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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 235 records · Page 13Linked to original sources

Plasma and pituitary concentrations of LH, FSH, and prolactin in aging C57BL/6 mice at various times of the estrous cycle.

Plasma and pituitary concentrations of LH, FSH, and prolactin (Prl) were measured by RIA in 2-4, 7-8, 12-13 and 16-20 month-old female C57BL/6 mice during various stages of the estrous cycle. In general, gonadotropin concentrations tended to rise with increasing age and Prl concentrations tended to decline. Pronounced differences existed, however, between the four age groups around the time of the LH surge. LH secretion declined progressively with increasing age at 21.00 hr of proestrus. Aged mice, 16-20 months old, had significantly lower plasma concentrations of LH than did other age groups. It is not known whether age-related changes in the ovary, pituitary, or hypothalamus are largely responsible for differences in the secretion of LH, FSH and Prl in aging C57BL/6 mice.

Aging↗

Plasma and pituitary concentrations of luteinizing hormone, follicle-stimulating hormone and prolactin in aged, ovariectomized CD-1 and C57BL/6 mice.

Plasma and pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (Prl) were determined by radioimmunoassay in young (2-4 months-old) and aged CD-1 (14-18 months-old) and C57BL/6 (16-22 months-old) mice one month after ovariectomy. In young, ovariectomized mice, plasma and pituitary concentrations of LH and FSH were significantly higher, whereas concentrations of Prl were significantly lower than those in control mice (sham-operated). In contrast, plasma concentrations of LH, FSH and Prl were not statistically different in aged, ovariectomized mice and aged, control mice. There were also no differences in pituitary concentrations of the three hormones when comparing the same aged C57BL/6 mice, although the aged, ovariectomized CD-1 mice exhibited higher pituitary levels of each hormone than those of their controls. The pituitary of the aged mouse responds differently to ovariectomy than that of the young mouse because of age-related changes in the ovary and/or hypothalamic-hypophyseal complex.

Aging↗

Site of origin of halothane--epinephrine arrhythmia determined by direct and echocardiographic recordings.

A constantly coupled bigeminal arrhythmia was induced in dogs anesthetized with thiopental-halothane by infusion of epinephrine (1 microgram.kg-1.min-1). The site of origin of the abnormal beat was localized to the interventricular septum by bipolar recordings from the left and right ventricular epicardium and two sites in the septum. Simultaneous echocardiograms showed early movement of the septum with a pattern similar to that seen in the left bundle branch block. Simulation at the recording sites resulted in movement patterns which indicate that assessment of septal and posterior left ventricular motion can be helpful in localization of the origin of ventricular arrhythmias, although only with left ventricular arrhythmias is there potential for anatomic localization to a small area of muscle.

Animals↗

Cardiac function in end-stage renal disease.

To assess cardiac status in end-stage renal disease, we compared clinical, ECG, and echocardiographic data from 37 patients on maintenance hemodialysis with data from 42 patients with functioning renal transplants. Cardiovascular symptoms and abnormal cardiovascular findings were more common in dialysis-maintained patients than in those with transplants. Follow-up studies indicated that despite a high prevalence of cardiac symptoms, abnormal physical signs, and dilated left ventricles among patients with end-stage renal disease, systolic left ventricular function was generally well preserved irrespective of renal failure therapy. Compared with maintenance hemodialysis, however, successful renal transplantation is associated with an overall enhancement of cardiac status, the majority of which is probably secondary to transplant-associated improvement in hemoglobin level and control of intravascular volume.

Adolescent↗

Luteinizing hormone levels in aged female laboratory rodents as measured by a radioimmunoassay and a radioreceptor assay.

Plasma levels of LH were measured in young sexually mature (2- to 5-month-old) and aged (13- to 20-month-old) female C57BL/6 mice, Syrian hamsters and Wistar rats using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). There were no statistically significant differences when comparing data from the two assays when examining young oestrous and dioestrous mice. Aged oestrous and dioestrous mice exhibited significantly higher levels of LH as measured by RIA than by RRA. Levels of LH analysed by RIA were also higher in aged mice compared with those in younger mice. Comparing LH hamsters produced similar results. In contrasts, aged pseudopregnant rats exhibited significantly lower levels of plasma LH than younger dioestrous females and there were no differences in RIA and RRA values. There were also no differences when comparing data from the two assays in younger rats. The mean (+/- S.E.M.) RRA: RIA ratios of 0.96 +/- 0.05 (oestrous) and 0.96 +/- 0.04 (dioestrous) for younger mice and 0.92 +/- 0.08 for younger hamsters were significantly higher than the ratios of 0.66 +/- 0.05, 0.72 +/-0.05 and 0.71 +/- 0.05 respectively of their aged counterparts. The mean RRA: RIA ratios in the two age groups of rats were almost identical (0.79 +/- 0.05 and 0.80 +/- 0.10). These studies suggested that a portion of the higher LH levels detectable by RIA in some aged female rodents results from qualitative changes in the LH molecule.

