Search PubMed⌕ Search

Biomedical subjects

R L Goodman

Publications and source records attributed to R L Goodman.

At least 73 records · Page 4Linked to original sources
PubMed1989

Functional organization of the catecholaminergic neural systems inhibiting luteinizing hormone secretion in anestrous ewes.

Both dopaminergic (DA) and noradrenergic (NA) neural systems contribute to the suppression of luteinizing hormone (LH) pulse frequency in intact anestrous ewes. In this study, we explored the functional relationship between these two inhibitory neural systems by determining if DA or NA antagonists could block the inhibitory actions of DA and NA agonists in ovariectomized anestrous ewes. If these systems are linked 'in series' with one (e.g. NA) exerting its effects by stimulating the other (e.g. DA), then one antagonist (e.g. DA) should block the inhibitory actions of both agonists. If they are organized 'in parallel', then each antagonist should only block the actions of the homologous agonist. In the first experiment, the DA agonist, apomorphine, suppressed LH pulse frequency and this action was blocked by the DA antagonist, pimozide, but not by the NA antagonist, phenoxybenzamine. Similarly, in experiment 2, the ability of the NA agonist, clonidine, to suppress LH pulse frequency was blocked by the NA antagonist. However, the DA antagonist also partially blocked the inhibitory effects of this NA agonist. We next repeated experiment 2 using a lower dose of the NA agonist. The lower dose of clonidine again inhibited LH pulse frequency and this effect was completely blocked by the DA antagonist. These results suggest that the NA agonist suppressed LH pulse frequency by stimulating a set of inhibitory DA neurons and are thus compatible with the hypothesis that the catecholaminergic neurons controlling LH secretion in anestrous ewes are organized 'in series' with the NA neurons stimulating a DA neural system that directly suppresses GnRH release.

Animals↗
PubMed1988

Definitive irradiation for early stage breast cancer: The University of Pennsylvania experience.

From 1977 to 1984, 552 breast cancers in 548 women were treated with definitive irradiation following breast-conserving surgery at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. All patients had invasive carcinoma and were AJC clinical Stage I or II. Pathologic axillary lymph node staging was known for all cases. The 5-year actuarial survival for the entire group was 93% with an NED survival of 81%. The 5-year survival for clinical Stage I and II patients was 97 and 87%, respectively, with a corresponding NED survival of 87 and 73%, respectively. For pathologic Stage I and II patients, the corresponding survival figures were 97 and 89%, respectively, with NED survival rates of 86 and 76%, respectively. The overall 5-year actuarial local failure rate was 6%, and the rate of local only as the first failure was 3%. The overall local-regional failure rate was 13% with a local-regional only first failure rate of 8%. These results compare favorably with other reported series and contribute a substantial number of patients to the increasing experience with definitive irradiation following breast-conserving procedures. The relatively low incidence of breast recurrence may be related to the emphasis on integrating the surgical, pathologic, and radiotherapeutic aspects of treatments, as well as the emergence of a re-excision policy for patients at high risk to have residual tumor.

Adult↗
PubMed1988

Effects of an opioid antagonist on pulsatile luteinizing hormone secretion in the ewe vary with changes in steroid negative feedback.

In ewes during the breeding season, estradiol (E) and progesterone (P) synergistically regulate pulsatile luteinizing hormone (LH) secretion. E primarily inhibits LH pulse amplitude and P inhibits LH pulse frequency. To determine if endogenous opioid peptides (EOP) mediate these negative feedback effects, we administered the long-acting opioid antagonist WIN 44,441-3 (WIN) to intact ewes during the luteal and follicular phases of the estrous cycle and to ovariectomized ewes treated with no steroids, E, P, or E plus P. Steroid levels were maintained at levels seen during the estrous cycle by Silastic implants placed shortly after surgery. WIN increased LH pulse frequency, but not amplitude, in luteal phase ewes. In contrast, during the follicular phase, LH pulse amplitude was increased by WIN and pulse frequency was unchanged. Neither LH pulse frequency nor pulse amplitude was affected by WIN in long-term ovariectomized ewes untreated with steroids. In contrast, WIN slightly increased LH pulse frequency in short-term ovariectomized ewes. WIN also increased LH pulse frequency in ovariectomized ewes treated with P or E plus P. WIN did not affect pulse frequency but did increase LH pulse amplitude in E-treated ewes. These results support the hypothesis that EOP participate in the negative feedback effects of E and P on pulsatile LH secretion during the breeding season and that the inhibitory effects of EOP may persist for some time after ovariectomy.

