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R L Goodman

Publications and source records attributed to R L Goodman.

At least 19 recordsLinked to original sources
PubMed1998

The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor.

Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0-12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12-24 hr, P implant removed; 24-36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3alpha-hydroxy-5alpha-pregnan-20-one, which operates through the type A gamma-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.

Animals↗
PubMed1997

The GnRH system of seasonal breeders: anatomy and plasticity.

Seasonal breeders, such as sheep and hamsters, by virtue of their annual cycles of reproduction, represent valuable models for the study of plasticity in the adult mammalian neuroendocrine brain. A major factor responsible for the occurrence of seasonal reproductive transitions is a striking change in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the inhibitory effects of gonadal steroids. However, the neural circuitry mediating these seasonal changes is still relatively unexplored. In this article, we review recent findings that have begun to define that circuitry and its plasticity in a well-studied seasonal breeder, the ewe. Tract tracing studies and immunocytochemical analyses using Fos and FRAs as markers of activation point to a subset of neuroendocrine GnRH neurons in the MBH as potential mediators of pulsatile GnRH secretion. Because the vast majority of GnRH neurons lack estrogen receptors, seasonal changes in responsiveness to estradiol are most probably conveyed by afferents. Two possible mediators of this influence are dopaminergic cells in the A14/A15 cell groups of the hypothalamus, and estrogen receptor-containing cells in the arcuate nucleus that project to the median eminence. The importance of GnRH afferents in the regulation of season breeding is underscored by observations of seasonal changes in the density of synaptic inputs onto GnRH neurons. Thyroid hormones may participate in this remodeling, because they are important in seasonal reproduction, influence the morphology of other brain systems, and thyroid hormone receptors are expressed within GnRH neurons. Finally, in the hamster, neonatal hypothyroidism affects the number of caudally placed GnRH neurons in the adult brain, suggesting that thyroid hormones may influence development of the GnRH system as well as its reproductive functions in the adult brain.

Animals↗
PubMed1996

Alpha adrenergic neurons inhibit luteinizing hormone pulse amplitude in breeding season ewes.

It is now clear that estradiol acts in the brain to inhibit LH pulse amplitude in breeding season ewes, but the neural mechanisms underlying this action of estradiol have yet to be determined. In this study, we performed four experiments to examine the role of alpha-adrenergic neurons in the control of LH pulse amplitude in the ewe. In the first experiment, implantation of the alpha-adrenergic antagonist phenoxybenzamine into the preoptic area (POA) during the follicular phase of the ovine estrous cycle significantly increased LH pulse amplitude. A similar stimulatory effect of POA implants of this antagonist was observed in estradiol-treated ovariectomized (OVX+E) ewes, but phenoxybenzamine implants had no effect in the absence of estradiol. In contrast, systemic administration of phenoxybenzamine decreased LH pulse amplitude in both OVX and OVX+E ewes. Finally, POA implants of the alpha 1-adrenergic antagonist, prazosin, increased LH pulse amplitude in OVX+E ewes, whereas the alpha 2-adrenergic antagonist, yohimbine, had no effect in these animals. These results suggest that a noradrenergic (or adrenergic) system acts in the POA via alpha 1-adrenergic receptors to inhibit LH pulse amplitude in the ewe. They also raise the possibility that this system may be involved in the negative feedback action of estradiol during the breeding season.

Adrenergic alpha-Antagonists↗
PubMed1996

Dopaminergic A14/A15 neurons are activated during estradiol negative feedback in anestrous, but not breeding season, ewes.

