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Biomedical subjects

M Ribeiro

Publications and source records attributed to M Ribeiro.

At least 19 recordsLinked to original sources
PubMed2001

Microencapsulation and tissue engineering as an alternative treatment of diabetes.

In the 70's, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.

Biocompatible Materials↗
PubMed2001

Proteins linked to a protein transduction domain efficiently transduce pancreatic islets.

The resounding success of a new immunosuppressive regimen known as the Edmonton protocol demonstrates that islet cell transplantation is becoming a therapeutic reality for diabetes. However, under the Edmonton protocol, a single donor does not provide enough islets to attain the insulin independence of a transplant recipient. This limitation is mainly caused by islet apoptosis triggered during isolation. In this study, we describe a highly efficient system of transiently transferring anti-apoptotic proteins into pancreatic islets, thus opening an exciting new therapeutic opportunity to improve the viability of transplantable islets. We fused beta-galactosidase to the 11-amino acid residues that constitute the protein transduction domain (PTD) of the HIV/TAT protein and transduced pancreatic islets ex vivo with this fusion protein in a dose-dependent manner with >80% efficiency. We observed that transduction of the anti-apoptotic proteins Bcl-X(L) and PEA-15 fused to TAT/PTD prevented apoptosis induced by tumor necrosis factor-alpha in a pancreatic beta-cell line, indicating that TAT/PTD anti-apoptotic proteins retained their biological activity. Finally, we demonstrated that TAT-fusion proteins did not affect the insulin secretion capability of islets, as determined by glucose static incubation and by reversion of hyperglycemia in diabetic immunodeficient mice.

Animals↗
PubMed2000

Considerations of nonconvulsive status epilepticus.

The original concepts of absence status (AS) and complex partial status (CPS) are critically reviewed. This review has been prompted by a modern concept of nonconvulsive status epilepticus (NCSE), portrayed as a rather common condition occurring chiefly in the critically ill elderly with high morbidity and mortality. This new view is a striking departure from the original concepts of AS and CPS as rare protracted epileptic events occurring usually in temporarily confused but otherwise satisfactorily healthy and ambulatory patients. This new trend appears to have been caused by a misinterpretation of EEG findings: prominent generalized spike activity is in reality the expression of a very severe encephalopathy rather than of NCSE, most often caused by an anoxic episode. The role of EEG is emphasized but a valuable interpretation depends on an expert integration of EEG and clinical data. A brief discussion of epileptic twilight states further stresses the difficult differential diagnosis.

Brain↗
PubMed1999

Use of the breast implant for liver graft malposition.

Transplantation of a small liver into a large patient may cause problems with correct reperfusion of the graft because of torsion of the hepatic pedicle, leading to malfunction of the transplanted organ. We describe the case of a 60-year-old man with alcoholic cirrhosis and hepatitis B virus who received a small-sized liver graft. Owing to the lack of adequate reperfusion of the transplanted organ arising from pedicular kinking caused by disparate sizes, a breast implant was placed behind the graft as a means of support, thereby resolving the problem. The use of prosthetic materials for the correct placement of grafts with size incongruity is also discussed, and the literature is reviewed.

Breast Implants↗
PubMed1999

Possible role of systemic inflammatory reaction in vascular access thrombosis.

BACKGROUND: Vascular devices are an integral part of modern medicine. Catheter thrombosis is a frequent complication that interferes with their use. METHOD: We have observed a series of patients in whom vascular access thrombosis occurred in close temporal association with infectious or inflammatory processes. RESULTS: Laboratory and clinical evidence suggests that activation of the coagulation system may be triggered by certain infectious or inflammatory disorders. Patients with vascular devices are prone to infections that could lead to a transient hypercoagulable state. CONCLUSIONS: We are proposing that infections or other inflammatory processes may be involved in some vascular access thrombotic events. On the basis of our observations, we believe further studies are warranted regarding a possible association between infections or inflammatory disorders and vascular devices thrombosis. If an association is proven to exist, patients with vascular devices and infectious or inflammatory processes may be candidates for short-term anticoagulation during acute episodes of infection or inflammation.

Adult↗
PubMed1999

3,5,3'-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity.