Animals↗
PubMed1988

Identification of a subgroup of patients with breast cancer and histologically positive axillary nodes receiving adjuvant chemotherapy who may benefit from postoperative radiotherapy.

Risk factors for isolated local-regional (LR) recurrence following mastectomy for breast cancer were analyzed in a review of 627 women entered into Eastern Cooperative Oncology Group (ECOG) adjuvant chemotherapy trials between 1978 and 1982. Premenopausal patients were randomized to cyclophosphamide, methotrexate, and fluorouracil (5-FU) (CMF), cyclophosphamide, methotrexate, 5-FU, and prednisone (CMFP), or cyclophosphamide, methotrexate, 5-FU, prednisone, and tamoxifen (CMFPT). Postmenopausal patients were randomized to observation, CMFP, or CMFPT. Median follow-up time was 4.5 years. At 3 years, 225 patients relapsed and in 70 (31% of failures, 11% of all patients) the initial site was LR without distant metastases. In a multivariate analysis, the risk of an isolated LR recurrence significantly correlated with the number of positive axillary nodes, the primary tumor size, the presence of tumor necrosis, and the number of axillary nodes examined. Factors that significantly discriminated between an isolated LR recurrence and distant metastasis were the number of positive nodes and primary tumor size. Patients with four to seven positive nodes or tumor size greater than or equal to 5 cm had a chance of developing an isolated LR recurrence almost equal to the risk of distant metastases. These findings suggest a potential for improved survival in this subset of patients with the addition of postmastectomy radiation to chemotherapy, and continue to emphasize the presence of a group of patients at high risk for isolated LR recurrence despite adjuvant chemotherapy.

Adult↗
PubMed1988

Integration of full-dose adjuvant chemotherapy with definitive radiotherapy for primary breast cancer: four-year update.

Controversy exists over the effect of definitive radiotherapy on the ability to administer full doses of adjuvant chemotherapy in primary breast cancer. Ninety-six consecutive women with clinical stage I and II breast cancer were treated with radiotherapy plus chemotherapy. Three combinations of drugs were used: cyclophosphamide and 5-fluorouracil (CF); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP). Chemotherapy consisted of two cycles of CF (cyclophosphamide at a dosage of 100 mg/m2 orally on days 1-14+5-fluorouracil at 600 mg/m2 iv on days 1 and 8) during concurrent radiotherapy, followed by six cycles of CMFP (same CF dosages+methotrexate at 40 mg/m2 iv on days 1 and 8+prednisone at 40 mg/m2 orally on days 1-14). The study included 63 premenopausal and 33 postmenopausal patients; 72 had 1-3 positive nodes, had greater than or equal to 4 positive nodes, and 9 had negative nodes and negative estrogen receptors. The mean CF doses delivered during concurrent radiotherapy were 95% of the optimal doses, and the mean CMF doses administered during the six cycles after radiotherapy were 89%. The CMF was delivered at level I (greater than or equal to 85% of optimal doses) to 73% of the patients. With a median follow-up of 36 months, 16 relapses have been observed. Two of these patients had treatment failure only in the breast or axilla and are disease free after mastectomy. Of the 72 patients with 1-3 positive nodes, 10 relapsed in distant sites, while 4 of 15 patients with greater than or equal to 4 positive nodes have had distant failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Treatment of patients with "minimal" stage IIIA Hodgkin's disease.

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Determination of depth for electron breast boosts.

A technique has been developed to determine the depth for the electron boost treatments for patients undergoing definitive irradiation for early stage breast cancer. A series of parallel link chains are placed on the breast over the clinically determined site of the boost. Using fluoroscopy, the physician confirms that the chains overlie the tumor bed which is outlined by radiopaque surgical clips placed at the time of the breast biopsy. A pair of orthogonal films and/or rotational stereo shift films are obtained with a standard simulator unit. Using the image of the chains to define the surface contour, the depth of each surgical clip is measured directly from the orthogonal films or calculated from the rotational stereo shift films. With this information, the physician can determine the appropriate electron energy to cover the target volume. This method was tested by comparison with depths measured from CT scan, and close agreement was demonstrated.

