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2.
BMC Complement Altern Med ; 17(1): 440, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28870250

RESUMO

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.


Assuntos
Nefropatias/psicologia , Nefropatias/cirurgia , Transplante de Rim/psicologia , Doadores Vivos/psicologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lua , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
3.
Zentralbl Chir ; 138(5): 563-9, 2013 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-21681696

RESUMO

INTRODUCTION: Emergencies in vascular surgery are often life-threatening and require a timely and prompt treatment. Little information is available in the literature about which demands must be made for this on the personnel and infrastructural resources of a hospital. METHODS: All vascular surgical emergency operations of the Surgical University Hospital of Munich - Grosshadern over a period of 2 years were evaluated concerning the emergency category, the leading clinical symptomatology, the genesis, the affected stream area, the intervention time, as well as the need for postoperative intensive medical care. RESULTS: The prevailing procedures were arterial operations (76 %). Ischaemia with 37 % and bleeding with 29 % were the leading clinical symptomatology. Thrombotic events (34 %) showed the most frequent genesis followed by embolism (13 %), stenosis (11 %), aneurysms (10 %) and iatrogenic impairments (10 %). 68 % of the emergencies were treated outside of the daytime working hours. A total of 77 % of the patients needed intensive care treatment or observation after surgery. CONCLUSION: The spectrum and the frequency of emergencies in vascular surgery make high demands on local infrastructure of the hospital and require a fair number of intensive care beds and an adequate and highly trained staff. Only under these conditions can a high quality of treatment be guaranteed for the sometimes life-threatened patients.


Assuntos
Emergências , Acessibilidade aos Serviços de Saúde/organização & administração , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Aneurisma/complicações , Aneurisma/epidemiologia , Aneurisma/cirurgia , Aneurisma Roto/complicações , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Artérias/cirurgia , Cuidados Críticos , Embolia/complicações , Embolia/epidemiologia , Embolia/cirurgia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/cirurgia , Hospitais Universitários/estatística & dados numéricos , Humanos , Doença Iatrogênica , Isquemia/epidemiologia , Isquemia/etiologia , Isquemia/cirurgia , Programas Nacionais de Saúde/organização & administração , Programas Nacionais de Saúde/estatística & dados numéricos , Cuidados Pós-Operatórios , Trombose/complicações , Trombose/epidemiologia , Trombose/cirurgia , Revisão da Utilização de Recursos de Saúde , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia
4.
Zentralbl Chir ; 136(2): 118-28, 2011 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-21424993

RESUMO

Acute abdominal pain represents the cardinal symptom behind a vast number of possible under-lying causes including several ones that re-quire surgical treatment. It is the most common sur-gical emergency, the most common cause for a surgical consultation in the emergency department and the most common cause for non-trauma related hospital admissions. The golden mis-sion statement is to rapidly identify whether the underlying cause requires an urgent or even immediate surgical intervention. However, behind the same cardinal symptom one may encounter harmless or non-urgent problems. By employing diagnostic means cost effectively and with the aim to avoid unnecessary exposure of the patient to X-rays in mind, the challenge remains to identify patients with an indication for emergency surgery from those who suffer from a less serious condition and thus can be treated conservatively and without any pressure of time. Dealing with such a highly complex decision-making process calls for a clinical algorithm. Many publications are available that have scrutinised the different aspects of the initial assessment and the emergency management of acute abdominal pain. How-ever, the large body of evidence seems to miss articles that describe a formally correct priority- and problem-based approach. Clinical algorithms apply to complex disease states such as acute abdominal pain and translate them into one clearly laid out, logically coordinated and systematic overall process. Our intention is to devel-op such an algorithm to approach acute abdominal pain from the surgeon's point of view. Based on daily practice and with reference to available literature, it is the aim of this study to define a work flow that simply summarises all steps in-volved and defines the required decision process in order to form the intellectual basis for an evidence-based clinical algorithm. The result is illustrated as a first draft of such an evidence-based algorithm to allow emergency evaluation of adult patients with acute abdominal pain.


