Increased levels of adenosine and ecto 5'-nucleotidase (CD73) activity precede renal alterations in experimental diabetic rats.

The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-ß as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.

[Psychomotor development in offspring of mothers with post partum depression]. / Alteración del desarrollo psicomotor en hijos de mujeres con depresión posparto de la ciudad de Valdivia-Chile.

BACKGROUND: Postpartum depression (PPD) has adverse effects on psychomotor development of the offspring. AIM: To evaluate the relationship between PPD and psychomotor development in children aged 18 months, consulting in primary care. MATERIAL AND METHODS: Cross-sectional study with 360 infants and their mothers. Children had their psychomotor evaluation at l8 months and mothers completed the Edinburgh Postnatal Depression Scale at 4 and 12 weeks postpartum. The prevalence of both PPD and psychomotor alteration was estimated. The association between PPD and psychomotor alteration, including confounding variables, was estimated through logistic multiple regression analysis. RESULTS: The prevalence of PPD and psychomotor alteration was 29 and 16%, respectively Mothers with PPD had twice the probability of having an offspring with psychomotor alteration (Odds ratio = 2.0, confidence intervals = 1.07-3.68). This probability was significantly higher among single mothers or those with an unstable partner. CONCLUSIONS: PPD has a detrimental impact on psychomotor development of children.

Alteración del desarrollo psicomotor en hijos de mujeres con depresión posparto de la ciudad de Valdivia-Chile / Psychomotor development in offspring of mothers with post partum depression

Background: Postpartum depression (PPD) has adverse effects on psychomotor development of the offspring. Aim: To evaluate the relationship between PPD and psychomotor development in children aged 18 months, consulting in primary care. Material and Methods: Cross-sectional study with 360 infants and their mothers. Children had their psychomotor evaluation atl8 months and mothers completed the Edinburgh Postnatal Depression Scale at 4 and 12 weeks postpartum. The prevalence of both PPD and psychomotor alteration was estimated. The association between PPD and psychomotor alteration, including confounding variables, was estimated through logistic multiple regression analysis. Results: The prevalence of PPD and psychomotor alteration was 29 and 16%, respectively Mothers with PPD had twice the probability of havingan offspring with psychomotor alteration (Odds ratio = 2.0, confidence intervals = 1.07-3.68). This probability was significantly higher among single mothers or those with an unstable partner. Conclusions: PPD has a detrimental impact on psychomotor development of children.

[Clinical and epidemiologic analysis of intestinal tract colonization with vancomycin-resistant enterococci in an intensive care unit]. / Análisis clínico-epidemiológico de la portación intestinal de enterococos resistentes a vancomicina en una unidad de terapia intensiva.

Intestinal tract colonization with vancomycin resistant enterococci (VRE) was studied during five months and 25 days. Out of 171 patients hospitalized in the intensive care unit, 124 (73%) were included in this study. Thirty five of them (28%) were recognized as colonized with VRE. VRE isolates (n = 35) were identified as Enterococcus faecium (n = 18), Enterococcus gallinarum (n = 16), and Enterococcus raffinosus (n = 1). All of them were resistant to vancomycin (MIC90 = 512 microg/ml) and to teicoplanin (MIC90 = 32 microg/ml), having the vanA gene. By means of molecular methods a high homology was found among E. faecium and E. gallinarum isolates, respectively, suggesting their spread as a kind of outbreak. No significant differences in age or sex were found among colonized and non-colonized patients (p > 0.05). On the other hand, the hospitalization time and the use of broad-spectrum antibiotics were associated with colonization. From this study we highlight the importance of enhancing all measures of control and prevention of hospital infections, carefully analyzing the empiric antimicrobial schemes, trying to reduce the hospital stage, and following the surveillance to evaluate the efficacy of such procedures.