Breast Neoplasms↗
PubMed1987

Changes in episodic luteinizing hormone secretion leading to puberty in the lamb.

In this study, we monitored episodic luteinizing hormone (LH) secretion throughout development in eight April-born ewe lambs to determine if a change in LH pulse patterns preceded first ovulation at puberty. LH pulses were measured in samples collected every 12 min for 6 h once in July, twice a month from 22 August to 2 October, and then weekly until puberty. Progesterone concentrations, measured in samples taken 3/wk, were used as an index of first ovulation, which occurred at 29.3 +/- 0.7 wk of age. LH pulse frequencies throughout most of this period ranged from 0 to 2 pulses/6 h, with no change over time. However, during the week prior to the first progesterone rise, there was a significant increase in pulse frequency to a level seen during the follicular phase in post-pubertal lambs. This increase in pulse frequency was evident in 7 of 8 lambs; pulses were not analyzed in the last lamb because samples were taken during the LH surge. In contrast, LH pulse amplitude did not increase prior to puberty. In fact, pulse amplitude declined linearly during the 3 wk before first ovulation and then increased during the follicular phase in post-pubertal animals. These results support the hypothesis that an increase in the frequency of episodic LH secretion is a key event leading to the onset of ovarian cycles in the lamb. Whether an increase in pulse amplitude is also necessary remains unclear. If so, it must occur just before the LH surge, since it was not detected in any samples taken before puberty in this study.

Animals↗
PubMed1987

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy.

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Canine tracheal injury by neodymium-YAG laser irradiation.

The relationship between endoscopic graded neodymiumyittrium aluminum garnet (Nd-YAG) laser intensity and the magnitude of effects on the tracheal wall was studied in two mongrel dogs. The dogs were anesthetized and graded Nd-YAG laser burns of 50, 100, and 200 Joules (J) were produced on the distal tracheal walls with a laser fiber inserted through a bronchoscope. One dog was killed immediately after injury and the other 24 hours later. At the time of killing, the trachea was excised and prepared for light microscopic (LM) and scanning electron microscopic (SEM) examination. We found that the injury produced by the 50 J intensity beam was confined to the mucosa and submucosa, with no destruction of the tracheal cartilage; by contrast, transmural penetration of the trachea was observed at intensities of 100 and 200 J. These results indicate that a strong correlation exists between laser intensity and the magnitude of the resulting tracheal injury. We suggest that the intensity of a Nd-YAG laser, endoscopically directed perpendicular to the tracheal wall, should not exceed 50 J in order to minimize the risk of perforating the tracheal wall.

Animals↗
PubMed1986

Results of re-excisional biopsy of the primary tumor in preparation for definitive irradiation of patients with early stage breast cancer.

From December 1977 through November 1984, 251 patients underwent a re-excisional biopsy procedure in preparation for definitive radiation therapy because of uncertainty in the extent of the initial biopsy procedure. Analysis of the cases was limited to patients with AJC Clinical Stages I or II breast cancer and whose initial biopsy procedure demonstrated invasive carcinoma. Sixty-three percent (158/251) of the 251 re-excisions were positive for residual tumor, and 37% (93/251) did not show any residual tumor. Of the positive re-excisions, 85% (134/158) revealed an invasive component of tumor; 15% (24/158) revealed only non-invasive disease. For patients whose initial biopsy was described as incisional only, 97% (64/66) had residual tumor; 51% (94/185) of patients with an initial excisional biopsy had residual tumor. Because of the extremely high rate of positive re-excision in patients with an initial incisional biopsy, these cases were excluded from the remainder of the analysis. When the pathologic margin of the initial biopsy specimen was described as positive, 60% (15/25) had residual tumor on re-excision and 49% (79/160) when the pathology margin was unknown. Of the clinical T1 lesions, 45% (57/126) had positive re-excision, and of the clinical T2 lesions, 63% (37/59) were positive. When a post-biopsy mammogram (i.e. following initial biopsy procedure but before re-excision) showed residual microcalcifications, 86% (12/14) had residual tumor found in the re-excision specimen. Based on these findings, indications for re-excisional biopsy of the primary tumor are: initial incisional biopsy, positive or unknown pathologic margin on an initial excisional biopsy specimen, or residual microcalcifications on post-biopsy mammogram. When inked margins were negative on pathological examination of an initial excisional biopsy specimen, re-excision of the primary tumor bed was not recommended. These results suggest that a re-excisional biopsy procedure may be an important component of the overall treatment approach to assure removal of all tumor, and should continue to be used when indicated prior to definitive irradiation of the breast for early stage breast cancer.

