Misleading lead: inflammatory pseudotumor of the mediastinum with digital clubbing.
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Child↗
Biomedical subjects
J Tovar
Publications and source records attributed to J Tovar.
Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass.
Familial hypercholesterolemia is the result of mutations in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL). In the homozygous form of the disease (HFHC), cellular LDL receptors either do not form, or, when present, cannot bond LDL and mediate its cellular uptake LDL, and the cholesterol that it transports accumulate in plasma, producing severe premature atherosclerosis and death from coronary artery disease usually before the age of 20. Currently, the only effective treatment is liver transplantation, which, alone or in association with medications, normalizes plasma cholesterol levels. The authors report the cases of 2 siblings with HFHC who underwent portocaval shunt at the ages of 2.5 and 1.5 years, respectively. Portocaval shunt produced an immediate, but insufficient decrease in cholesterol (by 40% and 35%, respectively), leaving them with cholesterol concentrations of about 500 mg/dL. One year later they each underwent ileal bypass without obtaining any significant response. Liver transplantation at the ages of 18 and 16 years, respectively, reduced plasma cholesterol concentrations to 129 and 225 mg/dL, respectively. The earlier operations seriously increased the technical difficulty of liver transplantation and did not produce a favorable effect on the natural course of the disease, so portocaval shunt and ileal bypass are not indicated in HFHC, not even for the purpose of delaying liver transplantation.
Adolescent↗
Rejecting family practice: why medical students switch to other specialties.
BACKGROUND AND OBJECTIVES: Medical schools have been encouraged to increase the number of primary care graduates. This study determined the proportion of medical students who change specialty preference during the clinical years and explored how ultimate choice is affected by perceptions of medical specialties acquired during this period. METHODS: A survey was mailed to 397 graduating medical students at the University of California, San Francisco (UCSF) after the National Resident Matching Program Match and before graduation in 1996, 1997, and 1998. RESULTS: The response rate was 81% (320/397). Of 41 respondents who reported that family practice had been their first specialty choice prior to beginning clinical rotations, only 15 (37%) eventually matched in family practice. Comparable numbers for internal medicine and pediatrics were 50% and 69%. Students rejecting family practice were more likely than their colleagues rejecting other specialties to cite insufficient prestige, low intellectual content, and concern about mastering too broad a content area as reasons. CONCLUSIONS: At UCSF, family practice retains fewer interested students than other primary care specialties. To reverse this trend, schools such as UCSF need to raise the prestige of family practice and counter concerns about its intellectual content being impossible to master.
Adult↗
[Kasai operation in the age of liver transplantation. Healing or merely palliative technique?].
AIM: To assess the results of portoenteroanastomosis (PEA) and liver transplantation (OLT) in extrahepatic biliary atresia (EHBA). METHODS: Out of a series of 148 EHBA, 92 cases primarily treated by us were selected. Survival with the native liver (end point = death or OLT) and its relationship with the age at PEA, type of EHBA, ductal size and bile flow restablishment were assessed. Patient survival was compared in those patients who had access to OLT when needed (Group I, n = 69) and those in whom only PEA was available (Group II, n = 23). (OLT program started in january 1986). RESULTS: At the end of follow-up, 32 children are alive with their native livers, 22 died and 38 had OLT. 40/85 patients who underwent PEA had complete restablishment of bile flow (47%). The no failure rate (survival of the native liver) at 1, 5, 10 and 20 years, was 91%, 49%, 38% and 21%, respectively. Bile flow restablishment was the only predictor significantly associated with good prognosis (survival of native liver at 5, 10 and 20 years of 89%, 86% and 51%, respectively). Differences in survival were significant (p < 0.001) between patients in groups I and II at 1 year (92% vs 74%), 5 years (78% vs 35%), 10 years (76% vs 30%) and 20 years (76% vs 30%). CONCLUSIONS: Bile flow restablishment after PEA can be obtained in experienced centers in about 50% of cases of EHBA. The combined and sequential use of PEA and OLT allows excellent long-term survival in EHBA.
Biliary Atresia↗
[Children with intestinal failure as candidates for intestinal transplantation].
Small bowel is not anymore considered a forbidden organ for transplantation, and intestinal transplantation (IT) is currently used as a therapeutic option in selected cases of permanent intestinal failure (PIF). Nevertheless, the experience is still scarce, and despite recent improvements, IT is nowadays only accepted as a life-saving option. However, small children are prone to suffer complications related to TPN, particularly end stage liver disease; moreover, suitable donor for the small baby who needs an IT is seldom available. Subsequently, a high pretransplantation mortality has been reported in the pediatric series. In those cases, the indication of IT shouldn't be delayed, and these children must be referred early for IT. Since we started our IT program, 17 children have been assessed, and 3 are currently on the waiting list; two for combined liver-small bowel transplantation (LSB), both with short bowel syndrome and end stage liver disease, and one patient with microuvillous dysplasia for isolated IT (indication loss of venous access). 3 children were referred too late and died, so did a fourth patient, candidate for LSB, before he could be transplanted.
