Estudio de cohorte retrospectivo de pacientes diagnosticados de cáncer de tiroides del área suroeste de Madrid. Factores pronósticos en el cáncer diferenciado de tiroides

ObjectivesTo analyze the clinical and histopathological features of patients with thyroid cancer in the southwest Madrid area and to identify poor prognostic factors in the subgroup with differentiated thyroid carcinoma (DTC) of the follicular epitelium.Patients and methodsA retrospective cohort study of patients diagnosed with thyroid cancer at our hospital from 1998 to 2009. Significant clinical, surgical, and histopathological variables were included in Cox proportional hazard and logistic regression models to identify baseline factors predicting for death, recurrence, and persistent disease in DTC.ResultsA total of 150 patients with a median age of 49 years and a median follow-up of 5.4 years were enrolled. Histological subtypes were: papillary carcinoma (86%), follicular carcinoma (6.6%), medullary carcinoma (4%), poorly differentiated carcinoma (2.7%), and anaplastic carcinoma (0.7%). At the end of the study, 68% of patients were cured, 3.3% had died (disease-specific mortality, 1.3%), 1.3% were lost to follow-up, 6.7% had persistent biochemical disease, and 2.7% persistent clinical disease, while 18% of patients were pending assessment. The best prognostic model for DTC recurrence was TNM staging (stage II-IV vs. I: HR 5.9, 95% CI 1.3-26.6), while the best model for persistent disease or death was ETA clinical staging (high risk vs. low or very low risk: OR 9.2, 95% CI 2.6-33.2).ConclusionsIn our study, disease-specific mortality and persistent clinical disease were low. Classification of DTC patients based on ETA staging after initial treatment was a good predictor of persistent disease or death.     

Gradient of nuclear volume changes in breast cancer and its relation to prognosis

OBJECTIVE: In a study of 112 cases of invasive breast cancer, the prognostic value of the gradient of nuclear volume (NV) changes was examined. STUDY DESIGN: On conventional histologic slides of surgically resected specimens, we studied the nuclear changes from early to advanced. The former was represented by the noninvasive area in the tumor periphery and the latter by the invasive area with true neoplastic stroma. We analyzed the difference in NV between the noninvasive area in the tumor periphery (NVcis) and the invasive area where the nuclei are large (NVlarge), a zone we assessed to have the greatest cancer progression. Based on these measurements, we defined NV gradient index (NVG index) as the ratio of NVlarge to NVcis. RESULTS: The NVG index in cases of cancer death (4.33 +/- 1.70, n = 35) was significantly larger than in relapsing survivors (2.76 +/- 1.31, n = 13, P = .002) and in relapse-free survivors (2.17 +/- 1.60, n = 64, P < .0003). In the group of cancer deaths, the correlation coefficient between NVG index and survival was -0.398 (0 < P < .02). Even in cases of stage I, NVG index in the group of cancer deaths (5.68 +/- 1.4) was significantly larger than in relapsing survivors (2.42 +/- 1.2) or relapse-free survivors (1.74 +/- 0.55). By multivariate analysis, NVG index was independently prognostic for disease-specific survival (P = .0001). CONCLUSION: The NVG index contributes to discrimination between possible survivors and cancer deaths. Though there are exceptions, cases with a small NVG index can be expected to survive for a longer period even after a relapse.     

Surgical treatment of prolactinomas. Short- and long-term results, prognostic factors

All 347 patients surgically treated for a prolactinoma from January 1, 1976 to December 31, 1982, in the neurosurgical ward of Foch Hospital, were retrospectively studied. The frequency of postoperative normalisation of plasma prolactin (PRL) depends on prolactinoma size, preoperative PRL level, duration of first clinical symptom, previous oestroprogestative contraception, and adenoma necrosis. Postoperative PRL values were normalized in 75% of small prolactinomas (grade 0, 1 or 2) with preoperative PRL values less than 200 ng/ml, and clinical duration less than 5 years (n = 102). There was no operative death and minor morbidity (2.7%). Among the 96 patients with postoperative PRL normalisation, operated between 1976 and 1979, 70 were followed up for an average time of 4.4 +/- 0.2 years. 17% of patients had hyperprolactinemia recurrence with a delay of 1.5 +/- 0.4 years. Postoperative PRL levels near the upper normal limit, and weak PRL response to TRH tests were found to be unfavourable prognostic factors for hyperprolactinemia recurrence. Pregnancy did not increase the risk of recurrence, but could reflect genuine long-lasting remission. Selective adenomectomy remains an interesting treatment for prolactinoma, particularly if the adenoma is small, recent and with PRL moderately increased. The frequency of postoperative PRL normalisation after surgery is less than with bromocriptine, but surgery is the only treatment able to achieve a definitive cure with a low iatrogenic risk.     

