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PubMed2004

Endometrial adenocarcinoma in situ in complex atypical hyperplasia: correlation with findings in subsequent hysterectomy specimen.

Well-differentiated endometrial adenocarcinoma can be difficult to distinguish from complex atypical hyperplasia (CAH) in a curettage or biopsy specimen. When a focus of back-to-back glands or cribriforming smaller than 2.1 mm is seen in a biopsy, we make a diagnosis of adenocarcinoma in situ (AIS). Whether this diagnosis translates into a more frequent diagnosis of carcinoma on the hysterectomy specimen is unknown. The objective of this study was to compare follow-up hysterectomy findings in biopsies showing AIS in CAH with biopsies showing only CAH without AIS. Twelve biopsy/curettage cases diagnosed as endometrial AIS in CAH and 12 biopsy/curettage cases diagnosed as CAH only were reviewed and correlated with corresponding hysterectomy material. A diagnosis of AIS was designated on biopsy/curettings when a focus of back-to-back glands or cribriforming less than 2.1 mm was present. Hysterectomy specimens showed endometrial carcinoma in 6 (50%) of 12 cases of CAH with AIS, and in 2 (17%) of 12 cases diagnosed as CAH only. Endometrial carcinoma with myometrial invasion was identified in 5 (42%) of the cases showing AIS on biopsy, but in none of the 12 cases diagnosed as CAH only on biopsy. Identification of AIS in CAH cases provides useful prognostic information.

Adenocarcinoma↗

PubMed2006

Defining the role of aromatase inhibitors in the adjuvant endocrine treatment of early breast cancer.

BACKGROUND: Over the past few years, data have been published concerning the relative efficacy and safety profiles of tamoxifen and the aromatase inhibitors (AIs) in the adjuvant therapy setting for women with early hormone receptor-positive breast cancer. Recently, debate has centred around trials which have studied primary tamoxifen and AI therapy, switching and sequencing strategies and extended adjuvant therapy. METHODS: Here, a group of 24 breast cancer experts review efficacy and safety data from the recent major trials investigating tamoxifen and the third-generation AIs in postmenopausal women, which have challenged the perception of tamoxifen as optimum adjuvant endocrine therapy. Data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, Breast International Group (BIG) 1-98 study, National Cancer Institute of Canada MA 17 trial, Intergroup Exemestane Study (IES), Italian Tamoxifen Anastrozole (ITA) trial, Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8 and Arimidex-Nolvadex (ARNO) 95 are considered to provide a rational interpretation of the impact of these data on current practice, and to highlight areas where further investigation is needed. CONCLUSION: We can be confident that AIs represent superior adjuvant endocrine treatment to tamoxifen in postmenopausal women, either as initial therapy or as an alternative for women who have started adjuvant therapy with tamoxifen. However, there remain issues regarding the best way to use AIs, such as the optimal length of AI treatment and how a sequence of tamoxifen followed by an AI compares with AI monotherapy; these will require further data to resolve.

Antineoplastic Agents, Hormonal↗

PubMed2006

Adjuvant endocrine therapy for postmenopausal breast cancer in the era of aromatase inhibitors: an update.

There is overwhelming evidence that optimal adjuvant endocrine therapy for hormone sensitive breast cancer in postmenopausal women should include a third generation aromatase inhibitor (AI). On current evidence, adjuvant anstrozole or letrozole should be used upfront in such patients especially in those with high risk disease (node positive and/or tumours > 2 cm). The sequential approach of tamoxifen for 2-3 years followed by exemestane or anastrozole for 2-3 years is a reasonable alternative to 5 years of AI monotherapy in patients with low risk disease (node negative and tumour smaller than 2 cm) especially if the tumour is positive for estrogen and progesterone receptors.Node-positive patients completing 5 years of adjuvant tamoxifen should be offered letrozole for up 48 months. Further research is required to establish the long-term cardiovascular safety of AIs especially that of letrozole and exmestane, the optimal AI to use, duration of AI therapy and whether monotherapy with an AI for 5 years is superior to sequencing an AI after 2-3 years of tamoxifen. The bone mineral density (BMD) should be measured at baseline and monitored during therapy in women being treated with AIs. Anti-osteoporosis agents should such as bisphosphonates should be considered in patients at high risk of bone fractures.

