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Biomedical subjects

R L Goode

Publications and source records attributed to R L Goode.

At least 19 recordsLinked to original sources
PubMed1992

Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma.

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.

Adenocarcinoma↗
PubMed1992

Tobramycin-impregnated methylmethacrylate for mandible reconstruction.

Reconstruction of the mandible to restore continuity following resection is described in four cases using a tobramycin-impregnated methylmethacrylate implant fabricated at the time of surgery. Methylmethacrylate has excellent biocompatibility and strength and has been used in surgery for over 20 years. The technique uses readily available materials and is similar in concept to reconstruction with a metal plate. Potential advantages are: (1) the presence of a potent antibiotic within the implant that is released over a period of months to minimize postoperative infection and (2) the capability of the material to accurately fit any defect, either when used alone or in combination with a plate or rod. Three of the four patients whom we present are doing well; one implant became exposed following postoperative radiotherapy and had to be removed.

Adolescent↗
PubMed1992

Inhibition of PAIII rat prostatic adenocarcinoma growth and metastasis by a new diarylsulfonylurea antitumor agent, LY181984.

LY181984 is a compound in a series of orally active diarylsulfonylureas with broad spectrum in vivo activity against syngeneic rodent and human xenograft tumor models. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this antitumor agent on the lymphatic and pulmonary metastasis of the tumor in male Lobund Wistar rats. LY181984 was inactive against the proliferation of PAIII cells in vitro. Following subcutaneous implantation of 10(6) PAIII cells in the tail, oral administration of LY181984 (25.0, 50.0, or 100.0 mg./kg./day) for 30 days had no significant effects on body weight gain. LY181984 treatment produced significant (p less than 0.05) dose-dependent inhibition of primary tumor growth in the tail (max. inhibition = 46% from untreated control levels). In these same animals, LY181984 administration produced significant (p less than 0.05) dose-dependent inhibiton of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 79% and 80% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by oral LY181984 treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (p less than 0.05) reduced by LY181984 administration in a dose-dependent manner (maximal reduction = 78% from control values). While the non-toxic doses (less than 100.0 mg./kg./day for 28 days) of LY181984 produced marked decreases in tumor growth and metastasis, administration of the compound had no effect on the survival of PAIII-bearing rats. These data support the contention that LY181984 represents a new class of orally active antitumor and antimetastatic agents with potential efficacy in the treatment of hormone-insensitive prostatic cancer. Further studies are needed to define maximal efficacy of LY181984 and other sulfonylurea agents in urogenital solid tumor animal models.

Adenocarcinoma↗
PubMed1992

Androgens lower prostaglandin E2 levels in neonatal mouse bulbourethral gland in in vitro cultures.

The neonatal mouse bulbourethral gland (BUG) in vitro culture model is useful to study hormone-induced genitourinary (GU) tract growth and differentiation. Like the prostate, the BUG is a derivative of the urogenital sinus and may have relevance to understanding growth processes involved in normal and pathological GU tract development. Previous studies have reported androgen-induced elevation of prostaglandin E2 (PgE2) levels in mouse GU tract in vivo. PgE2 has been proposed to mediate neonatal GU tract masculinization. In our studies, tissues were obtained from neonatal male mice and cultured in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (1:1) supplemented with varying concentrations of androgen. PgE2 levels were measured by RIA in the medium, and tissue specimens were cultured for 7 days or less. During this period, androgens induced proliferation and glandular morphogenesis in the BUGs. In the absence of androgen, tissue and medium PgE2 levels increased over 7 days. Significant (P < 0.05) PgE2 increases over day 1 control values were observed from days 5-7 in tissues and on day 7 in media. During this same time period, androgen supplementation decreased PgE2 levels. Significant (P < 0.05) PgE2 decreases from day 1 cultures were observed from days 3-7 in tissues and on day 7 in media. PgE2 was decreased significantly (P < 0.05) by androgen compared to control values from days 3-7 in tissues and from days 5-7 in media. On day 7 of culture, PgE2 levels were significantly (P < 0.05) inhibited by androgen in a concentration-dependent fashion in tissues and media. Maximal androgen-induced inhibition of PgE2 levels was 96% and 99% in tissues and media, respectively. Although the addition of indomethacin to control cultures markedly inhibited PgE2 production, BUG morphology was unaffected. In addition, the morphology of androgen-stimulated BUGs does not appear to be affected by the addition of exogenous PgE2. We conclude that although androgens induce development and decrease PgE2 levels, PgE2 does not appear to play a major role in in vitro BUG postnatal growth and morphogenesis. The BUG in vitro culture model may mimic growth and morphogenetic processes occurring in the human GU tract. Further understanding of the role of steroid hormones and PG metabolism may yield additional insight into developmental and proliferative GU tract disorders.

