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Biomedical subjects

R L Goodman

Publications and source records attributed to R L Goodman.

At least 91 records · Page 5Linked to original sources
PubMed1985

Excisional biopsy, axillary node dissection and definitive radiotherapy for Stages I and II breast cancer.

From 1977 to 1982, 189 patients with clinical Stage I and II breast cancer underwent excisional biopsy and axillary node dissection followed by definitive radiotherapy at the University of Pennsylvania. One hundred and nine patients had T1 lesions and 80 had T2 lesions. Histologically negative nodes were found in 136 patients (72%) and histologically positive nodes in 53 patients. Seventy-four percent of those with positive nodes had 1-3 positive nodes. Median follow-up from the completion of radiotherapy was 26 months. The cumulative probability of local-regional failure only at 48 months is 5%. The incidence of local recurrence was unrelated to T stage or nodal status. Regional failure was unrelated to T stage, but appeared more frequently in node positive patients. Three patients have died, two of disease and one of an unrelated cause. Ten patients are alive with disease. The four year actuarial disease free survival is 82% for pathologic Stage I (T1, pathologic N0) and 70% for pathologic Stage II (T1 pathologic N1, T2 pathologic N0 or N1). Cosmesis was judged to be good to excellent in 90% and fair in 9%. Complications included arm edema (7%), symptomatic pneumonitis (1%), rib fractures (1%), pericarditis (1%) and pleural effusion (1%). No patient experienced a brachial plexus injury. Primary radiotherapy for Stages I and II breast cancer produces a local-regional control rate of 95% and good to excellent cosmesis in 90% of the patients. While these results are preliminary, they compare favorably with other reported series.

Adult↗
PubMed1985

Modulation of pulsatile luteinizing hormone secretion by ovarian steroids in the rat.

In this study, we have examined the effects of estradiol and progesterone on pulsatile luteinizing hormone (LH) secretion in the rat. In the first experiment, regularly cycling rats were ovariectomized on metestrus and a Silastic implant containing estradiol in oil (7.5, 15 or 30 micrograms/ml) or crystalline progesterone (0.7 or 3 cm long) was placed s.c. immediately after surgery. Rats were cannulated 3 days later and frequent blood samples collected (every 10 min for 4 h) the next day. Estradiol treatment alone produced a dose-dependent suppression in mean LH by decreasing LH pulse amplitude without altering interpulse interval. Progesterone treatment alone had no effect, but when the low progesterone dose was combined with a subthreshold estradiol treatment, the combination decreased LH pulse amplitude, but had no effect on the interval between pulses. The combination of high progesterone and low estradiol completely suppressed LH secretion. In the second experiment, rats were bled 7 days postovariectomy to increase the postcastration LH rise and examine higher steroid treatments. Three progesterone treatments (0.7, 1.5 and 3 cm long implants) were combined with the low estradiol treatment; the high estradiol dose (30 micrograms/ml) was also tested. All treatments decreased LH pulse amplitude without altering interpulse interval, although the highest progesterone treatment again completely suppressed LH in most rats so that no statistical analysis could be performed. No firm conclusions can be drawn about the effects of the high steroid treatments that completely suppressed LH; such an effect could reflect either inhibition of pulse frequency or amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Evidence that the anterior hypothalamus contributes to the control of tonic secretion of follicle-stimulating hormone in the female rat.

A horizontal knife cut was placed between the dorsal anterior hypothalamic area (DAHA) and the medial basal hypothalamus to examine the role of the DAHA in the selective secretion of follicle-stimulating hormone (FSH) following unilateral ovariectomy (ULO) and bilateral ovariectomy of the rat. Complete cuts markedly attenuated the increase in FSH observed 8 h after ULO, whereas incomplete or sham cuts did not. Concentration of luteinizing hormone (LH) did not increase in any group. These cuts also blocked the prolongation of estrous FSH secretion observed in long-term hemicastrated rats, since FSH levels on estrus were significantly lower in rats with complete cuts than in those rats given sham or incomplete cuts. In contrast, neural surgery had no effect on proestrous FSH concentrations. Finally, when FSH levels were monitored 2 days after bilateral ovariectomy, the postcastration rise in FSH was not altered by any neurosurgical procedures. These results support the hypothesis that a neural system originating in, or passing through, the DAHA is necessary for the selective increase in FSH following ULO.