Assuntos
Abdome Agudo/etiologia , Algoritmos , Serviço Hospitalar de Emergência , Abdome Agudo/economia , Abdome Agudo/cirurgia , Adulto , Idoso , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Diagnóstico Diferencial , Erros de Diagnóstico , Documentação/economia , Diagnóstico Precoce , Serviço Hospitalar de Emergência/economia , Medicina Baseada em Evidências/economia , Alemanha , Humanos , Pessoa de Meia-Idade , Programas Nacionais de Saúde/economia , Medição da Dor/efeitos dos fármacos , Exame Físico/economia , Tomografia Computadorizada por Raios X/economia , Procedimentos Desnecessários/economia , Fluxo de Trabalho
5.
Langenbecks Arch Surg ; 392(3): 371-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17458577

RESUMO

BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, is fundamental in tumor growth, progression, and metastasis. Inhibiting tumor angiogenesis is a promising strategy for treatment of cancer and has been successfully transferred from preclinical to clinical application in recent years. Whereas conventional therapeutic approaches, e.g. chemotherapy and radiation, are focussing on tumor cells, antiangiogenic therapy is directed against the tumor supplying blood vessels. MATERIALS AND METHODS: This review will summarize important molecular mechanisms of tumor angiogenesis and advances in the design of antiangiogenic drugs. Furthermore, clinical implications of antiangiogenic therapy in surgical oncology will be discussed. RESULTS: First antiangiogenic drugs have been approved for treatment of advanced solid tumors in several countries. Leading antiangiogenic drugs are designed to inhibit vascular endothelial growth factor-mediated tumor angiogenesis. Combining antiangiogenic agents with conventional chemotherapy or radiation is currently investigated clinically with great emphasis to realize a multimodal tumor therapy, targeting both the tumor cell and tumor vascular compartment. CONCLUSION: Antiangiogenic tumor therapy represents a promising strategy for treatment of cancer and will most likely exhibit its clinical potential in combination with established standard tumor therapies in the future.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Proteínas Angiogênicas/fisiologia , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Indóis/uso terapêutico , Microcirculação/efeitos dos fármacos , Microcirculação/patologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Sorafenibe , Sunitinibe
6.
Surg Endosc ; 21(4): 532-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17177086

RESUMO

BACKGROUND: The incidence of Zenker's diverticulum is low (2/100,000). Standard surgical treatment is cricopharyngeal myotomy with diverticulectomy. Various minimally invasive surgical approaches pursued recently have treated Zenker's diverticulum adequately. The functional minimally invasive therapy is performed alternatively using an Endo-Gia stapler inserted transorally to perform an esophageal diverticulostomia, or using thermal coagulation applied by a carbon dioxide (CO2) or argon plasma laser. The key to a successful procedure is adequate exposure of the diverticulum by insertion of a pharynx spreader before the surgery. METHODS: Since 1996, 31 patients who underwent minimally invasive diverticulostomies performed in our clinic have been included prospectively in the current study. All the patients were examined endoscopically before and after surgery. Furthermore, the intraesophageal and intragastric pressure was examined by transesophageal manometry, and the pH in the esophagus and stomach was determined by pH-metry. A barium swallow was performed to exclude leakage at the stapler suture line as proof of sufficient anastomoses. Manometry showed that the upper esophageal sphincter functioned normally before and after surgery. The results were compared with those of patients undergoing conventional procedures. RESULTS: The median follow-up period after resection of the diverticulum was 46 months. Both the Gastrointestinal Quality-of-Life Index (GQLI) (p < 0.001) and the modified dysphagia score (GHDS) increased significantly, indicating that the operations were successful. The minimally invasive procedure is faster than cricopharyngeal myotomy and significantly safer. It is better tolerated by patients, and they are discharged earlier. CONCLUSION: Transoral esophagodiverticulosomy has become the standard procedure for Zenker's diverticulum in the authors' department. The endoscopic minimally invasive approach proved to be safer than standard surgical procedures. It offers a significantly shorter operation time and postoperative hospital stay (p < 0.001).


