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Biomedical subjects

L L Anderson

Publications and source records attributed to L L Anderson.

At least 91 records · Page 5Linked to original sources

Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors. Clinical Research Committee, American Endocurietherapy Society.

PURPOSE: A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.

Brachytherapy↗

A nomograph for permanent implants of palladium-103 seeds.

103Pd is being substituted for 125I in permanent implants for which it is desired to deliver a higher initial dose rate while maintaining readily achieved radiation protection. We have constructed a nomograph to assist in determining both the total seed strength required and the appropriate needle spacing for 103Pd implants. We have calculated the "matched peripheral dose" (MPD), that is, the dose for which the isodose contour volume is equal to the target volume, for 64 125I and 13 103Pd actual implants as if 103Pd had been used for all of them, employing a computer lookup table based on single-seed dose distribution measurements in solid water. The calculated data were used to obtain a least-squares fit to a linear relationship between the logarithm of the total seed strength for a given MPD and the logarithm of the average dimension, da (cm). We found that, for a nominal MPD of 11,500 cGy, total seed strength (in mCi) is given by 3.2 da2.56. A 103Pd nomograph has been constructed on the basis of this power function relationship. Our nomographic guide for planning 103Pd implants calls for total seed strength to increase significantly faster as a function of target volume average dimension than is the case for 125I. This nomograph will facilitate the application of 103Pd seeds in permanent implants.

Brachytherapy↗

A CT-based evaluation method for permanent implants: application to prostate.

A computerized tomography-based 3-dimensional evaluation scheme, using semi-automatic seed localization from transverse computerized tomography-images, has been developed for permanent implants. The treatment isodose contour is generated at each scan plane and overlaid on the corresponding target contour for coverage visualization. Volume and surface dose histograms are generated for the target and neighboring normal structures. Dose inhomogeneity within the target is also estimated from the full-width at half maximum of the differential volume dose histogram. The matched peripheral dose is calculated from the ellipsoidal volume approximation for the target. The present evaluation method has been applied here to 10 actual permanent I-125 prostatic implantations. Coverages by 150 Gy and 100 Gy levels are found to range from 78-96% and 91-99% of the target volume, respectively. The average matched peripheral dose is found to be about two times the average peripheral dose (the dose encompassing 99% target) and about three times the average minimum peripheral dose (the dose encompassing 100% target). The dose inhomogeneities within the target volume, in these 10 cases, range from 220-420 Gy.

Brachytherapy↗

Tumor control probability for permanent implants in prostate.

The tumor control probabilities (TCPs) for 11 transperineal permanent implants of the prostate with 125I seeds have been computed, based on target-specific volume-dose histogram data. Prostate dose-response of this modality is converted from that of external beam therapy based on biologically effective dose derived from the alpha beta model. The calculated TCPs for these transperineal prostate cases are compared with the results of 679 previous retropubic implants, providing interesting insight about these two techniques. Further refinement and validation of this model await long-term followup results of sufficient number of patients.

Brachytherapy↗

Stimulation of prolactin secretion in the pig: central effects of relaxin and the antiprogesterone RU 486.

Our previous study has shown that oral administration of a potent progesterone antagonist, RU 486, caused a marked elevation of plasma concentrations of both PRL and progesterone in hysterectomized pigs bearing aging corpora lutea. Hysterectomized pigs (hysterectomy performed on day 8; estrus = day 0) were subjected to cranial surgery for chronic placement of a head-mounted stereotaxic apparatus for intracerebroventricular (icv) administration of relaxin (300 U once daily on days 111 and 113; n = 6) and RU 486 (4 mg once daily on days 111, 113, and 115; n = 5) to test whether relaxin and RU 486 exert their actions within the central nervous system and/or pituitary gland to affect PRL and GH secretion. Control pigs (n = 3) received icv injection of vehicle. Intensive blood sampling revealed that icv injection of relaxin on day 111 markedly increased the plasma PRL concentration from 8 to 38 ng/ml within 10 min (P < 0.01). An identical icv injection of relaxin on day 113 caused only a modest increase in PRL, but the overall mean concentration of PRL after relaxin treatment was greater than that before treatment (14 vs. 8 ng/ml; P < 0.05). Intracerebroventricular injection of RU 486 on day 111 greatly elevated plasma PRL. The increase in PRL lasted more than 2 h, with several peak increases of 18-29 ng/ml (P < 0.01). The PRL response to subsequent icv infusion of RU 486 on days 113 and 115 was blunted, but the overall mean concentration of PRL (14 ng/ml) after icv injection of RU 486 remained greater (P < 0.01) than that before treatment (9 ng/ml). In contrast, PRL concentrations in the control group remained unchanged after injection. Plasma concentrations of GH, relaxin, and progesterone were significantly altered in neither hormone- nor vehicle-treated groups during this brief period of sequential blood sampling. This study provides strong evidence that relaxin has a central role in modulating PRL secretion in the pig. In addition, the antagonistic effects on progesterone receptor by RU 486 in the central nervous system and/or pituitary gland caused an abrupt increase in PRL secretion in these hysterectomized gilts.

