RESUMEN
The feather corticosterone concentration (fCORT) is increasingly used to assess long-term stress in birds as this indicator provides the potential to retrospectively evaluate the adrenocortical activity of a bird during the growth period of a feather over several weeks in one sample. However, there is still a lack of knowledge concerning external factors which can potentially influence fCORT in birds. The aim of the present study was to determine whether fCORT in laying hens is affected by previous fecal contamination of the plumage. Fully grown primaries 5 (P5s) of laying hens (n = 40) were used for the study. To test the effects of fecal contamination on fCORT, freshly defecated droppings from laying hens were collected and mixed manually. In order to simulate practical and at the same time standardized contamination, the upper surface of the previously determined middle third of the right P5 of each hen then was evenly coated with the paste prepared from fresh feces. The treated feathers were stored for 24 h protected from light at room temperature under a film cover to prevent evaporation. Thereafter, the applied layer of excreta was removed manually. Contralateral P5s of the same individuals were stored under identical conditions and served as controls. Both treatment and control feathers were washed in an aqueous soap solution, rinsed several times in pure water and air-dried subsequently. After pulverization and methanolic extraction, fCORT was analyzed by ELISA. The mean fCORT of treatment P5s (reference 'feather length': 12.88 ± 3.16 pg/mm; reference 'feather weight': 7.81 pg/mg ± 1.86 pg/mg) were significantly higher (P < 0.001) than those of control P5s (reference 'feather length': 9.76 ± 2.42 pg/mm; reference 'feather weight': 5.93 ± 1.44 pg/mg). Our results show that previous contamination with excreta can increase fCORT, which was detectable even after a washing procedure prior to analysis. In conclusion, fecal contamination of feathers is a significant influencing factor that has to be considered when applying fCORT measurements.
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Corticosterona , Plumas , Animales , Pollos , Heces , Femenino , Estudios RetrospectivosRESUMEN
The measurement of feather corticosterone concentrations (fCORT) is a comparatively new method for the evaluation of stress in wild and captive birds and may be a useful indicator in animal welfare research. The aim of this study was to assess the suitability of fCORT as an indicator of stress, and for this purpose a prolonged stress period was experimentally simulated by oral intake of corticosterone via drinking water and corticosterone concentrations were analyzed in feathers grown during this period. Layer pullets of both a control group (n = 20) and a CORT group (n = 20) were offered drinking water ad libitum throughout the entire experimental phase. The drinking water of the CORT group was supplemented with corticosterone at a concentration of 20 mg/l from the 64th to the 114th day of life. The vaned parts of the primaries 5 (P5s) were clipped on d 114 and fCORT was analyzed by ELISA after extraction. Body weights increased from day 64 until d 114 in both groups, however, at the end of the experiment, mean body mass in the CORT group was significantly lower than in the control group (P < 0.001). Pullets of the CORT group also showed shorter and lighter P5s as well as a retarded molt of the primaries. The supplementation of drinking water with corticosterone increased the average fCORT in the P5s of the CORT pullets compared with the control group (median: 110.3 pg/mm [interquartile range (IQR): 47.2] vs. 10.0 pg/mm [IQR: 2.5], P < 0.001). The results show that experimentally increased systemic corticosterone concentrations over a period of seven weeks in layer pullets are reflected in corticosterone concentrations of feathers grown during that time. This indicates that the measurement of fCORT may be a useful and minimally invasive tool for the evaluation of long-term stress in chicken and provides the basis for further investigations on its use in animal welfare research.
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Agua Potable , Plumas , Animales , Pollos , Corticosterona , Suplementos Dietéticos , FemeninoRESUMEN
BACKGROUND AND PURPOSE: Hereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the long-term efficacy and safety of inotersen are assessed in an ongoing open-label extension (OLE) study. METHODS: Patients who completed NEURO-TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score and the Short-Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed. RESULTS: Overall, 97% (135/139) of patients who completed NEURO-TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO-TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL-DN and SF-36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure. CONCLUSION: Inotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long-term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.