Quantitative light and electron microscopic correlations of nuclear features in papillary thyroid and ovarian carcinomas

The light microscopic (LM) and electron microscopic (EM) features of nuclear bodies and nucleoli were quantitatively compared in ten papillary carcinomas each of thyroid (PC-Thy) and ovarian (PC-Ovar) origins, along with eight nonthyroid, nonovarian papillary neoplasms from other organs (PN-Oth). In each neoplasm, 100 randomly selected nuclei were scored for the presence of characteristic nuclear bodies; these were defined at the LM level by the presence of a central density surrounded by a clear halo, which corresponded to four distinct quantifiable images at the EM level. Means (+/- standard deviations) of the nucleolar frequency factor, the nucleolar area and the computed total nucleolar area (the product of the nuclear frequency factor and the mean nucleolar area) were assessed for the EM images. The number of nuclear bodies was 11.9 +/- 10.7 for PC-Thy, 5.2 +/- 5.3 for PC-Ovar and 5.9 +/- 7.4 for PN-Oth; the means for PC-Thy and PC-Ovar were significantly different (P less than .03), as were the means for PC-Thy and PN-Oth (P less than .04). The nucleolar frequency factor was 0.60 +/- 0.19 for PC-Thy, 1.19 +/- 0.51 for PC-Ovar and 0.99 +/- 0.22 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .01) and for PC-Thy versus PN-Oth (P less than .001). The mean nucleolar area was 1.19 +/- 0.45 for PC-Thy, 1.91 +/- 0.92 for PC-Ovar and 1.94 +/- 0.76 for PN-Oth; the means were significantly different for PC-Thy and PC-Ovar (P less than .05) and for PC-Thy and PN-Oth (P less than .05). The computed total nucleolar area was 0.73 +/- 0.41 for PC-Thy, 2.17 +/- 1.09 for PC-Ovar and 1.94 +/- 1.00 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .001) and for PC-Thy versus PN-Oth (P less than .01). A comparison of the total number of nuclear bodies, as determined by both LM and EM, indicated a significant correlation for the PC-Ovar (P less than .01) and PN-Oth (P less than .001) groups using linear regression analysis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid

Nuclear grooving has recently been shown to be a useful morphologic feature in the diagnosis of papillary carcinoma of the thyroid in tissue sections and imprint smears. In order to assess the diagnostic value of nuclear grooving in cytologic specimens, the presence of this feature was evaluated in fine needle aspirates from 20 papillary carcinomas of the thyroid, 10 follicular adenomas, 3 follicular carcinomas, 1 medullary carcinoma, 10 nodular goiters and 4 cases of Hashimoto's thyroiditis. In each case, 30 random high-power fields (HPFs), or all fields in less cellular smears, were examined, and the percentage of the fields in which nuclear grooving could be seen was recorded. Seventeen of 20 papillary carcinomas (85%) showed nuclear grooves in more than 25% of the HPFs examined; in the remaining three cases, grooves were observed in less than 25% of the HPFs. In control cases (all other thyroid lesions), nuclear grooves either were absent or were present in less than 25% of the HPFs examined. These findings suggest that nuclear grooving, when seen in abundance, can be considered a reliable criterion for the diagnosis of papillary carcinoma in fine needle aspiration cytology of the thyroid. The presence of occasional grooves, however, should be regarded as a nonspecific finding.     

