RESUMO
Laboratory tests are a primary resource to diagnose patient's diseases. However, physicians often make decisions based on the available information, which commonly includes the last test results as a static picture and have limited perspective of the role of trends in commonly measured parameters in enhancing the diagnostic process. By providing a dynamic patient profile the diagnosis could be more accurate and, as a consequence, physicians could anticipate changes in recovery trajectory and prescribe interventions more effectively. Intensive care unit (ICU) patients need continuous monitoring, which commonly includes the assessment of several blood components. One of these components is the platelet count which is used in assessing blood clotting. However, platelet counts represent a dynamic equilibrium of many simultaneous processes including altered capillary permeability, inflammatory cascades, as well as the coagulation process. To characterize the value of dynamic changes in platelet counts we applied analytic methods to datasets of critically ill patients in (i) a homogeneous population of ICU cardiac surgery patients, where an observation appears to be predictive of patient's complications and mortality and (ii) a heterogeneous group of ICU patients to confirm the previous observation.
Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Contagem de Plaquetas , Estatística como Assunto/métodos , Bases de Dados Factuais , Humanos , PrognósticoRESUMO
Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.
Assuntos
Gastrinas/sangue , Precursores de Proteínas , Síndrome de Zollinger-Ellison/sangue , Cromatografia em Gel , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasia Endócrina Múltipla/sangue , Radioimunoensaio , Síndrome de Zollinger-Ellison/diagnóstico , Síndrome de Zollinger-Ellison/secundárioRESUMO
Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.
Assuntos
Antineoplásicos/farmacologia , Gastrinas/metabolismo , Somatostatina/análogos & derivados , Síndrome de Zollinger-Ellison/metabolismo , Adulto , Bucladesina/farmacologia , Humanos , Técnicas In Vitro , Masculino , Octreotida , Secretina/farmacologia , Somatostatina/farmacologiaRESUMO
A method is described that uses the avidin-biotin complex (ABC) immunoperoxidase technique to provide a rapid, sensitive, and specific means to quantitate isolated G cells in cultures and suspensions.
Assuntos
Mucosa Gástrica/citologia , Gastrinas/biossíntese , Animais , Avidina , Biotina , Células Cultivadas , Fixadores , Mucosa Gástrica/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , Antro Pilórico , Ratos , Ratos Endogâmicos , Síndrome de Zollinger-Ellison/patologiaRESUMO
To evaluate the responsiveness of isolated, hyperplastic antral gastrin-producing G cells to a variety of secretagogues, hyperplastic hypergastrinemia was produced in Sprague-Dawley rats by fundusectomy. Mean serum immunoreactive gastrin (IRG) concentration was elevated fivefold above controls 4 days after operation and rose steadily to an eightfold increase at 66 days. Mean antral G cell density remained at control levels for as long as 7 days, increased twofold at 14 days, then remained between twofold and threefold greater than controls for as long as 66 days after operation. Antral mucosa IRG content increased from 141 +/- 38 (control) to 262 +/- 58 ng IRG/gm mucosa (4 to 6 weeks after fundusectomy). Crude fractions of dispersed antral mucosa cells enriched in G cells from fundusectomized rats contained 6.5% +/- 1.4% G cells with 0.19 +/- 0.6 pg IRG/G cell. Corresponding preparations from nonoperated rats contained 5.1% +/- 0.5% G cells with 0.07 +/- 0.02 pg IRG/G cell. Viability averaged greater than 95% for all preparations. Gastrin secretion was monitored in cell preparations further enriched in G cells (9% to 10%) by Percoll density gradient centrifugation either in the absence (basal) or presence of bombesin (1 mumol, 1 nmol/L), carbachol (1 mmol/L), leucine (10 mmol/L), and ethylamine (10 mmol/L). The basal secretory rate of hyperplastic G cell populations averaged 250% greater than normal G cell basal rates. Hyperplastic G cell preparations had an increased IRG secretory rate in the presence of bombesin (1 mumol/L, 750%; 1 nmol/L, 191%), leucine (120%), ethylamine (236%), and carbachol (183%). These conditions failed to increase the IRG secretory rate above basal in preparations from normal antra. Viable, dispersed, hyperplastic G cells have increased IRG content and basal IRG secretory rate and are functionally responsive to a variety of secretagogues.
