Genotype-environment interactions for growth and carcass traits in different pig breeds kept under conventional and organic production systems.

The demand for special breeding programmes for organic pig meat production is based on the assumption that pigs kept under organic conditions need different biological properties compared with conventionally kept pigs in order to achieve a good performance. This would mean that genotype-environment interactions exist. Therefore, 682 pigs of seven different genotypes were tested for growth performance and carcass quality under conventional and organic environments at two testing stations to verify genotype-environment interactions. All genotypes achieved significantly better results within the conventional environment and there were significant interactions between genotype and environment for all the criteria of growth performance and carcass quality. The interactions are mainly caused by varying differences between organic and conventional systems within genotypes, but for all traits, except weight gain, no major shift of the ranking order within environment between genotypes. Although statistically significant genotype-environment interactions exist, the modern genotypes selected under conventional conditions are also superior to indigenous breeds under organic conditions in economically important traits. Hence, it can be concluded from these results that no special breeding programme is necessary for organic production systems.

Similar bioavailability of single-dose oral and intravenous mesna in the blood and urine of healthy human subjects.

Although mesna has been used for more than a decade to reduce the incidence of hemorrhagic cystitis induced by ifosfamide and cyclophosphamide, the disposition of i.v. and oral mesna has not been adequately described. To obtain accurate bioavailability data for the design of mesna regimens, we developed procedures to preserve and measure mesna and dimesna in the blood and urine and studied 25 volunteer subjects who received single doses of i.v. mesna and four different formulations of oral mesna in a five-way randomized crossover study. The dose-adjusted area under the blood concentration-time curve showed no difference in bioavailability for i.v. and oral mesna; however, the maximum mesna concentration after oral doses was 16% of that estimated for i.v. doses. The short initial half-life of i.v. mesna indicated that mesna was rapidly cleared; however, the blood concentrations of mesna uniformly exceeded those of dimesna after oral as well as i.v. doses, which suggested that reduced mesna and oxidized mesna disulfide are in equilibrium. The ratio of mesna:dimesna was higher in protein-free plasma than it was in the urine, which suggested that most urinary mesna is produced by glomerular filtration of mesna rather than by renal tubular reduction of dimesna. The sum of mesna and dimesna excretion after the i.v. doses (73% of the dose) and the four oral formulations (68-73%) showed no difference in urinary bioavailability, consistent with the blood data. However, the urinary bioavailability of the therapeutically active free-thiol mesna was greater after i.v. doses (40% of the dose) than it was after oral doses (31-33%). The ratio of oral:i.v. mesna excretion ranged from 0.52-1.23 (mean, 0.82) among the 24 subjects. Urinary mesna concentrations exceeded 50 microM in all subjects for up to 12 h after oral doses as compared to 4 h after i.v. doses. About 90% of this mesna was excreted by hour 2 after i.v. doses and by hour 9 after oral doses. The mean maximum concentration of mesna in blood and excretion into urine were both 2.6 h after dosing. The oral formulations thus showed sustained urinary excretion, and their urinary bioavailability approached that of i.v. mesna.

Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide.

PURPOSE: To compare the pharmacokinetics of the approved I.V. (intravenous) mesna regimen and an investigational I.V.-oral regimen that could be used in outpatients who receive ifosfamide. PATIENTS AND METHODS: The I.V. regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen included an I.V. mesna dose given concurrently with ifosfamide, followed 2 and 8 hours later by oral administration of mesna tablets. I.V. and oral mesna doses equaled 20% and 40%, respectively, of the ifosfamide dose. The study subjects were 12 lung cancer patients who received ifosfamide 1.2 g/m2 daily for 5 days. The patients were randomized to receive either the I.V.-oral or I.V. mesna regimen on day 1, followed by crossover to the other regimen on days 2 through 5 of ifosfamide treatment. The urinary profiles of mesna and dimesna excretion were determined on days 1, 2, and 5; pharmacokinetic parameters for blood samples were determined only on day 5. RESULTS: During the first 12 hours after ifosfamide administration, the amount of mesna excreted and the profile of urinary mesna excretion was similar for both regimens; however, the I.V.-oral regimen showed less fluctuation in the excretion rate and higher trough values. During hours 12 to 24, about eightfold more mesna was excreted by patients given the I.V.-oral than the I.V. regimen. CONCLUSION: These pharmacokinetic data show that the I.V.-oral regimen should be at least as uroprotective as the I.V. mesna regimen. Patients may also benefit from the I.V.-oral regimen because of the higher trough values during hours 0 through 12 and the sustained urinary mesna excretion during hours 12 through 24.

