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1.
Poult Sci ; 103(5): 103572, 2024 May.
Article in English | MEDLINE | ID: mdl-38428355

ABSTRACT

An experiment was conducted to determine the effect of feeding reduced crude protein (CP) diets to Ross × Ross 708 male broilers while providing adequate essential amino acid (AA) concentrations on growth performance, nitrogen (N) and ammonia output, and carcass characteristics from d 1 to 33 post hatch. Birds received 1 of 6 dietary treatments (10 replicate pens per treatment) varying in CP content. Diet 1 (control) was formulated with DL-Met, L-Lys, and L-Thr (23.2, 20.7, and 19.1% CP) in the starter (1-14 d of age), grower (15-25 d of age), and finisher (26-33 d of age) periods, respectively. Dietary L-Val, Gly (only in starter period), L-Ile, L-Arg, and L-Trp were sequentially supplemented in the order of limitation in Diets 2 through 6. Dietary CP was reduced gradually across the dietary treatments resulting in a CP reduction in Diets 1 to 6 by 3.4, 3.4, and 2.3% points in the starter, grower, and finisher periods, respectively. At d 14, 25, and 33 posthatch, feed conversion decreased (P < 0.05) with L-Val addition (Diet 2) and increased (P < 0.01) with L-Val to L-Trp addition (Diet 6) to the control. Dietary treatments did not alter weights and yields of carcass, breast, drum, or thighs. Dietary CP reduction with added L-Val (Diet 2), L-Val to L-Arg (Diet 5), or L-Val to L-Trp (Diet 6) increased abdominal fat (P < 0.01) compared with control. Nitrogen excretion (g/bird; P = 0.003) and equilibrium ammonia concentration (mg/kg; P = 0.041) at day 33 reduced by 16% and 48% respectively in birds fed reduced-CP diets with L-Val to L-Trp (Diet 6) compared with control-fed birds. This study indicated that sequential addition of supplemental AA in the order of limitation from DL-Met to L-Arg allowed reduction of dietary CP beyond 2%-point without depressing growth performance and meat yield of broilers from day 1 to 33 while reducing nitrogen excretion and ammonia emissions.


Subject(s)
Amino Acids, Essential , Ammonia , Animal Feed , Animal Nutritional Physiological Phenomena , Chickens , Diet , Nitrogen , Animals , Chickens/growth & development , Chickens/physiology , Animal Feed/analysis , Male , Nitrogen/metabolism , Ammonia/metabolism , Diet/veterinary , Amino Acids, Essential/administration & dosage , Amino Acids, Essential/metabolism , Animal Nutritional Physiological Phenomena/drug effects , Diet, Protein-Restricted/veterinary , Dietary Proteins/metabolism , Dietary Proteins/administration & dosage , Random Allocation , Meat/analysis , Dietary Supplements/analysis
2.
Poult Sci ; 101(2): 101568, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34923231

ABSTRACT

In modern fast-growing broiler chickens, meat quality becomes increasingly important due to the occurrence of novel breast myopathies such as white striping (WS), woody breast (WB), and spaghetti meat (SM), compromising the sustainability of the poultry industry. Therefore, strategies for reducing the incidence of those myopathies are needed. This study focuses on the impact of different standard ileal digestible (SID) His:Lys ratios on growth performance, meat quality variables like pH, drip loss and pale-soft-exudative (PSE) meat as well as the incidence and severity of breast myopathies (WS, WB, SM), including deep pectoral myopathies (DPM). Thus, 440 male Ross 308 chickens were divided into 5 treatment groups with SID His:Lys ratios of 0.41, 0.45, 0.49, 0.53, and 0.57 in the feed, respectively. Performance was assessed on d 1, 10, 20, 33, and 38 of life. From each treatment group, 22 representative birds were slaughtered on d 38, 39, 40, and 41, respectively. All right fillets were examined 24 h after slaughter by 6 trained testers to assess the outcome of breast myopathies (3-point scale) and PSE-meat (presence and absence). Fillet weight, pH, and drip loss were recorded for selected fillets at different time points. The results of this trial showed no influence of the SID His:Lys ratios on growth performance or drip loss, whereas pH was slightly affected. The study showed a correlation between the occurrence of WB and WS (P < 0.001, normalized contingency coefficient = 0.576). A lower incidence of WB (P = 0.008) was observed in the group fed an SID His:Lys ratio of 0.45 compared with the group fed the lowest ratio of 0.41. For WS, a higher incidence was observed in broilers fed an SID His:Lys ratio of 0.49 (P = 0.002) and 0.53 (P = 0.036) when compared to 0.41. The occurrence of PSE was increased by feeding SID His:Lys at 0.51 (P = 0.008) compared to the lowest ratio. This study showed that the level of His in broiler feed had an impact on the occurrence of breast myopathies, but only WB could be decreased.