To investigate the role of type II 5'-deiodinase (5'D-II) in the expression of mitochondrial uncoupling protein (UCP) in brown adipose tissue (BAT), we injected intact male rats with reverse (r) 3,5,3'-triiodothyronine (T3; 100 micrograms. 100 g body wt-1. day-1), an inhibitor of 5'D-II, for 2-5 days. UCP decreased by approximately 20% in rats kept at 28 degreesC and failed to increase during cold exposure (4 degreesC). Next, thyroxine treatment (1-10 micrograms. 100 g body wt-1. day-1) increased nuclear T3 in rats kept at 28 or 4 degreesC. In these rats, nuclear T3 correlated positively with UCP. In addition, T3 (1-50 micrograms. 100 g body wt-1. day-1) given to intact rats (5-15 days; 28 degreesC) induced an approximately twofold increase in UCP. In these T3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T3 induction of UCP (approximately 1.8- and approximately 2.3-fold). The results emphasize the importance of local 5'D-II and reveal an independent role of T3 in the expression of UCP.

Adipose Tissue, Brown↗
PubMed1999

Mixed-type encephalopathies: preliminary considerations.

This preliminary report deals with a polyetiological and pathophysiologically multifacted encephalopathy that is fairly common and yet in need of identification as a clinical (but not nosological) entity: Mixed-Type Encephalopathy (MTE). MTE is a mostly acute condition, characterized by change of mentation (confusion, delirium, etc.) with little or no neurological deficit but with impressive diffuse EEG slowing. A variety of medical conditions lead to MTE, especially at an age above 50 years, but status-post-surgery (leaving aside cranial neurosurgery, but also cardiac surgery in view of common embolic cerebral pathology) may also result in MTE, especially with the use of general anesthesia. An attempt is made to analyze the plethora of contributory factors and underlying pathophysiological mechanisms. All types of classical brain pathology such as strokes, meningitis-encephalitis and typical metabolic encephalopathies (hepatic, renal, etc.) and others must be excluded from the diagnosis of MTE. Special emphasis is being placed on behavioral and EEG criteria in the early state of impaired consciousness with subdivision into 4 types: obtundation, somnolence, morbid lethargy and delirium. Cases of MTE are best picked up by an interdepartmental consultation (liaison) service making use of neurological consultations and EEG assessment. The value of the latter cannot be overestimated in these cases, especially in view of the very limited contributions of neuroimaging methods. The prognosis tends to be good. Severe and fatal developments are usually due to intervening cerebral hypoxia or anoxia. In such a development, epileptic manifestations, which are usually absent or mild in MTE, can become quite prominent. A thorough multi-institutional and international study of MTE is already in the planning stage. It is hoped that preventive measures can minimize the cerebral complications.

Acute Disease↗
PubMed1999

Slow sharp waves.

Slow sharp waves (SSHW) are of longer duration (around 200 msec and longer) than typical sharp wave discharges (70 to 200 msec). This pattern is not merely of academic interest, as the electroclinical correlation showed that SSHW were found in 23 patients, mostly above age 50 years, with serious illnesses of various etiologies. Epileptic seizures occurred in a minority of the cases. The electrophysiological basis remains unclear and there is no answer to the question, "what causes the relatively long duration of these discharges?"

Adolescent↗
PubMed1998

[Hepatocellular carcinoma associated to porphyria cutanea tarda and hepatitis C virus infection without cirrhosis].

The molecular basis of porphyria cutanea tarda is defective activity of hepatic uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C virus markers has been demonstrated. We study a patient with PCT and hepatitis C virus markers that finally develops to hepatocellular carcinoma without previous cirrhosis. Previous studies with association of PCT and hepatitis C virus markers, have found liver diseases ranging from cirrhosis to hepatocellular carcinoma. The importance of this study is the absence of cirrhosis.

Carcinoma, Hepatocellular↗
PubMed1997

Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer.

Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.

Age Factors↗
PubMed1997

Isolated limb perfusion with fotemustine after chemosensitization with dacarbazine in melanoma.