Androgens↗
PubMed1991

In vivo assay for conversion of testosterone to dihydrotestosterone by rat prostatic steroid 5 alpha-reductase and comparison of two inhibitors.

An in vivo assay for steroid 5 alpha-reductase in rat ventral prostate has been developed and used to compare the inhibitory activity of N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and 6-methylene-4-pregnene-3,20-dione (LY207320). Immature rats (70-80 g) received test compounds 30 min prior to s.c. injection of [3H]-T. The rats were sacrificed 30 min later and the ventral prostates were analyzed for [3H]-T metabolites. Intraprostatic [3H]-T and [3H]-DHT reached peak levels within 5 min after injection of [3H]-T and declined to about 25% of peak levels after 2 hr. 4-MA was a very potent inhibitor of [3H]-DHT formation with an estimated IC50 of 0.2 mg/kg. LY207320, an inhibitor of 5 alpha-reductase in vitro, was weakly active in vivo and did not achieve greater than 45% inhibition at high doses (greater than 200 mg/kg, s.c.). Tissue uptake of [3H]-T was also inhibited by LY207320, which may contribute to its inhibitory activity on accessory sex organ growth in the rat.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Esophagography and esophagoscopy. Comparison in the examination of patients with head and neck carcinoma.

We carried out a prospective, double-blind study at three institutions, comparing esophagography with esophagoscopy for the detection of simultaneous cancer of the esophagus in patients with other squamous cell cancers of the head and neck. The goal was to determine whether esophagography and esophagoscopy are necessary for the examination of patients before treatment. One hundred eighty-two patients were studied; both examinations were done in 148 patients. Twenty-one patients could not undergo esophagoscopy; esophagography was inadequate in 9 patients; 4 patients could have neither examination. Concordance was noted between the two procedures in 86.5% of patients. Sixty-five percent were normal, and 21.5% were abnormal. One esophageal cancer was found in this series that was diagnosed by both methods. Our data suggest that esophagoscopy and esophagography may be complementary in evaluating squamous cell carcinoma of the head and neck in patients before treatment. Esophagography alone was useful in patients in whom esophagoscopy could not be performed.

Adult↗
PubMed1990

Endocrine effects of a new histamine H2-receptor antagonist, nizatidine (LY139037), in the male rat.

A new orally active histamine H2-receptor antagonist, nizatidine (LY139037), was evaluated in male rats for effects on mechanisms regulating accessory sex organ growth and function. Cimetidine antagonized androgen binding to cytosolic receptors in vitro while nizatidine had no effect. Nizatidine and cimetidine were administered at the ED50, 5 X ED50, or 10 X ED50 doses for inhibition of gastric acid secretion previously determined using in vivo dog and rat models. The relative potencies of both agents to antagonize histamine H2-receptor-mediated gastric acid secretory responses have been confirmed in human clinical trials. Neither nizatidine nor cimetidine antagonized the in vivo uptake or nuclear translocation of radiolabeled androgen into the hypothalamic-preoptic-amygdala, pituitary, or ventral prostate. Nizatidine, given at doses equal to and 10 X the ED50 gastric acid secretion inhibitory values, and cimetidine (10 X ED50 value) had no effect on the response of male accessory sex organs to a submaximally stimulating dose of androgen in castrated rats. High doses of dietary nizatidine (greater than 500 mg/kg-day) administered for 6 months did not alter intact rat male accessory sex organ weights or circulating androgen levels relative to untreated controls. Acute administration of either nizatidine or cimetidine produced transient elevations in plasma prolactin (PRL) levels. Cimetidine was more potent and consistent than nizatidine in producing these increases in circulating PRL. The data described herein support the contention that unlike cimetidine, nizatidine is not a pharmacological antagonist of androgen action and has less of a stimulatory effect upon plasma prolactin. Taken together, these studies indicate that in the male rat, nizatidine exhibits a large therapeutic index between its gastric antisecretory activity and potential endocrinological effects.

Androgens↗
PubMed1989

Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758).

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY156758; [6-hydroxy-2-(4-hydroxyphenyl)benzo(b) thien-3-yl] [4-(2-1-piperidinyl) ethoxyl] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen-maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration-dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen-induced hyperplastic response of the SVM, whereas no interference with androgen-induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen-sensitive SVE as well as the androgen/estrogen-sensitive SVM. Keoxifene-induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.

Androgen Antagonists↗
PubMed1989

Comments on "Acoustic Transfer Characteristics in Human Middle Ears Studied by a SQUID Magnetometer Method" [J. Acoust. Soc. Am. 82, 1646-1654 (1987)].