Subject(s)
Muscular Diseases , Poultry Diseases , Animals , Chickens , Histidine , Lysine , Male , Meat/analysis , Muscular Diseases/chemically induced , Muscular Diseases/epidemiology , Muscular Diseases/veterinary , Pectoralis Muscles , Poultry Diseases/epidemiology
3.
Poult Sci ; 100(11): 101393, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34530228

ABSTRACT

The high growth rates of modern broiler breeds increased the risk for novel breast muscle myopathies as serious quality issue, relevant for the industry. In affected muscles, a depletion of the dipeptides carnosine and anserine was reported. Therefore, this study was performed to test whether a supplementation of the precursors histidine and ß-alanine, alone or in combination can increase the dipeptide content in the breast muscle and improve meat quality. Ross 308 broiler chickens were supplemented with 3 different histidine:lysine ratios (0.44, 0.54, 0.64) of standardized ileal digestible amino acids (SID) combined with 0 or 0.5% ß-alanine in total. The birds' performance was recorded at different ages: birds were slaughtered in 2 batches after 33 and 53 d of life. Meat quality was tested at different time points after slaughter on breast fillets stored aerobically. The concentration of the dipeptides and amino acids in blood plasma and muscle tissue was tested postmortem at 35 and 54 d. All performance and meat quality data, as well as peptide and amino acid concentrations, of the 2 × 2 × 3 randomized block design were analyzed separately for the influence of both supplements and for slaughter age. Moreover, the influence of storage time was analyzed separately for meat quality parameters. At both slaughter ages, lesser feed intake (P ≤ 0.005) and breast yield (P ≤ 0.05) were observed in the birds receiving ß-alanine. A greater SID histidine:lysine ratio increased the carnosine concentrations in blood plasma (P < 0.001) and in skeletal muscle (P < 0.001), whereas ß-alanine increased carnosine in plasma at 35 d only (P = 0.004). Anserine was increased in plasma and muscle of older birds (P = 0.003), whereas carnosine was reduced in muscle tissue (P < 0.001). The main impact on meat quality parameters was seen for the age of the birds and storage time of the fillets. In conclusion, the supplementation of histidine increased carnosine in breast muscle but both supplements showed only minor effects on meat quality.


Subject(s)
Carnosine , Animal Feed/analysis , Animals , Chickens , Histidine , Meat/analysis , Pectoralis Muscles , Random Allocation , beta-Alanine
4.
Ann Oncol ; 29(6): 1386-1393, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29635438

ABSTRACT

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/mortality , Esophageal Neoplasms/therapy , Esophagectomy/mortality , Neoadjuvant Therapy/mortality , Adenocarcinoma/pathology , Aged , Carcinoma, Squamous Cell/pathology , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Docetaxel/administration & dosage , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate
5.
Ann Oncol ; 26(4): 709-714, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25605741

ABSTRACT

BACKGROUND: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS: In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS: The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS: Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00544700.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Prospective Studies , Survival Rate , Young Adult
6.
Nervenarzt ; 86(1): 9-15, 2015 Jan.
Article in German | MEDLINE | ID: mdl-25511626

ABSTRACT

This article questions why medicine fails to provide a general concept of disease for use by doctors, patients and society because the lack of such a unified concept inhibits any definitive distinction between "deviant" and "disease". By providing an historical overview of the particularities related to this question the authors demonstrate that the ever-changing concepts of disease were not driven by the process through which medicine became a science. In contrast to naturalistic concepts of disease, anthropological, sociocultural and psychosomatic concepts are grounded in an understanding of disease that cannot be determined, described and categorized by pathology alone. As a consequence, disease can only be determined or defined in relation to social and scientific frames of reference, as illustrated by an example from the Berlin Nervenklinik (psychiatric clinic) in the early twentieth century. The ways in which the definition of a disease concept represents a normative interpretation can be observed. The authors of this paper argue for the acceptance of this normative definition as a matter of societal agreement. Consequently, transparency is required in the shaping of general disease concepts.