Animals↗
PubMed1985

Potential application of perfluorochemicals in cancer therapy.

PFC emulsions, because of their excellent oxygen-transporting properties and possibly other properties as well, have broad and promising potential in cancer therapy. Although this potential is readily apparent to both laboratory and clinical investigators who are concerned with tumor hypoxia, it should be equally apparent that the formulations that are currently available are wholly inappropriate for such an application. The sublethal toxicities of these emulsions may appear to indicate a poor prognosis for this approach, but they may be a blessing in disguise. All known approaches to tumor hypoxia are limited by our inability to administer enough of the agents to be effective. In many cases, the limiting factor was not uncovered until the approach had been introduced into clinical trials. Had we relied on such parameters as lethality in the case of PFC emulsions, the same mistake might have been made here. Instead, the death of a single rat has caused us to focus our attention on what would surely have produced major problems in the initial clinical trials. Recognition of the sublethal toxic effects of PFC emulsions at this early stage should allow us to optimize our formulations at the preclinical stage, thereby increasing the likelihood that PFC emulsions will someday live up to their full potential.

Animals↗
PubMed1985

Intraductal carcinoma of the breast: results of treatment with excisional biopsy and irradiation.

Between 1976 and 1983, 40 women with intraductal carcinoma of the breast without invasion underwent excisional biopsy and irradiation as an alternative to mastectomy. The median age was 53 years (range, 28 to 77 years) and the median follow-up time since initiation of radiation was 44 months (range, 14 to 97 months). Twenty-seven patients presented with a palpable mass; in 13 patients the tumor was detected only by mammography. A limited axillary dissection was performed in 13 patients, and all lymph nodes removed were negative. Treatment was administered to the breast and adjacent chest wall to a dose of 4,600 to 5,000 rad, with 26 patients also receiving a boost dose of 1,000 to 2,000 rad to the site of the primary. Four patients have developed a recurrence in the treated breast, at 17, 19, 35, and 63 months after the beginning of radiation therapy. The 5-year actuarial rate of local recurrence is 10%. Three of the recurrences were in those four patients who presented with a nipple discharge and a central primary. In two cases, the recurrence consisted of only intraductal carcinoma; in the other two, both intraductal and invasive cancer were found. All four patients with recurrence underwent mastectomy and are well without evidence of distant metastases at 1, 12, 15, and 15 months since mastectomy. Cosmetic results were excellent. No patient has developed distant metastases. Since the number of patients treated is small and the period of follow-up is short, one must be cautious in the interpretation of these results. Nonetheless, the treatment of intraductal carcinoma of the breast by excision and irradiation appears to give acceptable local control and excellent survival when suitable precautions of patient selection and evaluation are taken.

Adult↗
PubMed1985

Neurotransmitters involved in mediating the steroid-dependent suppression of pulsatile luteinizing hormone secretion in anestrous ewes: effects of receptor antagonists.

Seasonal anestrus in the ewe results from two effects of inhibitory photoperiods: a steroid-dependent effect by which estradiol gains the capacity to suppress LH pulse frequency and a steroid-independent effect that decreases LH pulse frequency in ovariectomized ewes. We have previously proposed that these effects of anestrous photoperiods result from the activation of inhibitory neuronal mechanisms at this time of year. In the present study, we used specific receptor antagonists to test this hypothesis and identify the neurotransmitters involved. Initially, eight receptor antagonists were screened for their ability to increase pulsatile LH secretion in ovary-intact anestrous ewes. Of these, only pimozide, a dopaminergic antagonist, and phenoxybenzamine, an alpha-adrenergic antagonist, increased LH pulse frequency. In contrast, neither pimozide nor phenoxybenzamine increased pulsatile LH secretion in midluteal phase ewes during the breeding season. These drugs did, however, produce other biological responses at this time of year; pimozide increased serum PRL levels, and phenoxybenzamine decreased arterial blood pressure. Pimozide also increased pulsatile LH secretion in ovariectomized ewes treated with estradiol in anestrus to suppress LH pulse frequency, but phenoxybenzamine was ineffective in these animals. Neither drug increased LH in ovariectomized ewes not treated with estradiol. The seasonal variation in the ability of pimozide and phenoxybenzamine to increase LH secretion in ovary-intact ewes supports the hypothesis that inhibitory neural mechanisms suppressing GnRH are activated during anestrus and suggests that dopaminergic and/or alpha-adrenergic neurons are involved. In addition, the steroid-dependent effect of anestrous photoperiods may be exerted through the ability of estradiol to stimulate inhibitory dopaminergic neurons which are only active at this time of year.