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Neuropatías Amiloides Familiares , Calidad de Vida , Neuropatías Amiloides Familiares/tratamiento farmacológico , Neuropatías Amiloides Familiares/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oligonucleótidos , PrealbúminaRESUMEN
1. This trial investigated the effect of forced locomotor activity (training) on walking ability, leg posture, and growth performance, as well as carcass composition and meat quality in male fattening turkeys.2. A flock of 744 commercial turkeys was divided into three experimental groups, either without any training period (control), training from weeks 2 to 8 (short-term), or training from weeks 2 to 21 (long-term). All birds were slaughtered at an age of 21 weeks. To study the effect of short vs. long time lapse between shackling and stunning (suspension time), each training group was split into two halves that were hooked on the shackle for either 15 s or 3 min prior to stunning.3. Long-term physical training, compared to short-term or no training, resulted in better walking ability and in a lower percentage of leg malposition, as assessed at the end of fattening. No effect on final body weight was detected.4. In a subsample, the composition of 80 carcasses was determined by dissection. Long-term training favoured the percentage of the drumstick over that of the breast cut in comparison to the group without any training.5. Meat quality parameters were determined for breast muscle. The pH values 20 min post-mortem were reduced by long-term training, and the highest value was observed for a combination of no training with short suspension. After 24 h, pH values did not differ between experimental groups. The breast muscles were characterised as fast-glycolysing. Prolonged suspension time resulted in higher electrical conductivity after 24 h, and in higher a* values (redness).6. In conclusion, the study revealed that a long-term training period improved walking ability and leg posture of heavy male turkeys. Thus, training can contribute to the improvement of animal welfare in turkey husbandry. Meat quality variables of breast muscles were partially influenced by locomotor activity and suspension time.
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Pavos , Caminata , Animales , Pollos , Locomoción , Masculino , Carne/análisisRESUMEN
The domestic fowl (Gallus gallus f. dom.) is highly motivated to roost on elevated structures. Previous studies indicated that broiler chickens hardly use elevated perches but frequently use elevated platforms. However, it is unclear which height and type of elevated structures broilers prefer at various daytimes.We investigated the use of elevated perches and grids varying in height (10, 30, and 50 cm above the floor) by chickens of 3 strains differing in growth performance. In 2 successive trials, male chickens of Ross 308 (Ross, fast growing, n = 200), Lohmann Dual (Dual, medium growing, n = 200), and Lohmann Brown Plus (LB, slow growing, n = 200) were tested in 12 experimental compartments (each strain in 4 compartments), respectively. Usage of structures was recorded on video and analyzed with time-sampling observation for each week of age during dawn, the light period, dusk, and the dark period. In addition, behavioral activity was measured with an antenna-transponder system.The results showed that Ross and Dual chickens preferred grids to perches throughout the entire observation period. With increasing age, chickens of all strains increasingly used the elevated structures during all daytimes. In contrast to Dual and LB, Ross chickens reduced the use of structures from the 3rd to 4th week of age during the light but not the dark period. Additionally, during the dark period, chickens of all 3 strains at the end of fattening period used elevated structures at 50 cm height most often. The behavioral activity decreased significantly in all 3 strains but was much lower in Ross chickens compared with Dual and LB.The results indicated that chickens are motivated to roost at nighttime on high-elevated and suitable structures such as grids. Further studies are needed to assess the space requirements for elevated structures that should be offered to chickens.
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Conducta Animal/fisiología , Pollos/fisiología , Vivienda para Animales/normas , Factores de Edad , Bienestar del Animal , Animales , Pollos/crecimiento & desarrollo , Luz , Locomoción/fisiología , Masculino , Especificidad de la EspecieRESUMEN
The present study shows the prevalence and severity of foot pad dermatitis (FPD) in turkeys reared in organic production systems assessed at slaughterhouses in Germany. The investigations of altogether 1,860 turkeys of the strains Kelly Broad Breasted Bronze (Kelly BBB; 540 toms, 540 hens) and British United Turkeys (B.U.T.) 6 and the Test Product 7 (TP 7; 780 hens) showed that 97.7% of the examined turkeys were diagnosed with different degrees of FPD. Only 4.6% of the toms and 1.3% of the hens had feet without lesions. Most frequent were necrotic lesions measuring up to 2 cm in diameter (64.3% of all turkeys). Extensive necrotic lesions of the foot pads (toms: 29.8%; hens: 12.4%) and necrosis of superficial scales (toms: 11.3%; hens: 7.6%) were less frequent. Plantar abscesses were rare findings (1.9%). In general, the feet of the Kelly BBB hens were more affected by foot pad lesions than those of the Kelly BBB toms. There were significant differences between the investigated flocks concerning the occurrence of foot pad lesions. The aim in rearing turkeys must be the reduction of FPD.