Subject(s)
Clinical Medicine/history , Disease/history , Mental Disorders/history , Philosophy, Medical/history , Terminology as Topic , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , History, Ancient , History, Medieval , Humans
7.
Br J Cancer ; 103(9): 1318-24, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20877359

ABSTRACT

BACKGROUND: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00-CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. RESULTS: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of ≥50% vs <50%. CONCLUSION: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account.


Subject(s)
Biomarkers, Tumor/blood , CA-19-9 Antigen/blood , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/psychology , Quality of Life , Adult , Aged , Aged, 80 and over , Fatigue/complications , Female , Health Status , Humans , Male , Middle Aged , Pain/complications , Palliative Care , Pancreatic Neoplasms/drug therapy , Prognosis , Treatment Outcome
8.
Ann Oncol ; 21(12): 2390-2395, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20444846

ABSTRACT

BACKGROUND: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. RESULTS: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. CONCLUSION: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Organoplatinum Compounds/administration & dosage , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease Progression , Dose-Response Relationship, Drug , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Oxaliplatin , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Survival Analysis , Treatment Outcome , Gemcitabine
9.
Ann Oncol ; 20(9): 1522-1528, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19465425

ABSTRACT

BACKGROUND: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/therapy , Esophageal Neoplasms/therapy , Neoadjuvant Therapy , Adult , Aged , Carcinoma/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Digestive System Surgical Procedures , Docetaxel , Esophageal Neoplasms/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Radiotherapy , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome
10.
Ann Oncol ; 19(7): 1288-1292, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18349029

ABSTRACT

BACKGROUND: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/administration & dosage , Cetuximab , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Drug Administration Schedule , Exanthema/chemically induced , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/pathology , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Radiography , Switzerland , Time Factors , Treatment Outcome
11.
Br J Cancer ; 98(7): 1204-9, 2008 Apr 08.
Article in English | MEDLINE | ID: mdl-18349837

ABSTRACT

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Organoplatinum Compounds/administration & dosage , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Chemotherapy, Adjuvant , Combined Modality Therapy , Deoxycytidine/administration & dosage , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Oxaliplatin , Pelvis/radiation effects , Rectal Neoplasms/surgery
12.
Ann Oncol ; 14(4): 638-42, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12649113

ABSTRACT

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy naïve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Carboplatin/administration & dosage , Carcinoma/pathology , Doxorubicin/administration & dosage , Drug Administration Schedule , Female , Humans , Middle Aged , Neutropenia/chemically induced , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Treatment Outcome
13.
Br J Nutr ; 83(2): 123-30, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10743491

ABSTRACT

The aims of the present study were first to compare the amino acid dilution method performed using labelled animals with that using labelled diets, and second to determine real digestibilities and total ileal endogenous losses of N and amino acids. Two diets containing pea cultivars (Solara and Amino) and a protein-free diet were compared in a 3 x 3 Latin-square experiment. The three pigs were each prepared with an ileo-rectal anastomosis and were continuously infused with [1-13C]leucine. For each cultivar, 15N-labelled and unlabelled diets were formulated. The real digestibility and endogenous losses of leucine were higher when obtained by labelling the pig than by labelling the foodstuff. This was due either to the inadequate estimation of the endogenous protein enrichment in the first case or to the importance of dietary N recycling in the second case. However, in both cases the ileal endogenous losses of N and amino acids were higher than the basal losses determined with the protein-free diet. There were significant differences between the two pea cultivars in terms of phenylalanine and leucine when measured with labelled diets. It is suggested that, although ileal endogenous losses may be underestimated, using labelled feedstuffs is of great interest due to the direct estimation of the individual amounts of amino acids.


