inhaled ethylene oxide at the time of fertilization of their eggs or during early pronuclear stage of the zygote (before DNA synthesis), a high incidence of mortality among conceptuses and of congenital abnormalities among both the dead and the surviving fetuses was observed. The developmental stage at which death occurred ranged from near the time of implantation to day 17 of gestation when examination of the uterine contents was performed. In comparison, midgestation and late fetal deaths were absent or minimal when the females were exposed either before mating or when conceptuses were in later zygotic stages (pronuclear DNA synthesis) or had reached the early two-cell stage. The random types of congenital abnormality observed and the remarkable stage-dependent sensitivity suggest a genetic basis for the response. The effects differ, both from genetic damages induced in premating germ cells, which lead only to death near the time of implantation, and from teratogenic damage, which leads to malformations only when exposure of embryos occurs during the period of major organogenesis.

Abnormalities, Drug-Induced↗
PubMed1987

Bilateral posterior choanal atresia: a morphologic and histologic study, and computed tomographic correlation.

Bilateral posterior choanal atresia is an uncommon cause of respiratory obstruction in the newborn. Although the clinical syndrome and treatment options are well known, the abnormal histology has not been well described. Computed tomography (CT) is a useful tool in the radiologic diagnosis of choanal atresia, but has not been correlated with the histopathology. Two patients with CHARGE association (congenital heart defects, choanal atresia, retarded growth and development, hypogenitalism, and aural anomalies) and bilateral posterior choanal atresia were studied with CT. The atresia plates were removed at autopsy and sectioned in an axial plane for gross and microscopic study. The histopathology is described and correlated with the CT studies. These studies show that CT accurately defines the histopathologic abnormalities found in bilateral posterior choanal atresia.

Abnormalities, Multiple↗
PubMed1987

HPLC qualitative amino acid analysis in the clinical laboratories.

The authors have developed a rapid system for qualitative amino acid analysis by high-pressure liquid chromatography for use in the clinical laboratory. Reverse-phase, linear gradient, high-pressure liquid chromatography of stable dansyl chloride derivatives is accomplished with a C-18 column over 30 minutes, with ultraviolet detection. The resulting chromatograms are compared with template chromatograms that reflect high normal levels of serum and urine amino acids. Large elevations of amino acids associated with inborn errors of metabolism are easily pinpointed, with identification of specific amino acids made by the relative retention times. This technic makes available a rapid and specific qualitative method for investigation of aminoacidopathies and uses versatile and standard liquid chromatography equipment.

Amino Acids↗
PubMed1987

Kaliuretic regulatory factors in the rat.

To evaluate the role of aldosterone, plasma potassium, and sodium and urine excretion rates in controlling both total daily potassium excretion and the diurnal cyclic excretion of potassium, we performed experiments on unanesthetized, undisturbed rats kept in a 12-h light/12-h dark environment and fed a liquid diet. Independent variations were imposed on potassium intake, sodium intake, and, in groups of adrenalectomized rats, on aldosterone infusion rates. Potassium intake was 2.6, 10.6, and 18.7 meq/day. Sodium intake was 2.1, 6.7, and 17 meq/day. Aldosterone infusion was 0.1, 0.4, 1, and 10 times a basal rate of 1 microgram.day-1.100 g-1, with constant dexamethasone infusion at 1.43 micrograms.day-1.100 g-1. Twenty-four-hour excretion of potassium and sodium balanced 24-h intake of potassium and sodium regardless of the imposed combination of known regulatory factors. The amplitudes of potassium and sodium excretion during the diurnal cycle were each closely related to the ongoing levels of potassium and sodium intake. Plasma potassium was measured at the peak of the potassium cycle. It is suggested, based on analysis of the results, that when caloric balance was maintained, the amplitude of the diurnal potassium cycle was not importantly influenced by the rates of sodium and urine excretion, and, in addition to effects of aldosterone and plasma potassium concentration, the amplitude was importantly influenced by unspecified, homeostatically effective kaliuretic factors. Adrenalectomized rats receiving subbasal aldosterone replacement rejected the high potassium diet, were anuric, lost weight, and were severely hyperkalemic, observations indicating the necessity of adequate aldosterone for maintenance of potassium homeostasis.

Adrenalectomy↗
PubMed1987

Phenylalanine and tyrosine in serum and eluates from dried blood spots as determined by reversed-phase liquid chromatography.

We have developed a reversed-phase liquid-chromatographic procedure for simultaneously determining phenylalanine and tyrosine in serum and eluates of dried blood spots. Batch derivatization with phenylisothiocyanate and a 10-min linear gradient chromatographic assay with ultraviolet absorbance detection provide rapid sample throughput. Interrun precision (CV) is less than 12%; analytical recovery (from blood spot samples) exceeds 85%. Results for patients' samples correlate well with those from an amino acid analyzer and we encountered no apparent interferences. The speed and specificity of this assay facilitate the rapid diagnosis and monitoring of patients with phenylketonuria.

Chromatography, High Pressure Liquid↗
PubMed1986

Symptomatic and silent myocardial ischemia during exercise testing in coronary artery disease.