Assuntos
Sistema Cromafim/metabolismo , Células Enterocromafins/metabolismo , Mucosa Gástrica/metabolismo , Gastrinas/metabolismo , Animais , Centrifugação com Gradiente de Concentração , Células Enterocromafins/efeitos dos fármacos , Células Enterocromafins/patologia , Imunofluorescência , Fundo Gástrico/cirurgia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrinas/sangue , Histocitoquímica , Hiperplasia/metabolismo , Técnicas Imunoenzimáticas , Técnicas In Vitro , Laparotomia , Masculino , Antro Pilórico/patologia , Radioimunoensaio , Ratos , Ratos EndogâmicosRESUMO
Extracellular matrices have recently been demonstrated to alter cell morphology in culture. Altered cell morphology has been associated with changes in gene transcription and translation, but it is not known whether it also affects posttranslational processing. Using tyrosine-O-sulfation as a marker of processing, we studied the effects of various substrates on biologically active gastrin (IRG) production and sulfation in gastrin-containing tumor cells (GT cells). Dispersed GT cells were plated onto different substrates and then incubated. Culture media from days 4, 7, and 28 were assayed with specific antibodies that recognize total IRG and nonsulfated IRG. Cells cultured on plastic and dried films of laminin, collagen, and Matrigel (Collaborative Research Inc., Lexington, Mass.) flattened and formed monolayers of GT cells. Cells cultured on a porous membrane and hydrated gels of collagen and Matrigel did not flatten but formed spheroids of GT cells. The monolayer cultures showed an increase in sulfation with time but a decrease in IRG production. The spheroid cultures maintained a constant level of sulfation over time and, with the exception of Matrigel (gel), also showed a decrease in IRG production. These results indicate that the level of sulfation was unchanged from that of the original tumor when cells were grown in spheroids but increased when cultured as monolayers. It appears that alteration of the cellular milieu alters colony morphology, which in turn alters gastrin processing.
Assuntos
Gastrinoma/metabolismo , Gastrinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Processamento de Proteína Pós-Traducional , Sobrevivência Celular , Técnicas Citológicas , Gastrinoma/patologia , Humanos , Microscopia de Contraste de Fase , Neoplasias Pancreáticas/patologia , Sulfatos/metabolismoRESUMO
Hypergastrinemia is often attributed to loss of acid inhibition in the gastric antrum. Prior studies suggest, however, that hypergastrinemia after fundusectomy occurs earlier and to a greater degree than hypergastrinemia after total acid inhibition with high dose (8 mg/kg/day) famotidine. To explain the very early (0 to 21-day) gastrin response, 45 male Sprague-Dawley rats (250 to 350 gm) were equally allocated to fundusectomy alone, famotidine alone, and fundusectomy plus famotidine groups. Vena cava blood samples and antral tissue were harvested at 0, 4, 7, 9, 14, and 21 days. Fundusectomy produced dramatic, sustained hypergastrinemia as early as 4 days after the procedure. Minimal, transient hypergastrinemia was seen with famotidine treatment, but this returned to baseline in spite of total acid inhibition. Antral gastrin was comparable in all three groups at the intervals assessed. Furthermore, fundusectomy plus famotidine did not demonstrate a significant difference from fundusectomy alone. Thus it appears that fundusectomy produces early and sustained hypergastrinemia by a mechanism other than acid inhibition.
Assuntos
Gastrectomia , Fundo Gástrico/cirurgia , Gastrinas/metabolismo , Animais , Famotidina/farmacologia , Fundo Gástrico/fisiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Masculino , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/metabolismo , Ratos , Ratos Endogâmicos , Valores de ReferênciaRESUMO
Although adequate tissue oxygenation is essential to maintain cellular metabolism, the use of hyperoxia to improve oxygen delivery or to improve metabolic performance is controversial. For example, supplemental inspired oxygen is reportedly beneficial in the treatment of some experimental infections; however, oxygen therapy also has well-documented adverse side effects. To evaluate the effect of increased inspired oxygen concentration (FIO2) in animals with fulminant sepsis, 117 Sprague-Dawley rats underwent cecal ligation and puncture. Animals were then exposed to an FIO2 of either 0.21, 0.4, or 0.8. Twenty sham-operated controls had no mortality with any FIO2. Increasing the FIO2 increased mortality from 70% to 85% in animals receiving 40% O2, and to 100% in those receiving 80% O2. Autopsies revealed mild pulmonary oxygen toxicity with 80% O2 exposure in both control and septic animals, but normal lung histologic appearance in animals receiving lower levels of oxygen. Arterial blood gases documented maintenance of oxygenation and ventilation. Thus, pulmonary oxygen toxicity does not appear to be the mechanism for increased mortality. Supplemental oxygen may worsen, rather than improve, survival after fulminant infection.
