[Usage of antimicrobials on seven farms of beef producers in Switzerland]. / Einsatz von Antibiotika bei Aufzuchtkälbern für die Grossviehmast bzw. Fresseraufzucht auf sieben Schweizer Betrieben.

INTRODUCTION: It was the objective of this study to evaluate morbidity, mortality, use of veterinary drugs and production output on seven representative Swiss beef fatteners, who bought on a regular basis batches of calves from traders (mean age and weight: 31 day, 75 kg) and practised an all in-all out system. From March 2015 until May 2016, 51 batches with a total of 1307 calves were included. The use of drugs during the first eight weeks following delivery of calves from the trader, casualty rate and carcass performance of 837 bulls. The administration of antimicrobials was calculated per calf as the number of days with effective therapeutic concentrations (daily doses per animal; DD/A). The average weight of the calves at arrival on the fattening unit was 75 kg and the age 31 days. The group size was between 13 to 47 calves (median 22, Q1 = 21, Q2 = 30). In 36 batches (70,6 %), a veterinary entry examination was performed which demonstrated that at admission 20 % of the calves suffered from a relevant disease. The median for the number of DD/A was 16 for the first 56 days on the farm (Q1 = 11, Q3 = 21); 68 % of these DD/A were attributed to metaphylactic medications after delivery. Thereafter, pneumonia (54 %), diarrhea (33 %) and otitis (10 %) were the most frequent indications for subsequent therapeutic interventions. Over all batches, a median of 71 % (Q1 = 47, Q3 = 85) of all DD/A were due to critically important antimicrobials (CIM) and drugs containing several antibiotics including a CIM. The losses due to death or euthanasia averaged 3,7 % of all calves. The median for daily weight gain for the total fattening period (median 354 days; Q1 = 328, Q3 = 379) accounted for 1325 g (Q1 = 1216, Q3 = 1425). The profound variation between the farms in respect to the results of drug use and production output reveals evidence for the strong impact of farm-specific factors (such as pen space per calf, barn climate, vaccination protocol, supervision). Concurrently, the remarkable differences between the results of different batches on one farm depict that there are further important risk factors which are beyond the control of the farmer (in particular season of the year, transport). It is concluded that a systematic minimization of risk factors as part of a continuous veterinary consultation is useful two improve herd health and to reduce the input of drugs in the production of beef.

INTRODUCTION: L'objectif de cette étude était d'évaluer la morbidité, la mortalité, l'utilisation de médicaments vétérinaires et la production de sept engraisseurs suisses représentatifs, qui achetaient régulièrement des lots de veaux à des commerçants (âge et poids moyens : 31 jours, 75 kg). et pratiquant le système «  all in-all out ¼. De mars 2015 à mai 2016, 51 lots avec un total de 1307 veaux ont été inclus. On a étudié l'utilisation de médicaments pendant les huit premières semaines suivant la livraison des veaux, le taux de mortalité et la performance carcasse de 837 taureaux. L'administration d'antimicrobiens par veau a été calculée individuellement en nombre de jours avec des concentrations thérapeutiques efficaces (doses quotidiennes par animal ; JJ/A). Le poids moyen des veaux à l'arrivée sur l'unité d'engraissement était de 75 kg et l'âge de 31 jours. La taille du groupe était comprise entre 13 et 47 veaux (médiane 22, Q1 = 21, Q2 = 30). Dans 36 lots (70,6 %), un examen vétérinaire d'entrée a été réalisé qui a démontré qu'à l'admission 20 % des veaux souffraient d'une maladie nécessitant un traitement. La médiane du nombre de DD/A était de 16 pour les 56 premiers jours à la ferme (Q1 = 11, Q3 = 21) ; 68 % de ces DD/A ont été constitués par des médicaments métaphylactiques après la livraison. Par la suite, la pneumonie (54 %), la diarrhée (33 %) et l'otite (10 %) étaient les indications les plus fréquentes des interventions thérapeutiques ultérieures. Sur l'ensemble des lots, une médiane de 71 % (Q1 = 47, Q3 = 85) de tous les DD/A étaient dus à des antimicrobiens d'importance critique (CIM) et à des médicaments contenant plusieurs antibiotiques, dont un CIM. Les pertes dues à la mort ou à l'euthanasie représentaient en moyenne 3,7 % de tous les veaux. La médiane du gain de poids quotidien pour la période d'engraissement totale (médiane 354 jours ; Q1 = 328, Q3 = 379) représentait 1325 g (Q1 = 1216, Q3 = 1425). La variation importante entre les exploitations en ce qui concerne les résultats de l'utilisation de médicaments et la production est la preuve du fort impact des facteurs spécifiques à l'exploitation (tels que l'espace en enclos par veau, le climat de l'étable, le protocole de vaccination, la supervision). Parallèlement, les différences remarquables entre les résultats de différents lots sur une exploitation montrent qu'il existe d'autres facteurs de risque importants qui échappent au contrôle de l'agriculteur (en particulier la saison, le transport). Il est conclu qu'une minimisation systématique des facteurs de risque dans le cadre d'une consultation vétérinaire continue est utile pour améliorer la santé du troupeau et réduire l'apport de médicaments dans la production de viande bovine.