Anestrus↗
PubMed1985

Can the transition into anoestrus in the ewe be accounted for solely by insufficient tonic LH secretion?

It has been proposed that a seasonal increase in oestradiol negative feedback elicits anoestrus by preventing a key step in the preovulatory sequence of endocrine events, namely a sustained increase in tonic LH secretion. In the present study we compared the patterns of serum LH, FSH, oestradiol and progesterone after regression of the last corpus luteum of the breeding season, with their respective patterns during an ovulatory cycle in the late breeding season (samples obtained every 4 h from eight ewes). After regression of the last corpus luteum of the breeding season, serum LH and oestradiol showed distinct deviations from their respective late breeding season patterns. The rise in tonic LH secretion was curtailed. Further, there were no marked increases in oestradiol, despite a distinct, although brief, tonic LH rise; thus there were no gonadotrophin surges. If the hypothesis that the transition into anoestrus is caused solely by insufficient tonic LH secretion were correct, the brief increase in LH should have induced a transient rise in oestradiol. Since this was not the case, these results suggest that a decreased ovarian response to LH may also contribute to the termination of oestrous cyclicity at the transition to anoestrus.

Anestrus↗
PubMed1985

Conservative surgery and irradiation in the treatment of early breast cancer.

The treatment of early (stage I and II) breast cancer over the past 10 years has shown a trend towards conservative use of surgery. The role of mastectomy in achieving local-regional control has been challenged by procedures that preserve the breast, in which tumor excision and axillary node dissection are followed by breast irradiation. Data from retrospective studies as well as prospective randomized trials have shown that in selected patients conservative surgery and radiation achieve results comparable to those of mastectomy in terms of 10-year survival and local-regional recurrence. Studies have shown that conservative surgery, radiation, and adjuvant chemotherapy can be combined effectively in patients at high risk for systemic disease. Although the optimal treatment of early breast cancer remains controversial, the non-mastectomy approach represents major progress.

Actuarial Analysis↗
PubMed1984

Current status of high linear energy transfer irradiation.

Based on laboratory investigations, high linear energy transfer (LET) particle irradiation is capable of more efficient cell kill than that associated with conventional or low LET irradiation. The advantages of high LET irradiation include: (1) a greater ability to damage hypoxic cells; (2) a lesser ability for repair of sublethal and potentially lethal radiation-induced damage; (3) less variation in radiation sensitivity relative to the cell cycle; and (4) a greater ability to deposit the radiation dose in the region of the tumor as opposed to the normal surrounding tissue (neutrons do not have this advantage compared to other particle therapy). Despite these laboratory advantages, it has been difficult to demonstrate any advantage of high LET irradiation in the clinic. A number of new developments have occurred to test the role of high LET: (1) sophisticated technology to enable treatment delivery with higher dose rate and improved depth dose; (2) the construction of hospital-based facilities; and (3) the development of randomized studies involving diseases in which the risk of early metastasis is minimized. It is hoped that careful study in the clinic over the next decade will elucidate the role of high LET particle therapy.

Clinical Trials as Topic↗
PubMed1984

Perfluorocarbon emulsions in cancer therapy: preliminary observations on presently available formulations.

Perfluorocarbon (PFC) emulsions, due to their favorable oxygen transporting properties, have been proposed as tumor sensitizers for application in both radiotherapy and chemotherapy. While this application is a very promising one it is by no means simple, and presently available formulations are inadequate. Intravenous administration of these emulsions can produce a severe hemodilution which tends to offset the desired effect; these emulsions can alter the pharmacokinetics of simultaneously administered drugs. Unless these variables are taken into account the risk of false negative and false positive results will be excessive. Of more serious concern are the profound disturbances produced by these emulsions in the reticuloendothelial system. Using two of the more popular PFC, Fluosol-DA and DMA/NONANE, we have shown that daily administration of these emulsions can produce 9-fold increases in liver size and 27-fold increases in spleen size. This problem appears to involve the surfactant used in both emulsions, pluronic F-68. It will be necessary to circumvent this problem before further study of their potential application can proceed.