During exercise by patients with coronary artery disease (CAD), electrocardiographic evidence of myocardial ischemia may precede the onset of angina or may be unassociated with angina, even at peak levels of stress. However, neither the precise incidence of silent versus symptomatic ischemic episodes nor their interrelation in this setting has been clearly defined. The prevalence of silent and symptomatic myocardial ischemia during treadmill exercise testing was determined in 92 patients with angiographically documented CAD. The study group comprised 77 men (84%) and 15 women (16%) of mean age 57 years (range 32 to 79). Exercise testing resulted in ischemic ST-segment depression (greater than or equal to 1 mm for greater than or equal to 80 ms) only or in association with delayed (greater than or equal to 1 minute) angina in 39 patients (42%); angina only or in association with delayed ST-segment depression occurred in 42 patients (46%); and simultaneous occurrence of angina and ST-segment depression was noted in 11 patients (12%). Analysis of clinical, exercise and angiographic factors (age, sex, history of myocardial infarction, heart rate, maximal ST-segment depression, extent of CAD and left ventricular ejection fraction) revealed no significant correlation with the frequency of symptomatic and silent myocardial ischemia during exercise. Asymptomatic myocardial ischemia occurred commonly during exercise in patients with CAD, but there were no differences in the characteristics of patients with symptomatic and asymptomatic episodes.

Adult↗
PubMed1986

A balanced translocation in mice with a neurological defect.

A semisterile male translocation heterozygote [t(2; 14) 1Gso] that exhibited neurological symptoms and an inability to swim (diver) was found among the offspring of male mice treated with triethylenemelamine. All breeding and cytogenetic data showed a complete concordance between translocation heterozygosity and the neurological disorders. Homozygosity for the translocation seemed to be lethal at an early embryonic stage. Despite the distinctive neurologic symptoms, no anatomic or histological defects in either the ear or in the central nervous system were observed. Thus, a balanced chromosomal translocation can produce disease with an inheritance pattern that mimics a single dominant gene defect.

Animals↗
PubMed1986

Difference between two hybrid stocks of mice in the incidence of congenital abnormalities following X-ray exposure of stem-cell spermatogonia.

Unbalanced (duplication/deficiency) sperm from balanced reciprocal translocations induced in spermatogonial stem cells of mice generally lead to embryonic lethality around the time of implantation. In a recent study (Generoso et al., 1985), it was found that the incidence of X-ray-induced embryonic lethality differed markedly between two hybrid stocks of irradiated male mice. A parallel difference in the frequencies of reciprocal translocations was observed cytologically in the meiocytes of irradiated males. In the present report, which is an adjunct to the study by Generoso et al. (1985), it was determined whether or not similar differences between the two stocks exist for congenital defects resulting from genetic damage to stem-cell spermatogonia. The results indicate not only an association between the frequencies of induced reciprocal translocations and congenital abnormalities, but also a parallel greater frequency of induced malformations in the (C3H X 101)F1 stock versus the (SEC X C57BL)F1 stock of males.

Abnormalities, Radiation-Induced↗
PubMed1986

Acinar dysplasia: a new form of pulmonary maldevelopment.

A term neonate died of unrelenting respiratory distress several hours after birth. Autopsy of the normal-appearing infant revealed slightly small lungs with increased lobular markings, a right aortic arch, and bilateral thinned renal cortices. In contrast to most forms of pulmonary hypoplasia, the term neonate had deranged air spaces lined by ciliated bronchial epithelium, without development of alveoli, and with increased amounts of intervening fibrous tissue. It is proposed that an alteration in the epithelial-mesenchymal interactions during development accounted for both the unique pulmonary maldevelopment and the renal abnormalities.

Bronchi↗
PubMed1986

Congenital hybrid basal cell adenoma--adenoid cystic carcinoma of the salivary gland.

A congenital parotid gland tumor involving the facial nerve was excised, revealing histologic and ultrastructural features of a basal cell adenoma and adenoid cystic carcinoma. An asynchronous regional metastasis was successfully eradicated with adriamycin. Seven other similar appearing tumors occurring in neonates are documented in the literature and serve to establish this tumor as a clinicopathologic entity. The surrounding parotid gland had "dysplastic" changes attributed to obstruction during morphogenesis.

Adenoma↗
PubMed1985

Clinical evaluation of oral mexiletine therapy in the treatment of ventricular arrhythmias.

The effect of oral mexiletine therapy on ventricular arrhythmias was evaluated in 58 patients in whom conventional drugs had been unsuccessful. Mean daily dose of mexiletine was 652 mg (range 250 to 1,500) and mean duration of therapy was 14.4 months (range 0.1 to 34.4). Mexiletine was associated with a decrease of 52% in total premature ventricular complexes in 24 hours compared with control (6,841 +/- 1,053 [SEM] versus 3,248 +/- 734, p less than 0.005) and 19 patients (36.5%) had a greater than 83% decrease in ventricular ectopic rhythm. The drug was discontinued in 6 of these 19 patients because 5 of them (26%) experienced side effects after a mean period of 29.6 weeks (range 0.83 to 63.2) and sudden death occurred in 1 patient (5%); this indicates effective suppression of ventricular ectopic rhythm without significant side effects in 13 (25%) of 52 patients during long-term therapy. Adjustment of drug dosage to achieve therapeutic blood levels resulted in an efficacy on ventricular ectopic rhythm similar to that obtained with the maximal tolerated dose. There was no correlation between drug dose and therapeutic effectiveness. Mexiletine was associated with a 48% decrease in episodes of ventricular tachycardia (345.5 versus 179.3/24 h) and 5 of 10 patients with a history of cardiac arrest remained free of symptomatic ventricular tachyarrhythmias for 14.8 months (range 3.7 to 24.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