Análisis clínico-epidemiológico de la portación intestinal de enterococos resistentes a vancomicina en una unidad de terapia intensiva / Clinical and epidemiologic analysis of intestinal tract colonization with vancomycin-resistant enterococci in an intensive care unit

En un período de cinco meses y 25 días se investigó la portación intestinal de enterococos resistentes a vancomicina (EVR). Se estudiaron 124 pacientes (73%) de 171 admitidos en la unidad de terapia intensiva (UTI), 35 de los cuales (28%) resultaron ser portadores. Los aislamientos de EVR (n=35) fueron identificados como Enterococcus faecium (n=18), Enterococcus gallinarum (n=16) y Enterococcus raffinosus (n=1). Todos los aislamientos estudiados fueron resistentes a vancomicina (VAN) (CIM90= 512 µg/ml) y teicoplanina (CIM90= 32 µg/ml) y portaban el gen vanA. Los estudios de tipificación molecular mostraron un alto grado de homología entre los aislamientos de E. faecium (un clon dominante) y E. gallinarum (dos tipos clonales), sugiriendo su diseminación a modo de brote. No se encontraron diferencias significativas con la edad y el sexo de los pacientes no portadores (p>0,05), pero si con el tiempo de hospitalización y el uso de esquemas antibióticos de amplio espectro (p<0,05), estando estos dos factores asociados al estado de portación. Se deduce de este estudio, la importancia de maximizar las medidas de prevención y control de las infecciones nosocomiales, analizar los esquemas empíricos empleados, tratar de disminuir el tiempo de hospitalización y continuar con los estudios de vigilancia para evaluar la eficacia de las acciones implementadas.

Intestinal tract colonization with vancomycin resistant enterococci (VRE) was studied during five months and 25 days. Out of 171 patients hospitalized in the intensive care unit, 124 (73%) were included in this study. Thirty five of them (28%) were recognized as colonized with VRE. VRE isolates (n = 35) were identified as Enterococcus faecium (n=18), Enterococcus gallinarum (n=16), and Enterococcus raffinosus (n=1). All of them were resistant to vancomycin (MIC90= 512 µg/ml) and to teicoplanin (MIC90= 32 µg/ml), having the vanA gene. By means of molecular methods a high homology was found among E. faecium and E. gallinarum isolates, respectively, suggesting their spread as a kind of outbreak. No significant differences in age or sex were found among colonized and non-colonized patients (p>0.05). On the other hand, the hospitalization time and the use of broad-spectrum antibiotics were associated with colonization. From this study we highlight the importance of enhancing all measures of control and prevention of hospital infections, carefully analyzing the empiric antimicrobial schemes, trying to reduce the hospital stage, and following the surveillance to evaluate the efficacy of such procedures.

Formas atípicas de enfermedad por arañazo de gato, Valdivia / Atypical presentation of Cat Scratch Disease in Valdivia

La enfermedad por arañazo de gato (EAG), es considerada la causa más frecuente de linfoadenopatía benigna crónica en niños y adolescentes. En los casos existe el antecedente de contacto con gatos (90 por ciento) y de rasguño y/o mordedura (60 por ciento). La infección con Bartonella spp se manifiesta como desde una linfoadenopatía (EAG) a una enfermedad sistémica. El 10 po ciento tiene manifestaciones atípicas y 2 por ciento presenta complicaciones graves. Debe sospecharse EAG por exclusión de otras etiologías habituales y por el antecedente epidemiológico de contacto y/o rasguño de gato, con o sin lesión de inoculación primaria. Se presentan 4 casos de EAG atípicas en niños del S.S. Valdivia, donde se confirmó el agente por IFI IgG contra Bartonella henselae, con títulos > 1: 256.

Survey results of transplant patients' attitudes on xenografting.