Isolated limb perfusion (ILP) has been reported as the most effective treatment for localized recurrent melanoma of the limbs. In terms of local and regional control with melphalan, complete remission is achieved in about 40% of patients, with frequent toxicity causing significant short-term disability in many and long-term incapacity in a few. Since 1989, several studies have reported success using a combination of fotemustine and dacarbazine (DTIC) in the systemic treatment of disseminated melanoma and brain metastasis. In May 1995, we began a pilot study with systemic DTIC 400 mg/m2 given intravenously about 4 h before ILP using fotemustine in an intra-arterial bolus of 100-150 mg/m2 as the perfusion agent. By July 1996, 10 patients had been included in the study. The results were evaluated in terms of the response rate (five complete responses and one partial response in the six patients who could be evaluated), local toxicity (nine patients with level I and one with level II, measured on the Wieberdink scale) and systemic toxicity (nine patients with level 0 and one with level 1, measured on the World Health Organization scale). Treatment was effective, with a similar response rate to that obtained with melphalan but with much lower toxicity, so this protocol may represent an innovation in loco-regional therapy and should be further investigated in a large trial.

Adult↗
PubMed1996

Carcinoma of the rectum. Possible cellular predictors of metastatic potential and response to radiation therapy.

BACKGROUND: Preoperative radiation therapy can markedly improve local control of rectal carcinoma. However, some tumors do not respond well to moderate doses of preoperative radiation and would be better served by more aggressive preoperative treatment (e.g., chemoradiotherapy). Cellular predictors of responsiveness to radiation can help to select lesions for more aggressive treatment. In addition, there is a need for cellular predictors of metastatic potential. This is particularly important in the setting of preoperative radiation-downstaging by preoperative treatment can obscure the true pathologic stage of a tumor and confound the usual selection criteria for postoperative chemotherapy. PURPOSE: This study was undertaken to determine if proliferating cell nuclear antigen (PCNA), p53, DNA ploidy, and S-phase fraction are associated with response to radiation and/or risk for distant metastatic disease and to determine if these cellular markers are best evaluated from preradiation biopsy specimen or the larger (but possibly altered) final surgical specimen. MATERIALS AND METHODS: Archival specimens from 23 cases of ultrasound T3 or T4 rectal carcinoma treated preoperatively with radiation therapy were reviewed. Eligible lesions had preradiation biopsy specimens of sufficient size for flow cytometric review of archival tissue. Factors considered included PCNA positivity, presence of mutant nuclear p53, more than 30 percent tumor cells in S-phase, and presence of aneuploidy. RESULTS: With a median follow-up of three years, overall freedom from relapse was 83 percent, with all but one failure being extrapelvic. PCNA positivity in the preradiation specimen was significantly (P = 0.025) associated with a greater risk of tumor recurrence. In addition, there was a trend to greater likelihood of "probable downstaging" (defined as surgical T stage less than preradiation ultrasound T stage) for lesions that were PCNA-negative or lesions with normal p53. Biomarkers measured in the postradiation surgical specimen were not associated with either freedom from relapse or response to radiation. Radiation treatment appeared to produce false-negatives in the final specimen. Thus, there were significantly more specimens converting from PCNA-positive to PCNA-negative after preoperative radiation than would be expected solely on the basis of sampling errors (P = 0.004). Similar results were found for abnormal p53 findings (P = 0.02). CONCLUSIONS: Prospective studies of biomarkers should be based on pretreatment specimens if preoperative radiation is given. For carcinoma of the rectum, PCNA and p53 may be useful predictors of both metastatic potential and responsiveness to radiation.

Adenocarcinoma↗
PubMed1996

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group.

Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2 x 500 mg/m2/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m2/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30-74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML.

Adolescent↗
PubMed1996

[Shunt surgery versus disconnection in portal hypertension. A comparative study].