A major factor responsible for seasonal anestrus in sheep is a striking increase in the ability of estradiol (E) to inhibit pulsatile GnRH and LH secretion. Previous studies suggest that dopaminergic neurons in the A14 and A15 groups of the ovine hypothalamus play a key role in conveying the inhibitory effects of E in anestrous ewes. The present study tested the hypothesis that A14/A15 neurons in anestrous ewes are activated in response to E, and that this activation is specifically related to seasonal changes in E negative feedback. Expression of the immediate early gene products, Fos and the Fos-related antigens (FRAs), was used as a marker of neuronal activation. Ovariectomized anestrous ewes received either blank implants (no E) or 0.5-cm long E implants sc and were killed 6 h later (E+6h) or 7 days later (E+7d and no E groups). During the breeding season, two additional groups of ovariectomized ewes were perfused 7 days after insertion of either blank or E implants. During anestrus, E completely suppressed LH pulses in the E+7d group, but had no effect in the E+6h group. In the E+7d anestrous group, there was also a significant increase in the mean percentage of tyrosine hydroxylase (TH)-positive cells that expressed nuclear Fos/FRAs in A14 and A15 areas compared to that in either the no E or E+6h group. By contrast, during the breeding season, E had no effect on LH pulse frequency, and there were relatively few TH-positive cells in A14 and A15 that coexpressed Fos/FRAs in either the no E or E+7d group. No significant steroidal or seasonal differences in Fos/FRA expression were seen in other hypothalamic dopaminergic cell groups (A12 and A13) or in the preoptic area-anterior hypothalamus or suprachiasmatic nucleus. Furthermore, E did not alter the total number of TH-positive neurons in A14/A15 or other cell groups. There were seasonal differences in the number of TH-positive neurons, with a significantly greater number of cells in the A13 and A15 of breeding season animals compared to anestrous ewes. Thus, E increased Fos/FRA expression in A14/A15 neurons only during anestrus at a time when it also inhibited LH pulse frequency. These findings are consistent with the view that activation of dopaminergic cells in A14 and A15 is a critical link in the chain of events leading to seasonal shifts in sensitivity to E negative feedback in the ewe.

Anestrus↗
PubMed1996

Neural systems mediating the negative feedback actions of estradiol and progesterone in the ewe.

The ewe shows a marked seasonal variation in the effects of ovarian steroids on pulsatile GnRH secretion. In the breeding season, progesterone inhibits GnRH pulse frequency, while estradiol suppresses pulse amplitude. In anestrus, both steroids inhibit pulse frequency. The effects of progesterone in both seasons are mediated by endogenous opioid peptides (EOP) that act in the preoptic area (POA) and medial basal hypothalamus (MBH). However, knife cut studies indicate that actions in the MBH are most important. Moreover, blockade of EOP receptors activates (e.g., induces Fos) GnRH perikarya in the MBH, but not those in the POA. Thus interactions between EOP and GnRH neurons within the MBH may be critical for progesterone negative feedback. The neural systems mediating estradiol suppression of GnRH pulse amplitude in the breeding season are largely unknown, although alpha-adrenergic neurons may be involved. The seasonal variation in inhibition of GnRH pulse frequency by estradiol is postulated to be mediated by a group of dopaminergic (DA) neurons that have three important properties: (1) they inhibit GnRH pulse frequency; (2) their activity is stimulated by estradiol; and (3) they are functional in anestrus, but not the breeding season. Recent work examining the effects of lesions of DA neurons and the ability of estradiol to induce Fos in DA cells strongly suggests that DA neurons in the retrochiasmatic area (A15) and POA (A14) have all three characteristics. We thus propose that these DA neurons are responsible for the seasonal variation in the ability of estradiol to inhibit GnRH pulse frequency.

Animals↗
PubMed1995

Is the inhibitory action of estradiol on luteinizing hormone pulse frequency in anestrous ewes mediated by noradrenergic neurons in the preoptic area?

This study tested the hypothesis that estradiol inhibits luteinizing hormone (LH) pulse frequency in anestrous ewes by increasing the activity of an inhibitory noradrenergic (NE) system that acts in the ovine preoptic area (POA). The effects of estradiol on the release of NE and other neurotransmitters in the POA were determined using intracranial microdialysis. Microdialysis probes (5 mm membrane length) were inserted via chronic guide tubes into the POA. Ringer's solution was pumped through the probes at a rate of 2 microliters/min for 8 h, the alpha-adrenergic antagonist phenoxybenzamine (PBZ; 60 micrograms/ml of Ringer's solution) was then administered via the probe from hours 8 to 12, and Ringer's solution alone was given the last 4 h. The outflow from the dialysis probes was collected every 20 min from 2 to 16 h and concentrations of aminergic transmitters and gamma aminobutyric acid determined by high-performance liquid chromatography. Blood samples were collected every 10 min throughout the experiment and the LH pulse patterns determined. Dialysis was done in the same neural area twice in each ewe, without (ovariectomy only) and with estradiol treatment (ovariectomy and a 1.5-cm-long Silastic capsule filled with crystalline estradiol placed subcutaneously for 2 days); the order of dialysis was randomized. As expected, estradiol decreased the LH pulse frequency. This negative feedback action of estradiol was associated with a decrease in mean NE concentrations in dialysate samples and an increase in the intra-animal variability of NE. Estradiol had no effect on any other neurotransmitter measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1995

Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe.