Assuntos
Oxigênio/administração & dosagem , Peritonite/terapia , Doença Aguda , Animais , Modelos Animais de Doenças , Estudos de Avaliação como Assunto , Pulmão/patologia , Oxigênio/sangue , Oxigênio/uso terapêutico , Peritonite/sangue , Peritonite/mortalidade , Peritonite/patologia , Ratos , Ratos EndogâmicosRESUMO
Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
Assuntos
Sistema Cromafim/metabolismo , Células Enterocromafins/metabolismo , Gastrinas/metabolismo , Neoplasias Hepáticas/metabolismo , Síndrome de Zollinger-Ellison/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/antagonistas & inibidores , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Adulto , Células Cultivadas , Colforsina/farmacologia , Feminino , Humanos , Imuno-Histoquímica , Ésteres de Forbol/farmacologia , Radioimunoensaio , Secretina/farmacologia , Somatostatina/farmacologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
To evaluate the effect of 32% dextran 70 instillation on intra-abdominal adhesion formation and intestinal leaks, 100 animals were prospectively, randomly, and blindly treated with a sham laparotomy (n = 10), sham plus 5 ml dextran (10), intestinal abrasion plus 2 ml (20) or 5 ml (20) of dextran or saline, or intestinal division and anastomosis plus 2 ml (20) or 5 ml (20) of dextran or saline. Autopsies were performed on the animals without knowledge of treatment group at the time of death or sacrifice at 2 weeks. Adhesions were graded 0 to 3, anastomoses were examined for leaks, and the peritoneal cavity was searched for abscesses or peritonitis. Anastomosis produced more severe adhesions than abrasion. Dextran significantly (P greater than 0.01) reduced adhesion formation but resulted in peritonitis (5/40) rather than abscess (7/40) as seen with saline.
Assuntos
Dextranos/uso terapêutico , Peritonite/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Modelos Animais de Doenças , Avaliação de Medicamentos , Íleo/cirurgia , Peso Molecular , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Although associated primarily with the cardiovascular system, atrial natriuretic factor (ANF) has been found to increase the magnitude of duodenal contractions and may play a role in salt and water absorption across gastrointestinal epithelium. Because secretory diarrhea and increased peristalsis are commonly associated with conditions related to hypergastrinemia, we examined an animal model of hypergastrinemia (fundusectomy) to evaluate a possible role for ANF. Sprague-Dawley rats underwent either fundusectomy or sham operation. Circulating levels of gastrin (1085 +/- 105 vs 59 +/- 5 pg/ml), ANF (209 +/- 50 vs 59 +/- 10 pg/ml), and pro-ANF 1-98 (786 +/- 80 vs 599 +/- 49 pg/ml) were elevated significantly 3 months after fundusectomy versus control animals. The increased levels of ANF and pro-ANF 1-98 correlated with the increased gastrin levels (p less than 0.05). Tissue content of ANF and pro-ANF 1-98 were determined at sequential sites in the stomach and small intestine. In normal rats ANF concentrations were greatest in the small intestine; pro-ANF 1-98 content was similar in all tissues except ileum (increased). In rats that underwent fundusectomy, ANF and pro-ANF 1-98 were markedly increased in duodenum compared with all other tissues. Only duodenum showed a difference in peptide levels between normal rats and rats that underwent fundusectomy, (ANF, 1.5 +/- 0.5 vs 16.7 +/- 2.3 ng/gm; pro-ANF 1-98, 0.6 +/- 0.3 vs 51.2 +/- 36.1 ng/gm). Circulating ANF and pro-ANF 1-98 are increased in rats that have undergone fundusectomy. Our results suggest that duodenum may be the source of these increased levels.