Child↗
[Congenital fibrosarcoma. Diagnostic-therapeutic implications].
Most of the soft tissue sarcomas of childhood other than rabdomyosarcoma, have as final diagnosis fibrosarcoma, specially in the first months of life. Overlapping features between infantile myofibromatosis and congenital fibrosarcoma, hemangiopericytoma and fibrohistiocytoma have seen noted. Five patients with congenital fibrosarcoma were operated since 1991. Anatomical sites included lower limb, hand and forearm, and three of them had previous diagnoses of hemangiopericytoma, fibrohistiocytoma and myofibromatosis, with provocated non radical surgery and reoperation. The postoperative course was satisfactory and all are live one to eight years later. In our experience accurate histological diagnosis must be achieved to perform radical surgery on these cases.
Fibrosarcoma↗
The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica.
Ultrastructural analysis of Entamoeba histolytica reveals that this intestinal human pathogen lacks recognizable mitochondria, but the presence in its genome of genes encoding proteins of mitochondrial origin suggests the existence of a mitochondrially derived compartment. We have cloned the full-length E. histolytica gene encoding one such protein, chaperonin CPN60, and have characterized its structure and expression. Using an affinity-purified antibody raised against recombinant protein, we have localized native E. histolytica CPN60 to a previously undescribed organelle of putative mitochondrial origin, the mitosome. Most cells contain only one mitosome, as determined by immunofluorescence studies. Entamoeba histolytica CPN60 has an amino-terminal extension reminiscent of known mitochondrial and hydrogenosomal targeting signals. Deletion of the first 15 amino acids of CPN60 leads to an accumulation of the truncated protein in the cytoplasm. However, this mutant phenotype can be reversed by replacement of the deleted amino acids with a mitochondrial targeting signal from Trypanosoma cruzi HSP70. The observed functional conservation between mitochondrial import in trypanosomes and mitosome import in Entamoeba is strong evidence that the E. histolytica organelle housing chaperonin CPN60 represents a mitochondrial remnant.
Amino Acid Sequence↗
[Pediatric liver transplantation: now the patients are different and the problems are different as well].
AIM: 1. To show how in a program of pediatric liver transplantation (PLT) with 12 years of experience, the continuous use of technical innovations has allowed to improve the results and to treat the most complex cases. 2. To point out that when the immediate results of the transplant improve and the evolution time get longer, the late complications become the main source of concern. MATERIAL AND METHODS: The graft survival and the incidence of early surgical complications was compared between the first 100 PLT and the last 100 PLT (Total 235 PLT). The patients survival was also compared between the first and the last 5 years. In every case it was analyzed the age and weight of the children at the time of the transplant and the type of graft (full or reduced liver). The incidence of late complications in the global series was also analyzed, especially the posttransplant lymphoproliferative disease (PTLD) and the late biliary and vascular complications. RESULTS: There are significant differences between the first 100 PLT and the last 100 PLT in relation with the age of the patients (6.8 +/- 0.6 vs 4.2 +/- 0.5 years), the number of children younger than 1 year (4 vs 28), weight (22.4 +/- 1.2 vs 16.9 +/- 1.7 kg), number of PLT in children under 10 kg (7 vs 43), use of reduction techniques (7 vs 49), rate of hepatic artery thrombosis (12% vs 3%), and rate of early biliary complications (13% vs 4%). The 5 years survival of the graft was 51% in the first 100 PLT vs 65% in the last 100 PLT, and the 5 years patients survival was 70.1% in the first 5 years of the program vs 79.6% in the last 5 years. Among the late complications in the global series, 13 cases of PTLD (2 deaths) have special relevance, 6 cases of late anastomotic biliary stricture, 4 cases of portal stenosis, 1 arterial thrombosis, 1 death due to a fulminant sepsis and another death because of a colitis with multiple hepatic abscess. CONCLUSIONS: 1. The result of PLT improve, despite of the fact that in the last years the difficulty of the surgical procedures have increased (the patients are younger, with less weight and the reduction techniques are used more frequently). 2. The late complications have a significant influence in the prognosis, being that influence not completely established yet.
Age Factors↗
Chemical, physical and morphometric properties of Peruvian carrot (Arracacia xanthorrhiza B.) starch.
