Implications for adulthood and therapeutic optimization in diabetes mellitus.
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Biomedical subjects
Publications and source records attributed to M J Lopez.
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INTRODUCTION: The effectiveness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in patients with advanced hepatocellular carcinoma is controversial. AIM: Our goal was to assess the outcomes of patients with advanced hepatocellular carcinoma treated with chemotherapy after liver transplant. METHODS: Ten patients with liver transplants performed between 1993-2002 were men of mean age 55 years. The etiology of cirrhosis was hepatitis C in four patients, alcoholic cirrhosis in four, and cryptogenic cirrhosis in two. Immunosuppressive therapy was cyclosporine in five patients and tacrolimus in five. The chemotherapy regimen used adriamycin (20 mg/m2 weekly for 20 weeks). Six patients were stage IVA and four stage III. Hepatocellular carcinoma was known in five patients and incidental in the other five. Pathology revealed well-differentiated hepatocellular carcinoma in six patients and moderately differentiated hepatocellular carcinoma in four. Five patients had vascular invasion. RESULTS: After a mean posttransplant follow-up of 28 months, six patients (60%) were alive without tumor recurrence, three (30%) had died from tumor recurrence and one due to P. carinii pneumonia. Disease-free survival among patients with stage III was 50% and 80% for stage IVA. Three patients with vascular invasion died of tumor recurrence, and the other two are alive and free of disease. Disease-free survival rates were 83% in patients with well-differentiated hepatocellular carcinoma and 25% in those with moderately differentiated hepatocellular carcinoma. Tolerance of chemotherapy was good with two withdrawals due to nephrotoxicity and myelotoxicity and one death from pneumonia. CONCLUSION: The use of adriamycin in patients undergoing liver transplant due to advanced hepatocellular carcinoma may be useful to prevent tumor recurrence; it is well tolerated. The presence of vascular tumor invasion and a lower grade of histologic differentiation were associated with a poor prognosis.
AIMS: Characterization of the exopolysaccharide produced by Azotobacter vinelandii grown on 4-hydroxybenzoic acid (EPS I), and the comparison between this exopolysaccharide and commercial alginate, constituted the main objective of this work. METHODS AND RESULTS: Total carbohydrates, uronic acids, acetyl and pyruvyl groups and proteins were determined by colorimetric methods and composition was confirmed by Nuclear Magnetic Resonance studies. Rheological properties were analysed under different physical and chemical conditions. Results showed differences between EPS I and commercial alginate, in relation to both composition and viscosity. Higher amount of guluronnosyl residues were found in EPS I, whereas commercial alginate contained the same proportion of mannuronosyl and guluronnosyl residues. In accordance with this result, EPS I gave rise to solutions of higher viscosity than commercial alginate, although solutions of this polysaccharide showed greater stability when conditions were altered. CONCLUSIONS: The exopolysaccharide produced by A. vinelandii grown on 4-hydroxybenzoic acid showed a different composition in comparison with commercial alginate, which leads to higher viscosity values for the aqueous solutions of EPS I. SIGNIFICANCE AND IMPACT OF STUDY: This work describes for the first time the characteristics of an exopolysaccharide produced by A. vinelandii from 4-hydroxybenzoic acid, a substrate rarely used as sole carbon source.
The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.
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Post-transplant lymphoproliferative disease remains a complication with a high morbidity and mortality. The present study examined 291 pediatric liver transplants performed in 263 children from October 1984 to December 1999. Post-transplant lymphoproliferative disease has an overall incidence of 12%. Tacrolimus and cyclosporine had a similar incidence of post-transplant lymphoproliferative disease. Fifty-six per cent of patients who developed post-transplant lymphoproliferative disease were Epstein-Barr virus negative at the time of transplantation. Mean time of conversion to Epstein-Barr virus positivity was 1.1 years after liver transplantation. Ten per cent of those who developed post-transplant lymphoproliferative disease never had Epstein-Barr virus detected. Mean time from Epstein-Barr virus positivity to detection of post-transplant lymphoproliferative disease was 2.68 years, and 3.13 years from liver transplantation (OLTx) to post-transplant lymphoproliferative disease. There was a 35% incidence of mortality. Deaths occurred a mean of 0.76 years after diagnosis of post-transplant lymphoproliferative disease. Most cases of post-transplant lymphoproliferative disease had extranodal location. There was one recurrence in 10% of patients, and two in 3%. All recurrent cases were seen in recipients who became Epstein-Barr virus positive after transplantation. There has been a decrease in the incidence of post-transplant lymphoproliferative disease from 15% to 9% to 4%. Post-transplant lymphoproliferative disease should be diagnosed promptly and treated aggressively. The best treatment, however, seems to be prevention, starting in the immediate postoperative period. Survivors should be monitored for both recurrence of post-transplant lymphoproliferative disease and acute cellular rejection.
