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This randomised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer (NSCLC). We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0-2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chatelut's formula, equivalent to Calvert's AUC 5) on day 1 and vinorelbine 25 mg m(-2) on days 1 and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3 150, C6 147). Their median age was 65 years, 30% had PS 2 and 76% stage IV disease. Seventy-eight and 54% of C3 and C6 patients, respectively, completed all scheduled chemotherapy courses. Compliance with QoL questionnaires was 88%. There were no significant group differences in global QoL, pain or fatigue up to 26 weeks. The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks (P<0.05), but this finding was inconsistent across different methods of analysis. Median survival in the C3 group was 28 vs 32 weeks in the C6 group (P=0.75, HR 1.04, 95% CI 0.82-1.31). One- and 2-year survival rates were 25 and 9% vs 25 and 5% in the C3 and C6 arm, respectively. Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups, respectively (P=0.21, HR 0.86, 95% CI 0.68-1.08). In conclusion, palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC. [ABSTRACT FROM AUTHOR]

The present study evaluated whether a specific androstenone-binding protein is present in porcine and human serum, and in the cytosolic fraction of porcine testis. The binding of [(3)H]-androstenone to serum and testicular cytosol was measured in the absence (total binding) and presence (non-specific binding) of unlabelled androstenone. The optimization of the assay is described. As a part of the assay validation, the binding of [(3)H]-dihydrotestosterone ([(3)H]-DHT) to porcine and human serum was also examined. As expected, specific binding of [(3)H]-DHT was detected in human serum, but not in porcine serum. No specific androstenone-binding protein was detected, either in porcine or human serum, or in the cytosolic fraction of porcine testis. The amount of non-specific binding of [(3)H]-androstenone was slightly lower in porcine serum compared to human serum. Between-animal variations in [(3)H]-androstenone binding were studied in plasma samples from 15 animals with androstenone concentrations ranging from 1.1 to 23.1 ng/mL. Mean values+/-standard deviations of binding in these samples were 15.2+/-0.9% for total binding and 15.9+/-0.8% for non-specific bindings. Low between-animal variations indicate that androstenone binding does not affect androstenone accumulation in fat.

The effects of human chorionic gonadotropin (hCG) stimulation on fat skatole concentrations and hepatic activities of cytochromes P4502E1 (CYP2E1) and P4502A (CYP2A) were studied in Landrace and Duroc breeds of entire male pigs. Pigs were divided into four groups: two control groups of each breed, without hCG stimulation (n = 20 for each breed), and two experimental groups of each breed, with hCG stimulation (n = 18 for each breed). Pigs were slaughtered 3 days after hCG stimulation and activities of CYP2E1 and CYP2A were measured in liver homogenate. Activities of both CYP2E1 and CYP2A were lower in hCG-stimulated pigs than control pigs for both Landrace (p = 0.005 for CYP2E1, p = 0.016 for CYP2A) and Duroc breeds (p = 0.003 for CYP2E1, p = 0.001 for CYP2A), and skatole concentrations in fat were higher in the hCG-stimulated pigs of both breeds (p < 0.01). For both control and hCG-stimulated groups, Duroc pigs had lower skatole concentrations than Landrace pigs (p = 0.001 for both groups). The activity of CYP2E1 did not differ significantly between breeds in either the control group or the experimental group (p = 0.233 for control pigs and p = 0.210 for experimental pigs). However, whereas CYP2A activity did not differ significantly between breeds in the control groups (p = 0.181 for CYP2A), in the hCG-stimulated groups, CYP2A activity was lower in Duroc pigs than in Landrace (p = 0.011). Based on these findings, we conclude that hCG stimulation can suppress hepatic CYP2E1 and CYP2A activities, probably through an increase in the levels of testicular steroids. Between-breed variations in skatole levels in fat were not related to the activities of CYP2E1 and CYP2A.

The aim of the present study was to investigate the effect of active immunization against GnRH in mature Standardbred mares (three experimental and one control mare) on antibody titres, ovarian function, hormonal levels and oestrous behaviour. The mares were individually teased with a stallion once each day. During the first part of the experiment (period I: late April until November), blood was sampled every third day during the first 3 months, thereafter once per week. In the second part of the experiment (period II: December until August), sampling was carried out every second week. Progesterone, oestradiol-17beta and LH were analysed. Rectal gynaecological examination was made with the same intervals as the blood samplings and included palpation of the genital organs and ultrasonography. The experimental mares were immunized against GnRH with a GnRH-BSA conjugate. Equimune (Vetrepharm, Bracetown, Business Park, Clonee, Co. Meath, Republic of Ireland) was used as adjuvant. The mares were immunized on four occasions (20-30 day intervals) and GnRH antibody titre was determined. All immunized mares produced antibodies against GnRH but the maximum titres as well as the duration of a greater than 10% binding capacity varied between the mares (1 : 1600 to 1 : 50 000; 5 to 12 months, respectively). After the first injection, all mares showed one oestrus and ovulated at the regular time. In two of the mares, the immunization resulted in ovarian atrophy. Their hormone levels of progesterone, oestradiol- 17beta and progesterone decreased to basal levels and the cyclical hormone pattern was interrupted from approximately 30 days onwards. They continued to show oestrous signs but with irregular durations and intervals. The third mare showed ovarian suppression only for short periods and not in both ovaries at the same time; the hormone levels were basal for only about 20 days (days 50-70) and the mare ovulated on day 75 after start of immunization. The other mares ovulated after 13.5 and 15 months, respectively. It is concluded that the effect of immunization against GnRH in mature mares was individual concerning antibody titre response and the suppression of ovarian activity and hormone levels. Mares with totally inactive ovaries continued to show oestrous signs but with irregular intervals and durations.