[The use of biotechnology in animal breeding]. / Nutzung der Biotechnik in der Tierzüchtung.

Biotechnological techniques are extensively used in dairy breeding programs. Thus, artificial insemination and embryo transfer (and associated techniques) constitute an integral part of modern breeding programs. In pig breeding, embryo transfer is mostly restricted to special problem areas because of its high costs. Currently this technique is used for the exchange of genetic material on an international level, for the creation of specific pathogene free herds, and in connection with cryoconservation for the setup of embryobanks in the context of the preservation of genetic resources.

Dosing and side-effects of ifosfamide plus mesna.

In clinical practice and in most ongoing studies in adult and pediatric tumours, daily short-time infusions of ifosfamide (IFO) on 2-5 consecutive days with cycle doses between 6 g/m2 and 12 g/m2 are used at present. The continuous i.v. infusion of IFO/mesna over 1-5 days is still experimental. Since mesna prevents IFO-induced urotoxicity, the IFO dose could be increased to 16 g/m2 per cycle. As the dose and schedules of IFO/mesna were increased and varied, CNS and renal toxicity became more evident. CNS toxicity seems not to be dependent on i.v., but on oral dosing of IFO. Renal dysfunction and previous administration of cisplatinum predispose for CNS toxicity. The incidence or severity of CNS toxicity does not increase with subsequent courses of IFO i.v. The nephrotoxicity of IFO is dependent on IFO dose, diuresis, mesna dose and whether there has been previous cisplatinum and seems to involve preferentially the tubulus system, leading to 25 cases of Fanconi renal syndrome as published in 1988-1990. Fanconi's syndrome depends on the cumulative IFO dose, the previous administration of nephrotoxic drugs such as cisplatinum and the age of the children. Studies are continuing to determine the least nephrotoxic dose and schedule of IFO plus mesna. Leucopenia and thrombopenia are well-known dose-dependent side-effects of IFO, with similar incidence after i.v. short-time and continuous infusion.

Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells.

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Toxicity and response to high-dose ifosfamide + mesna as salvage therapy for advanced breast cancer.

Twenty-six cycles of high-dose ifosfamide + mesna (HD-IFO + M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO + M over 24 h appeared to be the best tolerated. One partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.

Studies on the mammary tumor-inhibiting effects of diethylstilbestrol and its mono- and diphosphate.

Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono- or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES greater than DES-MP much greater than DES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.

Comparative activity of ifosfamide and cyclophosphamide.

Antitumor activity (increase in lifespan and cure) was greater for ifosfamide (IFO) in several experimental tumors, some of which were primarily resistant to cyclophosphamide (CYC). IFO has been shown to be active in anthracycline-resistant and in adriamycin/cisplatin-resistant sublines of an Ehrlich ascites tumor, as well as in tumor cells primarily resistant to CYC. The few comparative controlled clinical trials available suggest superior single-agent activity of IFO compared with CYC in soft tissue sarcoma and ovarian cancer. Combination chemotherapy with IFO has been effective in second-line treatment of sarcomas, malignant lymphomas, lung cancer, and testicular cancer, most of them pretreated with or refractory to CYC. Although it is difficult to obtain clinical proof that there is no cross-resistance between IFO and CYC, IFO has been shown to be active in multirefractory malignant lymphomas, in small cell lung cancer not responding to adriamycin, vincristine, and etoposide, and in soft tissue and bone sarcomas. Testicular cancer and pancreatic cancer are some of the tumors in which IFO activity is currently being evaluated and in which CYC has so far failed to show sufficient clinical activity. More comparative controlled clinical trials are needed in ovarian cancer, breast cancer, malignant lymphomas, sarcomas and cervical cancer, in which IFO has already shown sufficient single-agent activity. Due to its lower level of cross-resistance with a variety of heterocyclic products, but also with other alkylating agents, in addition to its use in induction chemotherapy, IFO is an important second-line agent in many clinical situations.

[Nutrient supply of health and sick fluid fed calves]. / Zur Nährstoffversorgung gesunder und erkrankter Tränkkälber.

In the department for calves being fed with fluid feed of a specialised enterprise for calf rearing the daily intake of fluid feed (skim milk improved with milk substitute), concentrated feed and hay of a total of 341 female animals and the daily intake of energy and protein was calculated thereof. The average consumption of nutrients of the 206 healthy calves was compared with some international and national norms for the demand of nutrients. The comparison with some international values of demand and the results of the partial correlation analysis between energy and protein intake and live weight increase showed that the applied nutrition regime (particularly the kind of fluid feed) has resulted in an excessive supply of the calves with proteins and an insufficient supply with energy. This could not be realised from the GDR nutrients norm for the raising of calves published in 1976. Based on theoretical considerations and some recent findings of the science of nutrition we derived values of the protein and energy demand of our own. Subsequently an attempt is made to assess the supply with nutrients for sick calves.

[Treatment of bronchitis with cefaclor (Panoral) (author's transl)]. / Behandlung von Bronchitiden mit Cefaclor (Panoral).

14 patients from the Allergy Unit of an outpatient clinic suffering from acute exacerbation of chronic bronchitis and 13 outpatients with acute bronchitis were treated with 250 mg cefaclor (Panoral) 3 times daily per os for 5 days. 59% of the organisms isolated from cefaclor-sensitive sputum at the time of prominent clinical symptoms were resistent to tetracycline, 53% of them were resistant to penicillin, and 37% were resistant to ampicillin. 12 out of the 14 patients with acute exacerbation of chronic bronchitis became asymptomatic, and no organisms could be detected in the sputum of 13 out of the same 14 patients two days after cessation of cefaclor treatment. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment.

[Hypersensitivity to antibiotics: Frequency, risks, cross-allergies (author's transl)]. / Uberempfindlichkeit gegenüber Antibiotika: Häufigkeit, Riskiken, Kreuzallergie.

The present paper gives a systematic review of the clinical manifestations of allergic reactions and the underlying immunological mechanisms. Attention is drawn to the relatively high proportion of cases of anaphylactic shock and serum disease related to the total number of cases of allergic reaction, and to the diagnostic techniques available for detection of sensitization towards antibiotics. Structural allergenicity is mentioned, using penicillin allergy as an example. The frequency of allergy to several antibiotics and the frequency of cross-reaction between penicillins and cephalosporins reported in the literature are discussed critically.

[Effect of diseases on the nutrient intake by suckling calves]. / Zum Einfluss von Erkrankungen auf die Nährstoffaufnahme von Tränkkälbern.

An energy and protein intake test was applied to 341 female nursed calves under production conditions. Their daily intakes of skim milk enriched with milk substitute, fodder concentrates, and hay were recorded and their daily energy and protein intakes calculated. Their feed consumption was characterised by cumulative nutrient intake curves, depending on the time of foremilk feeding (K-I-period). Energy and protein intake figures were related to the findings obtained from daily health control, with the view to defining the effects of pneumonia or diarrhoea on feed intake. Both diseases were found to cause significant reduction in nutrient intake, depending on the given type of disease and severity, with their negative impact having been most markedly shown in the context of dry feed intake. The delay caused to the development of dry feed consumption by diseases of the respiratory and digestive tracts was many times longer than the time of the clinical course. The above observations provided some cues for conclusions regarding the approach to be taken by the veterinarian to diagnosis, therapy, and rehabilitation of affected calves. Certain concepts were derived from the findings as to how to feed calves to forestall developmental disorders.