Assuntos
Esofagoscopia/métodos , Qualidade de Vida , Grampeadores Cirúrgicos , Divertículo de Zenker/diagnóstico , Divertículo de Zenker/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Segurança de Equipamentos , Esofagoscopia/efeitos adversos , Feminino , Seguimentos , Alemanha , Humanos , Complicações Intraoperatórias/fisiopatologia , Masculino , Manometria , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/fisiopatologia , Probabilidade , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do Tratamento
7.
Chirurg ; 77(11): 1063-78; quiz 1079-80, 2006 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-17051402

RESUMO

Appropriate nutritional therapy of surgical patients intends to supply calories for the maintenance of essential body functions. Beyond this goal, nutritional support may also significantly reduce nosocomial morbidity if applied properly and to the right patients. In surgical patients, nutritional therapy should start preoperatively by identifying and treating malnutrition and be continued postoperatively as a patient-tailored supportive measure. Oral/enteral nutrition is feasible in the majority of patients. Rare exceptions are patients with intestinal leakage, overt ileus, and circulatory shock. If the upper gastrointestinal tract is not functioning (as in swallowing disorders or after construction of surgical anastomoses), tube systems may be used. They can be placed endoscopically or at the time of surgery (needle catheter jejunostomy) to allow continuous enteral nutrition. If oral/enteral nutrition cannot completely meet caloric requirements of the patient, additional parenteral supply is indispensable to reach the intended caloric goal.


Assuntos
Nutrição Enteral/métodos , Gastroenteropatias/cirurgia , Complicações Pós-Operatórias/terapia , Ingestão de Energia , Humanos , Avaliação Nutricional , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Desnutrição Proteico-Calórica/terapia , Infecção da Ferida Cirúrgica/terapia
9.
Intensive Care Med ; 29(6): 995-1002, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12739012

RESUMO

OBJECTIVE: To investigate the effects of combined selective inducible nitric oxide synthase (iNOS) inhibition using 1400 W with nicotinamide (NAD) as a PARS-inhibitor on hepato-splanchnic hemodynamics, O(2) kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled, interventional experiment. SETTING: Animal research laboratory. SUBJECTS: Seventeen domestic pigs. INTERVENTIONS: After 12 h of continuous i.v. endotoxin (LPS) infusion 17 pigs received either no drug (CON, n=9) or 1400 W, titrated to maintain mean arterial pressure (MAP) at pre-endotoxin level, plus 10 mg.kg.h NAD ( n=8;). Measurements were obtained before, 12 h, 18 h, and 24 h after starting LPS infusion. MEASUREMENTS AND RESULTS: In addition to systemic and pulmonary hemodynamics and gas exchange, we measured hepatic arterial and portal venous blood flow, liver and portal venous drained viscera O(2) exchange, ileal mucosal-arterial PCO(2) gap, and portal as well as hepatic venous lactate/pyruvate ratios. Expired NO and plasma nitrate levels were assessed as a parameter of NO production. Without affecting cardiac output, therapy maintained MAP and blunted the LPS-induced rise in expired NO levels, attenuated the progressive fall in liver lactate clearance, and blunted the impairment of hepato-splanchnic redox state. The rise of ileal mucosal-arterial PCO(2) gap was not influenced. CONCLUSIONS: Combining selective iNOS inhibition with NAD as a PARS blocker may prevent circulatory failure and attenuate the detrimental consequences of LPS in intestinal and hepatocellular energy metabolism. Given the potential hepatotoxicity of high-dose NAD treatment, more potent PARS blockers with higher selectivity might further enhance the benefit of this therapeutic approach.


Assuntos
Amidinas/uso terapêutico , Benzilaminas/uso terapêutico , Modelos Animais de Doenças , Endotoxemia/tratamento farmacológico , Niacinamida/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases , Amidinas/farmacologia , Animais , Benzilaminas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Endotoxemia/imunologia , Endotoxemia/metabolismo , Endotoxemia/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Circulação Hepática/efeitos dos fármacos , Masculino , Niacinamida/farmacologia , Estudos Prospectivos , Circulação Pulmonar/efeitos dos fármacos , Distribuição Aleatória , Circulação Esplâncnica/efeitos dos fármacos , Suínos , Fatores de Tempo
10.
Arch Surg ; 136(11): 1301-6, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11695977

