RESUMO
BACKGROUND: Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine. METHODS: The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508). RESULTS: Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group. INTERPRETATION: Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients.
Assuntos
Fármacos Anti-HIV , Darunavir , Quimioterapia Combinada , Infecções por HIV , Lamivudina , Ritonavir , Carga Viral , Humanos , Infecções por HIV/tratamento farmacológico , Darunavir/uso terapêutico , Darunavir/administração & dosagem , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , HIV-1/efeitos dos fármacos , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. METHODS: In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. RESULTS: There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (ß 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (ß - 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (ß -0.34, p 0.03) and by immigrants (ß -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (ß 0.19/0.19/0.20/0.25; each p < 0.01). CONCLUSION: Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Assistência ao Convalescente , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , SobreviventesRESUMO
OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Carga ViralRESUMO
BACKGROUND: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. MATERIAL AND METHODS: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. RESULTS: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). CONCLUSION: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
Assuntos
Neoplasias da Mama/patologia , Contagem de Células/métodos , Citodiagnóstico/métodos , Imuno-Histoquímica/métodos , Separação Imunomagnética/métodos , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
SUMMARY: A 41-year-old pregnant woman with multiple virological failures started darunavir, enfuvirtide, zidovudine and lamivudine at week 28 of pregnancy. During week 38, the patient had a viral load <400 copies/mL and a CD4 count of 180 cells/mm(3) (13%). The child was found to be in good health, with negative HIV-polymerase chain reactions at birth, at two and at six months.
Assuntos
Terapia Antirretroviral de Alta Atividade , Proteína gp41 do Envelope de HIV/uso terapêutico , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Darunavir , Farmacorresistência Viral Múltipla , Quimioterapia Combinada , Enfuvirtida , Feminino , Proteína gp41 do Envelope de HIV/administração & dosagem , Inibidores da Fusão de HIV/administração & dosagem , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Humanos , Recém-Nascido , Fragmentos de Peptídeos/administração & dosagem , Gravidez , Resultado da Gravidez , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Carga ViralRESUMO
HER2 overexpression in breast cancer is associated with a poor prognosis, resistance to endocrine therapy and chemosensitivity to anthracyclines and paclitaxel. Moreover, trastuzumab (Herceptin) shows therapeutic benefit in patients with HER2 overexpressing tumors. Therefore, knowledge of the pretherapeutical HER2 status allows an optimal selection of patients for treatment. In addition to a definitive histological diagnosis, core biopsies of tumors offer the opportunity to evaluate the HER2 status preoperatively. In 64 patients with invasive breast cancer, sections of core biopsies and of the subsequently removed whole tumor were investigated immuno-histochemically with the DAKO HercepTest. Fifteen tumors (23%) revealed HER2 overexpression, and 44 tumors (69%) were negative in both, the core biopsy and the whole tumor sections. Two core biopsies were negative whereas the corresponding final specimen was 2+ positive. In 3 cases weak overexpression was observed in the core biopsy, but the whole tumor was negative. The overall concordance of the results achieved at core biopsy and whole tumor sections was 92% (kappa = 0.8). A negative HER2 result on core biopsy was never associated with a score 3+ tumor specimen nor was there a case of negative whole tumor specimen with a preceding 3+ score in the biopsy. If one demands the highest degree of overexpression (3+), 100% of our study patients would have been selected correctly using the results on core biopsy alone. We thus conclude, that the immunohistochemical investigation of core biopsies offers the opportunity for a valid preoperative estimation of HER2 overexpression.
Assuntos
Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Receptor ErbB-2/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/imunologia , Feminino , Genes erbB-2 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Manejo de EspécimesRESUMO
We studied the conversion of acute edematous pancreatitis (AEP) to acute hemorrhagic pancreatitis (AHP) in an experimental model in cats. In the model, 16,16 dimethyl PgE2 effects this conversion by increasing microvascular permeability. First, we induced AEP in cats and then gave PgE2 at increasing intervals after the induction of AEP to see how long an interval would still allow conversion. In 6 groups of cats, PgE2 was administered for 2 h, starting at 2, 4, 6, 8, 10, or 12 h after the creation of AEP. Twelve h later, the cats were sacrificed and the pancreases were graded for inflammation and hemorrhage. Significant pancreatic hemorrhage did not occur when the PgE2 was administered at 12 h compared to 2 h. Next, we determined that PgE2 still retained its ability to increase pancreatic vascular permeability when administered 12 h after the creation of AEP. This was done by perfusing a marker molecule through the MPD (fluorescein isothiocyanate labeled dextran: FITC-D, mol wt 20,000) and then finding it in portal venous blood (PVB). The presence of FITC-D in PVB signified increased vascular permeability, since normally none was present. We concluded that conversion of AEP to AHP was possible during the first 12 h after induction of AEP. Lack of conversion at 12 h was not caused by a lack of vascular reactivity at that time.
