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P A Findlay

Publications and source records attributed to P A Findlay.

30 records · Page 2Linked to original sources

Dietary excesses of urea influence the viability and metabolism of preimplantation sheep embryos and may affect fetal growth among survivors.

In the first of two experiments investigating the effect of dietary urea on the survival and metabolism of ovine embryos, 30 Border Leicester x Scottish Blackface ewes received a maintenance diet (milled hay, molasses, minerals, vitamins) with no urea (control, C; n = 10) or with added urea at 15 g (low urea, LU; n = 10) or 30 g (high urea, HU; n = 10) kg-1 feed for a 12 week period. The degraded nitrogen (N) status relative to estimated rumen microbial N requirements was -2, +9 and +20 g per day, respectively. One week after allocation to diets, progesterone priming (12 days) commenced. Ewes received 800 IU of equine chorionic gonadotrophin at progesterone withdrawal, were inseminated 52 h later (Day 0) and embryos were collected from five ewes per group at Day 4 and from five ewes at Day 11. If available, one embryo was returned to each ewe; the rest were cultured in vitro. There was no effect of treatment on progesterone, luteinizing hormone (LH), or time of oestrus onset C, LU and HU plasma urea (P < 0.001) and ammonia levels (C vs. HU, P < 0.01; LU vs. HU, P < 0.05) differed. Day 4 HU embryos were retarded relative to C and LU embryos. After 3 days of culture, 70%, 66% and 0% of C, LU and HU embryos, respectively, were viable. Mid-term pregnancy rates following transfer were 63%, 43% and 33%. Only one HU lamb (male) was born following embryo transfer, its birthweight (10.1 kg) exceeded that of its C (n = 3; 7.0, 7.0, 7.5 kg) and LU (n = 2; 7.3, 8.2 kg) counterparts (P < 0.025). In the second experiment, C2 (2.5 g urea kg-1; n = 5) and HU2 (30 g kg-1; n = 7) diets which provided similar intakes of degraded N relative to microbial requirements as those for C and HU ewes in Experiment 1 were fed to Border Leicester x Scottish Blackface ewes superovulated with 16 mg of porcine follicle-stimulating hormone. Urea and ammonia levels in utero-oviductal samples were elevated in HU2 ewes (P < 0.05). At collection (Day 3), HU2 embryos used more glucose (P < 0.01) and, following culture, some exhibited up to a 2.8-fold increase in metabolism. In conclusion, excess rumen degradable N in ewe diets elevates urea and ammonia in plasma and in utero, with an associated increase in embryo mortality. Nevertheless, metabolism appears to be up-regulated in some embryos and, among those that survive, fetal growth appears to be enhanced.

Ammonia↗

Effect of nutrition on testicular growth and plasma concentrations of gonadotrophins, testosterone and insulin-like growth factor I (IGF-I) in pubertal male Soay sheep.

Nutritional effects on puberty were studied in Soay rams. Testicular growth is initiated at birth in April and testes reach maximum size in October. Groups of eight lambs were fed for 18 weeks, starting in August, a ration that restricted growth (Group R), the same diet ad libitum (Group F), or a restricted diet for 8 weeks followed by ad libitum feeding (Group R/F). Seasonal increases of plasma FSH, testis size, sexual skin flush and plasma testosterone occurred with similar timing but reduced magnitude in Group R compared with Group F lambs. Testis size and sexual skin flush peaked in all groups at 11 weeks (30 October); the testes of Group F animals were larger before the peak, but similar in size thereafter, compared with testes from Group R/F, and larger throughout the experimental period than testes from Group R. Plasma testosterone was higher in Group F than in Group R lambs from 7 to 17 weeks, but in Group R/F was similar to Group R before 10 weeks (23 October) and similar to Group F thereafter. Testis size, plasma testosterone, plasma insulin-like growth factor I (IGF-I) and liveweight were positively correlated. Ad libitum feeding in August-September (Group F) stimulated increased plasma FSH and LH above values for Group R, but ad libitum feeding initiated in October did not affect gonadotrophin concentrations (Group R/F). Therefore, the effects of improved nutrition on the hypothalamo-pituitary axis, which may have been mediated by circulating IGF-I, were season- or age-dependent, and those on the testes included direct stimulation, independent of changes in gonadotrophin concentrations. Nutrition modified the intensity, but not the timing, of peak pubertal reproductive activation.