RESUMO

HYPOTHESIS: Characteristic of the hypermetabolic response to a thermal injury is the massive protein catabolism and compromised structure and function of essential organs. Nutrition has been suggested to affect protein metabolism and clinical outcome after a severe injury but published studies show controversial data. The purpose of this study was to determine the effect of enriched nutritional support during the postburn hypermetabolic state on protein metabolism in serum, liver, muscle, and skin. SETTING: Laboratory. INTERVENTION: Twenty-two rats were given burns covering 60% of their total body surface area and randomized to receive either standard rat chow (control) or a diet high in vitamins, protein, amino acids, and omega3 fatty acids. MAIN OUTCOME MEASURES: Five weeks after injury, body weight, serum, muscle, and hepatic protein content, insulin-like growth factor I concentration, and wound healing (reepithelization) were determined. RESULTS: Rats receiving the enriched diet showed a gradual improvement in body weight 1, 2, 3, 4, and 5 weeks postburn compared with controls (P< .001). Diet-fed rats demonstrated higher protein and insulin-like growth factor 1 content in serum, muscle, and liver 5 weeks after trauma (P< .001). Serum protein, albumin, and transferrin levels were significantly increased in rats receiving the diet compared with control rats (P< .001). Reepithelization was accelerated in rats receiving the enriched diet 4 (diet-fed, mean +/- SD, 23% +/- 1% vs controls, 17% +/- 1%; P< .001) and 5 (diet-fed, 24% +/- 1% vs controls, 18% +/- 1%; P< .001) weeks postburn compared with control rats. CONCLUSIONS: Nutritional intervention high in protein, vitamins, amino acids, and omega3 fatty acids improves protein net balance during the hypermetabolic response to thermal injury. Compromised organ function and structure and clinical outcome during the hypermetabolic response may be improved.


Assuntos
Queimaduras/metabolismo , Queimaduras/terapia , Alimentos Fortificados , Fenômenos Fisiológicos da Nutrição , Proteínas/metabolismo , Animais , Fator de Crescimento Insulin-Like I/análise , Fígado/química , Masculino , Músculo Esquelético/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Cicatrização
11.
Intensive Care Med ; 27(2): 416-25, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11396287

RESUMO

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.


Assuntos
Clorobenzenos/farmacologia , Endotoxemia/tratamento farmacológico , Endotoxemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Circulação Hepática/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Piridinas/farmacologia , Animais , Gasometria , Glicemia/análise , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Escherichia coli , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/fisiopatologia , Hidratação , Hemodinâmica/efeitos dos fármacos , Hemoglobinas/análise , Lactatos/sangue , Estudos Prospectivos , Ácido Pirúvico/sangue , Distribuição Aleatória , Estatísticas não Paramétricas , Suínos
12.
Intensive Care Med ; 26(10): 1531-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11126268

RESUMO

OBJECTIVE: To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO). INTERVENTIONS: Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg). MEASUREMENTS AND RESULTS: Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment. CONCLUSIONS: Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.


Assuntos
Modelos Animais de Doenças , Endotoxemia/tratamento farmacológico , Endotoxemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Iloprosta/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Animais , Gasometria , Avaliação Pré-Clínica de Medicamentos , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Escherichia coli , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/fisiopatologia , Feminino , Hidratação/métodos , Hemodinâmica/efeitos dos fármacos , Hemoglobinas/análise , Iloprosta/farmacologia , Ácido Láctico/metabolismo , Lipopolissacarídeos , Fígado/irrigação sanguínea , Masculino , Microcirculação/efeitos dos fármacos , Estudos Prospectivos , Ácido Pirúvico/metabolismo , Distribuição Aleatória , Ressuscitação/métodos , Suínos , Fatores de Tempo , Vasodilatadores/farmacologia
13.
Shock ; 14(2): 163-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10947161

