The porcine liver supports metabolic homeostasis in the nonhuman primate: experimental study in a model of orthotopic liver transplantation from h-DAF transgenic pig to baboon.
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Biomedical subjects
Publications and source records attributed to A Muñoz.
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Daytime sleepiness, impaired cognitive performance and dysphoric mood are often present in patients with obstructive sleep apnoea syndrome (SAS). This prospective controlled study evaluates the effects of treatment with continuous positive airway pressure (CPAP) during 1 yr on daytime functioning in a large group of patients with SAS. The authors studied 80 patients (mean+/-sem 49+/-1 yrs) with SAS with a mean apnoea-hypopnoea index of 60+/-2 h-1, and 80 healthy control subjects matched for sex and age (46+/-1 yrs.). Measurements were obtained at the beginning of the study and 12+/-1 months later, and included: daytime sleepiness (Epworth scale), depression and anxiety (Beck tests), vigilance (Steer-Clear) and reaction time (Psychometer Vigilance Test 192). Drug, coffee and alcohol intake, as well as the sleep schedule, were also recorded. Results showed that, before treatment, patients were more somnolent (p<0.001), anxious (p<0.01) and depressed (p<0.001) than control subjects. Also, they had a longer reaction time (p<0.05) and poorer vigilance (p<0.01). The use of CPAP improved significantly the levels of somnolence (p<0.0001) and vigilance (p<0.01), but failed to modify anxiety and depression. Reaction time changes were minor. Variables with a potential confounding effect did not change during the study. These results provide firm evidence to substantiate the use of continuous positive airway pressure in patients with sleep apnoea syndrome.
This study evaluates the outcome of myeloablative chemo-radiotherapy and autologous stem cell transplantation (ASCT) in children with Hodgkin's disease (HD). Twenty children aged 5 to 18 years (median 10.8 years) at diagnosis, with relapsed, refractory or very poor prognosis HD, underwent ASCT in eight hospitals of our country. Status at transplant was: second complete remission (CR2): n = 12; further CR (CR >2): n = 3, partial remission (PR): n = 2, relapse: n = 2 and first CR (CR1): n = 1. Eighteen patients received chemotherapy-based conditioning regimens: cyclophosphamide, carmustine and etoposide (CBV): 11 (55%), carmustine, etoposide, cytarabine and melphalan (BEAM): 5, other: 2; and two patients were conditioned with TBI/Cy. Peripheral blood (PB) was the source of progenitor cells in 12 patients, BM in seven, and BM plus PB, in one. All patients engrafted. One patient died of sepsis and multiorgan failure at day 28 after transplantation. All four patients with measurable disease (PR or relapse) at transplantation attained complete remission. Five patients relapsed 5-34 months after transplant (median: 11 months). Eighteen children remain alive with a median survival time of 40 months. The projected 5-year overall survival and event-free survival (EFS) rates were 0.95 and 0.62. High-dose therapy with stem cell rescue can lead to durable remissions in children with advanced HD. Bone Marrow Transplantation (2000) 25, 31-34.
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G protein-coupled receptor kinase 2 (GRK2) and beta-arrestin 1 are key regulatory proteins that modulate the desensitization and resensitization of a wide variety of G protein-coupled receptors (GPCRs) involved in brain functions. In this report, we describe the postnatal developmental profile of the mRNA and protein levels of GRK2 and beta-arrestin 1 in rat brain. The expression levels of GRK2 and beta-arrestin 1 display a marked increase at the second and third week after birth, respectively, consistent with an involvement of these proteins in brain maturation processes. However, the expression attained at birth and during the first postnatal week with respect to adult values (45-70% for GRK2, approximately 30% for beta-arrestin 1) is relatively high compared to that reported for several GPCRs, indicating the existence of changes in the ratio of receptors to their regulatory proteins during brain development. On the other hand, we report that experimental hypothyroidism results in changes in the patterns of expression of GRK2 and beta-arrestin 1 in cerebral cortex, leading to a 25-30% reduction in GRK2 levels at several stages of development. Such changes could help to explain the alterations in GPCR signaling that occur during this pathophysiological condition.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep inducer, and it is involved in the control of odor and pain responses and body temperature. In addition, PGD synthase transports lipophilic molecules in the subarachnoid space and CSF. By northern and western assays we show that the synthetic glucocorticoid dexamethasone, an inhibitor of PG production in most tissues, induces L-PGDS mRNA and protein in a dose- and time-dependent fashion in mouse neuronal GT1-7 cells. Accordingly, dexamethasone increases cellular L-PGDS enzymatic activity. Dexamethasone induced L-PGDS gene transcription in run-on assays and activated the mouse L-PGDS gene promoter in transiently transfected cells. It is interesting that the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA), which induces the synthesis of PGs in many tissues, inhibited the increase in L-PGDS expression induced by dexamethasone. In contrast, neither dexamethasone nor TPA affected the expression of cyclooxygenases-1 and -2. Our data demonstrate that dexamethasone induces L-PGDS gene transcription in neuronal cells.
