Review: Update of nutritional requirements of goats for growth and pregnancy in hot environments.

Goats play an important role in the agricultural business, providing valuable income sources through producing high-quality animal protein. They are widespread livestock for rural households due to their inherent resiliency, adaptability to many environments, and suitability in sustainable production systems. While goats are reared in highly diverse environments, a great portion of their population is reared in hot environments. Heat stress is known to affect goats' productive and reproductive performance negatively. However, goats can remarkably thrive in harsh conditions due to physiological, metabolic, and molecular adaptive mechanisms. In the face of it, in the last decades, the nutrition of goats, particularly their nutritional requirements, has received special attention. Research groups worldwide have dedicated their efforts to updating feeding systems for goats. Our objective was to present the recent findings on the energy and nutrient requirements of growing and pregnant goats in hot environments. Energy and protein requirements for the maintenance and growth of goats are influenced by sex and genotype only when mature weight is not considered in the models. Sex and genotype affect the efficiency of energy use for growth but do not affect the efficiency of protein use. Major mineral requirements for maintenance and growth are not affected by sex, except for magnesium. However, the phosphorus, sodium, and potassium requirements of goats raised in hot environments differ from those in the feeding systems. This difference may be related to the adaptation mechanisms goats employ to cope with the hot environmental conditions. Regarding requirements for pregnancy, there was no effect of days of pregnancy on the energy or protein requirements. The efficiency of metabolizable energy utilization for pregnancy increased with the progress of pregnancy. Mineral accretion for pregnancy differs between single and twin pregnancies and, irrespective of pregnancy type, the mineral requirements increase as pregnancy progresses. The differences between the estimated dietary requirements of goats raised in hot environments and the most widely adopted feeding systems suggest that these goats may be using energy and nutrients to cope with heat stress and other stressors associated with hot environments. The recent findings on energy, protein, and mineral requirements of growing and pregnant goats can be an important resource of information for enhancing feeding systems worldwide.

Energy and protein requirements for maintenance of Texel lambs.

It can be hypothesized that the body composition characteristics of different sheep breeds affect their nutritional requirements. However, no study has yet been carried out to determine the nutritional requirements for maintenance of Texel purebred lambs, despite their growing importance in sheep meat production globally. Our objective was therefore to determine the energy and protein requirements for maintenance of Texel lambs. Thirty-four Texel lambs were used, all intact males that were weaned at 50 days old, and confined in individual pens. Two experiments were conducted, as follows. In Experiment 1, a digestibility assay was performed to determine the dietary energy value, in a 3×3 double Latin square design, in which lambs were submitted to three levels of feed restriction (0%, 55% and 70% of ad libitum feed intake). In Experiment 2, the energy and protein requirements for maintenance of Texel lambs from 21 to 40 kg BW were determined using a randomized block design, in which lambs were also submitted to three levels of feed restriction (0%, 55% and 70% of ad libitum feed intake). The requirements for net energy for maintenance (NEm), metabolizable energy for maintenance (MEm), net protein for maintenance (NPm) and metabolizable protein for maintenance (MPm) were determined. The digestibility of dry matter, energy, protein and metabolizability were similar between food restriction levels, averaging 74.4%, 75.5%, 80.3% and 0.636, respectively. The NEm determined for growing Texel lambs was 263 kJ/kg of the metabolic fasting BW (FBW), the MEm was 417 kJ/kg0.75 FBW and the efficiency of use of MEm was 0.63. In addition, the NPm was 1.24 g/day per kg0.75 FBW and the MPm was 2.98 g/day per kg0.75 FBW. The energy requirements of Texel lambs are different from those reported in the literature, possibly due to differences between breeds, diets and environmental effects, whereas the protein requirements are different from literature mainly due to methodological differences; further studies are need to address these aspects that affects the nutritional requirements for raising sheep from different breeds in different environments.

Energy and protein requirements for maintenance of dairy goats during pregnancy and their efficiencies of use.

