Diabetes de inicio precoz en pacientes con fibrosis quística, a propósito de 3 casos / Early-onset diabetes in patients with cystic fibrosis, about 3 cases

INTRODUCCIÓN. La diabetes es la complicación extrapulmonar más frecuente en adultos con fibrosis quística. Existen escasas publicaciones de diabetes relacionada a la fibrosis quística en preescolares a nivel mundial. En Chile se desconoce su prevalencia. MÉTODO. Reportamos una serie de tres casos de niños con fibrosis quística (FQ) y diagnóstico de diabetes a muy temprana edad. RESULTADOS. Caso 1: Niño de 8 años, con diagnóstico de fibrosis quística a los 3 meses de vida por test de sudor y estudio genético p.Phe508del /-. Presenta hiperglicemia no cetósica desde los 6 meses de edad, con colonización traqueal de Staphylococcus Aureus (SA) y Pseudomona Aeruginosa (PA) y debut de diabetes a los 2 años 1 mes. Caso 2: Niño de 16 años, a los 7 meses de vida se diagnostica FQ por test de sudor y estudio genético p.Phe508del /-. Presenta colonización traqueal por SA y múltiples infecciones por PA. A los 5 años 7 meses se diagnostica diabetes presentando cetosis al debut. Caso 3: Niño de 13 años, con diagnóstico de FQ a los 7 meses de vida mediante test de sudor y estudio genético p.Phe508del/-. Presenta colonización traqueal por SA y múltiples infecciones por PA, se realiza diagnóstico de diabetes a los 2 años 7 meses de edad. DISCUSIÓN: La diabetes asociada a fibrosis quística es una complicación frecuente en adultos con fibrosis quística, pero puede presentarse desde edades tempranas. Se debe tener alto nivel de sospecha para el diagnóstico oportuno y óptimo manejo.

INTRODUCTION: Diabetes is the most common extra pulmonary complication in adults with cystic fibrosis (CF). There are few reports of diabetes related to (CF) in preschool children worldwide. Prevalence in Chile is unknown. MÉTODO: We report ta serie of three cases of children with CF and diagnosis of diabetes at an early age. Case 1: Boy 8 year old, CF diagnosed at the age of 3 months by sweat test and genetic study p.Phe508del/-. He presented non-ketotic hyperglycemia since he was 6 months old, with tracheal colonization of Staphylococcus Aureus (SA) and Pseudomona Aeruginosa (PA) , and diagnosis of diabetes at the age of 2 years 1 month. Case 2: Boy patient, 16 years old, with diagnosis of CF at the of age 7 months by sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple PA infections. At the age 5 years 7 months, diabetes is diagnosed, presenting ketosis at the beginning. Case 3: Boy 13 years diagnosed with CF at the age of 7 months, presented sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple infections. DISCUSSION: CF related diabetes is common in adults with cystic fibrosis, but it can be diagnosed in early childhood. A high level of suspicious is required for a proper and timely diagnosis

Modelo de suplementação nutricional com fatores hepatotróficos aumenta proliferação celular em fígado de ratos sadios / Model of nutritional supplementation with hepatotrophic factors increases cell proliferation in the liver of healthy rats

Foram avaliados dois protocolos de administração, em ratos sadios, de uma solução de fatores hepatotróficos (FH), composta por aminoácidos, vitaminas, sais minerais, glicose, insulina, glucagon e triiodotironina (T3). A solução foi administrada durante 10 dias, 40mg/kg/dia, i.p., em duas, grupo 2xFH (n=15), ou três doses, grupo 3xFH (n=15), diárias. Foram observados os efeitos na proliferação celular dos hepatócitos, na angiogênese e na matriz extracelular hepática, assim como as possíveis reações adversas. Os animais dos grupos 2xFH e 3xFH apresentaram aumento da massa hepática de 30,1 por cento e 22,5 por cento, respectivamente, em relação ao grupo-controle (CT; n=15). O índice de proliferação hepatocelular foi maior nos grupos 2xFH (1,4 por cento) e 3xFH (1,2 por cento) em relação ao grupo CT (0,53 por cento), e a densitometria relativa do fator de crescimento do endotélio vascular pelo imunoblot não revelou diferença estatística entre os três grupos. Nos grupos 2xFH e 3xFH, houve redução do colágeno intersticial em relação ao grupo CT. A solução de FH estimulou o crescimento hepático e reduziu o volume de colágeno perissinusoidal. A administração em três doses diárias resultou em mortalidade de 26,7 por cento, possivelmente pelo excessivo estresse da manipulação e pela menor adaptação fisiológica dos ratos, o que não ocorreu nos grupos 2xFH e CT. Para esse tipo de abordagem em ratos, o procedimento experimental mais apropriado, seguro, com melhor chance de adaptação dos animais e com resultados significativos é a aplicação dos FH em duas doses diárias.