For centuries, many cultures have described mythical creatures with bodies that combined human and animal features, often the result of violating taboos. This study attempted to investigate the beliefs of transplant patients about xenografting. A survey was given to 100 patients ranging in age from 17 to 74 years old, with 65 men and 35 women, including 72 whites, 18 Hispanics, 5 African Americans, and 4 Asian Americans. The subjects included liver, heart, kidney, lung, and multi-organ transplant patients. The patients were not aware of plans for xenografting at the center under study. Eighty patients agreed with xenografting in an emergency situation. Ten subjects replied, "under no circumstances." Ninety percent believed animal research has advanced medical science. In descending order, the patients preferred human (96%), monkey (44%), mechanical (43%), pig (42%), or dog (34%) organs. Twenty-four patients thought a xenograft would change their appearance, personality, or eating or sexual habits. Twenty patients believed animals have souls. The patients also documented any ethical concerns about xenografting.

Common medical problems in sports.

This article reviews the most common medical problems encountered in the day-to-day care of athletes at all levels of competition. Common medical conditions affecting the pulmonary, gastrointestinal, urological, and endocrine systems are reviewed, as well as common infectious diseases. Review of environmental factors affecting athletes, including sleep disorders, travel, and exposure to the environment during athletic competition, are discussed.

Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation.

We evaluated the effect of Liqui-E, a water-soluble vitamin E preparation, on cyclosporin A (CyA) whole blood concentration in liver transplant recipients, and its impact on the cost of CyA. Patients were 26 liver transplant recipients (19 adults, 7 children) who were unable to achieve and maintain therapeutic CyA whole blood concentrations with the standard recommended oral daily dose in the early post-transplant period. Liqui-E 6.25 IU/kg orally was administered with CyA every 12 hours (median time of starting Liqui-E day 14.5). With Liqui-E, the daily oral CyA requirements (mean +/- SD) were decreased in adults from 22.6 +/- 8.9 to 16.2 +/- 7.3 mg/kg/day (p < 0.001) and in children from 78.6 +/- 34.1 to 53.7 +/- 35.0 mg/kg/day (p < 0.02); intravenous administration of CyA was unnecessary. The CyA trough concentrations (mean +/- SD) before and after Liqui-E were 670 +/- 186 and 1012 +/- 216 ng/ml, respectively, in adults (p < 0.001) and 732 +/- 187 and 1052 +/- 166 ng/ml, respectively, in children (p < 0.01). When given with Liqui-E, the daily cost of CyA decreased by 26% in both adults and children. No clinical or biochemical evidence of Liqui-E toxicity was observed. Thus its administration in the early post-transplantation period can enhance CyA absorption in adults and children who are unable to achieve adequate whole blood concentrations with the usual recommended oral dosages. In addition, a significant cost saving can be realized by coadministration.

Detection of hepatitis C virus with RNA polymerase chain reaction in fulminant hepatic failure.

The role of hepatitis C virus (HCV) infection in fulminant hepatic failure is controversial. The frequency of serum HCV RNA positivity in previously reported patients with fulminant hepatic failure (FHF) of indeterminate cause ranged from 0 to 12% in the United States and Europe and from 43% to 59% in Asia. We assessed serum HCV RNA using polymerase chain reaction (PCR) and oligoprimers from the 5'UTR of the HCV genome in 26 consecutive patients with FHF. Another laboratory independently performed PCR on 21 of the serum samples using different oligoprimers from the 5'UTR and NS3 region of the HCV genome. Serum HCV RNA was detected in two of seven (28%) patients with hepatitis B, 9 of 15 (60%) with an indeterminate cause, and in none with hepatitis A (n = 2) or drug-induced hepatotoxicity (n = 2). HCV RNA PCR results were concordant between both laboratories in 17 of 21 (81%) of samples. In patients with an indeterminate cause, HCV RNA positivity was significantly associated with the transmission risk factor of low socioeconomic status and Hispanic ethnicity. Eighteen patients underwent liver transplantation (LT) and 15 (83%) survived. Among patients with FHF of indeterminate cause, recurrent or acquired HCV infection after transplantation occurred in three of five (60%) and one of four (25%) patients, respectively. Three of four (75%) patients with hepatitis C virus infection post-LT also developed histologic hepatitis. HCV appears to be the causative agent of a substantial number of cases of FHF classified as indeterminate in the Los Angeles area. Differences in patient populations or risk factors may explain the discordant incidences of HCV infection in FHF observed among different programs.