This study was designed to test the hypothesis that endogenous opioid peptides (EOP) mediate the negative feedback action of estradiol on GnRH pulse size in breeding season ewes. If this hypothesis is correct, one would predict that an EOP antagonist should increase GnRH pulse size in estradiol-treated ovariectomized (OVX+E), but not in OVX, ewes. We, therefore, examined the effects of naloxone on GnRH pulse profiles in the hypophyseal portal blood of OVX and OVX+E ewes (n = 6/group). Samples were collected every 10 min for 6 h before, 6 h during, and 4 h after naloxone infusion. Estradiol treatment decreased GnRH pulse size and increased GnRH pulse frequency. Naloxone treatment had no effect on GnRH pulse frequency, but significantly increased GnRH pulse size. However, this stimulatory action of naloxone on GnRH pulse size was evident in both OVX and OVX+E ewes. These results are thus not consistent with the hypothesis that EOP mediate the negative feedback action of estradiol. Interestingly, naloxone not only increased GnRH pulse amplitude, but also prolonged the duration of GnRH release during a pulse. To obtain a more precise characterization of the effects of naloxone on the dynamics of GnRH release, pulse profiles in six OVX ewes were examined in hypophyseal portal blood sampled every minute for 4 h before and 4 h during naloxone infusion. Naloxone again increased both the amplitude and duration of GnRH pulses. The increase in GnRH pulse duration was caused by a prolongation of both the plateau and declining phases of the GnRH pulse. In addition to these effects on GnRH release during a pulse, naloxone increased the amount of GnRH collected between pulses in both experiments. The stimulatory effects of naloxone on GnRH release in OVX ewes indicate that the role of EOP in the control of GnRH is not limited to mediating the feedback actions of steroids. In particular, the dramatic effects of naloxone on GnRH pulse shape and interpulse GnRH levels raise the possibility that EOP play an important role in synchronizing the activity of the GnRH neurons involved in episodic GnRH secretion.

Animals↗
PubMed1994

The importance of mammographic screening relative to the treatment of women with carcinoma of the breast.

BACKGROUND: The use of mammographic screening for the early detection of breast cancer has been shown to reduce the mortality from breast cancer. However, the impact of mammographic screening relative to the local treatment of the breast (ie, breast-conservation treatment vs mastectomy) is not well established. METHODS: An analysis was performed of 206 newly diagnosed and treated breast cancers in 201 women identified in 1989 from a health maintenance organization (US Healthcare, Blue Bell, Pa). The 206 breast cancers were evaluated for eligibility for and actual local treatment of the breast with breast-conserving surgery and definitive breast irradiation as a function of mammographic screening for the early detection of breast cancer. RESULTS: Eligibility for local treatment of the breast with breast-conserving surgery and definitive breast irradiation was significantly increased for the breast cancers detected in women who had undergone mammographic screening compared with the breast cancers detected in women who had not undergone mammographic screening (88% vs 60%, respectively; P < .0001). For the breast cancers that were eligible on chart review for treatment with breast-conserving surgery and definitive breast irradiation, there was no significant difference in the actual local treatment of the breast with breast-conserving surgery and definitive breast irradiation for the eligible breast cancers detected in women who had undergone mammographic screening compared with the eligible breast cancers detected in women who had not undergone mammographic screening (44% vs 37%, respectively; P = .40); however, there was a statistically significant difference for the subgroup of women aged 50 years or more (49% vs 21%, respectively; P = .016). CONCLUSIONS: These results show that breast cancers detected in women who had undergone mammographic screening were more likely to be eligible for breast-conserving surgery and definitive breast irradiation compared with breast cancers detected in women who had not undergone mammographic screening. For women aged 50 years or more, there was a significant increase in the use of breast-conserving surgery and definitive breast irradiation for eligible breast cancers detected in women who had undergone mammographic screening compared with eligible breast cancers detected in women who had not undergone mammographic screening.