Editorial↗

PubMed2006

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer.

INTRODUCTION: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. This study evaluated changes in Ki-67 labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy. METHODS: Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. Tissue from pre-treatment biopsy, day 21 and surgery was analysed for Ki-67 index and AI. RESULTS: The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histological criteria; two patients had a near-complete pathological response. A reduction in Ki-67 index was observed in 68% of patients at day 21 and 72% at surgery; Ki-67 index increased between day 21 and surgery in 54%. AI decreased in 50% of tumours by day 21, increased in 45% and was unchanged in one patient; 56% demonstrated rebound increases in AI by the time of surgery. Neither pre-treatment nor post-chemotherapy median Ki-67 index nor median AI at all three time points or relative changes at day 21 and surgery differed significantly between clinical or pathological responders and non-responders. Clinical responders had lower median Ki-67 indices at day 21 (11.4% versus 27.0%, p = 0.02) and significantly greater percentage reductions in Ki-67 at day 21 than did non-responders (-50.6% versus -5.3%, p = 0.04). The median day-21 Ki-67 was higher in pathological responders (30.3% versus 14.1%, p = 0.046). A trend toward increased AI at day 21 in pathological responders was observed (5.30 versus 1.68, p = 0.12). Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive markers is available, clinical decision-making should not be based upon individual biological tumour marker profiles.

Adult↗

PubMed2005

Review: aromatase inhibitors for ovulation induction.

CONTEXT: For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION: We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS: Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.

Anovulation↗

PubMed2000

The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome.

Although androgen status affects bone mass in women and men, an androgen requirement for skeletal normalcy has not been established. Women with androgen insensitivity syndrome (AIS) have 46,XY genotypes with androgen receptor abnormalities rendering them partially or completely refractory to androgen. Twenty-eight women with AIS (22 complete and 6 high grade partial), aged 11-65 yr, responded to questionnaires about health history, gonadal surgery, and exogenous estrogen use and underwent bone mineral density (BMD) assessment by dual energy x-ray absortiometry. BMD values at the lumbar spine and proximal femur were compared to age-specific female normative values and listed as z-scores. Average height for adults in this cohort, 174 cm (68.5 in.), was moderately increased compared with the average height of adult American women of 162.3 cm, with skewing toward higher values: 5 women exceeded 6 ft in height, and 30% of the 18 adult women with complete AIS exceeded 5 ft, 11 in. in height. The average lumbar spine and hip BMD z-scores of the 6 women with partial AIS did not differ from population norms. In contrast, the average lumbar spine BMD z-score of women with complete AIS was significantly reduced at -1.08 (P = 0.0003), whereas the average value for hip BMD did not differ from normal. When BMD was compared between women who reported good estrogen replacement therapy compliance and those who reported poor compliance, there was a significantly greater deficit at the spine for women with poor compliance (z = -2.15 +/- 0.15 vs. -0.75 +/- 0.28; P < .0001). Furthermore, hip BMD was also significantly reduced in the noncompliant group (z = -0.95 +/- .40). Comparison of BMD values to normative male standards gave z-score reductions (z = -1.81 +/- 0.36) greater than those observed with female standards. Because of the high prevalence of tall stature in this study sample, we calculated bone mineral apparent density, a variable that adjusts for differences in bone size. Even for the estrogen-compliant group, bone mineral apparent density z-scores were subnormal at both the spine (z = -1.3 +/- 0.43; P < 0.01) and the hip (z = -1.38 +/- 0.28; P = 0.017). Six women with complete AIS had sustained cortical bone fractures, of whom 3 reported multiple (>3) fractures. We conclude that even when compliance to exogenous estrogen use is excellent, women with complete AIS show moderate deficits in spine BMD, averaging close to 1 SD from normative means, and that with correction of BMD for bone size, skeletal deficits are magnified and include the proximal femur. The results suggest that severe osteopenia in some women with AIS probably reflects a component of inadequate estrogen replacement rather than androgen lack alone.