Failure of liver transplantation to diminish cardiac deposits of amylopectin and leukocyte inclusions in type IV glycogen storage disease.

Orthotopic liver transplantation has been used to treat glycogen storage disease type IV. Most long-term surviving patients who have undergone liver transplantation have been free of neuromuscular and cardiac morbidity, and regression of cardiac amylopectin infiltration has been reported after liver transplantation. Leukocyte inclusions in glycogen storage disease type IV have also been reported. We present the case of a child who underwent orthotopic liver transplantation for glycogen storage disease type IV. In contrast to previous reports, at autopsy 2 1/2 years after transplantation, there was massive amylopectin deposits in his heart. Further, peripheral leukocytes never showed loss of amylopectin inclusions after transplantation. Orthotopic liver transplantation for type IV glycogen storage disease may not, in all cases, result in improvement in other affected organs. Consideration of multiorgan transplantation appears warranted.

Portal vein patency in candidates for liver transplantation: MR angiographic analysis.

PURPOSE: To assess the accuracy of magnetic resonance (MR) angiography for evaluating portal vein patency in candidates for liver transplantation. MATERIALS AND METHODS: MR angiography was performed in the main portal vein and proximal confluence of the portal vein in 102 candidates for liver transplantation (64 male patients and 38 female patients aged 8 months to 74 years; mean age, 47 years). The MR angiographic results were compared with the surgical and histologic findings in the explanted liver and excised main portal vein. RESULTS: MR angiography depicted 10 portal vein clots, all of which were confirmed at transplantation. Ninety-two portal veins were patent at MR angiography, a finding that was confirmed at transplantation. One tiny chronic clot in a small, intrahepatic branch of the portal vein was not seen at MR angiography or transplantation. It was identified at histologic analysis of the explanted liver. CONCLUSION: MR angiography is accurate in the evaluation of portal vein patency.

Hepatic resection for malignancy in the elderly.

Although elderly patients are accounted for in all large series of major hepatic resections, the role of age as a determinant of outcome remains unclear. At Cedars-Sinai Medical Center, we review a series of 20 major hepatectomies for neoplasia performed in patients older than 66 years of age (4 of them > or = 80 years old) over a 5-year period. A retrospective comparison was conducted with a group of 22 hepatectomies for malignancy performed in 20 patients younger than 59 years of age during the same time period. The younger group had a significantly greater degree of liver resected (12 trisegmentectomies vs 3). Although one operative death (5% mortality) was observed in the elderly group, no statistically significant difference was noted, when compared to the younger group (Chi-square, P = 0.48). Likewise, no significant difference in the complication rate (20% vs 33%) was noticed (Chi-square, P = 0.8). Severe postoperative liver dysfunction was present in 2 cases (10%) in the elderly group and one (4%) in the younger group. These patients underwent a right trisegmentectomy (TS). Nine patients from each group were resected without red blood cell transfusion. We conclude that major hepatic resection in elderly patients without severe comorbid disease is a safe procedure that is not associated with an increased perioperative morbidity or mortality rate.

Malignant vascular tumors of the liver presenting as liver failure and portal hypertension.

We describe three patients referred for orthotopic liver transplantation with liver failure and portal hypertension who were found to have malignant vascular tumors: two patients with angiosarcoma and one patient with epithelioid hemangioendothelioma. Their clinical presentation mimicked decompensated chronic liver disease. None had tumor masses on computed tomography and ultrasonography. Massive tumor involvement of the liver was identified in the two patients studied by magnetic resonance imaging. Pathological examination of the explanted liver at the time of transplantation in one patient and autopsy in a second patient showed angiosarcoma. Laparoscopic liver biopsies in the third patient showed epithelioid hemangioendothelioma. The vascular origin of the tumor was established by histopathologic examination and confirmed with immunohistochemistry. Malignant vascular tumors of the liver should be included in the differential diagnosis of liver failure of unclear etiology.