Extended lactation in high-yielding dairy cows. I. Effects on reproductive measurements.

The objective of this prospective field study was to evaluate the effects of extending the lactation period on various reproductive measurements of high-yielding Holstein cows. On 40 d in milk (DIM), cows were gynecologically examined (transrectal palpation, sonography, vaginoscopy). Cows without signs of clinical endometritis were blocked by parity and were randomly allocated to 1 of 3 experimental groups with a voluntary waiting period (VWP) of 40, 120, and 180 d, respectively (G40, n = 135; G120, n = 141; G180, n = 139). Cows of G120 and G180 were reexamined at the end of the VWP. If natural estrus was detected within 46 d after the end of the VWP, an artificial insemination was performed. If no estrus was detected, the respective cows were synchronized by applying the classical Ovsynch protocol. We found no difference in the proportion of cows in which estrus was detected between 40 to 86 DIM or in the days to first estrus between the 3 groups. Estrus detection in this period was lower in cows with body condition score <3 on 90 DIM compared with body condition score ≥3 (61.5 vs. 76.0%) and in cows with high energy-corrected milk production (ECM) on 92 DIM [58.6 vs. 70.1%, for cows with higher and lower than the median (39.9 kg) ECM, respectively]. The proportion of cows that estrus was detected within 46 d after the VWP was greater in G120 (88.9%) and G180 (90.8%) compared with G40 (70.4%). These effects were more apparent in cows with high ECM. The rate of estrus detection and of becoming pregnant in this period was greater for G120 (hazard ratio = 2.2 and 1.6, respectively) and for G180 (hazard ratio = 2.4 and 1.8) compared with G40. Cows in both groups with extended lactation had greater overall first service conception rates (G120 = 48.9%; G180 = 49.6%) and a lower number of services per pregnant cow (G120 = 1.56 ± 0.1; G180 = 1.51 ± 0.1) compared with G40 (36.6%; 1.77 ± 0.1). We observed no difference in pregnancy loss or in the proportion of cows culled up to 305 d of lactation between the 3 groups. The number of Ovsynch protocols per 1,000,000 kg of ECM was reduced by 75% in G180 and by 74% in G120 compared with G40 (5.9 vs. 7.1 vs. 25.1). In conclusion, extending the lactation of dairy cows can improve main reproductive measurements in high-yielding cows.

Intensive rearing of male calves during the first three weeks of life has long-term effects on number of islets of Langerhans and insulin stained area in the pancreas.