Uptake of erythrocyte-associated component of blood testosterone and corticosterone to rat brain

To study transport of steroids by erythrocytes, the tissue uptake of erythrocyte-associated testosterone and corticosterone was studied in vivo using a single injection technique into the carotid artery of rats. A brain uptake index (BUI) was calculated by dividing the ratio of [3H]steroid to [14C]butanol (internal reference) in the brain tissue by that in the injection material, and multiplying by 100%. BUIs of testosterone and corticosterone in an erythrocyte suspension were 131 +/- 3% (mean +/- SE, n = 6) and 57.0 +/- 2.7% (n = 6), respectively, which were greater than those in buffer (100 +/- 4%; n = 4, P less than 0.01 and 39.8 +/- 4.6%; n = 4, P less than 0.01, respectively). The erythrocyte accounted for 83.9% and 76.7% of the total testosterone and corticosterone delivered to the tissues, respectively, when calculated on the assumption that the BUIs of steroid in buffer and in the supernatant of an erythrocyte suspension are the same. BUIs of corticosterone in hemolysate and in a suspension of erythrocyte plasma membranes (60.8 +/- 7.0%; n = 4 and 69.5 +/- 3.7%; n = 4, respectively) were also greater than those in buffer (P less than 0.05 and P less than 0.01, respectively). Our results suggest that the erythrocyte-associated component of testosterone and corticosterone are delivered to the tissue of rat brain, and that their membranes may play a major role in their capacity to transport steroids to the tissues.     

Diagnostic relevance of the amino-terminal cleavage peptide of procalcitonin (PAS-57), calcitonin and calcitonin gene-related peptide in medullary thyroid carcinoma patients

We have identified the amino-terminal cleavage peptide of procalcitonin (PAS-57) in the plasma of normal human subjects and of medullary thyroid carcinoma (MTC) patients together with calcitonin (CT) and CT gene-related peptide (CGRP). Major components on reversed-phase high-pressure liquid chromatography had the retention times of synthetic PAS-57, CT and CGRP as well as of precursor proteins. Plasma levels of PAS-57 (290 +/- 50 pgeq/ml; mean +/- S.E.M.), CT (27 +/- 8 pgeq/ml) and CGRP (8.4 +/- 0.8 pgeq/ml) were respectively 2.3-, 1.6- and 1.5-fold higher in normal men (n = 10) than in women (n = 8). In response to 1 min intravenous calcium infusions (2 mg per kilogram body weight) PAS-57 and CT were increased 3.5- and 2.7-fold (P less than 0.001), respectively, but CGRP remained unchanged. In MTC patients (n = 57) with raised levels of PAS-57 and CT, the molar ratio between PAS-57 and CT was 1.7-times higher than in normal subjects (P less than 0.01). We have found that PAS-57 is a predominant CT/CGRP gene derived product in the circulation of normal subjects and of MTC patients and a potential new MTC tumor marker.     

Implications of nuclear diameter in small cell lung carcinoma

The nuclear diameter of 5,117 malignant cells from 42 small cell lung carcinoma (SCLC) patients was assessed either on pretreatment tissue sections (35 cases) or cytologic smears (7 cases) by ocular micrometry. The SCLCs were subtyped as 30 oat cell carcinomas and 12 intermediate cell carcinomas according to the World Health Organization classification, based on the predominant histology of the tumor. The median number of nuclei measured from each patient was 110. All patients were treated identically by sequential hemibody and local irradiation combined with chemotherapy and had a median follow-up time of 310 days. The mean nuclear diameter (+/- standard error) obtained from tissue sections was 8.2 +/- 0.03 microns (median = 8.0), including 7.3 +/- 0.03 microns (median = 7.0) for oat cell cases and 9.5 +/- 0.06 microns (median = 9.0) for intermediate cell cases (P less than .001). In 28.6% of these patients, the nuclear diameter overlapped in the range of 8 microns to 9 microns between both subtypes. Comparisons between the nuclear diameter of primary and metastatic SCLC cells revealed no statistically significant differences. The nuclear diameter of malignant cells correlated with the mitotic index and stage of disease, but did not correlate with the other nuclear morphologic variables or with survival. The only identified prognostic factor was the stage of disease; these results indicate that the nuclear diameter of malignant cells should not be considered a prognosticator or a guide for therapy in SCLC patients.     