Starch was isolated from Peruvian carrot (PC)--or arracacha--(Arraccacia xanthorrhiza B.) roots. Its chemical, physical, physicochemical and granular structural properties were compared to those of commercial cassava starch. Scanning electron microscopy revealed a granular size for PC starch ranging between 4 and 26 microns in diameter, with spherical and truncated-egg shapes. PC and cassava starches were similar regarding gross chemical composition and basic physical characteristics but differed in pasting properties, with PC starch showing lower breakdown and consistency indices. The two starches also showed different water absorption and solubility patterns.
Daucus carota↗
Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival.
A trans-dominant mutational strategy was used to down-regulate trypanothione reductase (TR) activity levels in Leishmania donovani, the causative agent of visceral leishmaniasis in humans. TR, regarded as an ideal drug target against trypanosomatid infections, is a homodimeric flavoprotein oxidoreductase unique to these organisms that plays a central role in the enzymatic regeneration of the thiol pool. Extrachromosomal, heterologous expression of a trans-dominant mutant version of the Trypanosoma cruzi enzyme in L. donovani resulted in the formation of inactive cross-species heterodimers and in a dramatic decrease of endogenous TR activity levels. Recombinant cells depleted of up to 85% of TR activity were significantly impaired in their ability to regenerate dihydrotrypanothione from trypanothione disulfide following oxidation with diamide. Nonetheless trans-dominant mutant recombinants were still capable of maintaining a reduced intracellular environment during cell growth in culture and were able to metabolize hydrogen peroxide at wild-type rates in vitro. Importantly, however, cells expressing the trans-dominant mutant enzyme displayed a decreased ability to survive inside activated macrophages in a murine model of Leishmania infection. The apparent inability of Leishmania to modulate the expression of active TR homodimers in response to the expression of trans-dominant mutant protein suggests that specific inhibitors of this enzyme should be useful anti-leishmanial agents.
Animals↗
A mitochondrial-like chaperonin 60 gene in Giardia lamblia: evidence that diplomonads once harbored an endosymbiont related to the progenitor of mitochondria.
Diplomonads, parabasalids, as represented by trichomonads, and microsporidia are three protist lineages lacking mitochondria that branch earlier than all other eukaryotes in small subunit rRNA and elongation factor phylogenies. The absence of mitochondria and plastids in these organisms suggested that they diverged before the origin of these organelles. However, recent discoveries of mitochondrial-like heat shock protein 70 and/or chaperonin 60 (cpn60) genes in trichomonads and microsporidia imply that the ancestors of these two groups once harbored mitochondria or their endosymbiotic progenitors. In this report, we describe a mitochondrial-like cpn60 homolog from the diplomonad parasite Giardia lamblia. Northern and Western blots reveal that the expression of cpn60 is independent of cellular stress and, except during excystation, occurs throughout the G. lamblia life cycle. Phylogenetic analyses position the G. lamblia cpn60 in a clade that includes mitochondrial and hydrogenosomal cpn60 proteins. The most parsimonious interpretation of these data is that the cpn60 gene was transferred from the endosymbiotic ancestors of mitochondria to the nucleus early in eukaryotic evolution, before the divergence of the diplomonads and trichomonads from other extant eukaryotic lineages. A more complicated explanation requires that these genes originated from distinct alpha-proteobacterial endosymbioses that formed transiently within these protist lineages.
Amino Acid Sequence↗
HGPRT and APRT activities in hemolysates during the first year of life.
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Adenine Phosphoribosyltransferase↗
Long-term follow-up of patients with biliary atresia successfully treated with hepatic portoenterostomy. The importance of sequential treatment.
The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range 10.7-22.5 years; mean 15.4+/-0.7 years) treated with hepatic portoenterostomy (HPE) and jaundice-free for more than 10 years without liver transplantation (LT) is analyzed retrospectively. Eight of these patients subsequently required LT (age at LT 12. 8+/-0.5 years, range 10.5-15.2 years); 3 children (aged 11.6, 13.2 and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding associated with other signs of severe disease and are now candidates for LT; and among the 7 asymptomatic patients (age range 11.2-22.5 years; mean 15.9+/-2.1 years), 5 had sonographic and biochemical signs of moderate portal hypertension (PH). In order to analyze whether the age at transplantation influences the survival of children transplanted for BA, we also reviewed the outcome of 71 BA patients transplanted at our hospital between 1986 and 1996. All the children older than 10 years at the time of LT were alive; only patients younger than 10 years died following LT (n = 15). We conclude that the natural outcome of extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases successfully treated with HPE. In our experience, the results of sequential treatment with HPE and LT were excellent.
Adolescent↗
Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus.