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Crianza de Animales Domésticos , Dermatitis/veterinaria , Enfermedades del Pie/veterinaria , Agricultura Orgánica , Enfermedades de las Aves de Corral/epidemiología , Pavos , Mataderos , Animales , Dermatitis/epidemiología , Dermatitis/etiología , Femenino , Enfermedades del Pie/epidemiología , Enfermedades del Pie/etiología , Alemania/epidemiología , Pezuñas y Garras , Masculino , Enfermedades de las Aves de Corral/etiología , PrevalenciaRESUMEN
Africa born (immigrant) women comprise a disproportionate number of Black women living with HIV in the United States. Though they are at risk for mental health disorders, including psychological distress and depression, little is known about their experience with these important predictors of quality of life, retention in care and adherence to antiretroviral therapy. In this qualitative study, we used constructivist grounded theory to explore the psychosocial and mental health challenges of African born women living with HIV in Boston and New York City. We conducted one-on-one semi-structured interviews with 45 women. Major themes contributing to psychological distress and depressive symptoms included (1) pre-immigration HIV-related stigma; (2) persistent HIV-related stigma post-immigration, (3) undocumented immigration status, (4) economic insecurity, and (5) intimate partner violence (IPV). Many participants described ongoing depressive symptoms or histories of depressive episodes. Yet, most had not been formally diagnosed or treated for depression. Prayer, consultation with faith leadership, and support groups were described most frequently as useful interventions. Future research should explore these thematic areas among a larger, more representative sample of African born women living with HIV to determine differences by country of origin across thematic areas. These data would be useful to inform development of innovative and culturally appropriate interventions.
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Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Adulto , África/etnología , Fármacos Anti-VIH/uso terapéutico , Boston , Femenino , Humanos , Violencia de Pareja/psicología , Cumplimiento de la Medicación , Salud Mental , Persona de Mediana Edad , Ciudad de Nueva York , Investigación Cualitativa , Calidad de la Atención de Salud , Religión , Estigma Social , Estados UnidosRESUMEN
Reflection and fluorescence properties of feathered and non-feathered body regions of white- and bronze-colored fattening turkeys of various ages were examined by ultraviolet (UV) photography. The examinations were carried out on 20 white-feathered fattening turkeys (B.U.T. 6; 10 males, 10 females) and 20 bronze-feathered fattening turkeys (Grelier 708; 10 males, 10 females) over a period of 21 weeks. The turkeys were photographed once a wk under long-wave UV (UVA) radiation illumination (λ = 344-407 nm) using a digital camera. A bandpass filter was used for UV reflectography to filter out the visible components of the used light source. A longpass filter was used for UV fluorescence photography to avoid blurring in the image due to chromatic aberration as a result of UV illumination. We found that natal down feathers of white-feathered turkeys showed an intense yellowish-green fluorescence under UVA light. UVA fluorescence also was shown by the natal downs of the slightly melanized plumage areas of bronze turkeys. Vaned feathers of white fattening turkeys reflected UVA radiation. Freshly molted feathers were optically distinguishable from the previous feather generation due to their more intense UVA reflection. In bronze turkeys, both the bright end seams of the dark pennaceous feathers and rectrices and the bright banding of primary and secondary remiges reflected UVA radiation. Intense UVA fluorescence was recognizable in day-old chicks of both color variants on the scutellate scales of the legs and toes. In male turkeys of both color variants, UVA-reflecting parts were recognizable with increasing age on the featherless head region. The UVA-fluorescent and UVA-reflective characteristics of the plumage of fattening turkeys were closely related to the plumage color, the feather type, the molting state, and the age of the birds. Further research is needed regarding the UVA-reflecting properties of the turkey plumage and the effects of full-spectrum illumination, including the UVA spectrum, on the behavior and health of fattening turkeys.
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Plumas/fisiología , Fluorescencia , Fenómenos Fisiológicos de la Piel , Pavos/fisiología , Rayos Ultravioleta , Animales , Color , Femenino , MasculinoRESUMEN
Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests.
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Neuropatías Amiloides Familiares/diagnóstico , Vías Autónomas/fisiopatología , Examen Neurológico , Adulto , Anciano , Neuropatías Amiloides Familiares/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Neurofisiología , Adulto JovenRESUMEN
In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.