PURPOSE: To evaluate the effect of monopolar radiofrequency energy (RFE) on intact and lacerated meniscal tissue. TYPE OF STUDY: In vitro study. Application of monopolar RFE to soft tissue for treatment of various musculoskeletal disorders has been explored recently, although its effect on meniscal tissue has not been critically evaluated. Monopolar RFE denatures and fuses collagen. Given that menisci are composed primarily of type I collagen, we proposed that RFE could be applied to meniscal tears with minimal effect on healthy meniscal tissue. METHODS: Adult sheep menisci were given 1 of 2 treatments (65 degrees C, 15 W or 75 degrees C, 10 W) with a monopolar RFE generator. Specimens were processed for scanning electron microscopy (SEM), transmission electron microscopy (TEM), light microscopy, and confocal laser microscopy. A computer-based area-determination program was used to calculate the treated area in confocal laser images. RESULTS: SEM changes in treated tissue consisted of surface smoothing with collagen fibril fusion. Changes apparent with TEM included tissue homogenization with loss of cross-striations and fusion of collagen fibrils. Histologic changes consisted of fusion and loss of collagen fiber individualization, pyknosis of fibrochondrocyte nuclei, and loss of lacunae surrounding fibrochondrocytes. There were clear demarcations between treated and untreated tissue with both treatments. There were no discernible differences between treatment groups on SEM, TEM, or histologic examination. Confocal laser microscopic evaluations showed distinct treatment areas. The mean area affected ranged from 6.6% for 65 degrees C, 15 W to 8.8% for 75 degrees C, 10 W. CONCLUSIONS: The primary effects of monopolar RFE treatment of menisci in this study were consistent with thermal tissue damage limited to the treatment area. Monopolar RFE treatment of a meniscal laceration may stabilize the tear by fusing collagenous tissue in the surrounding area and prevent propagation along tissue lines. This study presents preliminary in vitro results. Further studies are necessary before clinical applications can be recommended.
OBJECTIVE: To determine risk factors for development of sequestra in cattle and identify factors associated with a successful outcome. DESIGN: Retrospective study. ANIMALS: 110 cattle. PROCEDURE: Medical records of cattle treated at veterinary teaching hospitals in North America were reviewed. To determine risk factors for osseous sequestration, breed, age, and sex of cattle with osseous sequestration were compared with breed, age, and sex of all other cattle admitted during the study period. RESULTS: 110 cattle were included in the study. Three had 2 sequestra; thus, 113 lesions were identified. Most sequestra were associated with the bones of the extremities, most commonly the third metacarpal or third metatarsal bone. Ninety-two animals were treated surgically (i.e., sequestrectomy), 7 were treated medically, 3 were initially treated medically and were then treated surgically, and 8 were not treated. Follow-up information was available for 65 animals treated surgically and 6 animals treated medically. Fifty-one (78%) animals treated surgically and 5 animals treated medically had a successful outcome. Cattle that were 6 months to 2 years old had a significantly increased risk of developing a sequestrum, compared with cattle < 6 months old. Cattle in which sequestrectomy was performed with the aid of local anesthesia were significantly more likely to undergo 2 or more surgical procedures than were cattle in which sequestrectomy was performed with the aid of general anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sequestrectomy will result in a successful outcome for most cattle with osseous sequestration.
Radiofrequency energy may provide a relatively noninvasive method to stabilize joints with excessive laxity by thermally shrinking redundant joint capsular tissue. The authors determined the percentage of shrinkage associated with five radiofrequency treatment temperatures and evaluated the effect of this energy on the structural properties of joint capsular tissue in vitro. First, 36 adult sheep femoropatellar joint capsular specimens were treated with one of five treatment temperatures (n = 6 per group) or served as a control to determine tissue shrinkage. An additional 24 specimens were treated with three temperatures that resulted in different shrinkage: 45 degrees C, 65 degrees C, and 85 degrees C. Tissue stiffness, relaxation, and failure strength were determined for each specimen (n = 6 per group). Tissue shrinkage was correlated significantly with treatment temperature. There was a significant decrease in tensile stiffness in the 65 degrees C and 85 degrees C treatment groups. There were no significant differences between stress relaxation before treatment and after treatment. Relaxation properties after treatment were not different from each other or from control values either normalized to pretreatment values or expressed as raw data. Failure strength was not affected significantly at any temperature.
The objective was to evaluate the ability of mixed rumen microbes to synthesize isopropanol from acetone or 3-D-hydroxybutyrate. Rumen fluid from seven mature, nonpregnant, dry Holstein cows was incubated with starch or cellulose and additions of acetone, 3-D-hydroxybutyrate, or saline. Rumen fluid was analyzed for isopropanol after 0, 3, 6, and 9 h. No isopropanol was present in any sample at 0 h, and none was present in incubations containing saline or 3-D-hydroxybutyrate at any subsequent time. Incubations that included acetone produced small amounts of isopropanol from 0 to 3 and 3 to 6 h and significantly larger amounts from 6 to 9 h. With starch as the energy substrate, production from 6 to 9 h was 3.8 micromol/min per liter of rumen fluid and 3.7 micromol/min per liter with cellulose as the energy substrate; however, these values did not differ significantly. Mixed rumen microbes could synthesize isopropanol from acetone but not from 3-D-hydroxybutyrate, and rumen microbial metabolism of acetone was the likely source of plasma isopropanol seen in ketotic ruminants.