Assuntos
Pancreatite/etiologia , 16,16-Dimetilprostaglandina E2/administração & dosagem , Doença Aguda , Animais , Permeabilidade Capilar/efeitos dos fármacos , Gatos , Modelos Animais de Doenças , Edema/etiologia , Edema/patologia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/patologia , Suco Pancreático/enzimologia , Pancreatite/patologia , Fatores de TempoRESUMO
Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with 113mIn or 99mTc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with 113mIn and of chicken liver labeled with 99mTc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as 99mTc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food.
Assuntos
Alimentos , Esvaziamento Gástrico , Pancreatina/fisiologia , Adulto , Idoso , Animais , Cães , Feminino , Humanos , Radioisótopos de Índio , Masculino , Microesferas , Pessoa de Meia-Idade , Tamanho da Partícula , Cintilografia , Estômago/diagnóstico por imagem , Estômago/fisiologia , TecnécioRESUMO
Available methods for measuring in vivo gallbladder absorption preclude the use of animals in which hepatic bile enters the gallbladder via accessory or aberrant channels. However, accessory bile ducts are present in many of the animal models currently used in gallstone research. The aim of this study, therefore, was to evaluate a new dual-isotope technique that corrects for accessory bile flow and to compare data on electrolyte and water absorption with those derived from the standard, single-isotope technique. Prairie dogs underwent gallbladder exclusion by cystic duct ligation and common bile duct cannulation. Carbon 14-polyethylene glycol-labeled lactated Ringer's solution was instilled into the gallbladder while tritiated cholic acid was administered intravenously to label the bile acid pool. There is no correlation between water or electrolyte absorption and time, nor between water and electrolyte absorption, when these parameters are calculated by the standard, single-isotope technique. In contrast, use of the dual-isotope technique quantifies accessory bile duct flow and yields a linear increase in water and electrolyte absorption, both of which are time dependent. These data suggest that the dual-isotope technique provides a means to accurately measure in vivo gallbladder absorption in animals with or without accessory bile ducts.
Assuntos
Vesícula Biliar/metabolismo , Absorção , Animais , Ductos Biliares/fisiologia , Radioisótopos de Carbono , Eletrólitos/metabolismo , Marcação por Isótopo , Masculino , Sciuridae , Trítio , Água/metabolismoRESUMO
The hypothesis that the presence of cholelithogenic bile during the early stages of cholesterol gallstone formation promotes gallbladder absorption of water and electrolytes was tested in a prairie dog gallstone model. An increase in gallbladder transport of water and sodium was observed in cholesterol-fed prairie dogs at a time when cholesterol crystals were present, but before gallstone formation. These data suggest that in the presence of cholesterol-saturated bile, in vivo gallbladder absorption is increased during the early stages of cholesterol gallstone formation. The resulting increase in the solute concentration may promote nucleation and, therefore, be an important etiologic factor in cholesterol gallstone formation.
Assuntos
Colelitíase/metabolismo , Colesterol/metabolismo , Vesícula Biliar/metabolismo , Absorção , Animais , Bile/análise , Ductos Biliares , Transporte Biológico , Água Corporal/metabolismo , Eletrólitos/metabolismo , Masculino , Análise de Regressão , Sciuridae , Fatores de TempoRESUMO
Recent studies suggest that pancreatic polypeptide (PP) alters gallbladder pressure and reduces delivery of bile to the duodenum. Whether this peptide influences gallbladder emptying and/or filling is not clear. Using the prairie dog model, we tested the hypothesis that exogenous PP induces gallbladder filling. Animals maintained on control diets underwent laparotomy with placement of catheters into the gallbladder and common bile duct. The gallbladder was perfused with [14C]polyethtyleneglycol ([14C]PEG)-labeled lactated Ringer's solution (LR) at 0.1 ml/min. Effluent from the common bile duct was collected at 5-min intervals during 30-min intravenous infusions of LR, LR + 2% serum albumin, and LR + 2% serum albumin + bovine PP (10 and 50 ng/kg/min). Gallbladder pressure was continuously recorded. Total and incremental fillings were calculated based on volume and [14C]PEG concentration changes. Infusion of PP, 50 ng/kg/min, induced significant gallbladder filling. The filling response was progressive and peaked during the final 10 min of peptide infusion. These findings coupled with the observation that serum PP levels are increased for up to 6 hr postprandially suggest that PP may play an important role in the regulation of interdigestive gallbladder filling.