RESUMO

Nitric oxide-releasing drugs have been shown to reduce ischemia/reperfusion (I/R) injury by acting as radical scavengers. However, their therapeutic application is hampered by specific side effects and rapid bioreduction in vivo. The half-life and antioxidant activity of nitroxides may be enhanced by their covalent binding to human serum albumin, resulting in polynitroxyl albumin (PNA). Thus, PNA may represent a novel antioxidative drug. The objectives of this study were to elucidate 1) whether PNA is able to diminish I/R injury; 2) the most effective dose of PNA in vivo; and 3) whether the addition of the nitroxide tempol enhances and/or prolongs the effect of PNA. Experiments were performed using a 4-h tourniquet-induced ischemia model in the hamster dorsal skinfold chamber. In the first part, five groups (n = 6) of animals received an infusion of 1) 1% body weight (b.w.) saline (0.9%); 2) 0.5% b.w. albumin (20%); 3) 0.5% b.w. PNA (20%); 4) 1% b.w. albumin (20%); and 5) 1% b.w. PNA (20%) 15 min prior to reperfusion. In the second part of the study, tempol (17 mg/mL) was added either to albumin or PNA (1:9), and 0.5% b.w. of this solution was infused (Group 6: tempol + albumin 0.5% b.w.; Group 7: tempol + PNA 0.5% b.w.). Intravital fluorescence microscopy allowed for quantification of functional capillary density (FCD), leukocyte adherence, extravasation of fluorescein isothiocyanate-labeled Dextran and non-viable (Propidium-positive) cell count prior to ischemia and 0.5 h, 2 h, and 24 h after reperfusion. PNA and--to a lesser extent albumin--effectively reduced postischemic microvascular perfusion failure, leukocyte adhesion, and tissue injury. PNA was most effective in the dose 1% b.w. Although free oxygen radical scavenging seems to be an underlying mechanism leading to the beneficial effects of PNA on I/R injury, hemodilution and known radical scavenging properties of pure albumin contribute in part to the observed effects. Although the combination of tempol and PNA revealed further short-term effects on microvascular perfusion and leukocyte adhesion, it did not result in a long-term improvement of tissue injury.


Assuntos
Albuminas/uso terapêutico , Óxidos N-Cíclicos/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Isquemia/tratamento farmacológico , Doadores de Óxido Nítrico/uso terapêutico , Óxidos de Nitrogênio/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Pele/irrigação sanguínea , Albuminas/administração & dosagem , Albuminas/farmacologia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Viscosidade Sanguínea , Adesão Celular , Corantes , Cricetinae , Óxidos N-Cíclicos/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Corantes Fluorescentes/análise , Corantes Fluorescentes/farmacocinética , Sequestradores de Radicais Livres/farmacologia , Isquemia/patologia , Leucócitos/patologia , Mesocricetus , Microscopia de Fluorescência , Doadores de Óxido Nítrico/farmacologia , Óxidos de Nitrogênio/administração & dosagem , Óxidos de Nitrogênio/farmacologia , Estresse Oxidativo , Próteses e Implantes , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Pele/patologia , Marcadores de Spin
14.
Clin Nutr ; 19(3): 177-84, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10895108

RESUMO

BACKGROUND: LCT lipid emulsions and even more fish oil-containing lipid emulsions are under debate regarding their tocopherol and PUFA content as well as their effect on the antioxidative status especially in patients with oxidative stress. METHODS: Thirty-three patients undergoing major abdominal surgery were randomly assigned to receive either an alpha-tocopherol-supplemented (562 micromol/l) MCT/LCT/omega-3-acid triglycerides (MLF, 5/4/1 w/w/w, 20%) emulsion or a soybean oil-based LCT emulsion (20%). The TPN regimen continuously provided 1.4 g fat kg bw(-1)d(-1)over 5 days. RESULTS: Plasma antioxidant concentrations were strongly reduced by surgical treatment. Following 5 days of TPN with the MLF emulsion, mean plasma alpha-tocopherol increased by 20.0 micromol/l (1.98 micromol/mmol lipid), while nearly no change was observed in the LCT emulsion group. In both groups, plasma concentrations of all non-supplemented antioxidants (vitamin C, carotenoids, selenium) as well as serum total antioxidant capacity further decreased during TPN. The concentrations of plasma cholesterol oxidation products as a measure of in vivo lipid peroxidation revealed no changes over the TPN period in either group. CONCLUSION: In contrast to the LCT emulsion, administration of the a-tocopherol supplemented MLF lipid emulsion normalized a-tocopherol plasma concentrations. Despite its high long-chain PUFA content, no hint for increased lipid peroxidation was found.