Two protocols of hepatotrophic factors (HF) administration, in solution composed by aminoacids, vitamins, mineral salts, glucose, insulin, glucagon, and triiodothyronine were evaluated in healthy rats. This solution was administered for 10 days, (40mg/kg/day) i.p., in two (group 2xFH; n=15) or three daily doses (group 3xFH n=15). The effects on hepatocytes cell proliferation, angiogenesis, and hepatic extracellular matrix, and also possible adverse reactions were analyzed. Animals of groups 2xFH and 3xFH presented an increase in hepatic mass of 30.1 percent and 22.5 percent, respectively, when compared rats of control group (CT; n=15). Hepatocellular proliferation index was higher in rats of groups 2xFH (1.4 percent) and 3xFH (1.2 percent) when compared to CT group animals (0.53 percent), and the relative densitometry of the vascular endothelial growth factor analyzed with immunoblot did not show a significant difference among the three groups. Rats of groups 2xFH and 3xFH showed a reduction of interstitial collagen when compared to CT rats. HF solution stimulated hepatic growth and reduced the volume of perisinusoidal collagen. Administration in three daily doses resulted in 26.7 percent mortality, possibly due to excessive stress from manipulation and lower physiological adaptation of rats, which did not occur in rats of groups 2xFH and CT. The more appropriate and safer experimental procedure for this approach in rats with higher chance of animal adaptation and significant results is the application of HF in two daily doses.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53 percent), TIMP-1 (-31.7 percent), TGF-β1 (-57.7 percent), and MMP-2 (-41.6 percent), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1 percent), ALT (-17.6 percent), and AST (-12.2 percent) serum levels; c) increased liver weight (11.3 percent), and reduced liver collagen (-37.1 percent), regenerative nodules size (-22.1 percent), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat.

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL.kg-1.day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-alpha1 (-53%), TIMP-1 (-31.7%), TGF-beta1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

Impact of steatotic grafts on initial function and prognosis after liver transplantation.

Steatotic grafts are considered a risk factor for dysfunction or even primary nonfunction of liver transplants; grafts with more than 50% fatty infiltration are routinely discarded. This retrospective study evaluated the impact of macrovesicular and microvesicular steatosis on postoperative initial liver function and prognosis by comparing outcomes to nonsteatotic grafts in 48 liver transplantation patients. Fifteen grafts had macrovesicular steatosis, 13 (27.09%) up to 50% fatty infiltration (MG2), and 2 (4.16%) more than 50% (MG3). Thirty-three (69.75%) grafts had no macrovesicular steatosis (MG1). Initial liver function was adequate in 26 (78.78%), 10 (76.93), and 2 (100%) patients, respectively, in subgroups MG1, MG2, and MG3 (P =.892). Thirty-day survival rates were 90.90%, 100%, and 100%, respectively, in subgroups MG1, MG2, and MG3 (P =.606). Twenty-six grafts showed microvesicular steatosis: 18 (37.50%) showed less than 50% fatty infiltration (mG2), and 8 (16.67%) more than 50% (mG3). Twenty-two (45.83%) grafts had no microvesicular steatosis (mG1). Initial liver function was adequate in 16 (72.72%), 16 (88.88%), and 6 (75%) patients, respectively, in subgroups mG1, mG2, and mG3 (P =.547). Thirty-day survival rates were 90.90%, 100%, and 87.5% respectively, in subgroups mG1, mG2, and mG3 (P =.380). In conclusion, macrovesicular and microvesicular steatotic liver grafts displayed adequate initial function, did not compromise survival, and thus should not be routinely discarded.