It has been suggested that maintenance requirements are similar among animals of different physiological stages; however, important physiological changes occur in the maternal body during pregnancy. Therefore, the aim of this study was to determine the energy and protein requirements for the maintenance of pregnant dairy goats and to estimate their efficiency of energy and protein utilization for maintenance and pregnancy. We used 66 multiparous pregnant goats having 49.0 ± 1.59 kg initial BW (around the third or fourth parturition) arranged in a randomized block design with a 3 × 3 factorial scheme including slaughter at different days of pregnancy (DOP; 80, 110, and 140 d) and feed restriction (0, 20, and 40% feed restriction). The comparative slaughter technique was used to estimate energy and protein maintenance requirements. Goats slaughtered at 140 DOP were subjected to digestibility trials at around 80, 110, and 140 DOP to estimate diet metabolizability and N balance (NBAL). Metabolizability decreased with feed restriction and was 63.3 ± 2.16, 55.7 ± 2.35, and 58.2 ± 2.30% at 0, 20, and 40% of feed restriction, respectively ( < 0.01). There was no effect of DOP on NE or the requirements of ME for maintenance (ME), which were 197 and 315 kJ/kg empty body weight (EBW), respectively, and the efficiency of ME utilization for maintenance (k) was 0.63. Similarly, DOP did not affect thedaily net protein requirements for maintenance (NP) estimated using the comparative slaughter technique (1.38 ± 0.512 g/kg EBW; = 0.003) or the NP estimated using NBAL (2.49 ± 0.594 g/kg EBW; < 0.01). The MP requirement for maintenance (MP) estimated using the comparative slaughter technique was not affected by DOP and was 3.22 g MP/kg EBW ( < 0.01). The efficiency of MP utilization for maintenance (k) was 0.43. The efficiency of ME utilization for pregnancy (k) increased with the progress of pregnancy and was 0.058, 0.10, and 0.19 at 80, 110, and 140 DOP, respectively. Similarly, the efficiency of MP utilization for pregnancy (k) increased with DOP and was 0.12, 0.21, and 0.43 at 80, 110, and 140 DOP, respectively. There was no evidence that pregnancy affected NE, ME, NP, and MP or k and k, which were also unaffected by DOP. However, k and k increased with pregnancy progress as a response to the physiological changes that pregnant females are subjected to.

Net mineral requirements of dairy goats during pregnancy.

Mineral requirements of pregnant dairy goats are still not well defined; therefore, we investigated the net Ca, P, Mg, Na and K requirements for pregnancy and for maintenance during pregnancy in two separate experiments. Experiment 1 was performed to estimate the net Ca, P, Mg, Na and K requirements in goats carrying single or twin fetuses from 50 to 140 days of pregnancy (DOP). The net mineral requirements for pregnancy were determined by measuring mineral deposition in gravid uterus and mammary gland after comparative slaughter. In total, 57 dairy goats of two breeds (Oberhasli or Saanen), in their third or fourth parturition, were randomly assigned to groups based on litter size (single or twin) and day of slaughter (50, 80, 110 and 140 DOP) in a fully factorial design. Net mineral accretion for pregnancy did not differ by goat breed. The total daily Ca, P, Mg, Na and K requirements for pregnancy were greatest in goats carrying twins (P<0.05), and the requirements increased as pregnancy progressed. Experiment 2 was performed to estimate net Ca, P, Mg, Na and K requirements for dairy goat maintenance during pregnancy. In total, 58 dairy goats (Oberhasli and Saanen) carrying twin fetuses were assigned to groups based on slaughter day (80, 110 and 140 DOP) and feed restriction (ad libitum, 20% and 40% feed restriction) in a randomized block design. The net Ca, P and Mg requirements for maintenance did not vary by breed or over the course of pregnancy. The daily net requirements of Ca, P and Mg for maintenance were 60.4, 31.1 and 2.42 mg/kg live BW (LBW), respectively. The daily net Na requirement for maintenance was greater in Saanen goats (11.8 mg/kg LBW) than in Oberhasli goats (8.96 mg/kg LBW; P<0.05). Daily net K requirements increased as pregnancy progressed from 8.73 to 15.4 mg/kg LBW (P<0.01). The findings of this study will guide design of diets with adequate mineral content for pregnant goats throughout their pregnancy.