Animals↗

Alcoholism in a coronary care unit population.

To estimate prospectively the concordance between diagnoses of alcoholism by a physician and by use of a questionnaire-type screening test in patients in a coronary care unit, we studied 608 patients admitted to a coronary care unit in a 5 1/2-month period. The results from the Self-Administered Alcoholism Screening Test (SAAST) were compared with the diagnoses by physicians recorded in the medical records for the same patients. A strong association (P < 0.001) existed between the clinicians' identification of an alcohol problem and the SAAST scores indicative of such a problem. However, 23 (4.2%) patients were identified as alcoholics by the SAAST but not by clinicians, and 16 (2.9%) patients were identified as alcoholics by clinicians but not by the SAAST. The SAAST was well accepted in this coronary care unit and can complement and extend the clinicians' impression, although each approach may identify some patients that the other will miss. Routine use of the SAAST in the coronary care unit or other hospital settings is feasible and, with appropriate clinician assessment and physician involvement, should yield more complete evaluation and case finding for alcoholism.

Adult↗

Attenuation of antepartum relaxin surge and induction of parturition by antiprogesterone RU 486 in sheep.

Pregnant ewes were injected with either the antiprogesterone, RU 486 (4 mg kg-1 body weight, i.m.; n = 5), 3000 iu relaxin (i.m.; n = 9), or diluent (n = 8) at 12:00 h on days 144 and 145, to determine its effect on progesterone and relaxin secretion, and on induction of lambing. RU 486 induced earlier lambing (P < 0.01) compared with diluent treatment, but relaxin treatment did not significantly reduce the interval to parturition. Mean injection-lambing intervals were 31 +/- 2, 109 +/- 23 and 121 +/- 27 h for the RU 486, relaxin and diluent groups, respectively. There was no incidence of difficult birth (dystocia); all lambs were vigorous at birth; and placenta delivery was rapid (within 207 min) with RU 486 and relaxin treatments compared with diluent treated controls. Plasma progesterone concentrations averaged 11 ng ml-1 during the pretreatment period for all animals. RU 486 had a biphasic effect on progesterone concentrations, causing an initial increase (P < 0.05) within 2 h, and then an abrupt drop (P < 0.01) to 6 ng ml-1 by 18:00 h on day 145. Progesterone concentrations remained consistently lower (P < 0.05) in relaxin-treated ewes than in diluent-treated controls from days 144 to 147 and then began a steady decrease to 4 ng ml-1 on the day of parturition (days 149 and 150) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulation of collagen secretion by relaxin and effect of oestrogen on relaxin binding in uterine cervical cells of pigs.

The role of relaxin and oestrogen in the remodelling of connective tissue was investigated by testing collagenase-dispersed cells (3 x 10(5) cells per well) from the uterine cervix of gilts for relaxin binding and collagen secretion. Relaxin-binding sites on these cells were quantified by specific binding of a saturating dose of 125I-labelled monotyrosyl relaxin at optimal conditions. Oestrogen at doses from 0.4 to 50 ng ml-1 increased relaxin binding in a time- and dose-dependent manner. Scatchard plot analysis exhibited curvilinearity, which suggested two classes of relaxin-binding sites. The addition of relaxin (0, 100, 500 ng ml-1) alone (P < 0.05) or in combination with oestrogen (oestradiol benzoate: 0, 50, 250 ng ml-1) increased protein secretion into the culture medium. Hydroxyproline concentration (as an index of collagen) in the medium was increased (P < 0.05) only in the presence of both relaxin and oestrogen. Actinomycin D (500 ng ml-1) and cycloheximide (500 ng ml-1) inhibited hydroxyproline secretion induced by combined relaxin and oestrogen treatment. Dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cAMP: 0, 0.1, 1.0, 5.0 mmol l-1) was a potent stimulator of hydroxyproline secretion. These results indicate that relaxin, probably via a cAMP pathway, stimulates hydroxyproline secretion in the presence of oestrogen through a protein- and RNA-synthesis dependent process. Oestrogen plays a role in augmenting the sensitivity of uterine cervical cells to relaxin in the pig.