Assuntos
Vesícula Biliar/fisiologia , Polipeptídeo Pancreático/farmacologia , Animais , Masculino , Polipeptídeo Pancreático/sangue , Pressão , Radioimunoensaio , SciuridaeRESUMO
Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.
Assuntos
Doenças da Vesícula Biliar/prevenção & controle , Nutrição Parenteral Total/efeitos adversos , Nutrição Parenteral/efeitos adversos , Sincalida/uso terapêutico , Animais , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Colestase/etiologia , Colestase/prevenção & controle , Colesterol/metabolismo , Ácido Cólico , Ácidos Cólicos , Vesícula Biliar/metabolismo , Doenças da Vesícula Biliar/etiologia , Masculino , Técnica de Diluição de Radioisótopos , Sciuridae/metabolismoRESUMO
Ileal resection has been shown to increase the risk of cholelithiasis. Earlier studies in humans suggested that ileal resection increases the cholesterol saturation index. Recent data from patients on long-term parenteral nutrition and from animals, however, have suggested that ileal resection predisposes to pigment gallstone formation. We therefore tested the hypothesis that ileal resection alters bile calcium and bilirubin metabolism without affecting the cholesterol saturation index. Adult male prairie dogs underwent either sham laparotomy (eight prairie dogs) or ileal resection (16 prairie dogs). All animals were fed a trace cholesterol (nonlithogenic) diet before and for 4 weeks after operation. Pigment gallstones were present in 44% of the ileal-resected animals and in none of the sham animals (p less than 0.05). Calcium bilirubinate crystals were present in 94% of the ileal-resected animals and in none of the sham animals (p less than 0.01). Gallbladder bile calcium (25.6 +/- 2.4 versus 17.2 +/- 1.1 mg/dl; p less than 0.05) and total bilirubin (29.3 +/- 4.0 versus 9.4 +/- 1.8 mg/dl; p less than 0.01) concentrations were significantly greater in ileal-resected animals. The cholesterol saturation index of gallbladder bile, however, was no different in ileal-resected (0.53 +/- 0.04) and in sham-operated animals (0.50 +/- 0.04). Although initial studies suggested that the cholesterol saturation index of hepatic bile was increased after ileal resection, a second set of experiments demonstrated that this phenomenon resulted from washout of bile salts that were already in extremely low concentrations in hepatic bile. We conclude that alterations in bilirubin, but not cholesterol, metabolism result in pigment gallstone formation after ileal resection.
Assuntos
Bilirrubina/metabolismo , Colelitíase/etiologia , Colesterol/metabolismo , Íleo/cirurgia , Animais , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Cálcio/metabolismo , Colelitíase/metabolismo , Vesícula Biliar/metabolismo , Humanos , Fígado/metabolismo , Masculino , Complicações Pós-Operatórias/metabolismo , SciuridaeRESUMO
Patients on long-term total parenteral nutrition (TPN) have an increased incidence of gallstones. To determine the pathophysiologic mechanisms responsible for gallstone formation in these patients, we fed three groups of prairie dogs intravenously for 10 days with continuous infusions of isocaloric, isovolemic, and isonitrogenous solutions with either 0, 25, or 50% of nonprotein calories provided as Intralipid. A fourth group of prairie dogs was hyperalimented with the 25% solution for 28 days. Control animals were fed Purina rat Chow ad libitum. Each animal's bile salt pool was labeled with iv 3H-cholic acid 16 hr prior to collecting gallbladder and hepatic bile specimens. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (dpm/mol of bile acid), an index of gallbladder stasis, was significantly (p less than 0.05) lower in TPN animals (less than 0.65 +/- 0.19) compared to controls (1.07 +/- 0.11). This finding indicates that gallbladder stasis developed in all animals fed by TPN. TPN did not alter gallbladder or hepatic bile lithogenic index. Two of five 28-day TPN animals developed biliary sludge, and one of these animals formed pigment gallstones. TPN without lipid decreased serum cholesterol concentration. As the lipid concentration of the TPN solution was increased, serum cholesterol increased. These data indicate that TPN induces gallbladder stasis regardless of caloric source but does not increase bile lithogenic index despite a dose-related rise in serum cholesterol as the percent of calories provided as lipid is increased. We conclude that TPN-induced gallbladder disease results from gallbladder stasis and not from increased bile cholesterol saturation.
