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Biomedical subjects

L L Anderson

Publications and source records attributed to L L Anderson.

At least 109 records · Page 6Linked to original sources

Endocrine changes in beef heifers superovulated with follicle-stimulating hormone (FSH-P) or human menopausal gonadotropin.

The effects of superovulatory treatment (FSH-P vs human menopausal gonadotropin, HMG) and of route of administration (i.m. vs. i.v.) of prostaglandin F2 alpha (PGF2 alpha) on hormonal profiles were determined in 32 Angus x Hereford heifers. Heifers were superstimulated with either FSH-P (total of 26 mg) or HMG (total of 1,050 IU) beginning on d 9 to 12 of an estrous cycle and PGF2 alpha (40 mg) was administered at 60 and 72 h after the beginning of superovulatory treatments. Heifers were artificially inseminated three times at 12-h intervals beginning 48 h after PGF2 alpha treatment. Blood serum samples were collected immediately before treatments began, at 12-h intervals during the first 60 h, each 4 h during the next 96 h, and each 12 h until day of embryo collection. Concentrations of LH and FSH were not affected by hormone treatments, route of PGF2 alpha injection, or interactions between them. Estradiol-17 beta (E2-17 beta) levels were higher (P less than .05) in HMG- than in FSH-P-treated heifers 60 h after gonadotropin treatment. Peak concentration of E2-17 beta occurred earlier (P less than .05) in HMG- than in FSH-P-treated heifers and earlier in heifers injected with PGF2 alpha i.m. than in those injected i.v. Progesterone concentrations were not influenced by treatment or route of PGF2 alpha administration, but were affected (P less than .01) by the interactions between treatment and route of PGF2 alpha administration. Progesterone declined to basal levels earlier in the FSH-P- than in the HMG-treated heifers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation.

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.

Adenocarcinoma↗

CT-based optimized planning for transperineal prostate implant with customized template.

A computerized planning procedure has been developed for CT-guided transperineal prostate implants. The segment for custom planning of perineal needle orientations allows placement of I-125 seeds in the entire prostate gland while avoiding the pubic bones. Least-squares optimization (LSO) is used to obtain the seed-loading pattern along the needles. The optimized seed distribution produces a better fit between treatment and target volumes than that obtained from our previous manual technique. Also, the present semi-automatic technique reduces planning time by about a factor of 10 compared to that of the manual approach.

Brachytherapy↗

Abrupt shifts in relaxin and progesterone secretion by aging luteal cells: luteotropic response in hysterectomized and pregnant pigs.

Although a prominent role of conceptuses in the hormonal control of normal parturition in the pig is well founded, mechanisms are entrained that cause a timed relaxin release and an abrupt decrease in progesterone secretion in the complete absence of the uterus. This study focused on the steroidogenic and peptide hormone secretory capacities of aging porcine luteal cells in culture on specific days during a narrow window (days 110-116) when abrupt shifts occur in their function. Dispersed luteal cells (3 x 10(5) cells/well) from hysterectomized and pregnant gilts on days 110, 113, and 116 after estrus were cultured for 24 h with porcine (p) LH, pPRL, prostaglandin E1 (PGE1), PGE2, and (Bu)2cAMP. Progesterone and relaxin concentrations in cells preceding culture and in the spent medium were quantified by RIA. Progesterone in cells before culture was less (P less than 0.05) than that released into the medium, while relaxin levels were greater (P less than 0.05) than those in the medium. Relaxin stored in luteal cells of hysterectomized gilts was consistently greater (P less than 0.01) than that during the same days of late pregnancy; however, progesterone was greater (P less than 0.01) in hysterectomized compared with pregnant gilts only on day 116. Relaxin release was greater (P less than 0.01) in hysterectomized compared with pregnant gilts on days 113 and 116, whereas progesterone was greater (P less than 0.05) on days 110 and 116 in hysterectomized compared with pregnant animals. pLH, pPRL, and (Bu)2cAMP increased (P less than 0.05) relaxin secretion in hysterectomized gilts on days 110, 113, and 116, but only on day 110 in pregnant animals. These hormones consistently increased (P less than 0.05) progesterone release only on day 110 in both groups of gilts. PGE1 increased (P less than 0.01) relaxin release in hysterectomized, but not pregnant, gilts; it was not effective in altering progesterone in either group. PGE2 increased the release of both hormones on day 113 in both groups. The percentage of large cells (i.e. greater than 20 microns in diameter) was consistently greater (P less than 0.01) on days 110-116 in hysterectomized compared with pregnant gilts. Both luteal cell relaxin concentrations and the population of electron-dense granules decreased from days 110-116 in pregnant, but not in hysterectomized, gilts; luteal cells from postpartum animals were nearly depleted of granules, and empty vesicles were prominent. The secretory response of the cells to tropic hormone stimulation is preprogrammed from the previous estrus that occurred more than 110 days previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Alprostadil↗