The nude rat is established as a model for endocrine studies: regulation of thyroid function and xenotransplantation of a thyroid tumor cell line.

The thyroid physiology of athymic nude rats, rnu/rnu, is characterized and established here as an animal model to study transplanted thyroid tumors. Male rats were catheterized 5 days before experiments were started. The mean thyroid-stimulating-hormone (TSH) plasma concentrations were 2.9 +/- 0.6 ng/ml during infusion of 0.25 ml/h of 0.9% NaCl (n = 12). T3 plasma concentrations were 2.6 +/- 0.4 ng/ml. T4 plasma levels were 22.0 +/- 5.6 micrograms/dl. A bolus of 0.1 mg thyrotropin-releasing hormone (TRH) significantly increased TSH plasma concentrations (P less than or equal to 0.001; from 2.9 +/- 0.6 to 7.8 +/- 1.1 ng/ml, n = 12). No pulsatile TSH secretion was observed in a 2-hour period with blood samples taken every 10 minutes (n = 12) and hourly sampling disclosed no circadian variation of TSH during a 24-hour period (n = 4). Successful xenografting was possible in 12 of 15 cases using a follicular thyroid carcinoma cell line (FTC 133). Measurement of human thyroglobulin (hTg) by a hTg IRMA revealed high levels in rats with functional FTC tumors, whereas no hTg was detected in untransplanted rats or animals with nonfunctional transplants.     

Evaluating the diagnostic significance of nuclear grooves in thyroid fine needle aspirates with a semiquantitative approach

OBJECTIVE: To clarify the diagnostic significance of nuclear grooves in thyroid fine needle aspirates, to search for other associated nuclear features and to identify possible diagnostic pitfalls. STUDY DESIGN: In total, 67 fine needle aspiration cases were retrospectively reviewed for selected nuclear features, including grooves, intranuclear cytoplasmic invaginations, enlargement, pleomorphism and status of nucleoli. A semiquantitative method was used to estimate the percentage of nuclear grooves in 5 high-power fields with the most frequent nuclear grooves. RESULTS: Unequivocal intranuclear cytoplasmic invaginations were a specific diagnostic feature of papillary carcinoma. In the absence of intranuclear cytoplasmic invaginations, the presence of > or = 20% nuclear grooves was virtually diagnostic of thyroid neoplasms, predominantly papillary carcinoma. Less than 10% of nuclear grooves virtually eliminated the possibility of papillary carcinoma. However, 10-19% of nuclear grooves may be seen in papillary carcinoma and benign lesions; therefore, such cases fell into the diagnostic category of "atypical cytology" or "indeterminate" cytology. Nuclear enlargement with elongation was a readily identifiable feature usually associated with nuclear grooves. Significant pleomorphism was more commonly seen in papillary carcinoma than in benign lesions. CONCLUSION: A semiquantitative method is helpful when nuclear grooves are encountered in thyroid cytology in the absence of other diagnostic features. It can significantly improve the diagnostic specificity of nuclear grooves for papillary carcinoma.     

Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm

Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (P(int)). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, P(int) were calculated with nonlinear regression. The P(int) at the level of the septal artery (diameter, 150-250 microm) was 23.2 +/- 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 microm, P(int) was 1.7 +/- 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, P(int) was 1.1 +/- 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 microm. The second waterfall is probably located in the small postcapillary venules.     