Aging↗

Ketoconazole blocks testosterone synthesis.

Ketoconazole, a new oral drug used to treat systemic and superficial mycoses, inhibits sterol synthesis in fungi. The development of gynecomastia in two patients prompted us to investigate the effect of the drug on testosterone production. After a 200-, 400-, or 600-mg dose, volunteer male testosterone serum concentrations fell markedly, but returned toward baseline eight to 24 hours later as ketoconazole serum concentrations waned. A marked but transient drop in testosterone levels occurred in patients receiving long-term therapy, and continuous testosterone depression was noted in one. A block of synthesis was demonstrated in vitro. Ketoconazole at concentrations achievable in serum with currently used doses blocked basal and gonadotropin-stimulated testosterone production by rat Leydig cells. The diminution of testosterone synthesis could be significant as further therapeutic trials may use larger doses or more than once-daily administration. The paucity of reports of endocrinologic toxicity may relate to the "escape" from the block demonstrated in vivo.

Adult↗

Physical and hormonal evaluation of transsexual patients during hormonal therapy.

The optimal hormonal therapy for transsexual patients is not known. The physical and hormonal characteristics of 38 noncastrate male-to-female transsexuals and 14 noncastrate female-to-male transsexuals have been measured before and/or during therapy with various forms and dosages of hormonal therapy. All patients were hormonally and physically normal prior to therapy. Ethinyl estradiol was superior to conjugated estrogen in suppression of testosterone and gonadotropins but equal in effecting breast growth. The changes in physical and hormonal characteristics were the same for 0.1 mg/d and 0.5 mg/d of ethinyl estradiol. The female-to-male transsexuals were well managed with a dose of intramuscular testosterone cypionate of 400 mg/month, usually given 200 mg every two weeks. The maximal clitoral length reached was usually 4 cm. Higher doses of testosterone did not further increase clitoral length or suppression of gonadotropins; lower doses did not suppress the gonadotropins. Based on the information found in this study, we recommend 0.1 mg/d of ethinyl estradiol for the noncastrate male-to-female transsexual and 200 mg of intramuscular testosterone cypionate every two weeks for the noncastrate female-to-male transsexual.

Adolescent↗

Plasma and pituitary concentrations of LH, FSH and prolactin after injection of GnRH in aged female C57BL/6 mice.

Plasma and pituitary concentrations of LH, FSH and prolactin (Prl) were compared by radioimmunoassay (RIA) in young mature (2-4 month-old) and aged (16-22 month-old) female C57BL/6 mice, following various experiments with IP injections of GnRH. Unanesthetized mice were bled by cardiac puncture either (1) at various time intervals following a single injection of 25 ng GnRH, (2) after several injections of 25 ng GnRH, or (3) after receiving excessively large doses of GnRH. From the RIA of plasma and pituitary concentrations of LH, it appeared that the pituitaries of aged mice were, in general, capable of responding to GnRH treatment, only to a lesser degree than that of the younger females. The exception was that the pituitaries of aged mice that were subjected to unusually high doses of GnRH continued to secrete higher levels of LH, whereas the response of the pituitaries in younger mice plateaued after receiving 25 ng GnRH. Plasma and pituitary concentrations of FSH and Prl remained fairly constant when aged GnRH-treated females were compared with aged controls. This was also true when FSH and Prl concentrations in the younger mice were compared with their controls, except for significantly higher plasma FSH and significantly lower pituitary FSH following several injections of GnRH. When the hormonal concentrations of the young and aged groups were compared in the various experiments, the older mice consistently exhibited higher levels of gonadotropin and lower levels of prolactin than those of the younger mice. In a separate experiment, in which a radioreceptor assay (RRA) was used to quantitate plasma LH in GnRH-treated mice, both age groups were found to have lower concentrations of LH (p less than 0.05) than those obtained by RIA from the same animals. The RRA to RIA ratio, however, was 0.84 for 2-4 month-old and 0.57 for 16-22 month-old mice. These studies suggest that the anterior pituitary of the aged mouse is less sensitive to GnRH stimulation.

Aging↗

New antiarrhythmic agents. 4. 1'-(Aminoalkyl)-1,2,3,4-tetrahydronaphthalene-1-spiro-3'-pyrrolidine-2',5'-dione derivatives.

A series of 33 1'-(Aminoalkyl)-1,2,3,4-tetrahydronaphthalene-1-spiro-3'-pyrrolidine-2',5'-dione derivatives was tested for antiarrhythmic and toxic effects in mice and dogs. In mice, 31 compounds produced some protection against chloroform-induced tachyarrhythmias at subcutaneous doses of 100 mg/kg, and 6 compounds produced no detectable toxicity at doses protecting 80% or more of the animals. Seven of the more potent and nontoxic derivatives were tested in dogs with surgically induced myocardial infarctions. All produced distinct antiarrhythmic effects at doses considerably lower than doses of lidocaine or tocainide producing comparable effects. The principal toxic effects observed in dogs were convulsion and depression of intracardiac conduction; they occurred generally at higher doses than those leading to antiarrhythmic effect. Several compounds also suppressed digitalis-induced arrhythmias in anesthetized dogs. Half-lives and total body clearance in dogs were determined for three compounds; two had half-lives comparable to that of tocainide, a long-acting, orally active antiarrhythmic agent, in clinical trials.