Antiprogesterone, RU 486, facilitates parturition in cattle.

RU 486, a potent progesterone antagonist with high affinity for progesterone receptor, was used alone or in combination with relaxin in late pregnant cattle to determine its effect on induction of parturition. Cross-bred beef cattle were bred by artificial insemination. An indwelling cannula was inserted into a jugular vein on day 269 (expected term = day 283) for repeated blood sample collection. On day 277, the cattle were assigned randomly to three groups (n = 6 each): group 1 received RU 486 (2 mg/kg BW, im) at 0800 h on days 277 and 278; group 2 received the same RU 486 treatment plus 3000 U relaxin, injected sc at 0800 h on day 278; and group 3 served as controls and received vehicle injection. Parturition occurred 55 h after treatment in group 1 and 53 h after treatment in group 2 compared with 210 h in the controls (P less than 0.01). The calves from treated groups were vigorous at birth, and their birth weights (32 and 33 kg in groups 1 and 2) were less than those of control calves (38 kg; P less than 0.01). There was no incidence of difficult birth (dystocia) with RU 486 treatment compared with that in the controls. Placenta delivery averaged 6.5 h after birth in both RU 486-treated groups and did not differ from the control value (5 h). Plasma progesterone concentrations averaged 8.2 ng/ml during the pretreatment period for all animals. Progesterone started to decrease markedly by 1200 h on day 278, dropped to about 4 ng/ml by 2400 h that same day, and was at basal levels on day 279, the day of calving, in two hormone-treated groups. In sharp contrast, progesterone was maintained at about 6 ng/ml in placebo-treated controls during this period and did not decrease to basal levels until 2 days before parturition on day 286 (P less than 0.01). Peak RU 486 in plasma was 7.2 ng/ml after the first injection and 14.3 ng/ml after the second injection, and averaged 7.9 ng/ml on the day of induced calving (day 279). Peak relaxin was 4.1 ng/ml after hormone injection. The results indicate that RU 486 alone or combined with relaxin precisely controlled the time of parturition in cattle in late pregnancy. Such treatment can be used to facilitate parturition and increase survival rates of neonatal calves without detrimental effects of dystocia, retention of placenta, and delayed postpartum fertility.

Animals↗

Divergent effects of antiprogesterone, RU 486, on progesterone, relaxin, and prolactin secretion in pregnant and hysterectomized pigs with aging corpora lutea.

Porcine corpora lutea produce progesterone and relaxin during pregnancy and after hysterectomy. Peak amounts of relaxin are released into peripheral blood in both pregnant and hysterectomized animals on about day 113 (estrus = day 0 and term = 114), and this release coincides with an abrupt decrease in the progesterone concentration. RU 486, a progesterone receptor antagonist, was used to investigate the effects of interruption of progesterone binding to its receptor on luteal function and gonadotropin secretion of pigs with aging corpora lutea. RU 486 was administered orally to hysterectomized gilts (surgery on day 8) once a day (0800 h) on days 111-115 at two dosages (group 1, 2 mg/kg BW; group 2, 4 mg/kg BW). During 5 days of RU 486 treatment, plasma progesterone concentrations in both treated groups were markedly elevated (32 and 37 ng/ml for groups 1 and 2) compared with 22 ng/ml in the controls (group 3; P less than 0.01). PRL concentrations increased in both groups (9 and 13 ng/ml) and differed significantly from those of the controls (3 ng/ml) (P less than 0.04). RU 486 treatment delayed the time of relaxin peak to days 116.1 and 117.0 in groups 1 and 2 compared with day 114.1 in the controls (P less than 0.01). Pregnant gilts received RU 486 orally once a day (0800 h) at 4 mg/kg BW beginning on day 111 until parturition occurred. Parturition was induced on day 112.7 after only two RU 486 treatments compared with day 114.7 in the control group (P less than 0.01). Progesterone decreased abruptly from a pretreatment mean of 11 to less than 0.6 ng/ml during the 2 days that RU 486 was given compared with a shift from 12 to 6 ng/ml during the same period in the controls (P less than 0.01). The time of the relaxin peak was advanced to day 112.1 in RU 486-treated gilts compared with day 113.9 in the controls (P less than 0.01). Results from this study provide strong evidence that the antagonistic effect of RU 486 on progesterone receptor results in an abrupt increase in PRL and progesterone secretion in hysterectomized gilts with aging corpora lutea. In marked contrast with hysterectomized animals, the acute luteolytic effects of RU 486 depend on the presence of the uterus and/or conceptuses in the pig. Disruption of the regulatory loop of progesterone secretion by RU 486 alters the ability of corpora lutea to produce and release peak quantities of relaxin.