Assuntos
Fator Natriurético Atrial/metabolismo , Mucosa Gástrica/metabolismo , Intestino Delgado/metabolismo , Precursores de Proteínas/metabolismo , Animais , Modelos Animais de Doenças , Fundo Gástrico/fisiologia , Fundo Gástrico/cirurgia , Gastrinas/sangue , Masculino , Fragmentos de Peptídeos , Radioimunoensaio , Ratos , Ratos EndogâmicosRESUMO
Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.
Assuntos
Gastrinas/metabolismo , Somatostatina/análogos & derivados , Síndrome de Zollinger-Ellison/tratamento farmacológico , Idoso , Cromatografia em Gel , Feminino , Gastrinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida , Somatostatina/uso terapêutico , Síndrome de Zollinger-Ellison/metabolismoRESUMO
Secretin appears to have a direct effect on gastrinoma cells, which results in a paradoxic increase in the serum gastrin level in patients with the Zollinger-Ellison syndrome. To evaluate this effect, gastrinoma cells were challenged with secretin in acute cell dispersion or after 2 weeks in culture. Acutely dispersed cells were incubated for 15 minutes or 3 hours with and without secretin 10(-6) mol/L. (sec). There was no significant difference in gastrin release between control and sec groups in the two acute incubation periods. At 15 minutes the control value was 47 +/- 1 and the sec value was 54 +/- 1 ng/ml, while at 3 hours the control value was 59 +/- 1 and the sec value was 61 +/- 1 ng/ml. In the cell culture preparation, secretin stimulated gastrin release at all doses (control 463 +/- 85, SEC 10(-10) mol/L 603 +/- 37, sec 10(-8) mol/L 706 +/- 37, sec 10(-6) mol/L 798 +/- 48 pg/ml ([p less than 0.05, Student t test]). These results indicate that secretin stimulates gastrin release directly from cultured gastrinoma cells in a dose-dependent manner but does not stimulate gastrin release from acute cell dispersion. This might be attributed partly to the recovery of secretin receptors in the cultured cells.
Assuntos
Gastrinas/metabolismo , Secretina/farmacologia , Síndrome de Zollinger-Ellison/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Gastrinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Fulminant acute pancreatitis is a disease of complex origin that results in activation of several of the proinflammatory cytokines. Because interleukin-1 (IL-1) is an integral early component of the acute inflammatory process, the use of an IL-1 receptor antagonist (IL-1ra) was investigated in experimental acute pancreatitis to determine the therapeutic potential of proximal cytokine blockade and to further establish the role of inflammatory cytokines in the pathogenesis of acute pancreatitis. METHODS: IL-1ra was administered in escalating doses either before or after acute edematous, necrotizing pancreatitis was induced in adult male mice by injection of cerulein. The severity of pancreatitis was quantified by serum amylase, lipase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels, pancreatic wet weight, and blinded histologic grading. RESULTS: Administration of medium (10 mg/kg) and high (100 mg/kg) doses of IL-1ra either before or after the induction of pancreatitis significantly decreased the expected rise in pancreatic wet weight, lipase, IL-6, and TNF-alpha (all, p < 0.01). Serum amylase was significantly reduced when IL-1ra was administered in either dosage before (p < 0.05), but not after, induction of pancreatitis. Pancreatic edema, necrosis, and inflammatory cell infiltrate were significantly diminished (p < 0.05) by histologic grading in all animals receiving medium or high doses of IL-1ra. Low doses of IL-1ra (1.0 mg/kg) had modest effects if given before, but no effect if given after, induction of pancreatitis. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha are elevated during experimental acute pancreatitis and correlate well with the severity of local pancreatic destruction. Blockade of the cytokine cascade at the level of the IL-1 receptor before or soon after induction of pancreatitis significantly attenuates the rise in these cytokines and is associated with decreased severity of pancreatitis and reduced intrinsic pancreatic damage.