Assuntos
Antioxidantes/análise , Emulsões Gordurosas Intravenosas/química , Ácidos Graxos Ômega-3/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Nutrição Parenteral Total , Vitamina E/farmacologia , Abdome/cirurgia , Idoso , Antioxidantes/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Cuidados Pós-Operatórios , Vitamina E/administração & dosagem
15.
Ann Surg ; 228(6): 756-62, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9860474

RESUMO

OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Leucovorina/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
16.
Vox Sang ; 73(4): 237-45, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9407641

RESUMO

BACKGROUND AND OBJECTIVES: Immunosuppression associated with blood transfusion may influence postoperative infection rates. It may also affect the prognosis of patients treated surgically for colorectal cancer. To control this effect, study protocols have applied autologous blood donation programs, which are thought to be immunologically neutral. However, evidence has emerged that blood donation itself might have suppressive effects on natural killer (NK) cell activities. At present, there are no data available on the effects of autologous blood transfusion on NK or lymphokine-activated killer (LAK) cells. This might be of interest as LAK cells may be active in tumor control. MATERIALS AND METHODS: 26 patients who underwent surgical resection for colorectal cancer, were assigned at random into two groups: (1) autologous blood donation and transfusion, or (2) allogeneic blood transfusion. NK and LAK activities were determined before blood donation, at surgery, and on the 3rd and 8th postoperative day. RESULTS: Blood donation induced a small decrease in NK and LAK activities. The postoperative courses of the two groups differed. In the allogeneic group, NK activity (-50%, p = 0.018) and LAK activity decreased (-60.7%, p = 0.043), whereas in the autologous group the decline in LAK was less pronounced (-33.7%, p = 0.091), and their NK activity even increased (+17.4%, p = 0.315). NK activity was modulated differently in the two study groups (0.0036). Differences in LAK activities were found between the 3rd and 8th day postoperatively (p = 0.354). CONCLUSIONS: In patients receiving autologous blood transfusion, postoperative suppressed NK and LAK activities were modulated. This implies that autologous blood transfusion is not immunologically neutral, but has an intrinsic immunomodulatory potential.


Assuntos
Transfusão de Sangue Autóloga , Neoplasias Colorretais/cirurgia , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Idoso , Neoplasias Colorretais/imunologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/imunologia , Transplante Homólogo
17.
Shock ; 8(6): 402-8, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9421852

RESUMO

Even though blood transfusion-associated immunomodulatory effects have been reported, the basic immune mechanism is still not understood. Data from studies on the clinical effects of allogeneic blood-induced immunosuppression are contradictory. However, there are indications that autologous blood transfusion is not immunologically neutral but has intrinsic immunomodulatory potential. Therefore we investigated in vivo different immunological mediators in 56 randomized patients of a study comparing autologous and allogeneic blood transfusion in colorectal cancer surgery. Soluble IL-2 receptor, which is an indicator of general immune activation and the following immunologic refractory phase, indicated immunosuppression was more elevated at the seventh postoperative day in patients with allogeneic transfusions (p = .013) and autologous transfusions (p = .0003). The immunologic determination of TNF-alpha showed a significant postoperative increase in patients with autologous transfusions only (p = .0031). However, postoperative increase of soluble TNF-receptors p55 and p75 was also significant in patients transfused with allogenic blood (p = .022; p = .0014). The response to tetanus toxoid vaccination, an indicator of humoral immunity, was higher in patients transfused with allogeneic rather than autologous blood (p = .082), whereas responses of patients with autologous transfusions were even lower than in nontransfused patients. The reciprocal was already found for cell-mediated immunity determined by epicutaneously tested delayed-type hypersensitivity-reactions. IL-10 levels, an indicator of cellular immunosuppression, were determined in 27 additional patients before operation, immediately postoperative, and at the seventh postoperative day. IL-10 was found elevated immediately postoperative in allogeneic (p = .011) and nontransfused patients only (p = .042). The data from this study substantiate recent findings of a different immunomodulatory potential of allogeneic and autologous blood transfusion. They furthermore support the hypothesis that autologous blood transfusion does not contain immunologically neutral effects of allogeneic blood, but itself exerts an immunomodulatory effect.


Assuntos
Formação de Anticorpos/imunologia , Transfusão de Sangue , Adjuvantes Imunológicos/sangue , Adulto , Idoso , Especificidade de Anticorpos , Transfusão de Sangue Autóloga , Neoplasias Colorretais/cirurgia , Cirurgia Colorretal , Citocinas/sangue , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Toxoide Tetânico/imunologia , Transplante Homólogo
18.
J Clin Oncol ; 12(9): 1859-67, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8083709

RESUMO

PURPOSE: Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression. PATIENTS AND METHODS: One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood. RESULTS: In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage. CONCLUSION: As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.