Mean nuclear volume in ovarian papillary serous cystadenocarcinoma

OBJECTIVE: To measure mean nuclear volume (MNV), estimated by the stereologic intercept method, in ovarian serous carcinomas and to compare that between omentum-positive cases (cases with omental metastasis) and -negative cases. STUDY DESIGN: This retrospective study consisted of 29 cases (stage I and II = 13 cases, and stage IIIb = 16 cases) of ovarian papillary serous cystadenocarcinoma. MNV of all cases (at primary and metastatic sites) was estimated with an image cytometer. The nuclear point intersection method was used to measure nuclear volume. Mean intercepted diameters of at least 50 nuclei were measured. MNV was correlated with histologic grade, International Federation of Gynecology and Obstetrics (FIGO) staging of ovarian malignancy and primary tumor versus metastatic deposits. RESULTS: MNVs estimated in omentum-negative (FIGO stage I and II) and omentum-positive (FIGO stage IIIb) cases were 1,022.48 +/- 608.45 and 2,152 +/- 1,317.51 microns 3 (P = .05, Student t test), respectively. Significant differences in MNV were also observed among the different grades of tumor. However, no significant difference was observed between MNVs of primary and metastatic tumors in omentum-positive cases. CONCLUSION: Estimates of MNV on conventional histopathology sections may provide objective and useful criteria for relatively subjective histopathology grading and staging (FIGO stage I and II vs. IIIb).     

Preoperative cytologic morphometry may assist in predicting patient outcome after surgery in papillary thyroid cancer

OBJECTIVE: To evaluate the quantitative estimations of various cytologic nuclear features on smears obtained by preoperative fine-needle aspiration and to examine their correlation with patient outcome after surgery for papillary thyroid cancer. STUDY DESIGN: The subjects consisted of 142 patients with common type papillary thyroid cancer. The aspirated smears were examined quantitatively with a standard microscope connected to a computerized video system, and the mean nuclear area, nuclear perimeter, form factor (FF) and the coefficient of variation of the nuclear area (NACV) were measured and calculated. All of the surgically treated patients were followed through serial clinical evaluations, and correlations between the cytologic parameters and patient outcomes were analyzed. RESULTS: Local relapses or distant metastases were identified in 13 (9.2%) of the 142 patients in the median follow-up period of 160 (range, 108-234) months. Recurred cases had higher FF values than disease-free cases (p = 0.0017), especially in local relapse (p = 0.0015). Distant metastases were frequently observed in the cases with a high NACV value (p = 0.0020). CONCLUSION: Preoperative quantitative estimations of cytologic nuclear features provide preoperative clinical information that may predict patient outcome and be useful for designing individual protocols.     

Diastolic pressure determines autonomic responses to pressure perturbation in humans

Arterial baroreceptors reflexly regulate sympathetic and heart rate responses to alteration of blood pressure. The primary mechanical determinant of arterial baroreceptor activity in humans remains unclear. We examined the influence of systolic, diastolic, pulse, and mean arterial pressures on efferent muscle sympathetic nerve activity (MSNA, microneurography) and heart rate responses during perturbation of arterial pressure in 10 normal human subjects [age 25 +/- 2 (SE) yr]. We directly measured arterial pressure, heart rate, and MSNA during intravenous vasodilator infusion (nitroprusside, 6 +/- 1 micrograms.kg-1.min-1, n = 6; or hydralazine, 16 +/- 2 mg, n = 4) while central venous pressure was held constant by simultaneous volume expansion. Changes in arterial pressures were compared with changes in heart rate and MSNA over 3-min periods of vasodilator infusion during which we observed increases in systolic and pulse pressures with simultaneous decreases in mean and diastolic pressures. During vasodilator infusion, there were increases in systolic (124.2 +/- 2.1 to 131.7 +/- 2.9 Torr, P less than 0.001) and pulse pressures (57.0 +/- 2.2 to 72.7 +/- 2.7 Torr, P less than 0.001) although mean arterial pressure fell (88.0 +/- 2.6 to 80.4 +/- 2.7 Torr, P less than 0.001) because of decreases in diastolic pressure (67.2 +/- 3.0 to 59.0 +/- 2.7 Torr, P less than 0.001). The changes in arterial pressures were accompanied by simultaneous increases in heart rate (66.4 +/- 3.0 to 92.6 +/- 4.8 beats/min, P less than 0.001) and MSNA (327 +/- 59 to 936 +/- 171 U, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma.