Biopsy↗
PubMed1986

A practical method of delivering the posterior axillary boost for the treatment of patients with breast cancer.

A practical technique for delivery of the posterior axillary boost is reported. A standard breast board is modified to allow for treatment of all fields in a single clinical set-up, and the posterior boost is delivered through a cut-out in the breast board. This technique is simple, is efficient, and eliminates problems of patient positioning and daily reproducibility.

Axilla↗
PubMed1986

Separate neural systems mediate the steroid-dependent and steroid-independent suppression of tonic luteinizing hormone secretion in the anestrous ewe.

In the ewe, two types of seasonal fluctuations in secretion of tonic luteinizing hormone (LH) have been described: a steroid-dependent change whereby estradiol gains the capacity to suppress LH pulse frequency in anestrus, and a steroid-independent decrease in pulse frequency in ovariectomized animals during anestrus. We have proposed that the former reflects activation, in anestrus, of estradiol-sensitive catecholaminergic neurons that inhibit gonadotropin-releasing hormone (GnRH). Three results reported here support this hypothesis: dopaminergic (pimozide) and alpha-adrenergic (phenoxybenzamine) antagonists increased LH in intact anestrous ewes without altering pituitary responses to GnRH; other dopaminergic (fluphenazine) and alpha-adrenergic (dibenamine) antagonists also increased LH in anestrus; agonists for dopaminergic (apomorphine) and alpha-adrenergic (clonidine) receptors suppressed LH secretion in both seasons, suggesting that the appropriate receptors are present in breeding-season ewes. In contrast, catecholamines do not appear to mediate the steroid-independent suppression of pulse frequency; neither pimozide nor phenoxybenzamine increased LH pulse frequency in ovariectomized ewes during anestrus. When antagonists for 6 other neurotransmitter receptors (muscarinic and nicotinic cholinergic, GABAnergic, serotonergic, opioid, and beta-adrenergic) were tested in anestrus, only cyproheptadine, the serotonergic antagonist, increased pulse frequency in ovariectomized ewes. Cyproheptadine had no effect on frequency during the breeding season. On the basis of these results, we propose that the steroid-dependent and -independent actions of anestrous photoperiod occur via catecholaminergic and serotonergic neurons, respectively.

Anestrus↗
PubMed1986

Delayed puberty in lambs chronically treated with oestradiol.

Intact female lambs were chronically treated with low levels of oestradiol by Silastic implant from 20 weeks of age. Reproductive cycles were initiated in only 33% of these lambs (3 of 9) compared to 80% of untreated females (11 of 14) by 45 weeks when the study was terminated. Moreover, in the 3 oestradiol-treated lambs which began cycles, the age at first oestrus was delayed 3 weeks (37 +/- 1 weeks of age vs 34 +/- 1 weeks of age for untreated controls). Retardation of the pubertal process was not due to absence of the pubertal rise in circulating LH. At about 32 weeks of age, chronic oestradiol treatment was no longer able to suppress tonic LH secretion and serum LH increased in intact, oestradiol-treated lambs. These results indicate that a maturational decrease in responsiveness to oestradiol inhibition of tonic LH secretion can be demonstrated in the intact female, as in the ovariectomized female. However, chronic oestradiol suppression of prepubertal LH secretion also delays onset of reproductive cycles. This finding raises the possibility that low tonic LH secretion, presumably in the form of slow pulses, is necessary for development or maintenance of ovarian function before puberty. In the absence of LH during the last part of sexual maturation, the ability of the ovary to respond to the high frequency LH pulses during the pubertal gonadotrophin rise may be delayed.

Animals↗
PubMed1985

A practical technique for the localization of the tumor volume in definitive irradiation of the breast.

In patients being treated with breast conserving surgery and primary irradiation for breast cancer, adequate treatment of the primary tumor bed is associated with improved local control rates. This report presents a practical method for defining the tumor bed. At the time of excisional biopsy, radiopaque surgical clips are placed at the margins of the tumor bed. These clips are used to localize the tumor volume for the simulation of the breast tangents and for planning the boost field. This technique will minimize the potential for a geographic miss during definitive irradiation for breast cancer.

Breast Neoplasms↗