Permanent effects of early postnatal nutrition on the development and function of tissues and organs have been previously demonstrated primarily in humans and rodents. The objective of this study in calves was to analyze the impact of rearing conditions during the first 3 wk of life on morphology of insulin-producing pancreatic ß-cells. Forty-two male Holstein calves were raised during the first 3 wk of life either intensively (intensively reared [INT]; ad libitum milk feeding and individual hutches; = 21) or according to an established restrictive rearing protocol (4 L milk/d) during wk 1 in hutches and 720 g/d milk replacer (MR) from d 8 to 21 in group pens (restrictively reared [CON]; = 21). Thereafter, all calves were housed and fed under comparable conditions. Birth weight and weekly BW up to wk 10 were recorded. Plasma glucose, insulin, IGF-1, and GH levels were assessed in wk 1, 2, 3, and 10 of life. Slaughtering took place after 8 mo and pancreatic tissue from the medium body (corpus pancreatic) was removed. The number of islets of Langerhans and the insulin stained area were examined histologically. Total milk intake of INT calves was nearly double the intake in CON calves in the first 3 wk of life ( < 0.01). Daily starter intake during wk 4 to 10 of life did not differ between groups ( = 0.24). During the first 3 wk, the ADG were up to 9 times higher in INT calves compared to CON calves ( < 0.01), yet BW at time of slaughter did not differ ( = 0.18). Intensive rearing led to increased plasma glucose, insulin, and IGF-1 concentrations after 3 wk of life compared with rearing to the established standard protocol (all < 0.05), whereas GH was lower in INT calves during the second week of life. At time of slaughter, the mean number of islets of Langerhans was higher in INT calves compared to CON calves (9.1 ± 0.3 vs. 7.8 ± 0.3; < 0.01). Also, the total insulin stained area per photograph was higher in INT calves compared to CON calves (107,180 ± 4,987 vs. 84,249 ± 4,962 µm; < 0.01). Number of islets of Langerhans was negatively associated with birth weight but positively correlated with insulin and in trend with IGF-1 plasma levels during the second week of life. Insulin stained area tended to be linked with IGF-1 concentration during the third week of life. In conclusion, differences in the morphology of pancreatic islets of Langerhans indicate that calves can be programmed metabolically by an altered postnatal rearing intensity.

Effects of two different rearing protocols for Holstein bull calves in the first 3 weeks of life on health status, metabolism and subsequent performance.

The aim of this study was to investigate the impact of weight gain of calves within the first 3 weeks of life on health status and subsequent performance. Holstein bull calves were reared either intensively (IR; individual hutches and ad libitum milk feeding for the first 3 weeks of life; n = 24), or according to the established protocol [ER; 4 l milk/day in hutches during week 1 and 720 g/day milk replacer (MR) from day 8 to 21 in a group pen; n = 24]. Water, hay and concentrates were freely available to all calves. From week 4, calves of both groups were housed together in a group pen and fed 720 g MR/day; step-down weaning was performed between week 5 and 10. Key metabolic blood parameters were analysed on day 2, 12, 21 and 70 of life. After weaning, all animals were fed concentrates and corn silage until slaughter at an age of 8 months. Within the first 3 weeks, average daily weight gain was threefold higher in IR calves in relation to ER calves (1.28 vs. 0.38 kg/day, p < 0.001). Neither incidence nor duration of scouring differed significantly between groups. Starter intake (week 4-10) was higher in IR calves in relation to ER calves (49.7 vs. 38.0 kg/calf, p = 0.006). Serum glucose, urea, albumin and insulin were higher at an age of 21 days in IR calves in relation to ER calves; no differences were obvious at an age of 70 days. Plasma GH and IGF-I concentrations revealed an uncoupling of the somatotropic axis in ER calves within the first 3 weeks of life. At slaughter, body weight of IR calves tended to be higher than that of the ER calves (320 vs. 309 kg, p = 0.07). In conclusion, intensive feeding and individual housing during the first 3 weeks of life had positive long-term effects on subsequent performance.

Gene expression analysis of protein synthesis pathways in bovine mammary epithelial cells purified from milk during lactation and short-term restricted feeding.

The objective of the study was to investigate selected key regulatory pathways of milk protein biosynthesis in primary bovine mammary epithelial cells (MECs) of dairy cows during the first 155 days of lactation. In addition, cows were exposed to feed restriction for a short period (FR) during different stages of lactation (week 4 and 21 pp) to study adjustment processes of molecular protein biosynthesis to metabolic challenge. Morning milk samples from twenty-four Holstein-Friesian cows were collected throughout the experimental period (n = 10 per animal). MEC from raw milk were purified using an immunomagnetic separation technique and used for real-time quantitative PCR analyses. As was seen in transcript abundances of all major milk proteins, mRNA levels of E74-like factor 5 (ELF5), an enhancer of signal transducer and activator of transcription (STAT) action, concomitantly decreased towards mid-lactation. Expression of ELF5 as well as of all milk protein genes showed a similar increase during FR in early lactation. Occasional changes in expression could be seen in other Janus kinase (JAK)/STAT factors and in mammalian target of rapamycin (mTOR) pathway elements. Amino acid transfer and glucose transporter and the ß-casein expression were also partially affected. In conclusion, our findings suggest a pivotal role of the transcription factor ELF5 in milk protein mRNA expression with complementary JAK/STAT and mTOR signalling for the regulation of protein biosynthesis in the bovine mammary gland.