Behavior of collagen extracellular liver matrix during regenerative growth after partial hepatectomy or after stimulation by exogenous hepatotrophic factors. Study in rats.

During regeneration after partial hepatectomy, the hepatic parenchyma grows by reproducing its histological elements at different rates. The hepatic cells grow more rapidly and the collagen components of the extracellular matrix more slowly. This report studies the behavior of liver tissue collagen in intact livers, increased in size by stimulation with exogenous hepatotrophic factors, comparing them to regenerated livers after hepatectomy. The series consists of a group of rats (n = 4), seven days after 70% hepatectomy, with an average growth of the residual liver mass of 71.55% and another group (n = 4), seven days after stimulation of the intact livers with an average growth of 121.05%. The exogenous hepatotrophic factors administered intraperitoneally (portal) included glucose, amino acids, insulin, glucagon and triiodothyronine. The hepatic collagen content was compared by studying slides stained with Picrossirius and examined with an optical microscope attached to a computer with an image analyzing program. The hepatic collagen was reduced from 2.07% +/- 0.13 to 1.14 +/- 0.08 (a difference of 44.57%; P < 0.001) after hepatectomy and from 1.98% +/- 0.19 to 1.24% +/- 0.07 (difference of 37.46%; P < 0.01) after exogenous hepatotrophic factors stimulation. It was concluded that the production of collagen in hepatic growth initiating with intact livers stimulated by exogenous hepatotrophic factors, occurs with a time difference similarly to what is observed after 70% hepatectomy.

Enhancement of liver size by stimulation of intact rat liver with exogenous hepatotrophic factors.

In mammals, liver size is related to animal body weight at the 2.5 to 3% proportion, a ratio mediated by the afflux of hepatotrophic factors. Formulas capable of modifying this ratio have been developed in previous studies on the rat, with enhancement of liver size brought about by intraperitoneal (portal) infusion of exogenous factors such as glucose, amino acids, insulin, glucagon, vitamins, electrolytes, and triiodothyronine. However, the efficacy of these formulations was accompanied by increased animal mortality (PARRA et al.). The present study, which was carried out with small methodological modifications on a larger number of rats using daily intraperitoneal injections of a solution of exogenous hepatotrophic factors (40 ml/kg) for seven days, confirms the previous findings, with a 114.16 +/- 7.90% enhancement of liver size beyond the expected value for the body weight of the animal. However, the problem of animal mortality was not fully resolved.

[Dose-dependence of the carboxymethylcellulose-papain combination in the prevention of peritoneal adhesions. Study in rats]. / Dose-dependência da associação carboximetilcelulose-papaína na prevenção de aderências peritoneais. Estudo em ratos.

The action of a low volume (one drop) of sodium carboxymethylcellulose (CMC)-papain (PP) association gel to prevent peritoneal adhesions were studied in female Wistar rats. After ether anesthesia and a midline laparotomy incision, the right parietal peritoneum was pinched with a fine hemostat and the pinched peritoneal fold was then ligated. This maneuver was repeated thrice creating four points as if they were little "polyps" with a standardized size. Before closing the incision it was deposited on each point 0.05 ml (one drop) of CMC 2% (group A) or CMC + PP 0.4% (group B), with a total volume of 0.2 ml. These groups were compared with another similar group (group C) of a previous research, in which was used 7 ml/kg of body weight of CMC + PP 0.4% (1.5 ml by animal). Statistically significance was not noticed between groups A and B but it was noticed between these two groups (A and B) and group C (p < 0.001 and p < 0.01, respectively). It was concluded that the lowest effective volume (between 0.2 and 1.5 ml/animal) which can allow the desired effect is to be determined in order to diminish the quantity of substance to be deposited in the abdominal cavity.