Animals↗
PubMed1984

Toxicity of WR-2721 administered in single and multiple doses.

Two hundred forty-three patients have received WR-2721 in Phase I-II studies. Separate studies were conducted in which patients with advanced malignancies received WR-2721 before single or multiple doses of radiotherapy or in single doses prior to cyclophosphamide, nitrogen mustard or cis-platinum. Single doses were escalated from 25 to 1330 mg/m2. An Acceptable Tolerated Dose (ATD) of 740 mg/m2 infused in 15 minutes has been established and is currently used in Phase II studies. Significant persistent hypotension (greater than 20 torr systolic) as a dose-limiting toxicity has occurred in 5% of patients in the single dose study. Fifty-five patients have been entered in the multiple dose trial. Dose levels of 340 mg/m2, four times a week for three weeks, and 250 mg/m2, four times a week for six weeks have been reached. There were five idiosynchratic reactions (fever, chills, rash, hypotension), one of which was severe. Some patients withdrew from the multiple dose study because of vomiting after each injection, or fear. No deaths nor any long-term untoward effects were observed. There is no suggestion of tumor protection.

Amifostine↗
PubMed1984

Effects of pentobarbital anesthesia on tonic luteinizing hormone secretion in the ewe: evidence for active inhibition of luteinizing hormone in anestrus.

In the ewe, seasonal anestrus appears to result from two effects of inhibitory photoperiod: 1) estradiol gains the capacity to suppress luteinizing hormone (LH) pulse frequency and hence becomes a potent inhibitor of tonic LH secretion and 2) a steroid-independent decrease in LH pulse frequency occurs in ovariectomized ewes. In this study, we have obtained evidence, using pentobarbital anesthesia, that both these actions of photoperiod reflect the activation, in anestrus, of an inhibitory neural system. Administration of pentobarbital to intact anestrous ewes produced a dramatic, 3-fold increase in LH pulse frequency during the 6 h of anesthesia. In contrast, during the breeding season, pentobarbital inhibited LH pulse frequency in luteal phase animals. There was also a seasonal variation in the effects of pentobarbital in ovariectomized ewes. During the breeding season this drug again suppressed LH secretion, inhibiting both LH pulse amplitude and frequency. In anestrus, pentobarbital also suppressed pulse amplitude, but it produced a transitory increase (lasting 3 h) in pulse frequency. To account for the stimulatory actions of pentobarbital, we propose that in anestrus, but not the breeding season, LH pulse frequency is held in check by a set of estradiol-sensitive inhibitory neurons. Further, we suggest that these neurons are activated by inhibitory photoperiod and account for both the steroid-dependent and steroid-independent actions of photoperiod.

Anesthesia↗
PubMed1984

Breast cancer in young women treated definitively with radiotherapy. An early report.

Between 1977 and 1982, 34 breast cancers in 33 women aged less than or equal to 35 years were treated with primary radiotherapy following excisional biopsy and axillary lymph node dissection. The records of these cases were reviewed and compared to 156 women greater than age 35 with 157 breast cancers treated similarly during the same time period. Analysis of these cases was limited to patients with invasive cancers who were AJC Stages I or II. In the women less than or equal to age 35, there were only six failures (two with locoregional failure only and four with distant metastases). The treated breast was preserved in all of the younger women except for the two patients with locoregional failure only who were treated for salvage with a mastectomy. The actuarial freedom from breast relapse alone at 3 years was 96% in women less than or equal to 35 years vs. 97% in women greater than 35 years. Freedom from locoregional relapse only was 88% vs. 95% at 3 years in the above groups, and the actuarial disease-free survival at 3 years was 76% vs. 87%, respectively. None of the above comparisons between younger and older women are statistically different. We conclude that definitive radiation therapy for Stages I and II carcinoma of the breast in women less than or equal to age 35 yields similar results to those for women greater than 35. Such treatment achieves excellent preservation of the breast and should continue to be considered as an alternative to mastectomy.

Adult↗
PubMed1983

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery; preliminary results of an RTOG study.