Multiparous cows categorized by milk protein concentration and energy-corrected milk yield during early lactation--metabolism, productivity and effect of a short-term feed restriction.

The objective of this experiment was to study milk productivity, metabolic adaptation and effect of a short-term feed restriction (FR) on key performance indicators during early lactation in cows classified according to energy-corrected milk (ECM) yield and milk protein concentration. Twenty-three multiparous Holstein-Friesian cows were categorized in four groups according to respective averaged values on Days 23-25 postpartum: high ECM yield and high protein concentration; low ECM yield and low protein concentration; high ECM yield and low protein concentration and low ECM yield and high protein concentration. Dry matter intake was reduced to 68.3% for three subsequent days. Our results showed that short-time FR in early lactation succeeded in enhancing energy deficit of cows in all groups. Milk fat, milk protein and lactose concentrations as well as milk fat yield were not influenced by FR. Several hepatic genes encoding for enzymes involved in catabolism of amino acids, ß-oxidation, gluconeogenesis and ketogenesis as well as mRNA encoding for insulin receptor showed increased transcript abundances after FR, primarily in cows with high milk yield and low milk protein concentration.

Effect of non-starch-polysaccharide-degrading enzymes as feed additive on the rumen bacterial population in non-lactating cows quantified by real-time PCR.

The effects of non-starch-polysaccharide-degrading enzymes, added to a maize silage- and grass silage-based total mixed ration (TMR) at least 14 h before feeding, on the rumen bacterial population were investigated. Six non-lactating Holstein Friesian cows were allocated to three treatment groups using a duplicate 3 × 3 Latin square design with three 31-day periods (29 days of adaptation and 2 days of sampling). Treatments were control TMR [69% forage and 31% concentrates on a dry matter (DM) basis] or TMR with 13.8 or 27.7 ml/kg of feed DM of Roxazyme G2 liquid with activities (U/ml enzyme preparation) of xylanase 260 000, ß-glucanase 180 000 and cellulase 8000 (DSM Nutritional Products, Basel, Switzerland). The concentrations of 16S rDNA of Anaerovibrio lipolytica, Fibrobacter succinogenes, Prevotella ruminicola, Ruminococcus flavefaciens, Selenomonas ruminantium and Treponema bryantii, and their relative percentage of total bacteria in rumen samples obtained before feeding and 3 and 7 h after feeding and from two rumen fractions were determined using real-time PCR. Sampling time had only little influence, but bacterial numbers and the composition of the population differed between the transition layer between rumen fluid and the fibre mat (fraction A) and the rumen fluid (fraction B) highlighting the importance to standardize sampling. The 16S rDNA copies of total bacteria and the six bacterial species as well as the population composition were mainly unaffected by the high levels of exogenous enzymes supplemented at all sampling times and in both rumen fractions. Occasionally, the percentages of the non-fibrolytic species P. ruminicola and A. lipolytica changed in response to enzyme supplementation. Some increases in the potential degradability of the diet and decreases in lag time which occurred collaterally indicate that other factors than changes in numbers of non-particle-associated bacteria are mainly responsible for the effects of exogenous enzymes.

Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows.