The aim of this study was to investigate the effect of gonadotrophin-releasing hormone (GnRH) immunisation on mature stallions that had been used for breeding. Four Standardbred stallions were used in the study: 3 experimental animals and 1 control animal. Semen was collected regularly, i.e. twice/week, during the 4 months prior to the experimental period. The stallions were immunised against GnRH with a GnRH-BSA conjugate. Equimune was used as the adjuvant. The stallions were immunised on 5 occasions, 4 at 2 week intervals, and the fifth 4 weeks after the fourth. Blood samples were taken once a week for analysis of GnRH antibody titre and every third week for testosterone and oestrone sulphate analyses. Semen was collected once a week, and libido and sexual behaviour were observed. Ejaculate volume, sperm concentration, total number of sperm in the ejaculate, sperm motility and sperm morphology were evaluated. Testicular size was measured once a week. At the end of the study, the stallions were castrated, and a histological examination of the testes performed. All immunised stallions produced antibodies against GnRH, and plasma testosterone concentration decreased. However, the effect of immunisation varied between stallions. In 2 of the stallions, high levels of antibodies were found, while in the third, the level was moderate. Four weeks after the first immunisation, a decrease in libido was observed. Two months after the first immunisation, marked changes in semen quality were observed in the 2 stallions with high antibody titres. Fourteen weeks after the first immunisation, the total number of sperm/ejaculate had decreased from >8.6 x 10(9) to <2.7 x 10(9), sperm motility from >59 to <10% and the frequency of morphological normal spermatozoa had decreased from >60 to <14%. The dominating abnormalities were abnormal head shapes, proximal cytoplasmic droplets and detached heads. In the third stallion, only slight changes in semen quality were found. No changes were observed in the control stallion. Decreases in testicular size were noted in all of the experimental stallions. Pronounced histological alterations in the testes were observed in 2 of the stallions. It is concluded that the vaccine was effective in stimulating production of GnRH antibodies and in suppressing testicular function and androgen secretion. However, there was an individual variation in the responses among the stallions and, further, libido was not totally suppressed.

To investigate the causes and mechanisms of foetal loss in Norwegian dairy goats, blood parameters in 40 goats that lost foetuses were compared with those in 40 goats that experienced a normal pregnancy. High mean levels of 15-ketodihydro-PGF2alpha, and low mean levels of oestrone sulphate throughout pregnancy were associated with foetal loss. The mean oestrone sulphate level was low before abortion, and the distinct peak that occurred at parturition in the control goats was not observed in connection with abortion. Association of other blood parameters with foetal loss was not detected. Infectious agents and toxins did not appear to be major causes of foetal loss in this study. The normal level of progesterone and cortisol in goats with foetal loss indicated that the function of the corpus luteum and adrenal glands, respectively, were not disturbed. The rapid decline in progesterone level associated with foetal loss may therefore be a result, rather than the cause, of foetal death. The lowered level of oestrone sulphate and elevated level of 15-ketodihydro-PGF2alpha in goats with foetal loss clearly indicated that the endocrine foetal-placental function was disturbed.