Aderências peritoneais: estudo experimental / Peritoneal adhesions: an experimental study

Os autores apresentam um estudo experimental realizado com ratos Wistar, com intuito de comparar a ocorrência de aderências peritoneais após estimulaçao por quatro tipos de lesoes da parede abdominal em sua face peritoneal. Vinte animais machos foram utilizados após laparatomia mediana de aproximadamente 6 cm de extensao e incluídos em um dos quatro grupos a seguir; Grupo A - áreas isquêmicas; Grupo B - áreas isquêmicas cruentas; Grupo C - áreas cruentas; Grupo D - áreas cruentas cauterizadas por bisturi elétrico. Observou-se que o Grupo C mostrou diferença estatisticamente significante em relaçao aos outros grupos (A, B e D), mostrando um menor índice de aderências.

[Prevention of peritoneal adhesion formation with a combination of carboxymethyl-cellulose and papain: experimental study]. / Prevenção da formação de aderências peritoneais pela associação carboximetilcelulose-papaína: estudo experimental.

The inhibitory action of sodium carboxymethylcellulose (CMC) and papain (PP) in peritoneal adhesions formation, were studied in Wistar rats. After ether anesthesia and a midline laparotomy incision, the right parietal peritoneum was pinched with a fine hemostat and the pinched peritoneal fold was then ligated. This maneuver was repeated thrice creating four point as if they were little "polyps" with a standardized size. Before closing the incision, it was deposited on the four points of each animal the following substances: group A--saline solution; group B--CMC 2%; group C--PP 0.4% in distilled water; group D--CMC 2% + PP 0.2%; group E--CMC 2% + PP 0.4%. After ten days, the rats were sacrificed and classified according to the number of "points" that showed adhesions with the abdominal structures. There was a statistically significant decrease in the incidence of adhesions only in the group E (CMC + PP 0.4%).

[Endoscopic evaluation of esophageal varices. Comparison of a classic method and the metric system]. / Avaliação endoscópica de varizes do esôfago. Comparação entre um método clássico e o sistema métrico.

The authors compare 2 endoscopic systems of classification of esophageal varices size, one metric system and the classification by degrees, evaluated simultaneously in 70 endoscopic examinations of 53 patients with portal hypertension. They show that the classification by degrees is inadequate, especially in serial evaluation, for its inherent subjectivity, even when executed by one sole examiner. The metric system, under these circumstances, is less liable to change under the subjective influences and gives more exact reproductions, thus being recommended by the authors.

[Inadequacy of using size variations of esophageal varices to evaluate the permeability of distal splenorenal anastomoses]. / Inadequação do emprego das variações do tamanho das varizes do esôfago par avaliar a permeabilidade da anastomose espleno-renal distal.

After portal hypertension surgical treatment, the esophageal varices size reduction as endoscopically observed, has been pointed out as an indirect permeability sign and good function of portal systemic shunts. Three cases of distal splenorenal anastomosis thrombosis, studied angiographically, were followed by decrease of esophageal varices volume, are discussed.

Sistema metrico para avaliacao de varizes e esofago. Resultados preliminares. / Metric system for evaluation of esophageal varices. Preliminary results

As classificacoes de varizes do esofago atualmente empregadas, pelo seu grande componente de subjetividade, nao vem satisfazendo a necessidade de precisar a evolucao do quadro varicoso apos tratamento cirurgico da hipertensao portal.Visando tornar mais objetiva sua avaliacao, e proposto um metodo de classificacao em que se utilizam criterios matematicos de medida, que o tornam menos sujeito a variacoes do julgamento individual: 1o.) avalia-se em centimetros a extensao de esofago, a partir da cardia, na qual repousam as varizes 2o.) mede-se em milimetros o diametro dos cordoes varicosos nos niveis de 5, 10 e 15 centimetros a partir da cardia. A apresentacao grafica deste sistema permite a visualizacao global e instantanea do quadro varicoso. Todavia, e muitas vezes de utilidade a referencia a variacoes volumetricas das varizes endoscopicamente visiveis em termos percentuais. Para tanto, integram-se as medias da areas de seccao das colunas varicosas, nos tres niveis, com sua altura. Os volumes assim obtidos sao em seguida relacionados em termos percentuais. A fim de exemplificar e testar o metodo sao apresentados quatro pacientes com hipertensao portal e varizes de esofago. Operados dois de desconexao azigo-portal externa e esplenectomia e dois de anastomose esplenorrenal distal termino-lateral