Assuntos
Interleucina-1/antagonistas & inibidores , Pancreatite/terapia , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/uso terapêutico , Doença Aguda , Amilases/sangue , Animais , Ceruletídeo , Edema/patologia , Edema/prevenção & controle , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-6/sangue , Lipase/sangue , Masculino , Camundongos , Necrose , Tamanho do Órgão , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/patologia , Pancreatite/prevenção & controle , Proteínas Recombinantes , Sialoglicoproteínas/administração & dosagem , Método Simples-Cego , Fator de Necrose Tumoral alfa/análiseRESUMO
During the last three decades, 2,4117 splenectomies have been performed at The Ohio State University Hospital. Indications for splenectomy include hypersplenism, incidental to other abdominal procedures, trauma, Hodgkin's staging, and other splenic disease. Hodgkin's staging has become the most frequent indication for splenectomy during the past five years, whereas splenectomy for hypersplenism has decreased. Thrombocytosis (platelet counts greater than 400,000/cu mm) was observed in 47% of all patients. Ninety-three percent of all thromboembolic complications occurred in this group. The overall morbidity of 39% has been decreased to 15% during the last five years. In-hospital mortality has decreased from 9.5% to 6%. Incidental splenectomy, even for benign disease, continues to be associated with complications and death.
Assuntos
Doença de Hodgkin/patologia , Esplenectomia , Esplenopatias/cirurgia , Humanos , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Baço/lesões , Esplenectomia/mortalidade , Esplenopatias/complicações , Esplenomegalia/cirurgia , Trombocitose/complicações , Tromboembolia/complicaçõesRESUMO
Intestinal absorption of ascorbic acid is believed to be mediated through a sodium-dependent active transport process in man and in the guinea pig, both species having a nutritional requirement for the vitamin. Vitamin C transport was studied in man and in the guinea pig by in vivo intestinal perfusion of concentrations of vitamin C ranging from physiologic to clearly pharmacologic levels. Triple lumen intestinal perfusion of seven human volunteers with vitamin C concentrations ranging from 0.85 to 11.36 mM demonstrated saturation kinetics of absorption with a Km = 5.44 mM. Net secretion of water was observed in three of seven humans with the highest (11.36 mM) concentration of vitamin C. Perfusion of isolated segments of guinea pig intestines with intact blood supply also revealed saturation kinetics (Km = 5.54 mM) in the range of 1.42 to 56.8 mM vitamin C but linear absorption below this range. The phenomenon of decreased water absorption noted with incremental vitamin C dose in human volunteers could not be reproduced in the guinea pig, nor were the intestinal tissue levels of cyclic AMP and GMP increased by high-dose vitamin C in this species. This study suggests that "megavitamin" doses of vitamin C (greater than 1 Gm) are probably not as efficiently absorbed as smaller multiple doses of the vitamin. Intestinal secretion of water may contribute to the diarrhea which is the most common side effect of large doses of vitamin C. The guinea pig is a useful but limited model for vitamin C absorption in man.
Assuntos
Ácido Ascórbico/metabolismo , Adulto , Animais , Água Corporal/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Feminino , Cobaias , Humanos , Técnicas In Vitro , Absorção Intestinal , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
Total parenteral nutrition (TPN) is thought to induce cholestasis. However, serum hepatic enzyme abnormalities were found in 70 percent of patients before TPN was started. Rate constants (alpha, beta, K(E] and total clearance (CIT) of sodium taurocholate (STC) and indocyanine green (ICG) were studied in 20 carefully selected patients not on TPN and who had no hepatic or renal disease. Clearance measurements were made prior to initiation and 7 days into dextrose-based TPN. Four modes of TPN administration were used; low calorie (35 cal/kg) versus high calorie (50 cal/kg), with or without protection of TPN solutions from ultraviolet light. Protein doses for all groups were isonitrogenous. TPN was uninterrupted and no patient had surgery, other major procedures, or food by mouth. While serum gamma-glutamyl transpeptidase (GGT) increased, no STC or ICG clearance parameter (total or subgroup) changed in response to TPN. These data do not support the hypothesis that TPN directly causes cholestasis, but suggest that cholestasis caused by concurrent liver disease may appear aggravated by TPN.