Animals↗

Effect of relaxin on facilitation of parturition in dairy heifers.

Purified pig relaxin (3000 U/mg) was injected i.m. into pregnant Holstein dairy heifers on Day 276 or 277 to determine its effect on parturition and sequential measurements of the pelvic area, cervical dilatation, and peripheral blood-plasma concentrations of progesterone and relaxin. Treatments included phosphate-buffer saline (2 ml, Group C, N = 7), relaxin once (1 mg, Group 1R, N = 7), and twice (2 mg, 12 h apart; Group 2R, N = 7). Intervals (mean +/- s.e.) between the first injection of relaxin or PBS and calving were 64 +/- 17, 80 +/- 19 and 125 +/- 34 h for Groups 2R, 1R and C, respectively. The calving intervals were reduced in Groups 2R (P less than 0.01) and 1R (P less than 0.05) compared with Group C. The incidence of dystocia was 29% (2 of 7) in Group 2R and 43% (3 of 7) in Group 1R compared with 57% (4 of 7) in Group C (P less than 0.01). Body weights and ratios of males to females of the calves were similar (P greater than 0.05) between groups. Progesterone plasma concentrations decreased (P less than 0.01) earlier in Groups 1R and 2R compared with Group C, and this acute decrease began within 6 h of treatment. At 24 h after relaxin or PBS injection, progesterone concentrations were 2.7 +/- 1.1 ng/ml for Group 2R, 3.5 +/- 0.9 ng/ml for Group 1R, and 6.0 +/- 0.1 ng/ml for Group C. Relaxin reached peak blood-plasma levels of 19 +/- 2.2 ng/ml 1 h after injection of relaxin, but remained unchanged, 0.3 +/- 0.01 ng/ml, in Group C. Pelvic area was increased 26%, 22% and 14% and cervical dilatation was increased 109%, 76% and 53% 48 h after injection in Groups 2R, 1R and C, respectively, but these responses were similar among groups at the time of parturition. We conclude that two i.m. injections of relaxin facilitated earlier calving, acutely decreased progesterone secretion, increased cervical dilatation and pelvic area expansion, and decreased the incidence of dystocia in dairy heifers.

Animals↗

Growth hormone and prolactin secretion in hypophysial stalk-transected pigs as affected by growth hormone and prolactin-releasing and inhibiting factors.