A long-term study over 25 months was conducted to evaluate the effects of genetically modified corn on performance of lactating dairy cows. Thirty-six dairy cows were assigned to two feeding groups and fed with diets based on whole-crop silage, kernels and whole-crop cobs from Bt-corn (Bt-MON810) or its isogenic not genetically modified counterpart (CON) as main components. The study included two consecutive lactations. There were no differences in the chemical composition and estimated net energy content of Bt-MON810 and CON corn components and diets. CON feed samples were negative for the presence of Cry1Ab protein, while in Bt-MON810 feed samples the Cry1Ab protein was detected. Cows fed Bt-MON810 corn had a daily Cry1Ab protein intake of 6.0 mg in the first lactation and 6.1 mg in the second lactation of the trial. Dry matter intake (DMI) was 18.8 and 20.7 kg/cow per day in the first and the second lactation of the trial, with no treatment differences. Similarly, milk yield (23.8 and 29.0 kg/cow per day in the first and the second lactation of the trial) was not affected by dietary treatment. There were no consistent effects of feeding MON810 or its isogenic CON on milk composition or body condition. Thus, the present long-term study demonstrated the compositional and nutritional equivalence of Bt-MON810 and its isogenic CON.

Effects of continuous milking during the dry period or once daily milking in the first 4 weeks of lactation on metabolism and productivity of dairy cows.

The objective was to compare the effects of 3 management systems in high-yielding dairy cows on metabolic profiles and milk production. Thirty-six multiparous Brown Swiss cows were randomly assigned to 1 of 3 treatment groups (n=12 cows/group): the control (C) group, in which cows were dried off 56 d before calving and milked twice daily throughout next lactation (305 d); the once daily milking (ODM) group, in which cows were dried off 56 d before calving and milked once daily for the first 4 wk of lactation and twice daily for the remaining lactation; and the continuous milking (CM) group, in which cows were milked twice daily until calving and also during the subsequent lactation. Serum glucose concentrations decreased between wk 1 and 4 exclusively in C cows. Serum concentrations of NEFA and BHBA in the first 4 wk of lactation were highest in C cows compared with ODM and CM cows. Decreased backfat thickness during early lactation and reduction of body condition score were markedly more pronounced in C cows compared with ODM and CM cows. Mean lactational milk yield of C cows [11,310+/-601 kg of energy-corrected milk (ECM)/305 d] was approximately 16% higher compared with ODM cows (9,531+/-477 kg of ECM/305 d) and CM cows (9,447+/-310 kg of ECM/305 d). The lactation curve of CM cows compared with C cows was characterized by a similar time of peak yield (wk 3), a reduced peak yield, and no obvious differences in persistency. Mean percentage of milk protein was significantly higher for CM cows (3.91%) compared with C cows (3.52%). In contrast, once daily milking was accompanied by a reduced and significantly delayed peak yield (wk 8) compared with the control treatment, whereas persistency was better and milk protein (3.79%) was higher in ODM cows than in C cows. In conclusion, continuous milking and once daily milking, targeting the interval before or after calving, respectively, substantially reduced the metabolic challenge of fresh cows and improved milk protein percentage. Continuous milking and once daily milking increased milk protein percentage markedly; furthermore, once daily milking during the first 4 wk of lactation improved the lactation curve.

Nuclear magnetic resonance and mass spectrometry-based milk metabolomics in dairy cows during early and late lactation.

Milk production in dairy cows has dramatically increased over the past few decades. The selection for higher milk yield affects the partitioning of available nutrients, with more energy being allocated to milk synthesis and less to physiological processes essential to fertility and fitness. In this study, the abundance of numerous milk metabolites in early and late lactation was systematically investigated, with an emphasis on metabolites related to energy metabolism. The aim of the study was the identification and correlation of milk constituents to the metabolic status of the cows. To investigate the influence of lactation stage on physiological and metabolic variables, 2 breeds of different productivity were selected for investigation by high-resolution nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. We could reliably quantify 44 different milk metabolites. The results show that biomarkers such as acetone and beta-hydroxybutyrate are clearly correlated to the metabolic status of the individual cows during early lactation. Based on these data, the selection of cows that cope well with the metabolic stress of early lactation should become an option.

Effect of feeding cows genetically modified maize on the bacterial community in the bovine rumen.

Rumen-cannulated cows (n = 4) were fed successively silage made from either conventional or genetically modified (GM) maize. Results revealed no effects of GM maize on the dynamics of six ruminal bacterial strains (investigated by real-time PCR) compared to the conventional maize silage.

Degradation of transgenic Cry1Ab DNA and protein in Bt-176 maize during the ensiling process.