Controversy remains about the best treatment for patients with esophagogastric variceal bleeding. In spite of different therapeutic alternatives and recent progress, such as liver transplantation of TIPS, many patients will finally be treated by standard surgery. With the aim to know the results of surgery in shunting vs non-shunting procedures, we have analyzed a recent and consecutive series of 68 cirrhotics patients operated on for variceal hemorrhage. According to the surgical technique there were three groups: I) 30 patients underwent a total portacaval shunt; II) 18 cases with an azygosportal disconnection; III) 20 patients with a partial portacaval shunt (8-10 mm H-portacaval PTFE graft). All groups were homogeneous considering age, sex etiology, Child-Pugh grade and timing of surgery (elective vs urgent). The complications and mortality rates were similar for the three groups. The overall operative mortality was 10%, and 5% in selected cases (Child-Pugh A-B, non urgent cases). With a follow-up for I, II and III group of 47, 44 and 27 months respectively, chronic encephalopathy have been seen in 61%, 15% and 15% respectively (p < .05). No patient in group I has rebled, and only one case in the II and III groups had a recurrence of hemorrhage. The actuarial three years survival was 76%, 86% and 85% (p NS), and the five year survival was 41% vs 86% for the groups I and II respectively (p < .05). In conclusion, in selected cases, surgery gives excellent immediate and long term results. In patients with variceal bleeding and failure of first line treatments, such as sclerosis or pharmacology, the partial H-portacaval shunt and non-shunting procedures are good alternatives, with low incidence of rebleeding and chronic encephalopathy.

Adult↗
PubMed1995

IL-6 upregulates protein S expression in the HepG-2 hepatoma cells.

Several pro-inflammatory cytokines have been shown to be important in the modulation of the procoagulant response. However, what role these cytokines may have in the regulation of coagulation inhibitors is poorly understood. While the hepatocyte is a primary site of synthesis for the anticoagulant protein C and S, it is also a major target cell for the proinflammatory cytokine, IL-6. We have found that stimulation of HepG-2 hepatoma cells with IL-6 (5 ng/ ml) significantly increased the production of the anticoagulant cofactor, protein S, in both a time and dose dependent fashion. This increase was seen at both the RNA and protein level. A mouse monoclonal neutralizing antibody to human IL-6 suppressed the IL-6 effect in a concentration dependent fashion. IL-6 also increased the release of the C4b-binding protein but had no effect on protein C production. When combined with either dexamethasone or soluble IL-6 receptor, the IL-6 response was significantly enhanced. Oncostatin M, a functionally related cytokine, had a similar effect while other related cytokines, IL-11 and leukemia inhibitory factor, only had a marginal effect. IL-1, TGF-beta, and TNF-alpha had no significant effect on protein S production. These results indicate that IL-6 may play an important regulatory role in the anti-coagulant pathway.

Animals↗
PubMed1994

Imaging methods in the study of urinary tract infections in children.

UNLABELLED: When studying a child with urinary tract infection it is important to detect and localize any renal (scar) or urologic anomaly. Here we study the information obtained using: renal and vesical ultrasound (US), DMSA scan and radiologic or isotopic cystogram. METHODS: We studied 148 children with more than one urinary infection and/or pyelonephritis; their mean age was 35.9 months (1-148 months); 55% were girls. The three diagnostic examinations--US, DMSA scan and cystogram were made in this order; the DMSA scan or cystogram was never made sooner than one month after the UTI. RESULTS: In 42% of the children the three exams were normal; 4 of these children had another UTI and the urodynamic study revealed vesical disfunction. 11% had renal scars (DMSA scan) with normal US and cystogram; 30% had VUR, 50% of which had an altered US and 57% had renal scars on the DMSA scan. 12% of the children had an altered US with a cystogram showing no VUR; 66% of these had renal scars. 4% had vesical anomalies in the US and cystogram. CONCLUSION: The three exams chosen were able to direct the diagnostic approach of UTI, being sufficient in most of the cases. We would like to emphasize the importance of the DMSA scan in diagnosing unsuspected renal scars.

Acute Disease↗
PubMed1994

[Endoscopic-pathologic correlation of rectocolonic lesions less than 10 mm].

Ninety eight rectocolonic lesions up to 10 mm in diameter found in 50 patients were analyzed. The relationship between endoscopic and pathologic diagnosis was established. Emphasis was made on the detection of adenomas based in the following: Yamada III or IV lateral vision, Yamada I and II with smooth but erythematous surface, and in pale with irregular surface lesions. The sensitivity of the method was 92% and the specificity was 72% for adenomas. Six percent of adenomas were pale, with mucous hypersecretion on histopathology, and can be mistaken for hyperplastic polyps. This mucous hypersecretion correlates with low grade dysplasia, which supposedly indicates a lower evolutive risk.

Adenoma↗