Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma.
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Biomedical subjects
Publications and source records attributed to A McMahon.
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A total of 169 consecutive injuries to ice skaters is reviewed. The majority resulted from falls and occurred in young people with little or no previous skating experience. Speed and crowding on the ice may be contributory. Injuries occur because of a casual attitude to the sport and because of a lack of awareness of the potentially serious injuries that can result. It would be beneficial for beginners to undergo specific instruction and, if possible, at separate times or in separate areas.
There is a need for a biomarker to evaluate numbers of oocytes in an ovary exposed to various exogenous toxicants. Experiments that had been previously reported were reviewed to assess the serum FSH as such a biomarker. Rats that had been exposed to direct ovarian radiation and direct ovarian radiation with cyclophosphamide were reviewed to ascertain the relationship of follicle numbers to the serum FSH. Under the conditions of reduced serum estrogen, linear regression analysis indicated that the serum FSH correlated best with the calculated volume of antral follicles. Receiver operating characteristic curves were calculated to determine that an elevation of the serum FSH two standard deviations above the mean had the greatest diagnostic power in predicting a significant loss in both the number of healthy follicles and the calculated volume of healthy antral follicles. The serum FSH as a biomarker appears to have utility as a measure of the ovarian content of healthy antral follicles rather than as a measure of the total number of oocytes alone.
The binding of 125I-labelled human chorionic gonadotropin (HCG) was studied using thick slices (300 micron) of rabbit ovarian tissue. Binding was saturable, reversible, stereospecific, and of high affinity. The amount of binding was proportional to the number of slices used and could be destroyed by boiling. Ovarian slices from eight individual rabbits were found to have two binding sites for 125I-labelled HCG with KD values of 272 +/- 64 and 1263 +/- 274 pM and Bmax values of 25.7 +/- 5.3 and 94.1 +/- 18.8 fmol/mg protein, respectively. In a comparative study the KD and Bmax values were 351 +/- 151 pM and 25.3 +/- 11.1 fmol/mg protein with slices from one ovary and 134 +/- 24 pM and 109 +/- 32 fmol/mg protein with membranes from the contralateral ovary. These data suggest that the binding of HCG can be determined in live tissue.
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To study the efficacy of topically administered thrombin as an adjuvant in tubal microsurgery, 24 rabbits underwent a 1-cm resection and microsurgical anastomosis of both fallopian tubes and were randomized to either thrombin or cautery for hemostasis. Ovarian wedge biopsies were done on the left ovary. The animals were mated 4 to 5 weeks postoperatively with a buck of proven fertility. They were killed at 2 to 3 weeks' gestation to note the number of fetuses per patent tube and presence or absence of pelvic adhesions. There was no effect of topical thrombin on the crude pregnancy rate but it was associated with a marked reduction in the number of fetuses per patent tube, despite similar rates of pelvic adhesions between groups. Topically administered thrombin appeared to reduce fertility in this experimental model by an undefined mechanism.
To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.
The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.
There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.
This report summarizes our recent studies on the protein known as sterol carrier protein (SCP) or fatty acid binding protein (FABP). SCP is a highly abundant, ubiquitous protein with multifunctional roles in the regulation of lipid metabolism and transport. SCP in vitro activates membrane-bound enzymes catalyzing cholesterol synthesis and metabolism, as well as those catalyzing long chain fatty acid metabolism. SCP also binds cholesterol and fatty acids with high affinity and rapidly penetrates cholesterol containing model membranes. Studies in vivo showed SCP undergoes a remarkable diurnal cycle in level and synthesis, induced by hormones and regulated in liver by translational events. SCP rapidly responds in vivo to physiological events and manipulations affecting lipid metabolism by changes in level. Thus SCP appears to be an important regulator of lipid metabolism. Preliminary evidence is presented that SCP is secreted by liver and intestine into blood and then taken up by tissues requiring SCP but incapable of adequate SCP synthesis.
Retinoblastoma occurs with increased frequency in children born with a deletion of the long arm of chromosome 13. Recent reviews have noted that the region 13q14 is consistently deleted in documented cases. Prometaphase and late prophase banding allowed Yunis and Ramsay to determine that a deletion in one patient included the sub-bands q14 . 12, q14 . 13, and q14 . 2, and a portion of q14 . 11 and q14 . 3. We report the results of similar cytogenetic techniques applied in the case of a 26 month old Caucasian female with unilateral retinoblastoma, moderate developmental delay, and subtle dysmorphology. Prometaphase banding of cultured skin fibroblasts revealed the karyotype: mos46,XX/46,XX,del(13)(q13 . 1q14 . 11). Only the sub-band q14 . 11 is deleted in both our patient and that of Yunis and Ramsay. The results are consistent with the localisation of the retinoblastoma susceptibility gene(s) in the sub-band 13q14 . 11. Electrophoretic analysis and activity assays of red blood cell esterase D are consistent with hemizygous expression of that marker in our proband. Comparison with published esterase D analyses in families with retinoblastoma permits the assignment of the esterase D locus to that same sub-band, 13q14 . 11.
Trustees will be confronting a number of new issues arising from the change to a prospective pricing system for Medicare. The author predicts what some of the effects of the new payment system will be, and the behavior changes that must be forthcoming, such as greater cooperation among boards, CEOs, and medical staffs, if hospitals are to succeed under the system.
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Electrophoretic variant forms of the X-linked enzyme phosphoglycerate kinase (PGK-1, E.C.2,7,2,3) have been used to examine X-chromosome mosaicism in tissues from 12 1/2-day post coitum heterozygous female mouse embryos. Samples of yolk-sac endoderm, neural ectoderm, heart (mesoderm), liver (endoderm) and germ cells were analysed from each embryo. In all tissues except yolk-sac endoderm, both PGK-1 isozymes were expressed. The extent of covariance among tissues with respect to the PGK-1 isozyme contribution is consistent with all tissues being derived from the same pool of cells after X-inactivation. The covariance among tissues gives an estimate of the size of this pool (47 cells) and places the earliest time of X-inactivation in epiblast cells between 4 1/2 and 5 1/2 days post coitum. From the independent variance among tissues within an individual, the average primordial precursor pool size for the three germ layers and the germ line itself was estimated as 193 cells.
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