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Amiloidosis/fisiopatología , Amiloidosis/terapia , Cardiopatías/terapia , Melfalán/administración & dosificación , Trasplante de Células Madre , Anciano , Amiloidosis/complicaciones , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Cardiopatías/complicaciones , Células Madre Hematopoyéticas/citología , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Estimación de Kaplan-Meier , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Péptido Natriurético Encefálico/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Troponina I/metabolismoAsunto(s)
Amiloidosis/terapia , Cadenas Ligeras de Inmunoglobulina , Trasplante de Células Madre , Amiloidosis/tratamiento farmacológico , Amiloidosis/inmunología , Amiloidosis/fisiopatología , Amiloidosis/cirugía , Terapia Combinada , Relación Dosis-Respuesta a Droga , Humanos , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
This project involves the prevalence of breast skin alterations (breast buttons, blisters, purulent bursitis) in male and female fattened turkeys (British United Turkeys Big 6) from conventional intensive farming. In this case, 24 turkey farms across Germany and 11,860 turkeys (5,740 toms, 6,120 hens) were clinically examined, and 16,200 birds (8,400 hens, 7,800 toms) were evaluated on slaughter lines at 7 turkey abattoirs. Each turkey farm included examination of at least 3 consecutive fattening cycles. Especially in the meat examinations, breast skin alterations were a frequent discovery, particularly in the form of breast buttons. The turkey toms exhibited a prevalence of 27.15%, and the toms were affected significantly more frequently (P < 0.001) by these variations than the turkey hens (7.77%). It is possible that the higher BW of the male specimens leads to increased lying times and is therefore connected with more severe strain on the breast region. The increased fattening period of the turkey toms (slaughtering at wk 21 to 22 of life) vs. the female specimens (slaughtering at wk 15 to 17 of life) must be discussed as a cause. Breast blisters and bursitis sternalis were discovered with a prevalence of 7.36 and 1.24% in toms and more seldom in hens, at 0.30% and 0.15%. Large differences in prevalence were partially recognizable between individual farms as well as between the 3 fattening cycles on a farm. Breast buttons and breast blisters are pathological skin variations for which the etiology is multifactorial. Clear correlations between the prevalence of breast skin alterations and the manner of rearing the birds were not able to be determined. An improvement in this situation, which is considered very problematic from the perspective of bird protection and economics, may be achieved only via cooperation to achieve optimized rearing methods, management, and breeding practices.
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Enfermedades de las Aves de Corral/epidemiología , Enfermedades de la Piel/veterinaria , Pavos , Crianza de Animales Domésticos/métodos , Animales , Femenino , Alemania/epidemiología , Masculino , Carne , Enfermedades de las Aves de Corral/patología , Prevalencia , Factores Sexuales , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/patología , Estadísticas no ParamétricasRESUMEN
The present study demonstrates the prevalence of footpad lesions in turkeys and their level of expression in both live birds and in carcasses. In clinical investigations of 11,860 turkeys (5,740 males, 6,120 females) of the strain British United Turkeys Big 6, individuals of all the observed flocks showed alterations to the plantar skin. In general, the degree and severity of skin alterations were higher in the 16th week of life than in the 6th or 11th week of life. Epithelial necrosis, however, was already apparent in about 45% of individuals in the 6th week of life. At this point, deep lesions on the footpad surface were still rare findings. In the 11th week of life, such skin changes were apparent in 14.7% of males and 25.7% of hens. In general, the feet of male turkeys were less affected by footpad damage than those of females in the subsequent fattening period. In hens, the prevalence of lesions of the footpads at wk 16 of age was 60.0%, almost twice as high as in males of the same age group (33.8%). A comparison of the findings from the right and left feet showed that the state of the 2 extremities was correlated (Spearman correlation: r = 0.830). During the visual inspection of 16,200 slaughtered turkeys (7,800 males, 8,400 hens), almost all carcasses studied showed alterations to the footpad skin. Only 2.1% of males and 0.6% of females were without lesions. The most frequently observed lesions measured up to 2 cm in diameter (males: 59.2%; hens: 57.7%). Pronounced skin lesions of the footpad (males: 21.1%; females: 29.5%) and necrosis of the superficial epithelium (males: 17.5%; females: 12.1%) were less common. Foot abscesses were diagnosed only sporadically (males: 0.1%; females: 0.1%).