Trypanothione reductase (TR), a flavoprotein oxidoreductase central to the unique thiol-redox system that operates in trypanosomatid protozoa, has been proposed as a potential target for the chemotherapy of trypanosomatid infections. In this study, targeted gene replacement was used to obtain evidence that TR is an essential cellular component and that its physiological function is crucial for parasite survival. Precise replacement of the Leishmania donovani tryA gene encoding TR was only possible upon simultaneous expression of the tryA coding region from an episome; in its absence, attempted removal of the last tryA allele invariably led to the generation of an extra copy of tryA, seemingly as a result of selective chromosomal polysomy. Partial replacement mutants were drastically affected in their ability to survive inside cytokine-activated macrophages in a murine model of Leishmania infection. As no compensatory mechanism for the partial loss of TR activity was observed in these mutants and as it was not possible to obtain viable Leishmania devoid of TR catalytic activity, specific inhibitors of this enzyme are likely to be useful anti-leishmanial agents for chemotherapeutic use.
Animals↗
Reduced-size lung transplantation from adult to neonatal swine.
BACKGROUND: Lung donor shortage is a critical factor limiting the expansion of pediatric lung transplantation programs. This report details the surgical technical feasibility of a training model of lobar lung transplantation as well as the perioperative monitoring to evaluate the appropriate pulmonary graft function. METHODS: Ten hybrid Large-White pigs underwent left lower lobe lung allotransplantation; Donors weighed 15 to 20 kg and recipients 5 to 7 kg. The first five animals were used to learn the surgical anatomy and to establish the surgical technique and instrumentation's model (Group A). One hour after transplantation the right lung was excluded. Lung function and hemodynamic data were collected sequentially in the following five animals (Group B). RESULTS: The left inferior pulmonary lobe was found to be the most suitable allograft for transplantation. Usually, bronchial size discrepancy allowed telescoping of the airway anastomosis. Left atrial clamping was well tolerated during the pulmonary vein anastomoses. Preoperative antiaggregation and postoperatively heparinization achieved with ACT values over 200 seconds, prevented left atrial thrombosis. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics were also modified, with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: The neonatal pig tolerates left lobar pulmonary transplantation satisfactorily. Although it is a useful and promising surgical learning model, questions remain regarding the applicability of this experience to clinical pediatric lung transplantation.
Animals↗
Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages.
Parasitic protozoa belonging to the order Kinetoplastida contain trypanothione as their major thiol. Trypanothione reductase (TR), the enzyme responsible for maintaining trypanothione in its reduced form, is thought to be central to the redox defence systems of trypanosomatids. To investigate further the physiological role of TR in Leishmania, we attempted to create TR-knockout mutants by gene disruption in L. donovani and L. major strains using the selectable markers neomycin and hygromycin phosphotransferases. TR is likely to be an important gene for parasite survival since all our attempts to obtain a TR null mutant in L. donovani failed. Instead, we obtained mutants with a partial trisomy for the TR locus where, despite the successful disruption of two TR alleles by gene targeting, a third TR copy was generated as a result of genomic rearrangements involving the translocation of a TR-containing region to a larger chromosome. Mutants of L. donovani and L. major possessing only one wild-type TR allele express less TR mRNA and have lower TR activity compared with wild-type cells carrying two copies of the TR gene. Significantly, these mutants show attenuated infectivity with a markedly decreased capacity to survive intracellularly within macrophages, provided that the latter are producing reactive oxygen intermediates.
Animals↗
A single locus minisatellite sequence which distinguishes between Trypanosoma brucei isolates.
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Alleles↗
Extrachromosomal, homologous expression of trypanothione reductase and its complementary mRNA in Trypanosoma cruzi.
Trypanothione reductase (TR), a flavoprotein oxidoreductase present in trypanosomatids but absent in human cells, is regarded as a potential target for the chemotherapy of several tropical parasitic diseases caused by trypanosomes and leishmanias. We investigated the possibility of modulating intracellular TR levels in Trypanosoma cruzi by generating transgenic lines that extrachromosomally overexpress either sense or antisense TR mRNA. Cells overexpressing the sense construct showed a 4-10-fold increase in levels of TR mRNA, protein and enzyme activity. In contrast, recombinant T.cruzi harbouring the antisense construct showed no significant difference in TR protein or catalytic activity when compared with control cells. Although increased levels of TR mRNA were detected in some of the antisense cells neither upregulation nor amplification of the endogenous trypanothione reductase gene (tryA) was observed. Instead, a proportion of plasmid molecules was found rearranged and, as a result, contained the tryA sequence in the sense orientation. Plasmid rescue experiments and sequence analysis of rearranged plasmids revealed that this specific gene inversion event was associated with the deletion of small regions of flanking DNA.
Animals↗