Adult↗
PubMed1994

Analysis of a claims database for the identification of patients with carcinoma of the breast.

To develop and optimize algorithms for the identification of newly diagnosed and treated cases of women with carcinoma of the breast, an analysis was performed of cases identified from the claims database of a large health maintenance organization (U.S. Healthcare). An initial algorithm was developed from the patterns of claims which suggested common clinical presentations of carcinoma of the breast, and the positive predictive value was 88% (411/469). To attempt to improve upon the positive predictive value, multiple modifications of the initial algorithm were performed. The best identified modification of the initial algorithm yielded a positive predictive value of 93% (400/432) with a loss of only 3% (11/411) of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of cases from claims data with specific clinical characteristics. The best algorithm identified provides a powerful and accurate tool to perform health care analysis and research on large populations of women with newly diagnosed and treated carcinoma of the breast.

Adult↗
PubMed1994

Effect of anterior hypothalamic deafferentation on the negative feedback of gonadal steroids on luteinizing hormone pulse frequency in the ewe.

Three experiments were performed to determined the effect of anterior hypothalamic deafferentation (AHD) on the inhibitory actions of estradiol and progesterone on luteinizing hormone (LH) pulse frequency in ovariectomized ewes during the anestrous season. The first experiment tested the effects of AHD on LH secretion in the absence of gonadal steroids. AHD was accomplished by a 180 degree knife cut (Halasz knife) placed at the posterior border of the optic chiasm (n = 4). Control ewes received sham cuts or no surgery (n = 6). LH pulses were monitored in blood samples taken every 12 min for 4 hr before and after surgery. AHD reduced LH pulse amplitude (pre 7.4 +/- 2.9 ng/ml; post 1.2 +/- 0.3 ng/ml), but had no effect on LH pulse frequency (pre 3.5 +/- 0.3/4 hr; post 3.3 +/- 0.3/4 hr) in ovariectomized ewes. In the second experiment all ewes were given a Silastic implant containing estradiol (1 cm long) and 2 d later bled at 12 min intervals for 4 hr before and after administration of pimozide (PIM, 0.08 mg/kg), a dopamine antagonist. Estradiol decreased LH pulse frequency in controls (2.8 +/- 0.4 to 1.5 +/- 0.3/4 hr) and this was reversed by PIM (2.5 +/- 0.4/4 hr). In contrast, estradiol did not decrease pulse frequency in AHD ewes (3.3 +/- 0.3 to 2.8 +/- 0.5/4 hr) and PIM did not increase it (2.7 +/- 0.7/4 hr). In the third experiment, all ewes were given Silastic implants containing progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1994

Dopaminergic structures in the ovine hypothalamus mediating estradiol negative feedback in anestrous ewes.

This study examined the role of two dopaminergic (DA) cell groups, the A-14 and A-15 DA groups, in the seasonal shift in the response of LH to estradiol negative feedback in ewes. Radiofrequency lesions were placed bilaterally, in the area of the A-15 or the ventromedial A-14 cell groups of ovariectomized ewes, while control animals underwent sham neurosurgery. The effect of estrogen was tested in anestrus by analyzing LH pulse patterns before and 3 and 10 days after the insertion of estradiol implants. To evaluate the effects of these lesions on DA inhibition of LH secretion, LH pulse patterns were compared before and after an iv injection of the DA antagonist pimozide on day 3 of estradiol treatment. LH pulses were also examined in these ewes during the breeding season before and 3 days after the insertion of estradiol implants. Also, the effect of the DA receptor agonist apomorphine was tested to determine any effect of lesions on DA receptors inhibitory to LH. Lesions in either the A-14 or A-15 area decreased, but did not completely abolish, estradiol inhibition of LH pulse frequency in anestrus. Both types of lesions also blocked the stimulatory effects of pimozide on LH pulse frequency in estradiol-treated ovariectomized anestrous ewes. During the breeding season, estrogen decreased LH pulse amplitude, but not frequency, in all groups. The DA receptor agonist apomorphine decreased LH pulse frequency in all groups. Furthermore, immunohistochemistry for tyrosine hydroxylase revealed catecholaminergic fibers apparently connecting the caudal A-14 and the rostral A-15 areas. These results suggest that both the A-14 and A-15 DA cell groups are involved in the inhibition of LH by estradiol in anestrous, but not breeding season, ewes. Seasonal shifts in the activity of these DA neurons may, thus, play a role in the annual reproductive cycle of the ewe.