Subject(s)
Amino Acids/metabolism , Ileum/metabolism , Animals , Carbon Radioisotopes , Digestion/physiology , Leucine/metabolism , Nitrogen Radioisotopes , Phenylalanine/metabolism , Radioisotope Dilution Technique , Swine
14.
Ber Wiss ; 23(3): 317-29, 2000 Sep.
Article in German | MEDLINE | ID: mdl-11640863

ABSTRACT

The historical shift in the function of the hospital from an asylum for the care of the indigent sick to a medical-therapeutic institution is intimately associated with the exploitation of the hospital as a clinical facility. Thus, over the course of the 19th century the space of the hospital and its disciplinary structure was permeated and reorganized by clinical practices. Drawing on the example of the Charite hospital in Berlin, it can be shown how the historical shift in the hospital's outward social function went hand in hand with the creation of a differentiated internal clinical space. In this compartmentalized clinical space the discipline of the hospital was replaced with methods of clinical examination, techniques of observation, and procedures of documentation, all of which helped to transform the hospital into a knowledge-space.


Subject(s)
Clinical Medicine/history , Hospitals/history , Science/history , Germany , History, 19th Century
15.
Psychother Psychosom Med Psychol ; 49(6): 202-7, 1999 Jun.
Article in German | MEDLINE | ID: mdl-10416340

ABSTRACT

In psychotherapy, there is a rising need to evaluate the therapeutic process and outcome quality. However, the effort for documentation binds manpower and is a burden on economic resources. Hence, we studied the usability of a new by developed, mobile, computer-assisted basis assessment (ComBas 1.3) in comparison with paper-and-pencil versions with respect to its effects on data structure and cost reduction. More than 9000 standardised psychometric tests (personality inventory: Giessentest, complaint checklist: Giessener Beschwerdebogen, mood checklist: Berliner Stimmungsfragebogen) were applied with each method to 1400 psychosomatic patients. It was found that usage of the mobile computer-assisted assessment reduced the time by 2/3 spent on documentation, because data organisation and accessibility for clinical, scientific, and educational needs were significantly improved. Moreover, no differences in stability coefficients and data distribution were seen between the two methods. In trait variables, there was also an equivalence in scale means, but in state variables, especially in complaint scales, we identified a tendency toward higher scale means in computer-assisted measurement. We cannot establish whether this is only a methodical effect or is additionally influenced by changes in samples during the evaluation period between 1989 and 1996. Hence, we concluded that comparison samples for state instruments should be adjusted to the applied test form and actualised for use in individual diagnostics.


Subject(s)
Diagnosis, Computer-Assisted/instrumentation , Psychometrics/instrumentation , Diagnosis, Computer-Assisted/economics , Humans , Microcomputers , Psychometrics/economics , Reproducibility of Results
16.
J Anim Sci ; 77(12): 3281-8, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10641875

ABSTRACT

An experiment was carried out to determine the effects of feeding level, body weight, and time after surgery on basal ileal endogenous amino acid (AA) and N losses in growing pigs. Three pairs of littermate pigs were surgically prepared with ileo-rectal anastomoses. One pig in each pair was anastomosed at 38 kg BW, and the remaining pigs were anastomosed at 67 kg BW. Each pig received at different periods 50, 70, or 90 g of dry matter per kilogram of BW.75 of a protein-free diet according to a Latin square design involving three pigs starting at 45 kg BW and involving six pigs starting at 77 kg BW. For most AA, the time after surgery x feeding level interaction was significant. The basal endogenous losses (in g/d) increased linearly with feeding level at both BW. At the higher BW, the basal endogenous losses (in g/kg DMI) were constant regardless of feeding level, whereas at the lower BW they responded quadratically. At the low feeding level, the endogenous losses were higher than at the medium or high feeding level. We concluded that the basal endogenous losses are proportional to DMI when the feeding level is higher than 70 g/kg BW.75. The AA profile was not influenced by these three variables, but there was a large animal effect. These results suggest that, in digestibility trials, an assessment of the basal ileal endogenous AA losses must be performed on each pig to correct the apparent ileal AA digestibility data.