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Dermatitis/veterinaria , Enfermedades del Pie/veterinaria , Alemania/epidemiología , Enfermedades de las Aves de Corral/epidemiología , Pavos , Animales , Dermatitis/epidemiología , Femenino , Enfermedades del Pie/epidemiología , Masculino , PrevalenciaRESUMEN
During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared with other rat CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the nuclear factor-kappa B (NF-kappaB) signaling cascade including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inhibitor of kappa B alpha (IkappaBalpha) in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS.
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Encéfalo/patología , Quimiocina CCL2/metabolismo , Plexo Coroideo/metabolismo , Citocinas/metabolismo , Regulación de la Expresión Génica/fisiología , Inflamación/patología , Análisis de Varianza , Animales , Encéfalo/metabolismo , Carragenina , Caspasa 1/genética , Caspasa 1/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Quimiocina CCL2/genética , Citocinas/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Clinical outcomes of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) are tightly linked to the achievement of a hematologic complete response (HCR). We conducted a prospective trial to determine whether a second cycle of HDM/SCT could induce HCR in patients in whom the plasma cell dyscrasia persisted following initial treatment with HDM/SCT. Sixty-two patients were enrolled. Nine patients (15%) were removed from the protocol. Of the 53 patients continuing in this study, four died within 100 days of treatment (8%), and 27 (55%) achieved an HCR at 6 months after the first cycle of HDM/SCT. Of the 22 patients who did not achieve an HCR after initial treatment, 17 received a second HDM/SCT, 1 died within 100 days of treatment (6%), while 5 (31%) achieved an HCR. Thus, the HCR rate was 67% (32/48) for surviving patients on study, 60% (32/53) for all patients who received initial cycle of HDM/SCT, and 56% (35/62) by intention-to-treat. The median survival for all patients enrolled on the trial has not yet been reached. Thus, tandem cycles of HDM/SCT can increase the proportion of patients who achieve an HCR.
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Amiloidosis/tratamiento farmacológico , Antineoplásicos Alquilantes/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Cadenas Ligeras de Inmunoglobulina , Melfalán/administración & dosificación , Adulto , Anciano , Amiloidosis/mortalidad , Amiloidosis/terapia , Antineoplásicos Alquilantes/efectos adversos , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Melfalán/efectos adversos , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Estudios Prospectivos , Tasa de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Throughout 4 fattening periods (summer and winter) the influence of a veranda (roofed outside run) on the performance, behaviour and health of tom turkeys was investigated in a pilot study. A second conventional naturally ventilated stable without a veranda was also included in the investigations for special aspects. The aim of this study was to investigate this first turkey stable with a veranda and to give first recommendation for the practical use. The use of the veranda and the differences in behaviour between inside the stable with a veranda and inside the veranda as well as inside both stables were analysed. From 100 turkeys in each period we examined feather condition, walking ability and leg posture in the 9th, 13th and 17th week of age in both stables. In addition, body weight, food consumption and mortality were recorded. The results of this pilot study indicate that the tom turkeys of the line BUT Big 6 used the veranda without negative effects on health and performance parameters. There was some indication for an improved health of animals or a reduced mortality in the stable with veranda. The decrease of walking ability and normal leg posture with increasing age and body weight in both stables suggests that the genetic influence seems to have a higher influence than the enrichment of environment in this study using the fast growing line BUT Big 6. On the other hand, in this pilot study only one stable with a veranda and another commercial stable without a veranda at a different location were included. For this reason the results should be interpreted carefully with respect to possible effects in the management between the two farms.
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Crianza de Animales Domésticos/métodos , Bienestar del Animal , Conducta Animal , Vivienda para Animales , Pavos/fisiología , Animales , Masculino , Proyectos Piloto , Distribución Aleatoria , Estaciones del AñoRESUMEN
SUMMARY: A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.
Asunto(s)
Amiloidosis/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/administración & dosificación , Amiloidosis/mortalidad , Amiloidosis/patología , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Femenino , Cardiopatías/terapia , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Enfermedades Renales/terapia , Leucaféresis , Masculino , Melfalán/toxicidad , Persona de Mediana Edad , Prednisona/administración & dosificación , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses.