Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.     

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

ASSESSMENT OF THE PREVALENCE INDEX ON SIGNS OF COMBINATION SYNDROME IN PATIENTS TREATED AT BAURU SCHOOL OF DENTISTRY,UNIVERSITY OF SAO PAULO

A group of destructive changes occurring in jaws in patients with maxillary complete dentures and mandibular removable partial dentures (bilaterally) has been described in the literature as the combination syndrome. However, this condition is not clinically observed in all patients. The aim of this study was to establish the prevalence index on signs of combination syndrome and to verify whether these changes also occurred in patients rehabilitated with a mandibular removable partial denture (unilaterally). Sample was composed of 44 patients, completely edentulous in the maxilla. Thirty-two patients had a Kennedy Class I removable partial denture and 12 a Kennedy Class II. Three major alterations were observed in 20.5% of the studied population. Nevertheless, these changes were present only in 25% of patients with Kennedy Class I removable partial denture. Based on the findings of this study, it can be concluded that patients with Kennedy Class II removable partial denture do not have similar signs that lead to the combination syndrome’s condition.     

Catatonia in obsessive-compulsive disorder: etiopathogenesis, differential diagnosis, and clinical management.

OBJECTIVE: We describe the case of a patient who developed an episode of catatonia during the course of her life-long obsessive-compulsive disorder (OCD) and discuss issues related to the etiopathogenesis, differential diagnosis, and therapeutic management of this association. BACKGROUND: Catatonia is conventionally considered a heterogeneous syndrome of motor dysregulation characterized by mutism, immobility, negativism, posturing (catalepsy), stereotypies, and echophenomena. The relationship between OCD and catatonia is still misunderstood and poses significant challenges to the diagnosis and treatment of patients with both conditions. METHOD: Naturalistic follow-up of a single case. RESULTS: A patient with OCD developed catatonia in concert with deteriorating mood, thought, and behavior. This atypical clinical presentation of individuals with OCD and the list of differential diagnosis raised during the patient's clinical assessment are discussed on 3 different levels: symptomatic presentation, comorbidity pattern, and pharmacodynamic mechanisms involved. CONCLUSIONS: The development of a systematic therapeutic plan for patients with OCD and comorbid catatonia includes: the fine-tuning of the antiobsessional treatment; management of comorbid disorders that may engender catatonia; prompt discontinuation, and subsequent slow reintroduction of drugs deemed to trigger toxic reactions or to worsen comorbid disorders and, ultimately, the catatonia; and the implementation of specific anticatatonia measures.     

Vertebral compression fracture as a presenting feature of acute lymphoblastic leukemia in children

Twenty-four (1.6%) of 1466 children with acute lymphoblastic leukemia (ALL) treated at St. Jude Children's Research Hospital had vertebral compression fractures at diagnosis. When compared with patients without this complication, they were more likely to have good prognostic features, including a leukocyte count of greater than 25 X 10(9)/l, a leukemic cell DNA index of greater than 1.15, and hyperdiploidy (greater than 50 chromosomes). Complete remission of ALL was induced in all patients, and symptoms of vertebral compression fractures abated following antileukemia therapy. Although the diagnosis of ALL was delayed for some patients because this unusual presenting complication was not recognized as such, their treatment outcome was as good as that for other children with "standard-risk" ALL.     

Gastrointestinal disorders in Down syndrome

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10‐year follow‐up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow‐up as well as adequate development and greater quality of life for patients with Down syndrome and their families.     

Lactobacillus johnsonii La1 attenuates Helicobacter pylori-associated gastritis and reduces levels of proinflammatory chemokines in C57BL/6 mice

In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P=0.038) and neutrophilic (P=0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P=0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P=0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.     

Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity

Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK.     

Fibrinolytic system of the armadillo <Emphasis Type="Italic">Chaetophractus villosus</Emphasis> (Xenarthra,Dasypodidae)

The fibrinolytic mechanism in the armadillo Chaetophractus villosus (Mammalia, Xenarthra, Dasypodidae) quite unknown until now was studied. Results were compared with those corresponding to healthy adult human beings. Whole blood lysis time and diluted blood lysis time were not detectable in armadillos. Euglobulin clot lysis time and plasminogen activity (Plg) were lower than in healthy humans. We established the presence of the fibrinolytic system in Ch. villosus through the measurement of fibrin fibrinogen degradation products. The activity of the plasminogen activator inhibitor was two to four times greater than in healthy humans. The activity of the alpha 2 anti-plasmin (α2AP) was similar and displaced toward lower values. The Plg/α2AP relation was lower. The results obtained suggest that Ch. villosus has a hypercoagulable and hypofibrinolytic profile. Our findings are not only the first contribution to elucidate the physiology of the fibrinolytic system in Xenarthra but also contribute to develop an animal model for studies in haemostasis and thrombosis.