Intragraft cytokine gene expression in human liver allografts.

Cytokines are thought to play an important role in the inflammatory and immune responses of allograft rejection. We evaluated the pattern of cytokine gene expression in 36 liver biopsy specimens obtained from 20 recipients of primary orthotopic liver allografts. Specific mRNA expression was identified by a polymerase chain reaction (PCR) using oligonucleotide primers specific for human interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10 Interferon (IFN) gamma, tumor necrosis factor (TNF)-alpha and beta-actin. We detected IL-1 beta, IL-6 and IFN-gamma cytokine message most consistently in patients with rejecting liver allografts. TNF-alpha and IL-2 were also observed in rejecting livers, but only during the early phases of the reaction. IL-4 was expressed in the majority of liver allograft biopsy specimens, regardless of the presence or absence of clinical or pathological evidence of rejection. Sequential biopsy specimens in rejecting allografts showed decreased cytokine expression after the induction of a positive response to immunosuppressive therapy. The analysis of biopsy specimens from stable liver grafts showed a predominance in the expression of IL-10. These results may reflect a differential production of inflammatory and regulatory cytokines in response to liver allograft rejection in transplant recipients. They suggest that three cytokines, IL-1 beta, IL-6 and IFN-gamma, may play an important role as markers for liver allograft rejection. Conversely, IL-10 expression was noted in patients with stable graft function. This pattern of expression may correlate with host immune responses that allow for prolonged, rejection-free survival of the graft.

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Late surgical complications of choledochal cystoenterostomy.

Choledochal cyst is a rare congenital abnormality of the biliary tract characterized by dilatation and stasis. Cyst excision is now preferred to internal drainage because of the predilection for development of cancer in the unresected cyst wall. We report on four patients who required reoperations for complications of prior cystoenteric drainage from 14 to 21 years after the original operations. Gastrointestinal bleeding from cyst ulceration as occurred in one patient is heretofore unreported. This reoperative experience emphasizes the importance of cyst excision as primary therapy and underscores these principles: 1) The spectrum of complications, including infection, pancreatitis, cancer, and bleeding may occur with or without intracyst and ductal stones; 2) Radical operative procedures may be required for treatment of the complications; 3) Despite these, cholangiocarcinoma has a dismal prognosis; 4) Patients whose cysts remain unexcised require meticulous lifelong scrutiny and strong consideration for planned reoperation at the time of the first complication.

Acute liver failure due to lymphoma. A diagnostic concern when considering liver transplantation.

Lymphomatous involvement of the liver may present as acute liver failure but is an absolute contraindication for liver transplantation. Therefore it is imperative to diagnose such patients since survival in this group is poor and recurrence is high. We describe two patients with acute liver failure referred for liver transplantation whose diagnostic testing revealed hepatic lymphoma. These cases underscore the importance of considering lymphoma in the differential diagnosis of acute liver failure prior to liver transplant.

Hepatic regeneration: current concepts and clinical implications.

Liver regeneration occurs as a result of hepatic tissue loss or injury. The process of liver regeneration is carefully regulated in a controlled biologic scheme with closely interactive relationships between hormones, free neurotransmitters, and nutrients; protooncogenes; and polypeptide and glycolipid growth factors. These relationships are now being studied at the molecular and cellular levels and attempts are being made to reconstruct the complete intricate process. Although significant breakthroughs have occurred in understanding the effects and regulation of several subsystems (such as insulin and its receptors; TGF-alpha and TGF-beta; HGF and its receptors), the integral process remains a mystery. Improved comprehension of the regeneration process will lead to rational treatment algorithms for now dreaded hepatic diseases.