Adult↗

PubMed2001

Bone loss rate in adrenal incidentalomas: a longitudinal study.

Although by definition patients with adrenal incidentalomas (AI) do not have evident clinical syndromes, they may frequently suffer from subclinical hypercortisolism (SH). This is of some importance because of evidence that SH may lead to clinical complications, including bone loss. Thus, the understanding of bone involvement due to SH may be extremely important in the management of AI. Unfortunately, the available data on bone mineral density (BMD) in AI patients come from cross-sectional studies, which, to further complicate our understanding, are also conflicting, probably due to a different selection of patients and/or the variability in cortisol secretion (CS) often described in AI. To gain further insight about this topic, we performed a longitudinal study evaluating the rate of spinal and femoral bone loss levels in 24 females with AI. AI subjects were subdivided in two groups on the basis of the median of urinary cortisol secretion (UFC): group I (n = 12; UFC, <140.4 nmol/24 h) and group II (n = 12; UFC, >140.4 nmol/24 h). Spinal BMD was measured by both single energy quantitative computed tomography (L1-L4) and dual energy x-ray absorptiometry (DXA; L2-L4), and femoral BMD was determined by DXA. Bone loss rate was expressed as the change in z-score per yr. The spinal bone loss rate was higher (P < 0.005) in group II than in group I when measured by both quantitative computed tomography (-0.19 +/- 0.14 vs. 0.00 +/- 0.15) and DXA (-0.19 +/- 0.17 vs. 0.00 +/- 0.11). Moreover, CS and spinal bone loss rate were significantly correlated when patients were considered together. In conclusion, our data show that 1) AI patients with higher CS have increased lumbar trabecular bone loss rate than those with lower CS; and 2) the degree of spinal bone loss rate is related to the degree of CS. Thus, lumbar spine (LS) BMD has to be evaluated for well balanced decision-making on the treatment of choice for AI female patients.

Adrenal Gland Neoplasms↗

PubMed2005

Changes in the localization of antigen presenting cells and T cells in the utero-vaginal junction after repeated artificial insemination in laying hens.

The goal of our present study was to observe whether the populations of antigen presenting cells (Ia+ cells) and T cell subsets (CD4+ and CD8+ T cells) change in the utero-vaginal junction (UVJ) of Rhode Island Red laying hens that showed dramatic declines in fertility after repeated artificial insemination (AI). Rhode Island Red laying hens were divided into two groups: a virgin group (R-V) and artificial inseminated group (R-AI), which was exposed to weekly AI for a period of 3 mo. Undiluted fresh semen collected from healthy Tosa-Jidori roosters, a native Japanese breed maintained in Kochi Prefecture, was used for AI. The UVJ tissues were processed for frozen sections, and Ia+ cells and CD4+ and CD8+ T cells were identified by immunohistochemistry. The Ia+ cells and CD4+ and CD8+ T cells were observed in the stroma and mucosal epithelium of UVJ in both the R-AI and R-V birds. The frequencies of them in the stroma were significantly higher in R-AI than R-V. The higher frequency of Ia+ cells in the UVJ of R-AI group indicated a greater potential capability for antigen presentation to CD4+ cells. The significant increase in CD8+ and CD4+ T cells in the UVJ of R-AI birds might be the result of a homing process of lymphocytes, which may affect sperm survivability and fertility.

Animals↗

PubMed2000

The influence of the peripheral reflection wave on left ventricular hypertrophy in patients with essential hypertension.