Assuntos
Verde de Indocianina/metabolismo , Fígado/metabolismo , Nutrição Parenteral Total , Ácido Taurocólico/metabolismo , Adulto , Idoso , Fosfatase Alcalina/sangue , Feminino , Humanos , Testes de Função Hepática , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality rates for surgical services in Veterans Health Administration. STUDY DESIGN: This cohort study was conducted in 44 Veterans Affairs Medical Centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measure was all-cause mortality within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. Risk-adjusted surgical mortality rates were expressed as observed-to-expected ratios and were compared with unadjusted 30-day postoperative mortality rates. RESULTS: Patient risk factors predictive of postoperative mortality included serum albumin level, American Society of Anesthesia class, emergency operation, and 31 additional preoperative variables. Considerable variability in unadjusted mortality rates for all operations was observed across the 44 hospitals (1.2-5.4%). After risk adjustment, observed-to-expected ratios ranged from 0.49 to 1.53. Rank order correlation of the hospitals by unadjusted and risk-adjusted mortality rates for all operations was 0.64. Ninety-three percent of the hospitals changed rank after risk adjustment, 50% by more than 5 and 25% by more than 10. CONCLUSIONS: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of risk-adjusted postoperative mortality rates after major noncardiac operations. Risk adjustment had an appreciable impact on the rank ordering of the hospitals and provided a means for monitoring and potentially improving the quality of surgical care.
Assuntos
Mortalidade Hospitalar , Hospitais de Veteranos/normas , Avaliação de Resultados em Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde , Procedimentos Cirúrgicos Operatórios/mortalidade , Estudos de Coortes , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Modelos Logísticos , Modelos Estatísticos , Medição de Risco , Albumina Sérica/análise , Procedimentos Cirúrgicos Operatórios/normas , Estados Unidos/epidemiologia , United States Department of Veterans AffairsRESUMO
BACKGROUND: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality and morbidity rates for surgical services in the Veterans Health Administration. STUDY DESIGN: This was a cohort study conducted at 44 Veterans Affairs Medical Centers closely affiliated with university medical centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measures in this report are 21 postoperative adverse events (morbidities) occurring within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. RESULTS: Patient risk factors predictive of postoperative morbidity included serum albumin level, American Society of Anesthesia class, the complexity of the operation, and 17 other preoperative risk variables. Wide variation in the unadjusted rates of one or more postoperative morbidities for all operations was observed across the 44 hospitals (7.4-28.4%). Risk-adjusted observed-to-expected ratios ranged from 0.49 to 1.46. The Spearman rank order correlation between the ranking of the hospitals based on unadjusted morbidity rates and risk-adjusted observed-to-expected ratios for all operations was 0.87. There was little or no correlation between the rank order of the hospitals by risk-adjusted morbidity and risk-adjusted mortality. CONCLUSIONS: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of postoperative mortality and morbidity rates after major noncardiac operations. Risk adjustment had only a modest effect on the rank order of the hospitals.
Assuntos
Mortalidade Hospitalar , Hospitais de Veteranos/normas , Avaliação de Resultados em Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde , Procedimentos Cirúrgicos Operatórios/mortalidade , Feminino , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medição de Risco , Procedimentos Cirúrgicos Operatórios/normas , Estados Unidos/epidemiologia , United States Department of Veterans AffairsRESUMO
Changes in medicine, medical education, and technology have influenced graduate medical education (GME) and have altered many traditional concepts of resident training. Three issues in particular have led to changes. The first is the shortage of time that academic and community physicians have to devote to medical teaching because of the demands to bring in revenue through clinical practice. The second is the limited exposure that residents have to various medical conditions due to a shift in training venues from hospitals to ambulatory care settings. Last is residents' lack of training in using information technologies. The resultant deficits the exist in GME make it more difficult for residents to practice medicine in the most efficient manner. Hence, there is a need for health care professionals' education to address the coming demands of the 21st century. Instructional computer technology can be useful in bridging this gap. Intranets, internal organizational networks, are private versions of the World Wide Web that are often available only to members of a particular organization. This paper reviews changes in medicine and medical education, describes how instructional intranets can be incorporated into GME, and discusses the impact intranet and Internet technologies can have on GME.