Control of growth hormone (GH) and prolactin (PRL) release was investigated in hypophysial stalk-transected (HST) and stalk-intact pigs by determining the effects of analogs of GH-releasing factors (GHRF), somatostatin (SRIF), arginine, thyrotropin-releasing hormone, alpha-methyl-rho-tyrosine, and haloperidol. HST and control gilts were challenged with intravenous injections of human pancreatic GHRF(1-40)OH, thyrotropin-releasing hormone, and analogs of rat hypothalamic GHRF. HST animals remained acutely responsive to GHRF by releasing 2-fold greater quantities of GH than seen in controls. This occurred in spite of a 38% reduction in pituitary gland weight and a 32 and 55% decrease in GH concentration and total content. During SRIF infusion, GH remained at similar basal concentrations in HST and control gilts, but increased immediately after stopping SRIF infusion only in the controls. Releasable pituitary GH appears to accumulate during SRIF infusion. GHRF given during SRIF infusion caused a 2-fold greater release of GH than seen in animals receiving only GHRF. Arginine increased (P less than 0.05) GH release in controls, but not in HST gilts, which suggests that it acts through the central nervous system. Basal PRL concentrations were greater (P less than 0.05) in HST gilts than in control gilts. TRH acutely elevated circulating PRL (P less than 0.001) in HST gilts, suggesting that it acts directly on the pituitary gland. Haloperidol, a dopamine receptor antagonist, increased circulating PRL in controls but not in HST animals. alpha-Methyl-rho-tyrosine did not consistently increase circulating PRL, however, suggesting that it did not sufficiently alter turnover rate of the tyrosine hydroxylase pool. The results indicate that the isolated pituitary after HST remains acutely responsive to hypothalamic releasing and inhibiting factors for both GH and PRL release in the pig.

Adrenal Glands↗

Role of brachytherapy in malignant melanoma: a preliminary report.

From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.

Adult↗

Ocular melanoma: total dose and dose rate effects with Co-60 plaque therapy.

From 1968 to 1987, 123 consecutive patients with nonmetastatic choroidal melanoma were treated with cobalt-60 plaques. One hundred sixteen patients were followed up for a mean of 3.8 years. Twenty patients had local failure, and 14 patients had distant failure. Complications included 32 cataracts, and seven enucleations were required. Local recurrence did not correlate with tumor height, tumor volume, dose, or dose rate. Increased volume (P = .004) and height (P = .01) correlated with increased rates of distant metastases. Dose adjusted for volume did not correlate with the rate of metastases.

Brachytherapy↗

Relaxin and prostaglandin on oxytocin secretion from bovine luteal cells during different stages of gestation.

The objective of this study was to determine whether bovine luteal cells from different stages of gestation secrete oxytocin and whether relaxin, cloprostenol (a potent analogue of prostaglandin F2 alpha), estradiol-17 beta, and LH can acutely alter oxytocin secretion. Bovine luteal cells (10(5)) were cultured for 24 h without treatment and with medium-hormone replacement every 24 h. Oxytocin was quantified by radioimmunoassay of the culture media. Basal oxytocin secretion was similar (22-31 pmol/l, p less than 0.05) for all stages of gestation (days 100, 145, 160, 185, 200, 210, and 240). Relaxin induced a dose-dependent suppression of oxytocin release. After 24 h of incubation, addition of 0, 16.7, 83.5, and 167 nmol/l porcine relaxin (3000 U/mg) induced 54 +/- 4, 105 +/- 16, 47 +/- 4, and 38 +/- 4 pmol/l of oxytocin in cells from 160-day-old corpora lutea and 138 +/- 12, 21 +/- 2, 19 +/- 3, and 15 +/- 2 pmol/l oxytocin in cells from 240-day-old corpora lutea. From luteal cells of 160- and 240-day-old corpora lutea, 2 micromol/l cloprostenol induced a marked increase (p less than 0.01) of 208 +/- 39 and 371 +/- 34 pmol/l oxytocin, respectively. Addition of 167 nmol/l relaxin did not prevent cloprostenol-induced oxytocin secretion during the first 48 h, but a decrease (p less than 0.05) in oxytocin occurred in day 3 cell cultures. These results indicate that cultured luteal cells obtained from different stages of gestation in cattle can secrete oxytocin and suggest a role for relaxin in the regulation of oxytocin release.

Animals↗

Thymosin-beta 4 concentrations during the estrous cycle and after hypophyseal stalk transection of female pigs.

Thymosin-beta 4 (ThB4) concentrations in the peripheral circulation of pigs were investigated during the first 30 days after weaning and after hypophyseal stalk transection of ovariectomized females. Significant increases in ThB4 were observed during the day of weaning, during follicular development, and during early luteal formation. During the first period of follicular development (Days 1 to 5 after weaning), ThB4 was uniformly elevated for 3 days whereas during the second period of follicular development (days 21 to 25 after weaning), the increase in ThB4 was bimodal. This period of bimodal secretion was closely associated with luteolysis. ThB4 concentrations were low during the luteal phase when progesterone concentrations were at their greatest. In ovariectomized pigs, ThB4 concentrations were not influenced acutely by a single intravenous injection (2 micrograms) of luteinizing hormone-releasing hormone in control (hypophyseal stalk intact) or hypophyseal stalk transected females. Both of these treatment groups responded to luteinizing hormone-releasing hormone with increased secretion of luteinizing hormone. These studies determined that ThB4 secretion changed dramatically throughout the estrous cycle of pigs but failed to identify an acute association between increased luteinizing hormone secretion and ThB4 in ovariectomized pigs. Our observations support the hypothesis that the thymus gland interacts with the hypothalamopituitary-ovarian axis primarily through changes in secretion of ovarian steroids.