The objective of this study was to clarify the relationship between afterload, which consists mainly of the vascular reflection wave, and left ventricular hypertrophy in patients with untreated essential hypertension using the fingertip photoplethysmogram (PTG) and second derivative wave (SDPTG) methods, the simplest and most convenient tools for pulse wave analysis. The augmentation index (AI) is defined as the ratio of the height of the late systolic peak, augmented by the peripheral reflection wave, to that of the early systolic peak caused mainly by left ventricular ejection in the pulse. Increased AI of the PTG and negative d/a, obtained by multiplying the ratio of the late re-decreasing wave (d wave) to the initial positive wave (a wave) of the SDPTG by -1, have the same meaning as increased ascending aortic AI. The left brachial artery blood pressure was measured in 60 patients. The PTG and SDPTG of the right second finger were recorded by a digital photoplethysmograph. The left ventricular mass index (LVMI) was investigated by ultrasonography. Subjects were assigned to one of two groups: a low AI (AI of PTG<1.6; group 1) or a high AI (AI of PTG> or =1.6; group 2) group. LVMI was significantly higher in group 2 than in group 1. In the study group as a whole, the LVMI was positively correlated with both the AI of PTG (r=0.60, p<0.0001) and negative d/a (r=0.63, p<0.0001). An increase in the LVMI was seen in subjects with an augmented late systolic component in the waveform. It was concluded that an increase in the peripheral reflection wave on the left ventricle is one of the important factors causing cardiac hypertrophy in patients with hypertension.

Adult↗

PubMed1981

Clinical investigation of aortic insufficiency by means of pulsed Doppler echocardiography.

Pulsed Doppler echocardiography (PDE) was performed on 41 patients with aortic insufficiency (AI), isolated or associated with other cardiac diseases, using an ATL 500A pulsed Doppler system. The diagnosis was confirmed by angiocardiography in 25 cases. The purpose of the present study was to analyze the disturbed flow due to AI, to investigate the sensitivity of PDE to this lesion, and to compare with the angiographic severity of AI (Sellers). The transducer was placed on the left sternal border and the flow pattern was recorded at the aortic valve orifice and the proximal and distal left ventricular outflow tract (LVOT), using a strip chart recorded at a paper speed of 100 mm/sec. The specific feature of AI was a widely dispersed dot pattern which began at the aortic valve closure and extended to late diastole. The severity of AI was graded by supravalvular aortogram in 25 patients. In grades I and II, the abnormal dot pattern due to AI was mostly detected at the aortic valve orifice and the distal LVOT, but it was rather difficult to detect the disturbed flow at the proximal LVOT. In contrast, in grades III and IV, the disturbed flow was recorded at all the sampling sites; with severe aortic regurgitation, it was detected at a wider range in the left ventricular cavity. In grades I and II, the abnormal dot dispersion at the proximal LVOT was not so large at its onset in diastole but it tended to increase after the mitral valve opening, whereas in the majority of patients of grades III and IV, a large dot dispersion was recognized from its onset to late diastole. The typical flow pattern due to AI was detected at the LVOT in 38 out of 41 patients (92.7%). Moreover, it was detected in all the patients with angiographically proved AI except for 1 case of grade I (96.0%).

Adolescent↗

PubMed1990

Effect of angiotensins on electrogenic anion transport in monolayer cultures of rat epididymis.