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A review of the history, indications, basic technique, end results, and complications of exenterative surgery for pelvic neoplasms is provided. The authors discuss their broad personal experience with the operation. Much of this experience evolved from work at Barnes Hospital and the Ellis Fischel State Cancer Hospital. The techniques are applicable to advanced neoplasms of the cervix uteri, scrotum, urinary bladder, and other, less frequent neoplasms still confined to the pelvis.
We report on a term infant with a severe fetomaternal hemorrhage that caused a serious anemia that was surmounted after several transfusions. After the initial complications, such as persistent pulmonary circulation, severe anemia and thrombocytopenia, the outcome was good. We discuss the importance of a long-term follow-up of affected children, as well as their mothers. No clear parameters for a real prognosis are available. A follow-up is needed in order to detect possible complications in neurological development.
A 24-hour-old cria was admitted for evaluation of stranguria evident shortly after birth. On physical examination, the prepuce appeared to be normally formed and small drops of fluid dripped from it as the cria strained to urinate. Testes could not be palpated. Ultrasonographic examination revealed that the bladder was distended. The only abnormality detected on serum biochemical analysis was high creatinine concentration. Tube cystostomy was performed, and the cria was treated with saline (0.9% NaCl) solution administered intravenously and antibiotics. Four days after admission, the cria could not urinate normally when the cystostomy tube was occluded. Five days after admission, normograde cystography and retrograde urethrography were performed. Radiographic findings indicated the cria was an intersex llama with urethral duplication. The llama was euthanatized at the owner's request. Necropsy revealed bilateral ovotestes with a phenotypically female reproductive tract and urethral duplication. Urethral duplication should be considered as a cause of stranguria in male neonatal crias, and hermaphroditism should be included as a cause of urethropathies in llamas.
Heat-stable enterotoxins (STa), which cause an acute secretory diarrhea, have been suggested to mediate their actions through the guanylyl cyclase-C (GC-C) receptor. The GC-C gene was disrupted by insertion of neo into exon 1 and subsequent homologous recombination. GC-C null mice contained no detectable GC-C protein. Intestine mucosal guanylyl cyclase activity was approximately 16-fold higher in wild-type mice than in the GC-C null mice, and STa-stimulable guanylyl cyclase activity was absent in the null animals. Thus, GC-C is the major cyclase activity present in the intestine, and also completely accounts for the STa-induced elevations of cGMP. Gavage with STa resulted in marked fluid accumulation within the intestine of wild-type and heterozygous suckling mice, but GC-C null animals were resistant. In addition, infection with enterotoxigenic bacteria that produce STa led to diarrhea and death in wild-type and heterozygous mice, while the null mice were protected. Cholera toxin, in contrast, continued to cause diarrhea in GC-C null mice, demonstrating that the cAMP signaling pathway remained intact. Markedly different diets (high carbohydrate, fat, or protein) or the inclusion of high salt (K+, Na+) in the drinking water or diet also did not severely affect the null animals. Given that GC-C is a major intestinal receptor in all mammals, the pressure to retain a functional GC-C in the face of diarrhea-inflicted mortality remains unexplained. Therefore, GC-C likely provides a protective effect against stressors not yet tested, possibly pathogens other than noninvasive enterotoxigenic bacteria.
A genetic model of salt-resistant hypertension has been developed recently through disruption of the guanylyl cyclase-A (GC-A) natriuretic peptide receptor gene (Lopez, M. J., Wong, S. K., Kishimoto, I., Dubois, S., Mach, V., Friesen, J., Garbers, D. L., and Beuve, A. (1995) Nature 378, 65-68). These genetically altered mice were used to determine which of the natural peptides with natriuretic peptide-like structures regulate blood pressure through the GC-A receptor. Atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed precontracted aortic rings in wild-type mice at about 24 nM, but failed to relax such aortas in GC-A null mice, even at micromolar concentrations. C-type natriuretic peptide (CNP), in contrast, caused half-maximal relaxation at concentrations of 335 and 146 nM in aortas from either wild-type or null mice, respectively, suggesting that this peptide acted through a receptor other than GC-A. Since the in vitro results with aortic smooth muscle do not necessarily reflect the physiology of the smaller blood vessels important in blood pressure regulation, the blood pressures of conscious mice infused with the various peptides were determined. ANP caused decreases in blood pressure when infused at rates of 500 ng/kg/min, a rate which resulted in a plasma concentration of 0.8 nM. In the null mice, in contrast, ANP failed to lower blood pressure even at infusion rates of 50 microg/kg/min. Much higher infusion rates for CNP (50 microg/kg/min), which yielded final plasma concentrations of 18.3 nM, were required to lower blood pressure in wild-type mice, but the effects of CNP were not altered in GC-A null mice. Thus, two natriuretic peptides (ANP, BNP) act through GC-A whereas another (CNP) acts through another receptor to regulate blood pressure.
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