Animals↗

Relaxin, oxytocin, and prostaglandin effects on progesterone secretion from bovine luteal cells during different stages of gestation.

To determine the effects of relaxin, oxytocin, and prostaglandin F2 alpha on progesterone secretion, bovine luteal cells from different stages of gestation were dispersed in Medium 199 with 200 units/ml penicillin, 1.0% kanamycin, 0.5% bovine serum albumin, and 400 units/ml collagenase. Cells (10(5) were cultured in 400 microliters of Dulbecco's modified Eagle's medium and Ham's F-12 medium containing fetal bovine serum and antibiotics, in Falcon multiwell plates, in a humidified environment of 95% O2 and 5% CO2 at 37 degrees C. Cells were cultured for 24 hr without treatment and thereafter with medium-hormone replacement every 24 hr. Progesterone was quantified from unextracted media by radioimmunoassay. Basal progesterone secretion after 24 hr was 1.81 +/- 0.14, 1.76 +/- 0.17, 0.54 +/- 0.49, and 0.57 +/- 0.21 pg/ml per viable luteal cell from 145-, 165-, 185-, and 240-day-old corpora lutea, respectively. Basal progesterone secretion increased (P less than 0.05) with time in culture. Relaxin induced a dose-dependent (greater than 100 ng/ml) increase in progesterone release, compared with the controls. Oxytocin and prostaglandin F2 alpha induced greater release (P less than 0.05) of progesterone than relaxin at all stages of gestation, but progesterone release was dependent on the stage of gestation and the duration in culture. Luteinizing hormone (100 ng/ml) stimulated whereas 17 beta-estradiol (50 ng/ml) inhibited progesterone secretion by luteal cells at all stages of gestation examined. Relaxin obliterated the prostaglandin- and oxytocin-induced progesterone secretion by bovine luteal cells from 145 to 214 days of gestation. Thus, relaxin, cloprostenol, and oxytocin regulate progesterone production by cultured bovine luteal cells, but hormone secretion was dependent on the stage of gestation.

Animals↗

A new DNA marker (D10S94) very tightly linked to the multiple endocrine neoplasia type 2A (MEN2A) locus.

Combined somatic cell hybrid and linkage studies between D10S94 and five pericentromeric loci (FNRB, D10Z1, MEN2A, RBP3, and D10S15) have localized the new DNA sequence pcl1/A1S-6-c23 at D10S94 to 10q11.2. No recombinants were observed between D10S94 and D10Z1 or MEN2A. D10S94 maps in proximal 10q11.2 very near to MEN2A. There are three possible orders for the six loci that we investigated from the centromeric region of chromosome 10. At present the genetic data do not allow us to order MEN2A with respect to D10Z1 and D10S94. The three possible orders are FNRB-D10Z1-D10S94-MEN2A-RBP3-D10S15, FNRB-D10Z1-MEN2A-D10S94-RBP3-D10S15, and FNRB-MEN2A-D10Z1-D10S94-RBP3-D10S15. In view of the fact that no recombinants between D10S94 and MEN2A or between D10S94 and D10Z1 were observed, the combined haplotypes formed from RFLPs and D10Z1 and D10S94 will increase the informativeness and accuracy of genotype prediction for at-risk members of the families having the MEN 2A syndrome, particularly when the affected parent is female. The localization of D10S94 with respect to MEN2A will prove valuable in experiments directed toward cloning the MEN2A locus.

Adrenal Gland Neoplasms↗

Progesterone secretion and mitochondrial size of aging porcine corpora lutea.