A randomized prospective study was performed to evaluate misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. The control arm, Group A, consisted of conventional radiation therapy (6000 cGy/6-7 weeks) to the whole brain plus BCNU (80 mg/m2 on day 3, 4, 5, and then repeated q 8 weeks for 2 years). The BCNU schedule was identical in both arms. In the experimental arm, Group B, misonidazole 2.5 gm/m2 was given once a week for six weeks, to a total dose of 15 gm/m2. It was given orally four hours prior to 400 cGy on Mondays. On Tuesdays, Thursdays and Fridays, 150 cGy was delivered to a total of 5100 cGy/6 weeks. An additional 900 cGy/5F/1 week was given without misonidazole. Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics among the treatment groups was comparable. As of March 1, 1982, 245 patients were randomized with follow-up information available on 202 patients. The median follow-up is 12 months (range 3-39 months). There is no significant difference in the survival of the two groups. The median survival for Group A was 12.6, and for Group B, 10.7 months. Misonidazole toxicity included an 11% peripheral neuropathy and a 3% central nervous system toxicity. BCNU toxicity included severe hematologic toxicity in 25%, including one death, and significant pulmonary toxicity in 6 out of 55 patients who received a minimum total dose of 960 mg/m2 of BCNU.

Adolescent↗
PubMed1983

The effect of adjuvant chemotherapy on cosmesis and complications in patients with breast cancer treated by definitive irradiation.

From 1978 to 1981, 46 patients received primary radiotherapy following excisional biopsy and axillary staging procedure for Stages I and II carcinoma of the breast. The patients were divided into 2 groups: 27 patients who received radiation and completed 12 cycles of adjuvant chemotherapy (CMF or CMFP) and 19 patients who received radiation alone. All patients received radiation to the breast and regional nodes (4600-5000 rad) and a boost to the site of the primary tumor (1500-2000 rad). Median follow-up from completion of radiation was 26 months in the non-adjuvant and 24 months in the adjuvant group with a range of 12 to 49 months. Cosmesis was judged to be good to excellent in 89% (17/19) of the patients receiving radiation alone and 81% (22/27) of the patients receiving adjuvant chemotherapy. Fair to poor cosmesis in the adjuvant group was attributed primarily to increased fibrosis and reduction of breast size. The single complication for which there was an increased incidence in the adjuvant group was arm edema (22 vs. 0%). The incidence of arm edema was unrelated to T stage, type of axillary surgical procedure, number of positive nodes, addition of prednisone or sequencing of chemotherapy. Further efforts should be directed towards minimizing complications and maximizing cosmesis without sacrificing relapse-free survival in patients receiving primary radiotherapy and adjuvant chemotherapy for early breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

A role for estradiol in enhancing luteinizing hormone pulse frequency during the follicular phase of the estrous cycle of sheep.

Experiments were conducted to test the hypothesis that the increased frequency of LH pulses during the follicular phase of the sheep estrous cycle can be explained by the withdrawal of progesterone. This steroid imposes a profound inhibition of LH pulse frequency in the luteal phase. Experimental ewes were ovariectomized in the late luteal phase of the estrous cycle and divided into three groups: 1) no estradiol provided; 2) basal estradiol maintained at 1-2 pg/ml by small sc Silastic estradiol implants; and 3) peak estradiol of 5-6 pg/ml provided by larger estradiol implants. Control ewes had intact ovaries; their follicular phases were synchronized by insertion and subsequent removal of progesterone implants. LH pulses were monitored beginning 24 h after ovariectomy of experimental ewes or progesterone implant removal from intact control ewes. In the follicular phase controls, LH pulse frequency increased 3- to 4-fold after progesterone withdrawal, reaching up to two pulses per h. When estradiol was not provided after ovariectomy of experimental ewes, LH pulse frequency also increased, but not to the extent seen in the follicular phase control. This high frequency was achieved, however, in experimental ewes treated with either basal or peak estradiol. Both estradiol treatments also reduced LH pulse amplitude. These results fail to support the hypothesis that the high frequency of LH pulses in the follicular phase is solely a consequence of progesterone withdrawal at luteolysis. Rather, they suggest that estradiol (but not necessarily rising estradiol) also contributes to the high frequency pulses of LH that occur in the ewe at this time.

Animals↗