Confluent monolayers cultured from the rat cauda epididymidis have been shown to respond to angiotensin I (AI) and angiotensin II (AII) when studied under short-circuit conditions and bathed on both sides with Krebs-Henseleit solution. Both the decapeptide AI and the octapeptide AII elicited transient increases in short-circuit current (SCC) when added to the basolateral as well as to the apical surfaces, with the effect of basolateral application greater than that of apical application. The maximal responses produced by AI and AII were similar with median effective concentrations of 20 to 80 nmol/l. The increase in SCC by AII was dependent upon extracellular Cl- and was inhibited by addition of a Cl- channel blocker, diphenylamine 2-carboxylate, to the apical surface. These patterns of activity suggest that the SCC responses to angiotensins result from electrogenic chloride secretion. Pretreating the monolayers with captopril (100 nmol/l), an angiotensin-converting enzyme (ACE) inhibitor, reduced the response to basolateral application of AI, but completely abolished the response to AI added apically. These results suggest that the response to apical addition of AI was due to conversion of AI to AII which interacts with apical angiotensin receptors. This conversion was mediated by ACE which has been detected in epididymal monolayers. Of the endogenous ACE activity, 86% was found to be inhibited by captopril (100 nmol/l). Responses of the epididymal monolayers to angiotensins were mediated by specific angiotensin receptors. [Sar1,Ile8]-AII, a specific antagonist of the AII receptor, completely inhibited the responses to AI and AII but had no effect on the responses to bradykinin and endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMedDate not supplied

[Disorder of adrenal gland function in chronic fatigue syndrome].

Chronic fatigue syndrome (CFS) is defined as constellation of the prolonged fatigue and several somatic symptoms, in the absence of organic or severe psychiatric disease. However, this is an operational definition and conclusive biomedical explanation remains elusive. Similarities between the signs and symptoms of CFS and adrenal insufficiency prompted the research of the hypothalamo-pituitary-adrenal axis (HPA) derangement in the pathogenesis of the CFS. Early studies showed mild glucocorticoid deficiency, probably of central origin that was compensated by enhanced adrenal sensitivity to ACTH. Further studies showed reduced ACTH response to vasopressin infusion. The response to CRH was either blunted or unchanged. Cortisol response to insulin induced hypoglycaemia was same as in the control subjects while ACTH response was reported to be same or enhanced. However, results of direct stimulation of the adrenal cortex using ACTH were conflicting. Cortisol and DHEA responses were found to be the same or reduced compared to control subjects. Scott et al found that maximal cortisol increment from baseline is significantly lower in CFS subjects. The same group also found small adrenal glands in some CFS subjects. These varied and inconsistent results could be explained by the heterogeneous study population due to multifactorial causes of the disease and by methodological differences. The aim of our study was to assess cortisol response to low dose (1 microgram) ACTH using previously validated methodology. We compared cortisol response in the CFS subjects with the response in control and in subjects with suppressed HPA axis due to prolonged corticosteroid use. Cortisol responses were analysed in three subject groups: control (C), secondary adrenal insufficiency (AI), and in CFS. The C group consisted of 39 subjects, AI group of 22, and CFS group of nine subjects. Subject data are presented in table 1. Low dose ACTH test was started at 0800 h with the i.v. injection of 1 microgram ACTH (Galenika, Belgrade, Serbia). Blood samples for cortisol determination were taken from the i.v. cannula at 0, 15, 30, and 60 min. Data are presented as mean +/- standard error (SE). Statistical analysis was done using ANOVA with the Games-Howell post-hoc test to determine group differences. ACTH dose per kg or per square meter of body surface was not different between the groups. Baseline cortisol was not different between the groups. However, cortisol concentrations after 15 and 30 minutes were significantly higher in the C group than in the AI group. Cortisol concentration in the CFS group was not significantly different from any other group (Graph 1). Cortisol increment at 15 and 30 minutes from basal value was significantly higher in C group than in other two groups. However, there was no significant difference in cortisol increment between the AI and CFS groups at any time of the test. On the contrary, maximal cortisol increment was not different between CFS and other two groups, although it was significantly higher in C group than in the AI group. Maximal cortisol response to the ACTH stimulation and area under the cortisol response curve was significantly larger in C group compared to AI group, but there was no difference between CFS and other two groups. Several previous studies assessed cortisol response to ACTH stimulation. Hudson and Cleare analysed cortisol response to 1 microgram ACTH in CFS and control subjects. They compared maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve. There was no difference between the groups in any of the analysed parameters. However, authors commented that responses were generally low. On the contrary Scott et al found that cortisol increment at 30 min is significantly lower in the CFS than in the control group. Taking into account our data it seems that the differences found in previous studies papers are caused by the methodological differences. We have shown that cortisol increment at 15 and 30 min is significantly lower in CFS group than in C group. Nevertheless, maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve were not different between the C and CFS groups. This is in agreement with our previous findings that cortisol increment at 15 minutes has the best diagnostic value of all parameters obtained during of low dose ACTH test. However, there was no difference between CFS and AI group in any of the parameters, although AI group had significantly lower cortisol concentrations at 15 and 30 minutes, maximal cortisol response, area under the cortisol curve, maximal cortisol increment, and maximal cortisol change velocity than C group. Consequently, reduced adrenal responsiveness to ACTH exists in CFS. In conclusion, we find that regarding the adrenal response to ACTH stimulation CFS subjects present heterogeneous group. In some subjects cortisol response is preserved, while in the others it is similar to one found in secondary adrenal insufficiency.