Animal Nutritional Physiological Phenomena↗

Effect of chronic food restriction on pulsatile luteinizing hormone secretion and hypothalamic neuropeptide Y gene expression in castrate male sheep.

Castrate male sheep (wethers, average liveweight 38 +/- 0.6 kg) were given one of the following diets for 10 weeks followed by euthanasia (n = 8/group): high-energy high-protein providing 1-5 times the energy required to maintain liveweight (maintenance) (group 1.5 M), low-energy low-protein at 0.5 maintenance (0.5 M), or low-energy high-protein at 0.5 maintenance (0.5 M + P). 1.5 M wethers gained 22% liveweight whereas 0.5 M and 0.5 M + P wethers lost 18 and 13% liveweight respectively. Relative to the 1.5 M group, the 0.5 M and 0.5 M + P groups had similar plasma concentrations of glucose and cortisol throughout, but elevated non-esterified fatty acids (P < 0.001) and reduced IGF-I and insulin (P < 0.05, 0.01 or 0.001) from 1 week onwards. Each week blood samples were taken every 12 min for 4 h and plasma assayed for LH. Mean concentration over 4 h, LH pulse frequency and LH pulse amplitude showed no progressive change in 1.5 M sheep. However, in both 0.5 M and 0.5 M + P groups mean LH increased (P < 0.001 and P < 0.01 respectively), pulse frequency decreased (P < 0.01 and P < 0.01) and pulse amplitude increased (P < 0.001 and P < 0.01) over the 10-week period. Anterior pituitary. LH content was greater in 0.5 M (P < 0.01) and 0.5 M + P (P < 0.05) than in 1.5 M sheep. Coronal sections (20 microns) of hypothalamic brain tissue were subjected to in situ hybridisation to determine gene expression for neuropeptide Y (NPY). NPY mRNA was concentrated in the arcuate nucleus and median eminence, with total amounts greater in both 0.5 M (310%, P < 0.001) and 0.5 M + P (333%, P < 0.01) groups than in 1.5 M sheep (100%). These data reveal that chronic low dietary energy intake by long-term castrates, with high or low protein intake, reduces LH pulse frequency but increases the circulating levels of LH by virtue of an increase in pulse amplitude, and concomitantly increases hypothalamic NPY gene expression.

Animals↗

The NCI-atlas of dose distributions for regular 125I brain implants.

In connection with the development of an optimization method for 125I brain implants in irregularly shaped target volumes, a systematic study was conducted toward optimizing seed configurations for regular target volumes. The intention was to find basic rules for the positioning of strings of seeds in the cylindrical implant pattern of the stereotactic neurosurgical procedure in use, and in accordance with the following criteria: (i) steep dose fall-off outside the target volume; (ii) coverage of the target volume by making the prescribed dose surface coincident with the target volume surface within 1 mm; (iii) uniformity of the dose distribution in the target volume as far as achievable with a seed implant. As a result of this study, an atlas of optimized regular 125I brain implant configurations was compiled. Regular implants were understood as being cylindrical or spherical. Diameters and heights from 2 to 5 cm were covered.

Brachytherapy↗

Complete axillary lymph node dissection for stage I-II carcinoma of the breast.