Maize silage is commonly used as feed for farm animals. The aim of this study was to monitor the time-dependent degradation of non-recombinant chloroplast DNA (exemplified by the rubisco gene) in comparison with the recombinant cry1Ab gene in the course of the ensiling process. In parallel, the Cry1Ab protein content and fragment sizes were determined. Fragments of the rubisco (173, 896, 1197, 1753 and 2521 bp) and of the cry1Ab gene (211, 420, 727 and 1,423 bp) were selected to investigate the DNA degradation process. The detection of the Cry1Ab protein was performed using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Rubisco gene fragments of 173 bp were still detectable after 61 days, while fragments of 1,197 and 2,521 bp were detectable up to 30 days and on the first day only respectively. Polymerase chain reaction (PCR) analyses revealed that fragments of the cry1Ab gene with sizes of 211 and 420 bp were detectable up to 61 days, fragments with sizes of 727 and 1,423 bp, 30 and 6 days respectively. The ELISA showed a decrease of the Cry1Ab protein in maize silage during the ensiling process. No marked degradation was observed during the first 43 h. Thereafter, a sharp decrease was measured. After 61 days, 23.6 +/- 0.9% of the initial Cry1Ab protein was still detectable. Immunoblotting confirmed the results of the ELISA showing a positive signal of approximately 60 kDa size for 8 days of ensiling; no further immunoactive fragments were detectable by immunoblotting. In conclusion, the ensiling process markedly decreases the presence of long functional cry1Ab gene fragments and full size Cry1Ab protein.

In situ studies on the time-dependent degradation of recombinant corn DNA and protein in the bovine rumen.

An in situ technique was adopted to investigate the time-dependent ruminal degradation of chloroplast compared with recombinant DNA of Bt176 corn using conventional and quantitative PCR assays. In parallel, the Cry1Ab protein content and fragment sizes were determined by ELISA and immunoblotting techniques. Triplicate nylon bags filled with 5 g of each substrate (whole-plant isogenic, whole-plant transgenic, ensiled isogenic, and ensiled transgenic corn) were positioned within the rumen of 5 rumen-cannulated, nonlactating cows and incubated for 2, 4, 8, 16, 24, and 48 h. To investigate the DNA degradation process, PCR assays were developed to detect fragments of the endogenous highly abundant rubisco gene (173, 896, 1,197, and 1,753 bp) and of the recombinant cry1Ab gene (211, 420, 727, and 1,423 bp). Short fragments of rubisco (<431 bp) and cry1Ab DNA (211 bp) were amplifiable in whole-plant and ensiled corn samples incubated in the rumen for 48 h, whereas the traceability of larger fragments depended on previous processing of the sample (whole-plant or ensiled corn), the length of the target sequence, and concomitantly on the length of time incubated in the rumen. Quantification of rubisco and cry1Ab gene fragments applying real-time PCR assays revealed degradation to <20% of initial 0-h values within 2 h and <0.5% after 48 h of ruminal incubation. Analysis of Cry1Ab protein in whole-plant corn using the ELISA technique revealed a decrease to 28.0% of the initial value within 2 h and to 2.6% within 48 h. The concentration of Cry1Ab protein of ensiled corn was only 10% that of whole-plant corn. Ensiled corn Cry1Ab protein decreased to 10% of initial values after 48 h of ruminal incubation. Using an immunoblotting technique, the full-size Cry1Ab protein was only detectable up to 8 h; thereafter, only fragments of approximately 17 and 34 kDa size were found. In conclusion, ruminal digestion decreased the presence of functional cry1Ab gene fragments. It is unlikely that full-size, functional Cry1Ab protein will be present after 8 h of incubation in the rumen. Therefore, results based on ELISA measurements should be interpreted carefully and verified by another detection method that discriminates between the full-size and fragmented Cry1Ab protein.

[Rationing in public health: what criteria, what priorities?]. / Rationierung im Gesundheitswesen: Welche Kriterien, welche Prioritäten?

Rationalization in clinical care has reached its limits. Facing the need of further reducing health care costs it is relevant to reflect which diagnostic and therapeutic procedures are justified considering the public economic interests. A prioritized list of covered medical care requires a consensus of physicians, insurance companies and patients organizations on the basis of evidence-based medicine.