Anestrus↗
PubMed1993

A new technique for positioning tangential fields.

PURPOSE: A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. METHODS AND MATERIALS: Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. RESULTS: Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. CONCLUSION: The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge."

Breast Neoplasms↗
PubMed1992

Conservative surgery and radiation therapy in black women with early stage breast cancer. Patterns of failure and analysis of outcome.

Between 1977 and 1986, 75 black and 615 white women with American Joint Committee (AJC) Stages I and II breast cancer were treated with excisional biopsy, axillary dissection, and radiation therapy for breast conservation. Cyclophosphamide, methotrexate, and 5-fluorouracil, with and without prednisone and tamoxifen, was given to 92% of premenopausal, 83% of perimenopausal, and 63% of postmenopausal node-positive women; 20 of 106 (19%) postmenopausal node-positive women received tamoxifen only. The clinical characteristics of the similarly treated patients were compared. The 5-year actuarial local only first failure rate was 5% for black women and 6% for white women (P = 0.53). Regional only failure as the first site of failure was 9% for blacks versus 1% for whites (P = 0.002), with regional recurrence as any component of first failure being 16% for blacks and 4% for whites (P = 0.001). The supraclavicular fossa was identified as the primary site of regional recurrence in black patients with either pathologically positive or negative axillae. Distant metastases as the only site of first failure were significantly greater in the black population with a 20% 5-year actuarial failure rate versus 11% in white patients (P = 0.01). The 5-year actuarial overall survival for the black patients was 82% versus 91% for the white patients (P = 0.01), with no-evidence-of-disease (NED) survival being 64% and 83% (P = 0.0002) and relapse-free survival (RFS) being 61% and 77% (P = 0.01), respectively. Black patients younger than 40 years of age or with pathologically positive axillary nodes had significantly worse NED, RFS, and overall survival compared with similarly staged white patients. Cosmetic results were analyzed at 3 and 5 years after completion of therapy. Although significantly fewer black patients had an excellent-to-good cosmetic result at 3 years compared with white patients, the results were not significantly different at 5 years. These results show that appropriately selected black patients with early stage breast cancer have excellent local control after conservative surgery and radiation therapy and should continue to be offered breast preservation as an alternative to mastectomy. Patterns of failure, however, demonstrated higher regional and distant recurrence rates and lower NED, RFS, and overall survival rates in most subsets of black patients reviewed.

Age Factors↗
PubMed1992

Evaluation of multileaf collimator design for a photon beam.

Various aspects of multileaf collimator (MLC) design are examined relative to clinical requirements. The characteristics studied included: (a) irregular field edge definition or "effective" penumbra, (b) optimum field coverage for the multileaf portion of the field, and (c) leaf velocity. A film dosimetry technique was developed to measure the rapid 2-dimensional change in dose at an edge defined by a multileaf collimator with the segments staggered. The method applies a correction factor which allows for the changing ratio of scattered to primary photons at the field edge so that the energy dependence of the film is corrected. Stepped lead alloy blocks were irradiated with 6 MV photons to obtain films simulating a double-focused multileaf collimator, and the results were compared to films of fields shaped with standard divergent blocks. The effect of the shape of the leaf face (the end of the leaf) on penumbra was also studied. Proper shaping of the leaf ends may eliminate the need to exactly match beam divergence so that the mechanical of the collimator system is simplified. Leaves having several different end shapes and moving horizontally to intercept a vertical beam were compared to the divergent design where a straight face moves along an arc. The measurements showed that the "effective" penumbra (measured as the distance from the 80 to 20% isodose lines) for the multileaf collimator is a function of the angle between the direction of leaf motion and the edge defined by the leaves. In addition, all leaf end shapes showed some increase in penumbra compared to standard divergent blocking and also had increasing penumbra width as they moved over or back from the field center line. A total of 459 treatment fields and six disease sites were examined to determine the percentage of fields potentially shaped by multileaf segments of specified length. This study showed 93% of the fields had lengths of 30 cm or less and 99% had widths of 25 cm or less. A study conducted to determine the required leaf velocity to shape various target volume configurations during complete rotation (at 1 RPM) showed that a leaf speed of at least 1.5 cm/sec at isocenter is needed for dynamic conformal treatment.