Subject(s)
Body Weight , Energy Intake , Ileum/physiology , Swine/growth & development , Amino Acids/analysis , Amino Acids/metabolism , Animal Feed , Animals , Female , Gastrointestinal Contents/chemistry , Male , Nitrogen/metabolism
17.
Ber Wiss ; 22(4): 266-80, 1999 Dec.
Article in German | MEDLINE | ID: mdl-11639070

ABSTRACT

The emergence of a 'norm of normalcy' in 19th century laboratories and hospitals was in no way simply a byproduct of the scientific search for knowledge. It was instead closely associated with expectations of social egalitarianism which merged with the moral economy of a new scientific objectivity. The establishment of normal people as a valid measure for a population socially divided and segregated in estates was thus an essential element of the processes of social formulation which created our modern society.


Subject(s)
Health Status , Science/history , Socioeconomic Factors , History, 19th Century
18.
J Nutr ; 128(11): 1969-77, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9808651

ABSTRACT

We assessed the influence of sampling site when using the isotope dilution method to determine ileal endogenous N losses. Three growing pigs were prepared with ileorectal anastomoses and fitted with three catheters (portal, jugular and carotid). A 15N-leucine solution was infused for 24 d, alternating between the carotid artery and the jugular vein. Blood was sampled from the portal catheter and from the systemic catheter not used for the infusion. The pigs were fed successively a protein-free diet, an isolated pea protein diet and a hydrolyzed pea protein diet according to a Latin-square design. The 15N was transferred from leucine to isoleucine, valine, alanine, glycine and proline. Free 15N alanine, glycine and valine enrichments were closer to the respective amino acid enrichments in secretory tissues in the portal vein than in the systemic blood. The enrichment of total nitrogen was higher in the trichloroacetic acid-soluble fraction of the plasma than in the ileal digesta of pigs fed the protein-free diet. Lysine enrichment was significantly different from zero in all tissues except muscle, suggesting that essential amino acids can be synthesized by microflora and used for protein synthesis in the host. We conclude that the total nitrogen isotope dilution method is inappropriate to determine the endogenous loss of amino acids. Moreover, the amino acid dilution method should be performed with portal blood sampling. The main limitation of this method is that a number of essential amino acid losses cannot be determined.


Subject(s)
Amino Acids/metabolism , Digestion , Ileum/metabolism , Indicator Dilution Techniques , Amino Acids/blood , Animals , Carotid Arteries , Dietary Proteins/administration & dosage , Dietary Proteins/metabolism , Hydrolysis , Jugular Veins , Leucine/administration & dosage , Leucine/metabolism , Mass Spectrometry , Nitrogen/metabolism , Nitrogen Isotopes , Portal Vein , Swine
19.
Theor Med Bioeth ; 19(3): 203-13, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9691784

ABSTRACT

Medical semiotics in the 18th century was more than a premodern form of diagnosis. Its structure allowed for the combination of empirically proven rules of instruction with the theoretical knowledge of the new sciences, employing the relation between the sign and the signified.


Subject(s)
Diagnosis , Philosophy, Medical/history , History, 18th Century , Humans
20.
J Nurses Staff Dev ; 14(3): 143-6, 1998.
Article in English | MEDLINE | ID: mdl-9679071

ABSTRACT

How will decreasing literacy levels impact hospital staff training in the 21st century? Will Workforce 2000 projections be relevant to healthcare facilities? Sinai Hospital of Baltimore is actively addressing these literacy and learning issues. If workforce predictions hold true, hospital employees in the years to come will require more training on all levels. In this article, the author provides ideas about ways to effectively train hospital workers who lack basic skills in reading, writing, and arithmetic.


Subject(s)
Educational Status , Inservice Training/trends , Personnel, Hospital/education , Staff Development/trends , Baltimore , Forecasting , Hospitals, Urban , Humans , Inservice Training/methods , Organizational Case Studies , Staff Development/methods
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