Net mineral requirements for growth of Saanen goat kids in early life are similar among genders.

The current mineral requirements for growing goat kids are based on sheep and cattle studies without differentiating between the stages of development or gender. The aims of this study were to determine the net requirements for growth of Ca, P, Mg, Na and K of Saanen goat kids during the initial stages of growth and to analyse the effect of gender on the net requirements for growth of these macrominerals. Eighteen female, 19 intact male and 10 castrated male Saanen goat kids were studied. The kids were selected applying a completely randomized design and slaughtered when their body weight (BW) reached approximately 5, 10 and 15 kg to determine the mineral requirements for growth at these stages. The net mineral requirements for growth were similar among genders. The goat kids had slightly increased net requirements of Ca, P and Mg for growth with increasing BW from 5 to 15 kg. The net requirements for growth of Ca, P, Mg, Na and K ranged from 9.61 to 9.67 g/kg of BW gain, 7.14 to 7.56 g/kg of BW gain, 0.34 to 0.37 g/kg of BW gain, 1.26 to 1.13 g/kg of BW gain, 1.88 to 1.82 g/kg of BW gain as the animals grew from 5 to 15 kg respectively. In conclusion, when formulating diets for Saanen goat kids in early growth stage mineral levels do not need to adjusted based on gender.

Net energy and protein requirements for pregnancy differ between goats and sheep.

Current feeding systems for goats estimate the energy and protein requirements for pregnancy using data from sheep. The objective of this study was to predict the NE and net protein requirements for pregnancy in goats carrying single and twin fetuses and to compare these requirements with those of sheep. Data were compiled from 2 studies with dairy goats and 3 studies with sheep. These studies measured the energy content (EC) and protein content (PC) of the gravid uterus and of the mammary gland using the comparative slaughter technique. The current study was performed as a meta-analysis using an exponential model, comparing species (sheep versus goats) and litter size (single versus twin) from 50 to 140 d of pregnancy. Total EC and total PC in the gravid uterus were similar in goats and sheep carrying a single fetus. Energy and protein contents of the gravid uterus of sheep carrying twins were, on average, 29% greater than that of goats with twins from 80 to 140 d of pregnancy. During pregnancy, EC and PC of the mammary gland in goats carrying singles and twins were, on average, greater than those of sheep by 9 and 24%, respectively, for EC and by 25% for PC for both litter sizes. In conclusion, the gravid uterus and the mammary gland of goats and sheep require different amounts of energy and protein. Sheep carrying twins have the greatest daily NE and net protein requirements for pregnancy followed by goats carrying twins and both species carrying a single fetus. Therefore, it is inappropriate to adopt data from sheep to predict the net pregnancy requirements of goats, and the results found in this study could be relevant to the nutritional management of dairy goats.

Mineral requirements for growth and maintenance of F1 Boer × Saanen male kids.

The objective of this study was to determine the net requirements of minerals for the growth and maintenance of intact male F1 Boer × Saanen goat kids in the initial phase of growth. The following 2 experiments were performed: Exp. 1 was performed to determine the net growth requirements for Ca, P, Mg, Na, and K by F1 Boer × Saanen goat kids from 5 to 25 kg of BW and Exp. 2 was performed to determine the maintenance requirements of F1 Boer × Saanen goats from 15 to 25 kg BW. In Exp. 1, 32 intact male goat kids were distributed in a completely randomized design and mineral body composition was fit to an allometric equation in the form of a nonlinear model. To determine the mineral requirements for maintenance in Exp. 2, 21 intact male goat kids were distributed in a randomized block design, where the goat kids were subjected to 3 levels of feed restriction (0, 30, and 60% feed restriction). At the onset of Exp. 2, 7 goat kids were harvested and used to estimate the initial body composition (15 kg BW). Initial body composition was used to calculate the retention of minerals. The maintenance requirements were estimated by regressions obtained from the retention of minerals in the empty body and the intake of the mineral. The concentration of Ca, P, Na, and K in the empty BW decreased by 11, 13, 26, and 23% with the increase in BW from 5 to 25 kg (P < 0.01). As a consequence, our results showed that net requirements of Ca, P, Mg, Na, and K for weight gain decreased by 27.5, 27.8, 4.25, 43.2, and 39.7%, respectively, with the increase in BW from 5 to 25 kg (P < 0.01). The net requirements (g/kg of ADG) decreased from 9.7 to 7.0 for Ca, 6.5 to 4.7 for P, 0.38 to 0.36 for Mg, 0.88 to 0.50 for Na, and 1.9 to 1.2 for K when BW increased from 5 to 25 kg. The daily net requirements for maintenance per kilogram of BW were 38 mg of Ca, 42 mg of P, 1.6 mg of Mg, 5.0 mg of Na, and 19 mg of K. These results for the nutritional requirements of minerals may help to formulate more balanced diets for F1 Boer × Saanen goat kids in the initial growth phase.

Mineral Metabolism in Singleton and Twin-pregnant Dairy Goats.

During pregnancy, the maternal body undergoes significant physiological changes. The present study assessed the changes on calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na) and potassium (K) metabolism in singleton and twin-pregnant dairy goats. The 42 goats used (49.5 kg±7.6 body weight [BW]) were assigned at random to treatments that were factorially arranged to account for 2 breeds (Oberhasli and Saanen), 2 pregnancy types (singleton and twin) and 3 gestation periods (80, 110, and 140 days). Digestibility trials were performed at 80, 110, and 140 days of gestation. Mineral retention during pregnancy was determined in the maternal body, femur, uterus, mammary gland, fetus and fetal fluid. Blood samples were taken during pregnancy before and after a meal, and Ca, P, Mg, Na, K ions and alkaline phosphatase activity determined in serum. Bone mineral density was determined in the right femur. Statistical analyses were performed using the SAS MIXED procedure. Dry matter intake decreased linearly up to 140 days of gestation. Maternal BW gain, and Ca, P, and Mg retention (g/kg) decreased linearly with the advance of gestation days. Macromineral retention in maternal body (g/kg) was greater in Oberhasli than Saanen goats, and their fetuses had higher Ca, P, and Mg deposition (mg/g). Mineral retention (mg/g) increased in fetuses according to pregnancy development, with no differences between singleton and twin pregnancy. In the mammary gland, the retention of all minerals (g) increased with the days of pregnancy. In conclusion, related to Ca, P, and Mg metabolism can be divided into two stages. Up to 80 days of gestation, was characterized by the preparation of the maternal body reserves for future mineral demands. From 80 days of gestation onward, was characterized by the transfer of maternal body reserves for fetal development and colostrum production. Na and K supply was provided by adjustments in endogenous excretion and an increase in intestinal absorption. Finally, mineral metabolism was specific to each genotype and, except for Na, was not affected by the number of fetuses.

Energy requirements in early life are similar for male and female goat kids.

Little is known about the gender differences in energetic requirements of goats in early life. In this study, we determined the energy requirements for maintenance and gain in intact male, castrated male and female Saanen goat kids using the comparative slaughter technique and provide new data on their body composition and energy efficiency. To determine the energy requirements for maintenance, we studied 21 intact males, 15 castrated males and 18 females (5.0±0.1 kg initial body weight (BW) and 23±5 d of age) using a split-plot design with the following main factors: three genders (intact males, castrated males, and females) and three dry matter intake levels (ad libitum, 75% and 50% of ad libitum intake). A slaughter group included three kids, one for each nutritional plane, of each gender, and all three animals within a group were slaughtered when the ad libitum kid reached 15 kg in BW. Net energy requirements for gain were obtained for 17 intact males, eight castrated males and 15 females (5.1±0.4 kg BW and 23±13 d of age). Animals were fed ad libitum and slaughtered when they reached 5, 10, and 15 kg in BW. A digestion trial was performed with nine kids of each gender to determine digestible energy, metabolizable energy and energy metabolizability of the diet. Our results show no effect of gender on the energy requirements for maintenance and gain, and overall net energy for maintenance was 205.6 kJ/kg(0.75) empty body weight gain (EBW) (170.3 kJ/kg(0.75) BW) from 5 to 15 kg BW. Metabolizable energy for maintenance was calculated by iteration, assuming heat production equal to metabolizable energy intake at maintenance, and the result was 294.34 kJ/kg(0.75) EBW and km of 0.70. As BW increased from 5 to 15 kg for all genders, the net energy required for gain increased from 9.5 to 12.0 kJ/g EBW gain (EWG), and assuming kg = 0.47, metabolizable energy for gain ranged from 20.2 to 25.5 kJ/g EWG. Our results indicate that it is not necessary to formulate diets with different energetic content for intact male, castrated male and female Saanen goat kids weighing from 5 to 15 kg.

[Length of hospitalization for inpatient treatment of depression. Results of a multicentre study on the effects of a new treatment model]. / Verweildauer in der stationären Depressionsbehandlung. Ergebnisse einer Multicenterstudie zum Effekt eines neuen Behandlungsmodells.

BACKGROUND: Patients with depression are treated for a relatively long period as inpatients in Germany. A new treatment model with symptom-orientated release management, post-hospitalization treatment and standardized referral to outpatient therapists could be suitable to specifically shorten the hospital stay of patients who have already profited sufficiently from treatment. MATERIALS AND METHODS: The aim of the present study was to investigate the effects of a new treatment method (intervention group) with hospitalized depressive patients in comparison to a standard protocol (treatment-as-usual control group) on the length of stay as part of a pragmatic randomized, controlled multicentre study. The evaluation was made using covariance analysis. RESULTS: Of the 202 randomized patients 184 could be included in the analysis. The estimated marginal mean of the length of stay (n = 83) was 57.3 days (range 1-305 days, SE = 3.8) in the intervention group and (n = 101) 57.6 days (range: 6-196 days, SE = 3.5) in the control group. There were no significant statistical differences between the groups (p = 0.966). CONCLUSIONS: An effect of the new treatment model on the inpatient length of hospital stay in depressive patients could not be demonstrated.

[Malignant neuroleptic syndrome associated with amisulpride]. / Malignes neuroleptisches Syndrom durch Amisulprid.

Malignant neuroleptic syndrome (MNS) is a rare side effect of antipsychotic medications but means a serious and life-threatening complication. The risk of MNS seems to be lower for second generation antipsychotics (SGA). We report the 9-month history of a 42-year-old female patient whose antipsychotic medication was switched to 800 mg per day of amisulpride. Two weeks after discharge she suffered muscular pain, stiffness, weakness of the legs, rigor, and fever. After attending our outpatient department and being diagnosed, she was transferred to the neurological intensive unit, where the creatine kinase (CK) level was measured at 160,000 U/l. Furthermore extensive rhabdomyolysis accompanied by a compartment syndrome was seen. Surgical intervention was necessary for the latter. The patient was then retransferred to the psychiatric department after treatment with lorazepam and withdrawal of antipsychotic medications. In addition a therapy with valproate sodium was conducted. Long-term high levels of CK and abnormalities in the electromyogram led to the hypothesis of myopathy as a possible risk factor, but a final diagnostic classification was not feasible. This report describes the appearance of a MNS as a consequence of SGA therapy, discusses risk factors and therapy options, and shows the 9-month course.

Níveis de fibra em detergente neutro na dieta de cordeiros: consumo, digestibilidade e fermentação ruminal / Levels of neutral detergent fiber in lambs diets: intake, digestibility and ruminal fermentation

Foram utilizados oito cordeiros castrados (35,0±6,0kg peso vivo) em um delineamento duplo quadrado latino 4 ´ 4 para avaliar o efeito de quatro níveis de fibra em detergente neutro (FDN) na dieta (25, 31, 37 e 43 por cento da matéria seca (MS)) sobre o consumo e parâmetros digestivos. O consumo de nitrogênio (N) variou de forma quadrática; o de MS, matéria orgânica (MO) e energia diminuíram (P<0,05) e de FDN aumentou (P<0,01) linearmente com o aumento de fibra na dieta. A digestibilidade da FDN e do N, assim como o pH e as concentrações de peptídeos no fluído ruminal foram similares em todos os tratamentos. A digestibilidade aparente da MS, da MO e da energia, assim como as concentrações ruminais de açúcares diminuíram linearmente (P<0,01) e a síntese de proteína microbiana ruminal, as concentrações ruminais de amônia e de aminoácidos variaram quadraticamente (P<0,05) com o aumento do teor de FDN das dietas. A redução do consumo e da digestibilidade foram mais evidentes somente pela inclusão do nível mais alto de FDN (43 por cento) e, sob o aspecto nutricional, a inclusão em torno de 30 por cento de FDN representa o nível mais adequado para formulação de dietas a base de silagem de sorgo e concentrado oferecido a cordeiros confinados.

Eight castrated raw lambs (35.0± 6.0kg live weight) were used in a replicated 4 ´ 4 latin square design to evaluate the effect of four neutral detergent fiber (NDF) levels (25, 31, 37 and 43 percent of dry matter (DM)) on intake and digestion traits. Nitrogen (N) intake varied quadratically; intake of DM, organic matter (OM) and energy decreased (P<0.05) and that of NDF increased (P<0.01) as fibre level increased. NDF and N digestibility, as well as pH and ruminal concentrations of peptides were similar for all treatments. Apparent digestibility of DM, OM and energy, as well as ruminal concentrations of sugars decreased (P<0.01) and, ruminal microbial protein synthesis and ruminal concentrations of ammonia and amino acids varied in a quadratic way (P<0.05) with increased levels of NDF. The effect of NDF in decreasing intake and digestibillity was more evident only at the highest level (43 percent). The inclusion of about 30 percent NDF represents the most adequate level for sorghum silage and concentrate based diets fed to feedlot lambs.

Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial.

Piperacillin/tazobactam was compared with ceftazidime for the empirical treatment of febrile neutropenia in patients with acute leukemia or following autologous peripheral blood stem cell transplantation. Owing to inclusion criteria, it was possible for the same patient to be randomized several times. A total of 219 individual patients were admitted to a prospective randomized clinical study: 24 patients were included twice. Patients (23.5%) remained afebrile. Patients who developed febrile neutropenia were randomized to receive intravenous ceftazidime (n = 74 patients, group I) or piperacillin/tazobactam (n = 87 patients, group II). Response to first-line antibiotic treatment was seen in 55% (group I) and 53% (group II). After the addition of vancomycin, a further 19% (group I) and 24% (group II) of the patients became afebrile. Causes of fever were: microbiologically documented infection in 36 and 34 patients of group I and II; Clostridium difficile in eight and 12 patients of group I and II, and fever of unknown origin in 30 and 41 patients of group I and II. One patient died in each group. Single-agent therapy with piperacillin/tazobactam is as effective as ceftazidime in the treatment of neutropenic fever and is well tolerated. Direct and indirect costs of both treatment regimes are equivalent.

Peripherally inserted central venous catheters for autologous blood progenitor cell transplantation in patients with haematological malignancies.

BACKGROUND: In contrast to the high risk of haemorrhage associated with the implantation of a central venous catheter (CVC) via the internal jugular or subclavian access, the use of a peripherally inserted catheter (PICC) offers the advantage of a lower risk of bleeding complications. However, the rate of phlebitis is higher with the PICC and its use has been declining. We have studied the benefits and adverse events of a new type of PICC and a common type. METHODS: From October 1999 to October 2001, 70 PICCs (Olimpicc, Vygon, Germany, n=40; and LIFECATH-PICC(PUR)5FR Vygon, Germany, n=30) were inserted into 66 patients with haematological malignancies and used for high-dose chemotherapy, total parenteral nutrition and autologous blood stem cell transplantation. While removing the catheter, central and peripheral blood cultures were taken. The catheter tip was investigated by the semi-quantitative roll-out method of Maki. RESULTS: Sixty-five PICCs were removed after a median of 8.9 days. In five cases a catheter-associated significant colonisation with coagulase-negative staphylococci occurred. In two instances catheter-related bacteraemia was found. CONCLUSION: In our study this catheter system was inserted in 94% of patients without problems and showed a low incidence of phlebitis (5/65). Because of the high rate of catheter malfunction reported during and after our study, the Olimpicc catheter is no longer available. The PICC system, and the LIFECATH-PICC(PUR)5FR in particular, offers a safe and effective alternative for central venous access to the internal jugular vein.

Use of erythropoietin in patients with multiple myeloma.

The prevalence of tumour anaemia in patients with multiple myeloma is greater than 80%. At the time of diagnosis 20% of these patients are already anaemic. In about 70% of patients with multiple myeloma, recombinant human erythropoietin (r-HuEPO) leads to a reduction in transfusion frequency, resulting in a drop in transfusion- related side-effects like infections and immune reactions, iron overload and hyperviscosity which often negatively influence the course of disease. A further reason for the use of erythropoietin is to achieve and maintain high haemoglobin levels (11-12 g/dl), which are of considerable prognostic significance in patients with multiple myeloma. Increasing Hb levels with r-HuEPO also improve the quality of life of patients, thus leading to better therapy compliance. The trade-off between high costs of an erythropoietin treatment and lower indirect costs (infusion material, personal equipment, patient transport costs, etc.) should be evaluated. Nevertheless, an exact definition of patients for whom the use of erythropoietin is beneficial is warranted. The pathogenesis of anaemia and the clinical experiences of erythropoietin in patients with multiple myeloma are discussed.

Continuous infusion of ceftazidime for patients with breast cancer and multiple myeloma receiving high-dose chemotherapy and peripheral blood stem cell transplantation.

This prospective study was performed to examine the safety and efficacy of a continuous infusion of ceftazidime in patients who developed febrile neutropenia after high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT) and to determine if the underlying disease represents a risk factor for infectious complications. From September 1995 to May 2000, 55 patients with breast cancer (BC, group I, 54 females, one male) and 32 patients with multiple myeloma (MM, group II, 10 female, 22 male) were included in this study. The febrile patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion over 24 h using a portable infusion pump. If the fever persisted for 72 h a glycopeptide antibiotic was added. The median age was 42 years (range 22-59) in group I and 52 years (range 35-63) in group II. Thirty-five BC patients (64%) and 20 MM patients (63%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, an additional 11 BC patients vs 10 MM patients became afebrile. The causes of fever in group I were fever of unknown origin (FUO) in 49 patients, microbiologically documented infection (MDI) in five patients, and clinically documented infection (CDI) in one patient. The causes of fever in group II were FUO in 22 patients, MDI in eight patients and CDI in two patients. Forty-one febrile episodes in BC patients (75%) and 22 episodes in the MM patients (69%) were successfully managed by out-patient treatment, resulting in a saving of an average of 20 days of inpatient care. Significantly more episodes of MDI and CDI occurred in patients with MM (P = 0.05). The results indicate that BC and MM patients with febrile neutropenia after HDCT and PBSCT can be treated as outpatients with close monitoring to ensure safety. This approach represents a better use of health care resources.

[Agoraphobia with panic disorder or epilepsy? Differential diagnostic considerations in a case]. / Agoraphobie mit Panikstörung oder Epilepsie? Differenzial-diagnostische Uberlegungen anhand eines Fallberichtes.

This paper describes a patient suffering from agoraphobia with panic disorder and with a history of self-induced epileptic seizures. The anxiety syndrome causing the admission to hospital could be diagnosed as non epileptic. He was treated successfully with a behaviour therapy. We discuss the possible interactions between anxiety disorders and epileptic seizures and some diagnostic demarcations. We conclude that even people with mild forms of epilepsy may develop an anxiety disorder arising from the fear of again getting epileptic seizures. To work out the different syndromes of epileptic seizures and of panic attacks should be part of the therapy.

Oligomerization of peptides analogous to the cytoplasmic domains of coatomer receptors revealed by mass spectrometry.

Members of the p24 family of type I transmembrane proteins are involved in budding of coat protein type I (COPI)-coated vesicles. They serve as coat protein receptors, binding via their cytoplasmic domains to coatomer, a stable cytosolic protein complex that represents the major coat component of these vesicles. Experimental evidence suggest that p23, a member of the p24 family, binds to coatomer in an oligomeric state and that this binding triggers polymerization of the coat protein. Toward an understanding of this process at the molecular level, formation of noncovalent complexes and their relative stabilities were analyzed by Fourier transform ion cyclotron resonance mass spectrometry using nanoelectrospray ionization. Specificity and stability of oligomers formed were established to depend on characteristic peptide sequence motifs and were confirmed by mass spectrometric competition experiments with control peptides. Mutations in the peptide sequence caused decreased interaction and destabilization of the noncovalent complexes. The formation and relative stabilities of dimeric and tetrameric complexes were assessed to be formed by cytoplasmic tails of coatomer receptors. The direct molecular identification provided by mass spectrometry correlates well with biochemical results. Thus, electrospray ionization mass spectrometry proves to be a powerful tool to investigate physiologically relevant peptide complexes.

The secretory pathway from history to the state of the art.

Maintenance of the structural and functional organization of a eucaryotic cell requires the correct targeting of proteins and lipids to their destinations. This is achieved by the delivery of newly synthesized material along the secretory pathway on one hand and by the retrieval of membranes on the other hand. Various models have been suggested over the years to explain traffic flow within the secretory pathway. The only two models that are under discussion to date are the "vesicular model" and the "cisternal maturation model". A wealth of information from various experimental approaches, strongly supports the vesicular model as the general mode of intracellular transport. Three major types of protein-coated transport vesicles are characterized in molecular detail, and have been attributed to various steps of the secretory pathway: COPII-coated vesicles allow exit from the endoplasmic reticulum (ER), COPI-coated vesicles carry proteins within the early secretory pathway, i.e. between ER and Golgi apparatus, and clathrin-coated vesicles mediate transport from the trans-Golgi network (TGN). In this review we will give an overview of the route of a protein along the secretory pathway and summarize the progress that was made within the last decades in the characterization of distinct intracellular transport steps. We will discuss the current models for the formation and fusion of vesicular carriers with a major focus on the mechanism underlying budding of a COPI-coated vesicle.

Mechanisms of vesicle formation: insights from the COP system.

The major cytosolic and membrane proteins that represent machinery of coat protein (COP)-coated transport vesicles within the secretory pathway are characterized to date. This has allowed investigation of the molecular mechanisms that underlie the formation of these vesicles. In vitro binding studies and reconstitution experiments have provided insights at the molecular level into the biogenesis of COPII- and COPI-coated vesicles.