Assuntos
Colelitíase/etiologia , Emulsões Gordurosas Intravenosas/efeitos adversos , Vesícula Biliar/fisiologia , Nutrição Parenteral Total/efeitos adversos , Nutrição Parenteral/efeitos adversos , Fosfatase Alcalina/sangue , Animais , Bile/análise , Bile/fisiologia , Ácidos e Sais Biliares/análise , Bilirrubina/sangue , Colesterol/análise , Colesterol/sangue , Lipídeos/análise , Masculino , Sciuridae , Fatores de Tempo , Triglicerídeos/sangueRESUMO
UNLABELLED: Quantitative reduction of portal blood flow following a portacaval shunt (PCS) adversely affects hepatocyte function, but does not alter HRES activity [L. P. Edgcomb , J. A. Knol , and F. E. Eckhauser . J. Surg . Res. 33: 233, 1982]. To determine whether similar changes occur after qualitative alteration of portal blood flow, portacaval transpositions (PCT) were constructed in six conditioned mongrel dogs. Estimated hepatic blood flow (EHBF) was determined scintigraphically by the rate of hepatic uptake of a 500-microCi dose of 99mTc -sulfur colloid (Tsc). Hepatic reticuloendothelial cell (RES) phagocytic (PI) and degradative (DI) indices were calculated from the half-time blood disappearance of 131I-labeled RES test lipid emulsion, and the half-time urine appearance of free 131I, respectively. Opsonic activity (OI) was determined by gelatin latex particle agglutination and normalized to control values. Hepatocellular function was assessed by serial determinations of albumin (Alb), and pyruvic and glutamic oxaloacetic transaminases (SGPT and SGOT). All studies were performed prior to and at 3, 6, and 9 weeks following PCS or PCT. CONCLUSIONS: In the dog, neither PCS nor PCT adversely affected HRES activity. Hepatocellular function and OI remained unchanged following PCT but deteriorated significantly after PCS. Observed changes in hepatocyte function and OI following PCS suggest that hepatocellular integrity and serum opsonic activity may be interrelated.
Assuntos
Circulação Hepática , Fígado/fisiologia , Sistema Fagocitário Mononuclear/fisiologia , Derivação Portocava Cirúrgica , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Proteínas Sanguíneas/metabolismo , Cães , Fígado/citologia , Proteínas Opsonizantes/fisiologia , Fagócitos/fisiologia , Veia Porta/fisiologia , Albumina Sérica/metabolismo , Veias Cavas/fisiologiaAssuntos
Cesárea/enfermagem , Gravidez Múltipla , Quadrigêmeos , Feminino , Humanos , Recém-Nascido , Masculino , Pais/educação , GravidezRESUMO
Recent observations indicate that the hepatic secretion of lithogenic bile, gallbladder mucus hypersection, and gallbladder stasis are all critical factors in the pathogenesis of cholesterol gallstones. Using the prairie dog gallstone model, we investigated the interaction of these factors and the sequence in which they develop. The results of this study indicated that (1) gallbladder bile mucus concentration is elevated before cholesterol precipitation and increases progressively with the formation of cholesterol crystals, (2) cystic duct resistance increases in the presence of cholesterol crystals, but not fine, sonicated crystals increase cystic duct resistance. We conclude that these alterations trigger a self-perpetuating cycle of mucus hypersecretion, cholesterol crystallization, and gallbladder stasis which culminates in the formation of cholesterol gallstones.
Assuntos
Colelitíase/etiologia , Colesterol/metabolismo , Muco/metabolismo , Animais , Bile/metabolismo , Colelitíase/metabolismo , Colesterol na Dieta/efeitos adversos , Vesícula Biliar/metabolismo , Fígado/metabolismo , Masculino , Modelos Biológicos , RoedoresRESUMO
Standard doses of chenodeoxycholic acid (15 mg/kg/day) fail to dissolve gallstones in 30 to 50 percent of patients with radiolucent gallstones in a functioning gallbladder. In humans, increasing dietary cholesterol produces increased biliary secretion of cholesterol. Restriction of dietary cholesterol reduces the minimum effective dose of chenodeoxycholic acid and speeds gallstone dissolution. In this study we investigated the interaction of dietary cholesterol and chenodeoxycholic acid in the prevention of gallstones in the prairie dog gallstone model. In animals fed a moderately lithogenic diet, standard doses of chenodeoxycholic acid failed to prevent gallstones. Reduction of the cholesterol stimulus or doubling the dose of chenodeoxycholic acid prevented the formation of gallstones. These findings support the hypothesis that the formation and dissolution of cholesterol gallstones are an expression of the relative strengths of saturating and desaturating stimuli. Therefore, rational therapy for cholesterol gallstone dissolution and prevention requires both reduction of lithogenic stimuli and optimal titration of chenodeoxycholic acid.