[Combined intravenous administration of diclofenac and apazone for postoperative analgesia A randomized study of 112 patients with access to i. v. on-demand analgesia after minor orthopaedic operations.]. / Kombinierte intravenöse Gabe von Diclofenac und Azapropazon zur postoperativen Analgesie : Eine randomisierte Doppelblindstudie an 112 unfallchirurgischen Patienten mittels der intravenösen On-Demand-Analgesie.

In a double-blind, randomized, placebo-controlled study, 112 patients scheduled for knee-joint arthrotomies or minor orthopaedic operations received 75 mg diclofenac, 600 mg apazone, the combination of 75 mg diclofenac and 600 mg apazone, or placebo (50 ml NaCl 0.9%) as a single i.v. dose immediately after operation. Postoperative pain intensity was measured by a numeric rating scale. All patients were allowed to self-administer piritramide from a PCA (patient-controlled analgesia) pump (Prominjekt, Pharmacia, Sweden) in 2-mg boluses every 5 min during the first 6 h and subsequently every 15 minfor another 18 h after surgery. The patients receiving diclofenac, apazone, or the combination of diclofenac and apazone required a significantly lower cumulated dose of piritramide during the first 24 h after operation than did placebo-treated subjects (38 mg vs 39 mg vs 27 mg vs 67 mg;P<0.05), but there were no significant differences among the former three groups of patients. The incidence of typical side effects of opioids and antipyretic anti-inflammatory analgesics (nausea, vomiting, stomach ache, headache, vertigo) was low, and they were easily controlled in all cases. Postoperative combined application of the nonsteroidal anti-inflammatory analgesics diclofenac and apazone results in a significantly lower opioid requirement (about 60%) after minor orthopaedic surgery. The opioid-sparing effect appears to be superior to that of diclofenac (44%) or apazone (42%) alone, but this was not statistically significant.

Cell proliferation in the dog (beagle) ovary during proestrus and early estrus.

Cell proliferation in the ovaries of 5 Beagle dogs was studied by autoradiography after pulse labelling with (3H)-thymidine during different periods of proestrus and early estrus. Indices of labelling and of necrosis were determined for different follicle types grouped according to their stages of atresia. Cell proliferation became most obvious during early proestrus in antral and in Graafian follicles, and during the periovulatory period in preantral follicles. By contrast, low labelling indices appeared in all follicle types during the middle of proestrus. All follicle types demonstrated a continuous decrease in labelling from early to late atresia with the exception of the granulosal layer of antral follicles during the periovulatory period. While many necrotic granulosal cells were found in antral follicles during the first 6 days of proestrus, there were few during the periovulatory period. Even Graafian follicles displayed necrotic granulosal cells now and then. It may be concluded that (1) intact ovarian follicles can show subtle changes indicating the beginning of atresia, and (2) during the proliferative phase of a long estrous cycle cell replication in the ovary is characterized by two bursts at the beginning and at the end of this period.

Cell proliferation in the principal target organs of the dog (beagle) ovary during various periods of the estrous cycle.

Cell proliferation in the principal target organs of the ovary was studied in 7 beagle dogs during proestrus, early estrus, secretory and regressive metestrus. Pulse labelling with (3H)-thymidine and autoradiography were applied and labelling indices were determined. Organs with squamous and with glandular epithelium except the mammary gland showed a proliferation peak during early proestrus, the incidence of labelling being higher in organs with squamous epithelium. During early proestrus the intensity of labelling decreased in organs with squamous epithelium in the following order: vulva, vagina, portio vaginalis, and portio supravaginalis. At this time cell replication was higher in the superficial glands of the cervix and corpus uteri as well as the circular layer of the myometrium compared with values from the basal glands or the longitudinal layer. The steepest decline of the proliferative activity occurred between the proestrous period. While some labelled cells were observed during secretory metestrus, labelling was almost absent during regressive metestrus. By contrast, the mammary gland began to develop at the periovulatory period and was at the height of its proliferative activity during secretory metestrus. It is concluded for species with a long estrous cycle that: (1) the rate of cell replication in the vulva, vagina, uterus and oviduct is at its peak at the beginning of the estrous cycle and declines during proestrus; (2) as compared to observations in species with short estrous cycles, cell proliferation is very low during metestrus.