Equipment Design↗
PubMed1992

Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation.

An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The 5-year actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = 0-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.

Adult↗
PubMed1992

Immunocytochemical localization of beta endorphin and gonadal steroid regulation of proopiomelanocortin messenger ribonucleic acid in the ewe.

In the ewe, estradiol and progesterone inhibit luteinizing hormone (LH) secretion during the breeding season. Endogenous opioid peptides (EOP) are also inhibitory to LH secretion, and both estrogen and progesterone have been reported to enhance EOP inhibition of LH release. Which EOP are involved in this inhibition is unclear. In this study, we concentrated on beta-endorphin because evidence for its ability to inhibit LH secretion exists in ewes. We first studied the distribution of beta-endorphin-immunoreactive neurons in 4 cycling ewes using immunocytochemistry. Cell bodies were found only within the medial basal hypothalamus (MBH) and were concentrated in arcuate nucleus and mammillary recess of the third ventricle, with a few in the median eminence. Extensive fiber tracts were seen in preoptic area (POA) and median eminence. We next tested the hypothesis that gonadal steroids increase the synthesis of EOP by measuring levels of mRNA for proopiomelanocortin (POMC), the precursor to beta-endorphin. Ovariectomized ewes were treated with no steroids (n = 7) or given subcutaneous Silastic implants containing either estradiol (n = 6) or progesterone (n = 6). After 4 days of treatment, EOP inhibition of LH secretion was measured by determining the LH response to WIN 44,441-3 (WIN), an EOP antagonist. LH pulse frequency and pulse amplitude were determined in blood samples collected at 12-min intervals for 3 h before and after intravenous administration of 12.5 mg WIN. WIN injection increased (p < 0.01) the LH pulse-frequency only in progesterone-treated and pulse amplitude only in estradiol-treated ewes. After blood sampling, the ewes were killed, and POA, MBH, and pituitary gland were removed. Total RNA was extracted from these tissues and dot blotted onto nitrocellulose membranes for hybridization with a DNA probe complementary to the POMC mRNA. The resulting autoradiographs were quantified densitometrically. Levels of POMC mRNA in the MBH were increased (p < 0.01) by both estradiol and progesterone as compared with the no steroid group. There was no detectable POMC mRNA in the POA. These results suggest that estrogen and progesterone enhance EOP inhibition of LH secretion by increasing POMC mRNA levels and thus synthesis of beta-endorphin.

Animals↗
PubMed1991

Results of the 1983 patterns of care process survey for definitive breast irradiation.

This report has documented the U.S.A. national averages for the results of the Process Survey for the 1983 Patterns of Care Study (PCS) for the processes of evaluation, work-up, and treatment for definitive breast irradiation. All women had been treated with definitive irradiation following breast-conserving surgery for early stage breast cancer. The data were collected from 191 patient charts which were randomly selected from five strata of radiotherapy practice to represent the U.S.A. national averages. Clinical and pathological characteristics of the primary tumor and regional lymph node status were similar to reported series as of 1983. Analysis of this Process Survey showed high compliance with the 1983 PCS standards of best current management of breast cancer. However, there was a wide variation in the technical delivery of the radiation fields and radiation doses used. There was good compliance with the use of documentation of the radiation treatments with simulation films, port films, implant films, and field descriptions. No systematic difference was seen amongst the various strata of radiotherapy practice. Although compliance with the majority of the parameters was relatively high, the small but important areas of lack of compliance with the standards of best current management document an incomplete transfer of technology to the radiation oncology community as a whole in 1983. Separate analysis for the outcome of treatment for these cases will be necessary to correlate process with outcome.

Adult↗