Anemia may worsen neurological outcomes following traumatic brain injury (TBI) by undefined mechanisms. We hypothesized that hemodilutional anemia accentuates hypoxic cerebral injury following TBI. Anesthetized rats underwent unilateral TBI or sham injury (n > or = 7). Target hemoglobin concentrations between 50 and 70 g/l were achieved by exchanging 40-50% of the blood volume (1:1) with pentastarch. The effect of TBI, anemia, and TBI-anemia was assessed by measuring brain tissue oxygen tension (Pbr(O(2))), regional cerebral blood flow (rCBF), jugular venous oxygen saturation (Sjv(O(2))), cerebral contusion area, and nuclear staining for programmed cell death. Baseline postinjury Pbr(O(2)) values in the TBI and TBI-anemia groups (9.3 +/- 1.3 and 11.3 +/- 4.1 Torr, respectively) were lower than the uninjured controls (18.2 +/- 5.2 Torr, P < 0.05 for both). Hemodilution caused a further reduction in Pbr(O(2)) in the TBI-anemia group relative to the TBI group without anemia (7.8 +/- 2.7 vs. 14.8 +/- 3.9 Torr, P < 0.05). The rCBF remained stable after TBI and increased comparably after hemodilution in both anemia and TBI-anemia groups. The Sjv(O(2)) was elevated after TBI (87.4 +/- 8.9%, P < 0.05) and increased further following hemodilution (95.0 +/- 1.6%, P < 0.05). Cerebral contusion area and nuclear counts for programmed cell death were increased following TBI-anemia (4.1 +/- 3.0 mm(2) and 686 +/- 192, respectively) relative to TBI alone (1.3 +/- 0.3 mm(2) and 404 +/- 133, respectively, P < 0.05 for both). Hemodilutional anemia reduced cerebral Pbr(O(2)) and oxygen extraction and increased cell death following TBI. These results support our hypothesis that acute anemia accentuated hypoxic cerebral injury after neurotrauma.     

Successful management of differentiated thyroid cancer in a community-based endocrine practice

ObjectiveTo describe the range of differentiated thyroid cancer (DTC) cases, disease complexity, and treatment outcomes seen in our 3-physician community-based general endocrine practice during an 8-year period in order to make comparisons with published cohorts from university settings.MethodsMedical records of patients with DTC treated between 2002 and 2009 at Mountain Diabetes and Endocrine Center (Asheville, North Carolina) were reviewed. Pathologic features, staging, and disease status at last contact were determined. Multivariate analyses of adverse prognostic risk factors at diagnosis, recombinant human thyroid-stimulating hormone use, and radioiodine use were compared with the ultimate outcome of patients.ResultsWe treated a total of 167 patients with DTC during the study period (mean age at diagnosis, 44.4 years; mean duration of follow-up, 6.2 years). In our study cohort, 88.6% had papillary thyroid cancer, 74% had stage I disease, and 32.4% of those with papillary thyroid cancer had microscopic tumors (≤ 1 cm). Remission occurred in 67.1%, 17.1% had persistent disease, and 11.8% were indeterminate for remission; non-thyroid cancer death occurred in 2.6% and disease-specific death in 1.3%. The mean number of adverse prognostic risk factors per patient was 2.0 in those with remission and 4.7 in those with persistent disease.ConclusionCommunity-based endocrinologists evaluate the full spectrum of thyroid cancer disease complexity and can achieve excellent outcomes. In our current study group, disease persistence and diseasespecific death occurred in 17.1% and 1.3%, respectively. Individualization of care based on prognostic variables guided our diagnostic and therapeutic decisions. (Endocr Pract. 2012;18:170-178)     

Seasonal variation in hypothalamic content of gonadotropin-releasing hormone (GnRH), pituitary receptors for GnRH, and pituitary content of luteinizing hormone and follicle-stimulating hormone in the mare