Assuntos
Transfusão de Sangue Autóloga , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/etiologia , Reação Transfusional , Idoso , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Tolerância Imunológica , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Fatores de Risco , Taxa de Sobrevida
19.
Infusionsther Transfusionsmed ; 21(1): 14-23, 1994 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-8173308

RESUMO

OBJECTIVE: To determine the effect of a pure glucose and of different glucose/fat regimens as nonprotein energy source on substrate metabolism, nitrogen balance, lipoprotein pattern and liver enzymes. Long-chain and mixed long-/medium-chain triglyceride emulsions as 10 and 20% solutions were infused. DESIGN: Prospective randomized study. SETTING: General ward of a university hospital. PATIENTS: 29 patients in five groups after colorectal surgery. INTERVENTIONS: According to Harris-Benedict an amount of 150% of the calculated daily calorie intake was infused. Besides nitrogen balance and routine laboratory tests the lipoprotein pattern was examined. RESULTS: No difference was observed in protein balance, while a pathological rise of liver enzymes was mainly seen with glucose 20% and long-chain fat emulsions in a concentration of 10%. Physiological lipoprotein balance could only be achieved with a 20% solution of long-chain and medium-chain emulsions. CONCLUSIONS: The results demonstrate a fast metabolism of the MCT/LCT 20% solution with physiological lipoprotein pattern and no change in liver enzymes. High-dose glucose infusions and long-chain fat emulsions may cause a fatty degeneration of the liver, and 10% MCT/LCT emulsions may cause a rise of phospholipids and a generation of lipoprotein X.


Assuntos
Metabolismo Energético/fisiologia , Emulsões Gordurosas Intravenosas , Enteropatias/cirurgia , Nutrição Parenteral Total , Triglicerídeos/administração & dosagem , Adulto , Idoso , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Proteínas Sanguíneas/metabolismo , Ácidos Graxos/sangue , Feminino , Humanos , Enteropatias/enzimologia , Lipoproteínas/sangue , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Triglicerídeos/sangue
20.
Lancet ; 342(8883): 1328-33, 1993 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-7901637

RESUMO

Homologous blood transfusion has been associated with an increased risk of postoperative infectious complications. To test the clinical consequences of this apparently immunosuppressive effect of homologous blood in a controlled trial, we designed a study in which the control group deposited autologous blood before their operations for use should transfusion be needed. We enrolled 120 patients with apparently curable colorectal cancer who were able to predeposit autologous blood (haemoglobin > 12.5 g/dL). 62 patients were assigned to receive homologous blood if blood transfusions were needed during operation, and the other 58 to receive their own predeposited blood followed, if necessary, by homologous blood [corrected]. Despite the similarity between the groups in factors known to affect the risk of postoperative infections, there was a significant difference in postoperative infection rate between the homologous and autologous blood groups (17 [27%] vs 7 [12%], p < 0.05; unadjusted odds ratio 2.75 [95% CI 1.07-7.11). The rates of non-infectious complications were similar Probably because their preoperative blood depositing caused the autologous blood patients to have lower haemoglobin concentrations, they were more likely to require transfusion than were the homologous blood group (53 [91%] vs 37 [60%], p < 0.001; relative risk 1.53 [1.24-1.89]). 20 (35%) required homologous as well as autologous blood. To adjust for the many infection-related factors, we did multivariate regression analysis; tumour location, preoperative ASA index, and study group assignment were the only significant risk factors. The odds ratio for postoperative infections adjusted for these factors was 2.84 (1.02-7.98, homologous vs autologous). Testing of delayed-type hypersensitivity responses before and after surgery showed decreases in both mean diameter and number of positive reactions in recipients of homologous blood and slight increases in those who received autologous blood. This study shows the clinical potential of blood-transfusion-mediated immunomodulation, which may be important also in tumour immunology.


Assuntos
Adenocarcinoma/cirurgia , Infecções Bacterianas/epidemiologia , Transfusão de Sangue Autóloga , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Adenocarcinoma/terapia , Idoso , Infecções Bacterianas/etiologia , Transfusão de Sangue , Neoplasias do Colo/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/terapia , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia
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