Disease control of acromegaly does not prevent excess mortality in the long term: results of a nationwide survey in Italy.

OBJECTIVE: This study aimed to assess the long-term outcome of patients with acromegaly. DESIGN: This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. METHODS: Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. RESULTS: A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4-2.0, p < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1-1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. CONCLUSIONS: Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.

Calving difficulty influences rumination time and inflammatory profile in Holstein dairy cows.

Difficult calving may adversely affect dairy cow health and performance. Maternal:fetal disproportion is a major cause of dystocia. Therefore, the main objective of this study was to assess the effects of dam:calf body weight ratio (D:C) on calving difficulty, rumination time, lying time, and inflammatory profile in 25 Holstein dairy cows. Using automatic monitoring systems, we monitored behavior and production in 9 primiparous and 16 pluriparous cows between dry-off and 30 d in milk. During the same period, we collected blood samples to monitor metabolism and inflammatory profile of these cows. Calvings were video recorded to assess calving difficulty and observe the duration of the expulsive stage. After parturition, the cows were separated into 3 classes according to their D:C: easy (E; D:C >17), medium (M; 14 < D:C <17), and difficult (D; D:C <14). The cows in class D showed relatively longer labor durations (108 min vs. 54 and 51 min for classes D, M, and E, respectively) and higher calving assistance rates (50% vs. 0 and 11% of calvings for classes D, M, and E, respectively) than those in the other 2 classes. Compared with the cows in classes M and E, those in class D exhibited shorter rumination times on the day of calving (176 min/d vs. 288 and 354 min/d for classes D, M, and E, respectively) and during the first week of lactation (312 min/d vs. 339 and 434 min/d for classes D, M, and E, respectively) and maintained lower rumination values until 30 DIM (399 min/d vs. 451 and 499 min/d for classes D, M, and E, respectively). Primiparous class D cows had shorter resting times during the first week after calving compared with those in class M (8 vs. 11 h/d for classes D and M, respectively). Interclass differences were found in terms of the levels of inflammation markers such as acute-phase proteins (ceruloplasmin, albumin, retinol, and paraoxonase). Moreover, cows in class D had lower plasma levels of fructosamine and creatinine after calving. Low D:C reduced postcalving rumination time and increased inflammation grade, suggesting a lower welfare of these animals at the onset of lactation. The D:C might serve as a useful index for the identification of cows at relatively higher risk of metabolic and inflammatory disease, thus helping farmers and veterinarians improve the welfare and health of these cows.

Influence of fiber degradability of corn silage in diets with lower and higher fiber content on lactational performance, nutrient digestibility, and ruminal characteristics in lactating Holstein cows.

The effect of neutral detergent fiber (NDF) degradability of corn silage in diets containing lower and higher NDF concentrations on lactational performance, nutrient digestibility, and ruminal characteristics in lactating Holstein cows was measured. Eight ruminally cannulated Holstein cows averaging 91 ± 4 (standard error) days in milk were used in a replicated 4 × 4 Latin square design with 21-d periods (7-d collection periods). Dietary treatments were formulated to contain either conventional (CON; 48.6% 24-h NDF degradability; NDFD) or brown midrib-3 (BM3; 61.1% 24-h NDFD) corn silage and either lower NDF (LNDF) or higher NDF (HNDF) concentration (32.0 and 35.8% of ration dry matter, DM) by adjusting the dietary forage content (52 and 67% forage, DM basis). The dietary treatments were (1) CON-LNDF, (2) CON-HNDF, (3) BM3-LNDF, and (4) BM3-HNDF. Data were analyzed as a factorial arrangement of diets within a replicated Latin square design with the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) with fixed effects of NDFD, NDF, NDFD × NDF, period(square), and square. Cow within square was the random effect. Time and its interactions with NDFD and NDF were included in the model when appropriate. An interaction between NDFD and NDF content resulted in the HNDF diet decreasing dry matter intake (DMI) with CON corn silage but not with BM3 silage. Cows fed the BM3 corn silage had higher DMI than cows fed the CON corn silage, whereas cows fed the HNDF diet consumed less DM than cows fed the LNDF diet. Cows fed the BM3 diets had greater energy-corrected milk yield, higher milk true protein content, and lower milk urea nitrogen concentration than cows fed CON diets. Additionally, cows fed the BM3 diets had greater total-tract digestibility of organic matter and NDF than cows fed the CON diets. Compared with CON diets, the BMR diets accelerated ruminal NDF turnover. When incorporated into higher NDF diets, corn silage with greater in vitro 24-h NDFD and lower undegradable NDF at 240 h of in vitro fermentation (uNDF240) allowed for greater DMI intake than CON. In contrast, for lower NDF diets, NDFD of corn silage did not affect DMI, which suggests that a threshold level of inclusion of higher NDFD corn silage is necessary to observe enhanced lactational performance. Results suggest that there is a maximum gut fill of dietary uNDF240 and that higher NDFD corn silage can be fed at greater dietary concentrations.

Effects of ad libitum or restricted access to total mixed ration with supplemental long hay on production, intake, and rumination.

Limiting feeding time has been a concept used in growing and nonlactating ruminant animals with good success, especially in improving feed efficiency while maintaining normal rumen function and fiber digestibility. This study evaluated the physiological and productive responses of cows fed a total mixed ration (TMR) available for 24 or 19 h/d with or without access to additional long hay. Eight multiparous Holstein cows were used in a replicated 4 × 4 Latin square design with 21-d periods. Rations were formulated to mimic a TMR used in the Parmigiano Reggiano cheese production area of Italy, consisting of all dry and nonfermented components. Intakes were reduced by 2.49 kg/d in cows with restricted TMR access and 1.16 kg/d without supplemental hay. Rumen characteristics were similar for all groups with improvements in energy-corrected milk. The results show that once cows adapted to diet changes, few differences were observed when offering TMR continuously or with limited access. Energy-corrected milk feed efficiency was improved in cows having access to feed 19 versus 24 h/d. In addition, the presence of long hay during the TMR restriction offered the optimal conditions for ruminal function and pH stability, yet no effects were observed on body weight change. A Latin square with 21-d periods could have a carry-over effect on energy storage, and mobilization of fat reserves might be able to mask negative energy balance during restriction. Restricted feeding could be used as a strategy to manage feed availability according to cow production and metabolic condition, to maximize the use of nutrient resources, reducing the cost of milk production and improving the cows' welfare and health.

Technical note: In vitro digestibility of amylase-treated, ash-corrected neutral detergent fiber, with addition of sodium sulfite, at 240 hours with or without rumen fluid reinoculation.

Long-term in vitro fermentation (240 h) evaluating amylase-treated, ash-corrected neutral detergent fiber, with addition of sodium sulfite (aNDFom) digestibility is required to quantify the indigestible fiber fraction. It is commonly accepted to inoculate rumen fluid more than one time during such fermentations, every 96 h or at 120 h. However, no studies have been conducted to verify if the reinoculation is actually required to properly carry out the fermentation process. The current study aims to evaluate the effects of these procedures on aNDFom digestibility at 240 h. The study was conducted on a total of 24 forage samples (8 alfalfa hays, 8 grass hays, and 8 corn silages). Samples were digested in triplicate at 240 h in vitro. Rumen fluid was added twice (at 96 and 192 h) in treatment 1, after 120 h in treatment 2, whereas no addition was made in treatment 3. At the end of the fermentations, residual aNDFom was quantified to calculate digestibility. Among treatments, no difference was found in digestibility of aNDFom. Moreover, treatment 1 resulted in higher variability compared with other treatments. Results obtained in the current study show that subsequent addition of rumen fluid is not necessary for a proper estimation of aNDFom digestibility, and can be avoided.

Overstocking dairy cows during the dry period affects dehydroepiandrosterone and cortisol secretion.

Stressful situations trigger several changes such as the secretion of cortisol and dehydroepiandrosterone (DHEA) from the adrenal cortex, in response to ACTH. The aim of this study was to verify whether overstocking during the dry period (from 21±3 d to the expected calving until calving) affects DHEA and cortisol secretion and behavior in Holstein Friesian cows. Twenty-eight cows were randomly divided into 2 groups (14 animals each), balanced for the number of lactations, body condition score, and expected date of calving. Cows in the far-off phase of the dry period (from 60 to 21 d before the expected calving date) were housed together in a bedded pack. Then, animals from 21±3 d before the expected calving until calving were housed in pens with the same size but under different crowding conditions due to the introduction of heifers (interference animals) into the pen. The control condition (CTR) had 2 animals per pen with 12.0m2 each, whereas the overstocked condition (OS) had 3 interference animals in the same pen with 4.8m2 for each animal. On d -30±3, -21±3, -15±3, -10±3, and -5±3 before and 10, 20, and 30 after calving, blood samples were collected from each cow for the determination of plasma DHEA and cortisol concentrations by RIA. Rumination time (min/d), activity (steps/h), lying time (min/d), and lying bouts (bouts/d) were individually recorded daily. In both groups, DHEA increased before calving and the concentration declined rapidly after parturition. Overstocking significantly increased DHEA concentration compared with the CTR group at d -10 (1.79±0.09 vs. 1.24±0.14 pmol/mL), whereas an increase of cortisol was observed at d -15 (3.64±0.52 vs. 1.64±0.46ng/mL). The OS group showed significantly higher activity (steps/h) compared with the CTR group. Daily lying bouts tended to be higher for the OS group compared with CTR group in the first week of treatment. The overall results of this study documented that overstocking during the dry period was associated with a short-term changes in DHEA and cortisol but these hormonal modifications did not influence cow behavior.

Effect of undigested neutral detergent fiber content of alfalfa hay on lactating dairy cows: Feeding behavior, fiber digestibility, and lactation performance.

The objective of this study was to investigate the effects of 2 alfalfa hays differing in undigested neutral detergent fiber content and digestibility used as the main forage source in diets fed to high producing cows for Parmigiano-Reggiano cheese production. Diets were designed to have 2 different amounts of undigestible NDF [high (Hu) and low (Lu)], as determined by 240-h in vitro analysis (uNDF240). Alfalfa hay in vitro digestibility [% of amylase- and sodium sulfite-treated NDF with ash correction (aNDFom)] at 24 and 240 h was 40.2 and 31.2% and 53.6 and 45.7% for low- (LD) and high-digestibility (HD) hays, respectively. The 4 experimental diets (Hu-HD, Lu-HD, Hu-LD, and Lu-LD) contained 46.8, 36.8, 38.8, and 30.1% of alfalfa hay, respectively, 8.6% wheat straw, and 35.3% corn (50% flake and 50% meal; DM basis). Soy hulls and soybean meal were used to replace hay to balance protein and energy among diets. Eight multiparous Holstein cows (average milk production = 46.0 ± 5.2 kg/d, 101 ± 38 d in milk, and 662 ± 42 kg of average body weight) were assigned to a 4 × 4 Latin square design, with 2 wk of adaptation and a 1-wk collection period. Dry matter and water intake, rumination time, ruminal pH, and milk production and composition were measured. Diets and feces were analyzed for NDF on an organic matter basis (aNDFom), acid detergent fiber, acid detergent lignin, and uNDF240 to estimate total-tract fiber digestibility. Dry matter intake and rumination times were higher in HD diets compared with LD diets, regardless of forage amount. Rumination time was constant per unit of dry matter intake but differed when expressed as a function of uNDF240, aNDFom, or physically effective NDF intake. No differences were found among treatments on average ruminal pH, but the amount of time with pH <5.8 was lower in Hu-HD diets. Milk production and components were not different among diets. Total-tract aNDFom and potentially digestible neutral detergent fiber fraction digestibility was higher for the LD diets (88.3 versus 85.8% aNDFom in HD), for which lower feed intakes were also observed. The Hu-HD diet allowed greater dry matter intake, longer rumination time, and higher ruminal pH, suggesting that the limiting factor for dry matter intake is neutral detergent fiber digestibility and its relative rumen retention time.

Effects of a completely pelleted diet on growth performance in Holstein heifers.

Forage neutral detergent fiber (NDF) content and particle size are important factors that affect rumen function. The aim of the current study was to evaluate the effects on rumen health, NDF digestibility, and animal performance of pelleting a forage-based diet. Eight Holstein heifers (age 336±30d, body weight 346±35kg) were randomly assigned to a repeated crossover design. Animals were housed in tie-stalls and fed for ad libitum intake. The study included 4 periods of 3 wk, the first 2 wk for adaptation to the diet and the last wk for data collection. Diets had the same ingredients but had a different physical form: total mixed ration (TMR) and pellet (diameter=8mm). The physically effective NDF (peNDF) differed between the 2 treatments (39.8 and 11.8% of NDF in the TMR and pellet diets, respectively). During the trial, dry matter intake (DMI), water intake, rumination time, rumen temperature, and pH were evaluated daily. Fecal samples were collected in wk3 of each period to determine total-tract digestibility of the potential digestible (pd)NDF. Average daily gain and feed conversion ratio were calculated at the end of each period. With the pellet diet, DMI, DMI/body weight, and water consumption were higher. We observed no significant difference in average daily gain or feed conversion ratio. Rumination time was lower for the pellet diet than for the TMR diet (241 vs. 507min/d, respectively). Diet had no effect on rumen temperature or rumen pH. The total-tract digestibility of the pdNDF was greater with the TMR diet than with the pellet diet (90.25 vs. 86.82% pdNDF, respectively). The results of the current study suggest that a complete-feed pellet diet was well accepted by the animals, as demonstrated by higher DMI. Rumination time was reduced with the pellet diet, but rumen pH was not different. The pdNDF digestibility was high for both diets, but significantly higher for the TMR diet. Given that animal performance was similar between the 2 diets, although they differed with respect to DMI and fiber digestion, we hypothesize that the 2 diets had different retention times, related to their physical form. A complete-feed pellet diet formulated to provide a sufficient level of NDF from forages could be fed to growing ruminants without apparent negative effects on rumen health and animal productivity, at least for a short period. More research over a longer growing period is needed before recommending this feeding strategy for growing heifers.

Using single or multiple liquor-donor cows for in vitro digestibility of amylase- and sodium sulfite-treated neutral detergent fiber with ash correction.

In vitro methods requiring ruminal microorganisms to ferment and digest feeds have been used for decades. Though commonly accepted, collecting and pooling rumen fluid from different donor animals to avoid individual characteristics could affect in vitro fermentations. The current study evaluated the effects of individual or pooled liquors on in vitro digestibility of amylase- and sodium sulfite-treated NDF with ash correction (aNDFom). The study was conducted on 24 samples (8 alfalfa hays, 8 grass hays, and 8 corn silages). The 3 donor animals (treatment 1, 2, and 3) were selected based on similar body weights, parity, days in milk, milk production, and milk composition. Samples were digested in vitro via inoculation of different rumen fluid at different time points (12, 24, 72, and 120h). An equal amount of each liquor collected was sampled and equally mixed with the others to obtain treatment 4. For the alfalfa hay group, differences were observed at 12 (29.95, 27.07, 29.02, and 32.55% aNDFom for treatments 1, 2, 3, and 4, respectively) and 24h (37.35, 35.54, 36.44, and 40.56% aNDFom for treatments 1, 2, 3, and 4, respectively). The inoculum source did not affect in vitro digestibility over longer time periods (72 and 120 h). Similar results were observed in the grass hay group, in which the mixed inoculum had greater digestibility values at both 12 (28.86, 26.89, 27.88, and 30.92% aNDFom for treatments 1, 2, 3, and 4, respectively) and 24h (37.35, 35.54, 36.44, and 40.56% aNDFom for treatment 1, 2, 3, and 4, respectively), but not over longer time periods. For the corn silage group, we observed differences for treatment 4 only at 12h (35.78, 33.87, 34.83, and 37.80% aNDFom for treatment 1, 2, 3, and 4, respectively). These results underline the differences among donor animals, especially when evaluating short incubation time points, and that pooling rumen contents is not equal to averaging across individual animals. Reported data require a deeper investigation on whether or not the method of inoculating a pool of rumen contents represents the actual ability of the animal to digest fiber.

Differential expression of living mammary epithelial cell subpopulations in milk during lactation in dairy cows.

Epithelial cells are shed into milk during lactation, and although they generally reflect the cellular characteristics of terminally differentiated luminal cells, previously the detection of more primitive cells was described in human milk where a cell population of epithelial lineage was detected expressing markers typical of progenitor cells. In this investigation, we report the development of flow cytometry analysis to allow multiparametric assessment of mammary epithelial cells observed in milk. Cells collected from milk samples of 10 healthy dairy cows were directly analyzed for 6 different markers: CD45, CD49f, cytokeratin 14, cytokeratin 18, presence of nucleus, and cell viability. Milk samples were collected in 3 different periods of lactation: early lactation (EL=d 0-30), mid-lactation (ML=d 90-120), and late lactation (LL=210-250). Here we identify the differential expression of precursor or differentiated cell markers (or both) in mammary epithelial cells present in bovine milk. Myoepithelial cells, as indicated by cells staining positively for cytokeratin 14(+)/cytokeratin 18(-), were observed to increase from EL to LL with a high correlation with nuclear staining inferring potential proliferative activity. Furthermore, a significant increase in CD49f(+) and cytokeratin 14(+)/cytokeratin 18(+) positive cells was observed in LL. This assay is a sensitive approach for evaluating the variations in the frequency and features of living epithelial cells, whose reciprocal balance may be significant in understanding mammary gland cellular function throughout lactation. These observations suggest that mammary epithelial cell immunophenotypes could be investigated as biomarkers for mammary gland function in dairy cows.

Influence of maturity on alfalfa hay nutritional fractions and indigestible fiber content.

This study focused on changes in fibrous and protein fractions, changes in fiber digestibility and amount of indigestible neutral detergent fiber (NDF) as a consequence of increased maturity in alfalfa. A total area of 720 m(2) was divided in 18 blocks randomly assigned to 3 treatments, differing in cutting intervals. Treatment 1 was harvested with a 21-d cutting schedule, at a prebloom stage; treatment 2 with a 28-d schedule, at about first-bloom stage; whereas a full bloom was observed in treatment 3, harvested with a 35-d cutting schedule. Treatments were replicated 4 times through the spring-summer period for 2 subsequent years, 2011 and 2012. Statistical differences were observed for crude protein [treatment 1: 20.8%, treatment 2: 17.3%, and treatment 3: 17.0%; standard error of the mean (SEM)=0.83], soluble protein, and nonprotein nitrogen among treatments on a dry matter basis. Similar results were observed for acid detergent lignin (6.3, 6.9, and 7.3%, respectively; SEM=0.39), lower in treatment 1 compared with others, and in vitro NDF digestibility at 24 or 240 h. Indigestible NDF at 240 h resulted in lower values for treatment 1 compared with treatments 2 and 3 (15.5, 17.2, and 18.3%, respectively; SEM=1.54). Moreover, the indigestible NDF:acid detergent lignin ratio varied numerically but not statistically among treatments, being as much as 9% greater than the 2.4 fixed value applied for rate of digestion calculation and Cornell Net Carbohydrate Protein System (Cornell University, Ithaca, NY)-based model equations. Assuming the diet composition remained unchanged, treatment 3 (35-d cutting interval) would be expected to yield 1.4 kg less milk per day based on energy supply, and 2.8 kg less milk daily based on protein supply than treatment 1.

Awareness and management of hyponatraemia: the Italian Hyponatraemia Survey.

BACKGROUND: Hyponatraemia is the most frequent electrolyte disorder in hospitalized patients and has been associated with increased morbidity, mortality and length of hospital stay. There is evidence that also mild chronic hyponatraemia may have clinical consequences, such as gait disturbances, attention deficits, falls, increased risk of fractures and reduced bone mineral density. Nevertheless, this condition appears to be rather often not taken into consideration, or inappropriately managed and treated, thus negatively affecting patients' outcome. AIM: The aim of this study was to investigate the awareness and management of hyponatraemia secondary to SIAD, a common cause of hyponatraemia, among Italian physicians (endocrinologists, nephrologists, internists) commonly involved as consultants. METHODS: A questionnaire, covering definition, diagnosis, management, treatment and prognosis of hyponatraemia secondary to SIAD, was developed with the support of the Italian Society of Endocrinology. RESULTS: Among the respondents (n=275), the majority was aware of the negative implications of hyponatraemia or of an inappropriate treatment. Nevertheless, the answers indicated that SIAD is still underdiagnosed and incorrectly managed in clinical practice. In particular, only 47% of respondents used the validated biochemical parameters to diagnose hyponatraemia secondary to SIAD. The survey also indicated a rather satisfactory knowledge of the therapeutic options, including the currently available vasopressin receptor antagonists. CONCLUSIONS: One of the main findings of the survey was that the diagnostic work-up of hyponatraemia still represents a critical issue. Therefore, there is urgent need of educational programs in order to improve the management of this condition and reduce morbidity, mortality and costs.

Effect of varying total mixed ration particle size on rumen digesta and fecal particle size and digestibility in lactating dairy cows.

The objective of this experiment was to evaluate the effects of feeding rations of different particle sizes on rumen digesta and fecal matter particle size. Four rumen-cannulated, multiparous, Holstein cows (104±15 d in milk) were randomly assigned to treatments in a 4×4 Latin square design. The diets consisted of 29.4% corn silage, 22.9% ground corn, 17.6% alfalfa haylage, and 11.8% dry grass hay [20% of forage dry matter (DM)] on a DM basis. Dry grass hay was chopped to 4 different lengths to vary the total mixed ration (TMR) particle size. Geometric mean particle sizes of the rations were 4.46, 5.10, 5.32, and 5.84 mm for short, medium, long, and extra long diets, respectively. The ration affected rumen digesta particle size for particles ≥3.35 mm, and had no effect on distribution of particles <3.35 mm. All rumen digesta particle size fractions varied by time after feeding, with soluble particle fractions increasing immediately after feeding and 0.15, 0.6, and 1.18-mm particle size fractions decreasing slightly after feeding. Particle fractions >1.18 mm had ration by time interactions. Fecal neutral detergent fiber (NDF) and indigestible NDF concentrations decreased with increasing TMR particle size. Fecal particle size expressed as total geometric mean particle length followed this same tendency. Fecal particle size, expressed as retained geometric mean particle length, averaged 1.13 mm with more than 36% of particles being larger than 1.18 mm. All fecal nutrient concentrations measured were significantly affected by time after feeding, with NDF and indigestible NDF increasing after feeding and peaking at about 12h later and then decreasing to preprandial levels. Starch concentrations were determined to have the opposite effect. Additionally, apparent digestibility of diet nutrients was analyzed and DM digestibility tended to decrease with increasing TMR particle size, whereas other nutrient digestibilities were not different among rations. These results show that the critical size for increased resistance to rumen escape is larger than 1.18 mm and this critical size is constant throughout the day. This study also concludes that, when using average quality grass hay to provide the range of particle sizes fed, DM digestibility tends to decrease with increasing ration particle size.

Limiting total mixed ration availability alters eating and rumination patterns of lactating dairy cows.

The objective of this study was to investigate the effect of restricting total mixed ration (TMR) eating time with or without supplemental long hay offered on diurnal total intake, rumination, and rumen pH patterns in mid-lactation dairy cows. Eight multiparous Holstein cows were used in a replicated 4 × 4 Latin square design study with 21-d periods. The basal diet was the same for all 4 treatments with or without additional long grass hay (the same hay used in the TMR). For cows on limited-time TMR, diets were taken away at 1500 h (5 h before evening milking and feeding), and dry matter intake (DMI), ruminating, and rumen pH were monitored and summarized every 10 m for 7 d in each period. With restricted feeding, cows changed DMI patterns by consuming a large meal after feed was reinstated, resulting in lower DMI. Ruminating patterns closely mirrored intake patterns, as could be expected. Rumen pH was not different between groups but resulted in different diurnal patterns due to differences in eating and rumination patterns between the groups. Limiting feed availability can be used to change eating and rumination patterns, resulting in different rumen pH patterns.

Effect of feed sorting on chewing behavior, production, and rumen fermentation in lactating dairy cows.

Ration sorting is thought to allow cows to eat different rations throughout the day, causing fluctuations in rumen fermentation patterns that can be detrimental to production and possibly animal health. The objective of this experiment was to study the effects of varying total mixed ration (TMR) particle size on sorting behavior of lactating dairy cows and to evaluate effects on chewing behavior, milk yield, milk components, and rumen fermentation. Eight multiparous, Holstein cows (90±32 d in milk; 4 rumen cannulated) were randomly assigned to replicated 4×4 Latin squares. Cows were fed diets that varied in the chop length of dry grass hay. The diet consisted of 29.4% corn silage, 22.9% ground corn, 17.6% alfalfa haylage, and 11.8% dry grass hay on a dry matter basis. The percentage of hay particles >26.9 mm was 4.2, 34.1, 60.4, and 77.6% for the short (S), medium (M), long (L), and extra long (XL) hays, respectively. This resulted in the TMR of each diet having 1.5 (S), 6.5 (M), 8.6 (L), and 11.7% (XL) of particles >26.9 mm. Daily ruminating time [19.3, 19.2, 22.4, and 21.3 min/kg of dry matter intake (DMI) for S, M, L, and XL] and eating time (13.9, 14.6, 17.2, and 16.1 min/kg of DMI for S, M, L, and XL) increased linearly as TMR particle size increased. Daily DMI decreased linearly as TMR particle size increased and was 26.9 (S), 27.0 (M), 24.1 (L), and 25.1 (XL) kg/d. No differences were found in rumen volatile fatty acids and NH(3), and only slight changes were found in rumen pH. Milk production and milk components were also similar among diets. Despite large differences in particle size among these diets and certain chewing and ruminating differences, no changes in rumen fermentation, milk production, or milk components were found in this study.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas.

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.