Seasonal changes in the hypothalamic-hypophyseal axis were investigated using tissue from 49 light-horse mares, of mixed breeding. Hypothalamic and pituitary tissues were collected at 5 intervals throughout the years 1981 and 1982, representing midbreeding season (July, n = 10), transition out of the breeding season (October, n = 11), midanestrus (December, n = 8), transition into the breeding season (March, n = 10), and again in the following midbreeding season (July, n = 10). The hypothalamic region was dissected into preoptic area, body and median eminence. Gonadotropin-releasing hormone (GnRH) was extracted from hypothalamic samples with methanol-formic acid and quantified by radioimmunoassay. The anterior pituitary was homogenized and receptors for GnRH were quantified in a crude membrane fraction. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in the resulting supernatant. Content of GnRH in each of the 3 hypothalamic areas varied with season (P less than 0.01) and was lowest during midanestrus (P less than 0.05). There was no effect of season (P greater than 0.01) on either concentration or total number of receptors for GnRH, or concentration of FSH in the anterior pituitary. Concentrations of LH in the anterior pituitary varied with season (P less than 0.001). Means (+/- SEM) for the 5 collection times were 15.5 +/- 2.7, 9.7 +/- 2.4, 2.3 +/- 0.5, 2.7 +/- 0.4 and 11.7 +/- 1.5 microgram LH/mg anterior pituitary, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung weight in vivo measured with computed tomography and rebreathing of soluble gases

In nine anesthetized dogs, accuracy of noninvasive measurements of lung weight (W) and gas volume in vivo was determined from volume and density determined by computed tomography (CT) and by rebreathing helium and the soluble gases dimethyl ether (WDME) and acetylene (WC2H2). Reference standards were obtained from the postmortem scale weight of the frozen lungs (Wscale) and compared with the CT lung weights measured in the living dog (WCT-38) and the frozen carcass (WCT-cold). WCT-cold did not significantly differ from Wscale [-2 +/- 9% (SD), P = 0.7]. WCT-cold was 10% greater than WCT-38 (0.10 greater than P greater than 0.05), suggesting an increase in lung weight despite immediately commencing freezing after death. WDME measured 64 +/- 6% and WC2H2 56 +/- 12% of WCT-38. Serial multiple measurements in three dogs over 14 wk showed a coefficient of variation (CV) of 10 +/- 2% for WDME, 18 +/- 2% for WC2H2, 4.1 +/- 0.9% for WCT, 2.6 +/- 0.8% for CT density, and 3.5 +/- 1.6% for functional residual capacity (FRC) by CT. FRC calculated from CT consistently underestimated FRC measured by rebreathing helium by 18 +/- 8% (P less than 0.005). This error, despite good agreement between WCT and Wscale, was explained by underestimation of CT total lung volume and overestimation of lung density by factors known to affect CT readings, such as partial volume effects, beam hardening, and limited number of input signals. These data show that CT scanning can provide serial measurement of the mass, density, and volume of the lungs with a CV in the order of 5%, but the rebreathing of soluble gases gives more than double this variability. Measurements of WDME performed on the same day had a CV of 3 +/- 1%, so that WDME provides a precise noninvasive means to measure lung weight in acute studies.     

Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease.

To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of oxytocin and PGF2alpha on the uterine involution and pregnancy rates in postpartum Arabian mares

In this study, the effects of oxytocin and an analog of prostaglandin (cloprostenol) on the uterine involution and pregnancy rates were investigated. Mares received 3 ml of 0.9% NaCl in Group C (n=10), 30 IU/mare of oxytocin in Group O (n=10) and 250 microg/mare of cloprostenol in Group P (n=10) within 12h after parturition. The gravid uterine horn's cross-sectional diameter was measured by ultrasonography. The mean uterine diameters did not differ significantly between the treatment (O and P) and the control (C) groups (p>0.05). The difference between the postpartum ovulation periods (Group C: 12.6+/-0.72 days, Group O: 15+/-1.33 days, Group P: 14.6+/-1.11 days), the pregnancy rates at foal heat (Group C: 60%, Group O: 60%, Group P: 80%) and the embryonic death rates at foal heat (Group C: 33.3%, Group O: 16%, Group P: 25%) were not found to be statistically significant between the treatment and the control groups. The mean progesterone concentrations were similar in all groups and decreased continuously from parturition to until foal heat (Group C: from 2.43+/-0.24 to 0.66 ng/ml, Group O: from 3.07+/-0.6 to 0.27+/-0.27 ng/ml and Group P: from 2.8+/-0.44 to 0 ng/ml) (p>0.05). In conclusion, it was decided that the oxytocin and PGF2alpha treatments performed on the mares with the purpose of stimulating involution had no effect on the duration of parturition-first ovulation, the shrinkage of the uterus diameter, the pregnancy and embryonic death rates.