Animals↗

Endocrine and behavioral effects of continuous exposure of male rats to a potent luteinizing hormone-releasing hormone (LHRH) agonist: evidence for central nervous system actions of LHRH.

Continuous exposure of intact male rats to [6-D-(2-naphthyl)-alanine]LHRH, a highly potent LHRH agonist, diminished testis and pituitary weights and decreased basal plasma levels of testosterone and LH. In addition, treatment with this analog abolished the pituitary hypertrophy and LH hypersecretion normally associated with castration. Alterations of male sex behavior were also noted in these animals. Analog-treated intact rats showed longer intromission latencies and mount latencies in early tests and ceased to show sexual behavior 6-8 weeks after initiation of treatment. In addition, the gradual decline in behavior normally observed after castration was markedly accelerated by analog administration. Castrates bearing 5-mm Silastic testosterone-containing capsules which maintained copulatory performance displayed behavioral deficiencies when given the peptide. No significant effect of analog was noted in rats with 30-mm Silastic implants, which provide a higher level of testosterone replacement. Continuous analog treatment promotes endocrine effects consistent with complete antagonism of the effects of endogenous LHRH. The behavioral disruption associated with this manipulation suggests a role for endogenous LHRH in maintaining sex behavior in a low testosterone environment.

Animals↗

Cardiac involvement in trichinosis.

During a small outbreak of trichinosis, two of four symptomatic patients developed moderate to large pericardial effusions. In neither was there ventricular dilatation nor impairment of systolic function. These observations suggest that pericardial effusion is more common than previously appreciated and that it may have a role in the genesis of the symptoms and signs mimicking congestive heart failure which occasionally complicate the course of this illness.

Acute Disease↗

Intra-arterial infusion chemotherapy in the treatment of advanced squamous carcinoma of the tongue and floor of the mouth.

Our present experience with Stage III disease suggests that the most effective means of treating advanced carcinoma of the floor of the mouth and tongue are with initial chemotherapy given as basal treatment by intra-arterial infusion followed by planned radiotherapy or operation, or both. Early carcinoma of the floor of the mouth and tongue can be managed effectively with conventional techniques using surgical treatment or radiotherapy, or both, and probably does not justify the increased time and increased problems of management involved in the use of chemotherapy regimens. Our experience in comparing the two programs of treatment in patients classified as having Stage IV lesions is too small to justify valid comparisons to be made at this stage, although we currently have under investigation similar management programs for these patients.

Aged↗

Uptake and secretion of carcinogenic chemicals by the dog and rat prostate.

Because the prostate of laboratory animals seems relatively resistant to the carcinogenic effects of systematically administered chemicals--an observation of some significance in attempts to establish the etiology of human prostatic adenocarcinoma and to produce animal models of prostatic cancer--we studied the penetration of eight carcinogenic chemicals into both the prostate gland and the prostatic secretion of the dog and the rat. The eight chemicals were 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene, N-hydroxyurethane, aflatoxin B1, 3-amino-1,2,4-triazole, 2-acetylaminofluorene, N-Methyl-N'-nitro-N-nitrosoguanidine, and cadmium. In both species all eight substances and/or their metabolites were found to rapidly enter the prostate, and all except cadmium were recovered from prostatic fluid. Thus, although the levels in prostatic fluid did not always reflect levels in the gland, there was little if any barrier to the penetration of these chemicals into the gland. The apparent relative refractoriness of the prostate to systematically administered carcinogenic chemicals cannot be due to failure of such substances to enter the gland.

Animals↗

Congenital hypoplasia of portions of both right and left ventricular myocardial walls. Clinical and necropsy observations in two patients with parchment heart syndrome.

Clinical and morphologic findings are described in two patients with congenital hypoplasia of portions of both right and left ventricular free walls in the absence of associated coronary or valvular heart disease. One, a 61 year old man who had never had clinical evidence of cardiac dysfunction, died suddenly and unexpectedly. The second, a 55 year old woman, died of progressive, eventually intractable congestive heart failure of 29 months' duration. Although at least 22 necropsy patients have previously been reported to have "parchment-like" thinning of portions of the right ventricular free wall, only one patient has previously been described with such thinning of portions of both right and left ventricular free walls. The spectrum of right or right and left ventricular wall congenital hypoplasia is a broad one, with nearly half of described patients dying of congestive heart failure in the 1st year of life and the other half reaching adulthood with or without manifestations of cardiac dysfunction.

Cardiomyopathies↗