Adrenal Cortex↗

PubMed2001

Effect of human chorionic gonadotropin on luteal function and reproductive performance of high-producing lactating Holstein dairy cows.

The objectives were to evaluate effects of human chorionic gonadotropin (hCG) (3,300 IU i.m.) administered on d 5 after AI on CL number, plasma progesterone concentration, conception rate, and pregnancy loss in high-producing dairy cows. Following the synchronization of estrus and AI, 406 cows were injected with either hCG or saline on d 5 after AI in a randomized complete block design. Blood sampling and ovarian ultrasonography were conducted once between d 11 and 16 after AI. Pregnancy diagnoses were performed on d 28 by ultrasonography and on d 45 and 90 after AI by rectal palpation. Treatment with hCG on d 5 resulted in 86.2% of the cows with more than one CL compared with 23.2% in controls. Plasma progesterone concentrations were increased by 5.0 ng/mL in hCG-treated cows. The presence of more than one CL increased progesterone concentration in hCG-treated cows but not in controls. Conception rates were higher for hCG-treated cows on d 28 (45.8 > 38.7%), 45 (40.4 > 36.3%), and 90 (38.4 > 31.9%) after AI. Treatment with hCG improved conception rate in cows losing body condition between AI and d 28 after Al. Pregnancy losses were similar between treatment groups. Treatment with hCG on d 5 after AI induces accessory CL, enhances plasma progesterone concentration, and improves conception rate of high-producing dairy cows.

Animals↗

PubMed2004

Methods to reduce or eliminate detection of estrus in a melengestrol acetate-PGF2alpha protocol for synchronization of estrus in beef heifers.

Three experiments were conducted to evaluate methods to decrease or eliminate the detection of estrus inherent to a melengestrol acetate (MGA)-PGF2alpha (PGF) protocol for synchronization of estrus in heifers. In each experiment, all heifers received 0.5 mg of MGA x animal(-1) x d(-1) for 14 d (d -32 to -19) and PGF (25 mg, i.m.; d 0, 0 h) 19 d after the last feeding of MGA (MGA-PGF protocol). In Exp. 1, heifers (n = 709) were assigned to each of the following protocols: 1) the MGA-PGF protocol with AI 6 to 12 h after detection of estrus (estrus AI; MGA-PGF); 2) MGA-PGF plus 100 microg, i.m. of GnRH on d -7 (1x GnRH) and estrus AI; or 3) MGA-PGF, GnRH on d -7, and GnRH (100 microg, i.m.) at 48 h after PGF, coincident with insemination (2x GnRH-TB48). In Exp. 2, heifers (n = 559) received the MGA-PGF protocol and were inseminated by either estrus AI or fixed-time AI (TAI) at 60 h, coincident with an injection of GnRH (GnRH-TB60). In Exp. 3, all heifers (n = 460) received the MGA-PGF protocol and were inseminated by estrus AI when detected up to 73 h. Heifers not observed in estrus by 73 h received TAI between 76 and 80 h. Half the heifers inseminated by TAI received no further treatment (TB80), and the remaining half was injected with GnRH at insemination (GnRH-TB80). Variance associated with the interval to estrus and the proportion in estrus from d 0 to 5 was similar for 1x GnRH and MGA-PGF treatments in Exp. 1. Pregnancy rate (d 0 to 5) did not differ for the MGA-PGF and 1x GnRH treatments (62.5 and 60.4%, respectively), and both were greater (P < 0.05) than TAI pregnancy rate in the 2x GnRH-TB48 treatment (42.3%). In Exp. 2, the peak estrous response occurred 60 h after PGF. Pregnancy rate during the synchrony period was greater (P < 0.05) for the MGA-PGF (255/401; 63.6%) than the GnRH-TB60 (74/158; 46.6%) treatment. In Exp. 3, 75.7% of heifers (348/460) were detected in estrus by 73 h and were inseminated, with a conception rate of 74.4%. Pregnancy rates after TAI did not differ between TB80 and GnRH-TB80 (14/56 = 25% and 19/ 56 = 33.9%, respectively). Total pregnancy rate was 63.5% for heifers inseminated after detected estrus and by TAI. Collectively, these data indicate that the exclusive use of TAI for heifers treated with the MGA-PGF protocol resulted in lower pregnancy rates than when AI was performed after detection of estrus. However, estrus AI for 3 d and TAI at the end of d 3 could result in pregnancy rates similar to those achieved after a 5-d period of detecting estrus.