We reviewed the complete axillary dissection specimens of 136 patients with stage I-II breast cancer to clarify the distribution of axillary lymph node metastases in this disease. Our series included 71 patients undergoing axillary dissection as part of a modified radical mastectomy (MRM) and 65 patients undergoing axillary dissection in conjunction with conservative surgery of the breast and definitive postoperative breast radiotherapy (CAD). These two groups of patients were comparable according to age, menopausal status, tumor size, and clinical stage. In all patients the pectoralis minor muscle was excised and all axillary tissue removed. Each specimen contained a median of 23 lymph nodes. The axillary levels (I, II, III) were determined according to the relationship of axillary tissue to the pectoralis minor muscle (lateral, inferior, medial). Thirty-nine percent of the lymph nodes were contained in level I, 41% in level II, and 20% in level III. There were no significant differences noted in the number of lymph nodes or in the distribution of lymph nodes according to axillary level between dissections performed as part of the MRM or those done as a single procedure (CAD). Sixty-five patients (47.8%) had one or more positive lymph nodes in their axillary specimen. The clinical and pathologic stage was determined and compared for all patients. Among patients judged to have a clinically negative axilla, 37.6% had histologically positive lymph nodes (clinical false-negative rate). For patients with a clinically positive axilla, 11.1% had, histologically, no evidence of metastatic disease (clinical false-positive rate). When the distribution of lymph node metastases according to axillary level was studied, it was found that 29.2% of lymph node-positive patients (or 14.0% of all patients) had metastases only to level II and/or III of the axilla, with level I being negative (skip metastases). This incidence of skip metastases was greater among clinically node-negative than among clinically node-positive patients, but was not related to the size or location of the primary tumor in the breast. In addition, it was found that 20.0% of lymph node-positive patients (or 9.6% of all patients) were converted from three or fewer to four or more positive nodes by analysis of lymph nodes contained in levels II and III. This conversion from three or fewer to four or more positive nodes was due primarily to information contained in level II, with level III contributing to a smaller degree.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

125I interstitial brachytherapy for primary malignant brain tumors: technical aspects of treatment planning and implantation methods.

Use of interstitial radiation holds promise in the treatment of primary malignant brain tumors, but optimal technical factors have yet to be determined. We have developed a method of precise CT directed stereotactic placement of radioactive sources in a predetermined target volume. We use low activity (1-2 millicurie/speed) sources of 125I loaded in silastic catheters, which are positioned in a parallel array in the target. Positioning of such multiple sources toward the periphery of the volume enhances achievable dose homogeneity. Seeds of various activities can be differentially loaded into each catheter and the catheters can be positioned at various radii from the central target so that the treated volume corresponds to the identified (often irregular) target volume. Although the implant is designed to be permanent, the sources can be removed easily in a second procedure.

Brachytherapy↗

Kaposi's sarcoma of the head and neck in the acquired immune deficiency syndrome.

Since 1981 a new syndrome of acquired immune deficiency (AIDS) has been recognized. Male homosexuals, male and female intravenous drug abusers, and recipients of blood products (i.e., hemophiliacs) appear to be the populations at risk. The syndrome has been manifested by community-acquired opportunistic infections and/or Kaposi's sarcoma (KS). Otolaryngologic manifestations of AIDS are not infrequent. Thirteen AIDS patients at the National Institutes of Health with KS of the head and neck region are presented. All 13 patients were homosexual or bisexual males. Nine initially presented with KS, five with KS of the head or neck. As a group the patients demonstrated lesions involving the oropharyngeal, tracheobronchial, and gastrointestinal regions. Their clinical course and complications are presented in detail. The mortality rate in this subgroup of AIDS patients is extraordinarily high (62%), with an average longevity of 11 months following initial diagnosis.

Acquired Immunodeficiency Syndrome↗

Pharyngeal obstruction by Kaposi's sarcoma in a homosexual male with acquired immune deficiency syndrome.

A homosexual man with AIDS developed multifocal KS with involvement of the palate, larynx, trachea, and esophagus. Symptoms included dysphagia and gagging with resultant inanition. Short-course local radiation therapy effectively resolved the mucosal KS lesions in the treated areas. Other otolaryngologic manifestations included herpes stomatitis and oral candidiasis.

Acquired Immunodeficiency Syndrome↗

Rapid, accurate, three-dimensional location of multiple sees in implant radiotherapy treatment planning.

The three-dimensional (3D) locations of the radioactive seeds in an interstitial implant can be obtained from stereo-shift or orthogonal radiographs. When an implant contains a large number of seeds, however, there are often ambiguities in identifying corresponding seed images on two radiographs. Our method achieves accurate spatial locations by using three radiographs whose x-ray source positions are (i) in a plane which does not intersect the implant and (ii) widely separated to achieve adequate parallax. All triangulation is done in an anatomical coordinate reference frame attached to the patient so that patient motion does not introduce errors. We achieve independent error-insensitive calibration of each radiograph, rapid and accurate data entry in the local coordinates of each radiograph, 3D seed location in the patient (anatomical) reference frame, and automatic verification of each calculation.

Brachytherapy↗