A functional dependency between the nongravid uterus and the ovaries is essential to luteolysis and the return to estrus in the pig. After mating of gilts, the corpora lutea develop, and they are required for the maintenance of pregnancy to a normal duration of about 114 days. Hysterectomy of luteal phase (day 6) nongravid gilts results in persistence of the corpora lutea to 150 days. We report that these corpora secrete greater quantities (P less than 0.025) of progesterone than during the later half of gestation (days 54-108). Although aging corpora lutea remain functional for at least an additional 35 days, an abrupt reduction by half in progesterone secretion (16 ng/ml) occurs about day 114 in hysterectomized gilts that coincides with the prepartum decrease to basal serum levels (less than 0.5 ng/ml) at parturition (day 114) and during lactation. Aging corpora lutea remain large (averaging greater than 450 mg) on days 124 and 136 in hysterectomized gilts, whereas they regress (averaging less than 75 mg) in the lactating dams. Mitochondria continue to increase in size in aging corpora lutea of hysterectomized gilts until day 136; in contrast, they decrease during the postpartum period in lactating dams. A precisely timed signal, possibly of ovarian origin or from the CNS and pituitary gland, entrains in hysterectomized and pregnant pigs at day 113 that results in marked shifts in relaxin and progesterone secretion. Progesterone secretion and mitochondrial features suggest that porcine corpora lutea seem genetically controlled and are preprogrammed at estrus for the duration of pregnancy, regardless of the presence of conceptuses or absence of the uterus.

Aging↗

Treatment planning for permanent and temporary percutaneous implants with custom made templates.

Nine patients who were presented at MSKCC with primary or recurrent pelvic or head and neck tumors and for whom surgery or further external radiation were excluded, were treated with percutaneous permanent or temporary implants, with individual pre-treatment planning and custom made templates. The tumor dose distributions achieved were as good as for implants performed at the time of surgical exploration. No serious complications have been encountered.

Brachytherapy↗

Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation.

Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain (57 patients), jaundice (45 patients), and weight loss (34 patients). All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass (36 patients), biliary bypass (49 patients), and partial or total pancreatectomy with incomplete resection (5 patients). The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed.

Adenocarcinoma↗

Prolactin maintains relaxin and progesterone secretion by aging corpora lutea after hypophysial stalk transection or hypophysectomy in the pig.

Porcine corpora lutea persist beyond 150 days in hysterectomized animals compared with about 114 days during normal pregnancy. To explore the mechanism(s) regulating the peak release of relaxin and secretion of progesterone by aging corpora lutea and to examine the direct effect of purified porcine (p) PRL on such corpora lutea, hypophysial stalk transection (HST), hypophysectomy (HYPOX) with or without PRL replacement, and sham operation control (SOC) were conducted on day 110 (estrus = day 0) on purebred Yorkshire gilts that were hysterectomized on days 6-8. The pPRL (0.5 mg every 6 h daily) or PBS (0.5 ml every 6 h daily) was given iv from days 110-120. HYPOX + pPRL, HYPOX + PBS, HST + PBS, and SOC + PBS formed four experimental groups. Peak relaxin concentrations in peripheral plasma (mean values ranged from 22-24 ng/ml) occurred on about day 113 for all groups [113.4 +/- 0.3 days (+/- SE)] regardless of the different surgical interventions. After peak release, relaxin decreased steadily in the HYPOX + PBS group, falling to less than 1.0 ng/ml by 6 days later, whereas relaxin in other groups remained elevated (approximately 7 ng/ml). In the HYPOX plus PBS group, progesterone decreased abruptly, remaining below 1 ng/ml from 1 week onward, lower (P less than 0.01) than that in controls (approximately 19 ng/ml); in the HYPOX + pPRL group, progesterone levels (approximately 17 ng/ml) remained similar (P greater than 0.05) to those in controls (approximately 19 ng/ml) and the HST + PBS group (approximately 15 ng/ml). These results clearly reveal that the pituitary gland plays no direct role in regulating the timed peak release of relaxin from aging corpora lutea in hysterectomized gilts and that the peak release of relaxin on about day 113 is preprogrammed and inherent within such aging luteal cells. This study provides strong evidence that purified pPRL maintains both relaxin and progesterone secretion as well as the morphology of aging corpora lutea for at least 10 days after hypophysectomy in hysterectomized gilts.

Animals↗