The study by Brenkman et al. [J. Acoust. Soc. Am. 82, 1646-1654 (1987)] of malleus umbo and anterior crus of stapes displacement in 14 human temporal bones shows a mean -7.3-dB/oct slope above 1.0 kHz for stapes displacement in response to a 80-dB SPL input at the eardrum. The slope they obtained for midfrequency (1.0-4.0 kHz) stapes displacement is significantly flatter than what was found previously [Gyo et al., Acta Otolaryngol. 103, 87-95 (1987); Gundersen, Prostheses in the Ossicular Chain (University Park, Baltimore, MD, 1971); Kringlebotn and Gundersen, J. Acoust. Soc. Am. 77, 159-164 (1985); Vlaming and Feenstra, Clin. Otolaryngol. 11, 353-363 (1986a)]; in these studies, stapes displacement rolled off at -12.0 to -14.9 dB/oct above 1.0 kHz. It appears that their mean midfrequency stapes displacement slope has been flattened by some unusual results in a small number of ears. Possible reasons for these results are discussed.

Acoustic Stimulation↗
PubMed1979

Squamous cell carcinoma of the soft palate.

We performed a retrospective study of 106 patients with carcinoma of the soft palate who were treated at two university hospitals. Computer analysis using a new interactive data base program called MING was made to determine Berkson-Gage survival and Gehan tests of statistical significance. Statistically significant associations with an increased survival included the following: smaller lesions, a clinically negative neck examination. well- and moderately well-differentiated histopathologic features, radiation therapy dose of less than or equal to 6,300 rads, absence of a simultaneous primary, and surgical salvage. No statistically significant differences were seen with age, sex, stage, or the number of days during which patients were treated with radiation therapy. There appears to be a need for a prospective, multi-institutional, randomized therapy study to solidify treatment policy. Consideration should be given to combine surgery-radiation vs radiation therapy alone.

Adult↗
PubMed1979

Radioactive suture in the treatment of head an neck cancer.

I-125 seeds in Vicryl suture have been used as a radioactive suture in 24 cases of advanced malignancy of the head and neck. Twelve cases had metastatic carcinoma attached to the internal or common carotid artery. The goal was to excise surgically as much tumor as possible, then implant any residual tumor with this radioactive suture which remains as a permanent implant (half-life of 60 days). This preliminary study shows that use of I-125 impregnated Vicryl suture in this manner appears to produce improved long-term palliation and may increase local cure rates.

Follow-Up Studies↗
PubMed1979

Eye protection in the paralyzed face.

All patients with a VIIth nerve paralysis with any limitation of closure of the eye should have in the office or out-patient clinic setting: 1. paper tarsorrhaphy of the upper or possibly lower lid; 2. artificial tears and/or ointment; and 3. glasses to protect the cornea from air currents. Kinetic and static surgical procedures are discussed. The kinetic procedures include facial nerve repair and grafting, VIIth-XIIth nerve anastamosis, muscle nerve block transplantation, transposition of nonparalyzed muscle and cross over. The principals of VIIth nerve repair and grafting and presented in the intracranial, internal auditory canal, labyrinthine, tympanomastoid and extratemporal sites. The static procedures include resection of redundant skin, fascia lata strip suspension, weakening of contralateral non-paralyzed musculature, and adjunctive procedures such as resection of ptotic melolabial fold, plication of parotid-masseteric fascia, dermal graft suspension, blepharoplasty, brow lift, canthoplasty, horizontal shortening of lower lid, fascial suspension of lower lip, McLaughlin tarsorrhaphy, and palpebral spring. Patient counseling is emphasized.

Blepharoptosis↗
PubMed1979

Effect of prophylactic antibiotics in radical head and neck surgery.

One hundred major head and neck operations performed on 77 patients were evaluated regarding the effectiveness of an aminoglycoside and cephalosporin antibiotic combination given prophylactically to prevent postoperative infection. The postoperative infection incidence was 6%, significantly lower than that reported in similar series where no antibiotics were used. The addition of the aminoglycoside did not appear to provide any additional protection compared with the use of cephalosporin alone.

Aminoglycosides↗
PubMed1978

The brow-lift operation in a man.

Various techniques of brow elevation, including their advantages and limitations, are discussed. Since there are no lines immediately above the eyebrow, the direct brow-lift operation results in a scar that cannot be camouflaged with makeup by a man. The approach via temporofrontal scalp produces limited and temporary brow elevation, and the scars may eventually become visible with hairline recession in men. A technique of the brow-lift operation in a man via the natural, horizontal forehead crease above the eyebrow has been found to be very effective. The complications have been minimal, the resulting scars have been unnoticeable.

Adult↗