Animals↗

PubMed1988

Expression of Fc gamma receptor-mediated phagocytosis by airway intra-luminal macrophages.

Macrophages in the conducting airways of the lower respiratory tract constitute an anatomically defineable subpopulation of pulmonary macrophages. Little information regarding the functional characteristics of the airway intra-luminal macrophages (AI-LM) is currently available. In this study, the AI-LM resident in the trachea and mainstem bronchi of the rat were harvested by an airway lavage technique and the ability of the AI-LM to phagocytize by Fc gamma-receptors was evaluated relative to the phagocytic activities of alveolar macrophages (AM) obtained by bronchoalveolar lavage. More than 60% of the AI-LM phagocytized sheep erythrocytes opsonized with IgG (SRBC-IgG) and the distributions of the engulfed SRBC-IgG in the phagocytic AI-LM were virtually identical to those in AM. The AI-LM may represent AM that have been translocated from the alveolar space compartment to the conducting airways; it remains possible, however, that at least some of the AI-LM may have an airway origin. Regardless, the results of our phagocytic studies suggest AI-LM may functionally provide a protective phagocytic role in the conducting airways.

Animals↗

PubMed1991

On the localization of effector cells in cyclosporin-induced autoimmunity.

Lethally irradiated rats, reconstituted with syngeneic bone marrow and given Cyclosporin A (CyA) for 6 weeks, developed disease resembling allogeneic graft-versus-host disease 2 weeks after withdrawal of CyA. Other studies have demonstrated the pivotal role of the thymus in the etiology of this CyA-induced autoimmune disease (CyA-AI). In this study the question was addressed whether inducer/effector cells of CyA-AI are generated in the thymus during or after CyA administration; whether these cells stay in the thymus, or, if they don't, whether they home to the secondary lymphoid organs. Adoptive transfer of thymocytes from donors treated for induction of CyA-AI obtained one and 14 days after cessation of CyA administration did not elicit CyA-AI in irradiated secondary recipients. Furthermore, adult thymectomy of rats immediately after the course of CyA did not influence the kinetics of development of skin pathology, although weight loss commenced later in thymectomized than in sham-thymectomized rats. Lymph node and spleen cells obtained from donors treated for induction of CyA-AI one and 14 days after withdrawal of CyA-AI caused CyA-AI upon adoptive transfer to secondary recipients, but the symptoms of acute disease (dermatitis, alopecia and weight loss) were strikingly less severe upon transfer of lymphoid cells obtained one day after stopping CyA than 14 days thereafter. Therefore, this study demonstrates that CyA-AI inducer/effector cells are generated in the thymus during the administration of CyA. These cells exit from the thymus during CyA administration; either they home predominantly peripherally (i.e. in the skin) rather than in the secondary lymphoid organs, or they leave the thymus as inducer cells which home in the lymphoid organs where they subsequently may trigger potentially autoreactive lymphocytes as probably also present in normal individuals, or both pathways may be operative.