The response to Claviceps purpurea sclerotia administration in pregnant goats was examined in terms of changes in the levels of plasma hormones, the development of pregnancy and kid production. Six treated goats were each given 15 mg milled sclerotia (i.e. 0.105 mg ergotamine) per kilogram live weight twice daily via a stomach tube from days 98 +/- 2 to 107 +/- 2 of gestation. Seven control goats were given water twice daily via a stomach tube during the same period of gestation. The goats were observed for clinical signs of disease, rectal temperatures and live weights were recorded and the condition of the foetuses was monitored by real-time ultrasonography. All control goats delivered live kids. In the treated group two goats aborted 33 and 47 days, respectively, after the start of the administration period, two goats each delivered one normal and one weak kid, and the two remaining goats delivered apparently normal kids. All six treated goats became depressed and had poor appetite during the period of sclerotia administration. Rectal temperatures were significantly increased and live weight changes significantly decreased in the animals in the treated group compared to the control group during the period of C. purpurea administration. Ultrasound examination revealed that foetal deaths occurred between 1 and 42 days before abortion or birth. The appearance of the aborted foetuses varied from fresh to mummified, depending on the number of days between foetal death and expulsion. Microbiological and serological investigations revealed no infectious causes of reproductive failure. The level of 15-ketodihydro-PGF2 alpha was high in goats that aborted following administration of C. purpurea compared with the level in control goats. The oestrone sulphate level did not increase before abortion in the treated goats as in the controls before parturition. There were also changes in these hormones in the four treated goats that delivered live kids, but the changes were considerably smaller. These findings indicate that the endocrine foetal-placental function was disturbed, probably due to injury caused by the C. purpurea toxin ergotamine in the placenta and foetus.

The effect of Listeria monocytogenes infection on hormone levels in pregnant goats was studied. Four goats (Group I) received an intravenous inoculation of a bacterial culture (Type 1) on Days 69-77 and another four goats (Group II) received a similar inoculation on Days 105-106 of gestation. Five non-inoculated goats were used as controls. Plasma was analysed for progesterone, oestrone sulphate and 15-ketodihydro-PGF2 alpha. The status of the foetus was followed using real-time ultrasonography. Three of the four goats in Group I aborted 8-10 days after inoculation. The fourth goat gave birth to a normal live kid at term. The three goats which aborted showed clinical signs of disease in connection with abortion. In Group II, all goats aborted after 9-11 days. All the goats showed clinical symptoms of disease from a few days after inoculation and the symptoms continued until abortion. The clinical symptoms of disease were more pronounced in Group II than in Group I. L. monocytogenes was isolated from all aborted foetuses. None of the control goats aborted. Ultrasound examination revealed foetal death either immediately before or up to 2 days before abortion. Mummification had begun in the foetus that had been dead for 2 days before expulsion. In comparison with pre-inoculation plasma levels in Group I, a significant decrease (P < 0.05) in progesterone levels and an increase in 15-ketodihydro-PGF2 alpha levels were observed from Days 4 and 6 after inoculation, respectively. In Group II, a significant decrease (P < 0.05) in progesterone levels and an increase in 15-ketodihydro-PGF2 alpha levels in plasma were observed from Days 8 and 6, respectively. The oestrone sulphate levels decreased slightly in the inoculated goats a few days before abortion. The pattern of changes in levels around abortion was similar to the pattern present in the control animals around parturition. However, oestrone sulphate levels did not increase in the inoculated groups before abortion in contrast to goats which delivered healthy kids. The changes in levels of 15-ketodihydro-PGF2 alpha in goats that aborted indicated that the endocrine foetal-placental function was disturbed, which was most likely due to the establishment and development of L. monocytogenes in the placenta and foetus.

In cattle, a translocation of the Robertsonian type between the largest and smallest chromosome leads to a reduction in fertility. This is substantiated by reduced nonreturn rates in daughter groups of bulls carrying the 1 29 translocation and in the heterozygous bulls themselves. This reduction in fertility is thought to be due to the early death of embryos with unbalanced karyotypes. The influence of semen from a bull known to be heterozygous for the 1 29 translocation on the outcome of a bovine IVF program was investigated. There was a significant difference (P<0.005) in terms of cleavage rate (59.8 vs 71.1%) and blastocyst rate (12.0 vs 20.0%) between the carrier and control bull, respectively. There was no difference in blastocyst quality as measured by cell number. The results observed in vitro are consistent with the field fertility records of the 2 bulls in terms of nonreturn rates (59.2 vs 70.6%, for the carrier and control bull, respectively).

Ten, bull calves of the Norwegian Red breed were hemicastrated at the age of 1 1 2 -3 months . Ten, normal bull calves of similar age served as controls. No significant differences were found in plasma testosterone levels or in weight between the two groups during the ensuing seven-month test period. Eight, male pigs were hemicastrated at 1-2 months of age. Eight, normal male pigs served as controls. Plasma testosterone, androstenone, and body weight were measured fortnightly in all pigs until the age of 6-7 months. Androstenone in adipose tissue was measured from 4-5 months of age. No significant differences were found between normal and hemicastrated animals in any monthly interval. However, when combining the measurement at 5-6 and 6-7 months of age for plasma testosterone and 5alpha-androstenone and 5alpha-androstenone in fat, the normal pigs had significantly higher values than the hemicastrates (p<0.05). The weight of the single testis from the hemicastrated pigs at slaughter nearly equalled the combined weight of both testes from the controls. Thus, hemicastration did not appear to have any significant effect on the level of testicular steroids in plasma in bulls or growth rate in bulls and boars, but did have a slight effect on testicular steroids in plasma in pigs at 5-7 months of age.