Animals↗

Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125.

Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20-78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope.

Animals↗

High dose rate gynecological applications--radiobiological considerations based on the alpha-beta model.

We compare the relative efficacy of high dose rate (HDR) and low dose rate (LDR) irradiation in gynecological implants, using formulations based on the linear-quadratic (alpha-beta) model. We consider both acute reaction and late effect as endpoints in evaluating equivalence for HDR and LDR treatments, at Point A (as defined in the text) and at other locations. We define a therapeutic factor gamma as an index for relative efficacy, with gamma > 1 indicating a gain in substituting HDR for LDR. It is found that gamma < 1 for most clinical situations, although a modest decrease (of about 15%) in dose to critical organs for HDR would raise gamma above unity.

Brachytherapy↗

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in a black.

Neuroendocrine carcinoma of the skin is an uncommon, small-cell neoplasm most commonly found on white, sun-exposed skin. Diagnosis by clinical and histologic means may be difficult. Immunohistochemical and ultrastructural analysis are often required. Because of the aggressive nature of neuroendocrine carcinoma of the skin, prompt diagnosis and treatment are essential. We present the rare occurrence of a neuroendocrine carcinoma of the skin on sun protected skin in a black. Clinical, histologic, immunohistochemical, and ultrastructural features are reviewed, and therapeutic options are discussed.

Black People↗

Chediak-Higashi syndrome in a black child.

Chediak-Higashi syndrome (CHS) is an uncommon genetic disorder with a constellation of clinical, pathologic, and immunologic manifestations. It is rarely reported in blacks. Pathognomonic intracellular inclusions in white blood cells are well recognized; however, characteristic abnormal melanin aggregation into giant melanosomes also occurs, as can be readily seen by histologic evaluation of hair. We present a case of CHS in a black child.

Black People↗

The gene for leukocyte antigen-related tyrosine phosphatase (LAR) is localized to human chromosome 1p32, a region frequently deleted in tumors of neuroectodermal origin.

In situ hybridization was employed to localize a cDNA probe from the human protein tyrosine phosphatase gene LAR to human metaphase chromosomes. LAR, a putative tumor suppressor gene, has been localized to 1p32, a chromosomal region that is frequently found deleted in human neuroblastoma and pheochromocytoma.

Adrenal Gland Neoplasms↗

Synergistic effects of insulin-like growth factor I and gonadotrophins on relaxin and progesterone secretion by ageing corpora lutea of pigs.

Insulin-like growth factor I (IGF-I) is involved in paracrine/autocrine regulation of gonadal steroidogenesis and peptide hormone biosynthesis. This study was designed to determine whether IGF-I alone, or an interaction of IGF-I, is involved in augmenting the actions of luteinizing hormone (LH) and prolactin in controlling relaxin and progesterone secretion from ageing corpora lutea of hysterectomized gilts at days 110, 113 and 116 after oestrus. Luteal tissue slices were incubated for 8 h with IGF-I (0, 50, 300 ng ml-1), LH (0, 100, 1000 ng ml-1), and prolactin (0, 100, 1000 ng ml-1) alone or in combination. Progesterone and relaxin concentrations were determined by radioimmunoassay of spent medium and of homogenates from luteal tissue slices before and after incubation. Porcine luteal tissue from day 110 had a net output of 25 ng progesterone and 26 ng relaxin in the control and of 65 ng progesterone and 2125 ng relaxin in the combined IGF-I, LH and prolactin treatment mg-1 of luteal tissue, respectively. IGF-I, LH and prolactin alone or in combination significantly increased (P < 0.01) progesterone production by luteal tissue from day 110, but they were partially effective at day 113 and ineffective at day 116. By contrast, the same hormone treatments increased relaxin production by luteal tissue from days 110 and 113. Even at day 116, prolactin alone or with LH or IGF-I continued to stimulate relaxin production. In conclusion, IGF-I augments the ability of prolactin and LH to increase relaxin production by ageing corpora lutea; however, a decrease in progesterone secretion and an increase in relaxin secretion at day 113 indicate that different mechanisms control progesterone and relaxin secretion in pigs.

Animals↗