Animals↗

PubMed2003

Intravaginal progesterone insert to synchronize return to estrus of previously inseminated dairy cows.

An intravaginal progesterone insert (CIDR insert; 1.38 g of progesterone) was evaluated for synchronization of returns to estrus (SR), conception rate (CR), and pregnancy rate (PR) in dairy cows previously artificially inseminated (AI). Healthy, nonpregnant, lactating Holstein cows, > or = 40 and < or = 150 d postpartum at eight commercial farms were used. Cows detected in estrus and receiving AI 2, 3, or 4 d after one injection of PGF2alpha (25 mg) were assigned as either controls (n = 945), or to receive a CIDR insert (n = 948) for 7 d (14 to 21 +/- 1 d after AI). Cows were observed for returns to estrus from 18 to 26 +/- 1 d after initial AI (resynchrony period) and were reinseminated if in estrus. Vaginal mucus on CIDR inserts (97.3% retention) at removal was scored: 1 = no mucus; 2 = clear; 3 = cloudy; 4 = yellow; and 5 = red or brown. Percentage of cows in estrus (SR) during the 3 d after CIDR insert removal was contrasted to the highest 3-d cumulative percentage in estrus for controls. Cows conceiving to initial AI were omitted in calculations of SR, CR, and PR during resynchrony. Mucous scores of 3 or 4 (mild irritation) were observed in 65% of cows and a score of 5 (more severe irritation) was observed in 2%; otherwise, health was unaffected. The PR to initial AI was lower for cows subsequently receiving CIDR inserts than for controls (32.7 vs. 36.7%). The CIDR insert increased SR (34.1 vs. 19.3% in 3 d) and overall estrus detection (43% in 4 d vs. 36% in 9 d) compared with controls. For the 9-d resynchrony period, CR and PR for CIDR-treated (26.7, 12.2%) and control (30.9, 11.1%) cows did not differ significantly. The CIDR inserts improved synchrony of returns to estrus, slightly reduced PR to initial AI, but did not affect CR or PR to AI during the resynchrony period.

Abortion, Veterinary↗

PubMed2006

Effect of sire fertility and timing of artificial insemination in a Presynch + Ovsynch protocol on first-service pregnancy rates.

Sire fertility may influence pregnancy rate (PR) by differences in sperm survival in the female reproductive system and time required for capacitation and transport of sperm to site of fertilization. A predicted fertility index, Estimated Relative Conception Rate, was used to select 3 high-fertility artificial insemination (AI) sires (+3) and 3 average AI sires (-1). Ovulation can be predicted to occur at approximately 28 h following GnRH administration when used in an Ovsynch protocol. The objective of this study was to determine if AI at 2 times, 0 or 24 h after GnRH administration, in a Presynch + Ovsynch protocol resulted in different first-service PR when average or high-fertility sires were used. Lactating Holstein cows (n = 1,457) from 2 dairy herds located in the Piedmont region of North Carolina were utilized for 12 mo. Timing of AI did not affect first AI PR and no interaction of sire-fertility group and timing of AI was detected. First AI PR did not differ between sire-fertility groups (23.2 vs. 29.4%) for average and high-fertility groups, respectively. First-lactation cows were 53% more likely to conceive than older cows, and cows bred during April through June were 66% less likely to become pregnant compared with cows bred from October through January. No interactions were detected among parity, season, sire-fertility group, or time of AI. Using only 3 sires per group based on Estimated Relative Conception Rate estimates resulted in large variability of sire conception within groups, although group averages differed by 6 points.

Animals↗