The cell surface hydrophobicity of micro-organisms is a characteristic that has been associated with the colonization of mammalian epithelia and with their capacity to induce diseases. Melatonin is a hormone produced by the pineal gland that affects the immune response mechanism. This study investigated, as an expression of the virulence of Neisseria meningitidis, how its hydrophobic characteristics were affected by exposure to increasing concentrations of melatonin. An increase in the cell surface hydrophobicity of N. meningitidis was found at concentrations of 1 mmol l(-1), while lower concentrations of melatonin did not significantly affect this particular cell surface characteristic of the micro-organism. It may be concluded that melatonin clearly influences the cell surface hydrophobicity of N. meningitidis, a circumstance that should be taken into account in future studies to determine whether this hormone plays a role in the variable pathogenicity of the bacteria in different hosts.
Patterns of circadian and ultradian rhythms in the heart rate (HR) are described in a full-term baby with birth asphyxia and convulsions. A 24h HR recording was carried out at the age of 1, 15, 56, 289, and 295 days; West syndrome diagnosis was made when the patient was 3 months old. The HR showed no circadian rhythm in the follow-up, whereas it is known that the circadian rhythm appears in healthy infants at the age of 1 month and remains thereafter. This observation may be an indirect indicator of the interference of West syndrome with centers of neurological maturity.
The natural history of human immunodeficiency virus type 1 (HIV-1) viremia and its association with clinical outcomes after seroconversion was characterized in a cohort of homosexual men. HIV-1 RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) in stored longitudinal plasma samples from 269 seroconverters. Subjects were generally antiretroviral drug naive for the first 3 years after seroconversion. The decline in CD4 lymphocyte counts was strongly associated with initial HIV RNA measurements. Both initial HIV RNA levels and slopes were associated with AIDS-free times. Median slopes were +0.18, +0.09, and -0.01 log10 copies/mL, respectively, for subjects developing AIDS <3, 3-7, and>7 years after seroconversion. In contrast, HIV RNA slopes in the 3 years preceding AIDS and HIV RNA levels at AIDS diagnosis showed little variation according to total AIDS-free time. HIV RNA load at the first HIV-seropositive visit ( approximately 3 months after seroconversion) was highly predictive of AIDS, and subsequent HIV RNA measurements showed even better prognostic discrimination.
BACKGROUND: To explore Bacillus Calmette-Guérin vaccine (BCG) as a protective factor against tuberculosis (TB) and how human immunodeficiency virus (HIV) infection modifies the effect of BCG on TB. METHODS: Two matched case-control studies were conducted. One study compared TB cases and controls who were HIV positive. The second compared TB cases and controls who were HIV negative. The study population consisted of 88 TB cases and 88 controls among HIV-positive individuals and 314 TB cases and 310 controls among HIV-negative individuals. Cases were new TB diagnoses, confirmed by either bacteriology, pathology, radiology or clinical response to treatment; controls were selected from people without TB symptoms and who sought medical attention in the same institution where a case was enrolled. BCG was assessed by the presence of a typical scar. RESULTS: The level of protection against all clinical forms of TB was 22% among HIV positive individuals (odds ratio [OR] = 0.78, 95% CI : 0.48-1.26) and 26% among HIV negatives (OR = 0.74, 95% CI : 0.52-1.05). There was a significant difference (P = 0.002) in the level of protection against extrapulmonary TB (ETB) between HIV-negative (OR = 0.54, 95% CI : 0.32-0.93) and HIV-positive individuals (OR = 1.36, 95% CI : 0.72-2.57). CONCLUSION: BCG has a modest protective effect against all forms of TB independent of HIV status, and BCG confers protection against extrapulmonary TB among HIV-negative individuals. However, HIV infection seems to abrogate the protective effect of BCG against extrapulmonary TB. Our data support the public health importance of BCG vaccine in the prevention of extrapulmonary TB among immunocompetent individuals.
RATIONALE AND OBJECTIVES: To demonstrate that gadodiamide injection is a safe and efficient contrast agent for MRI in infants younger than 6 months of age. METHODS: The authors designed a phase III multicenter nonrandomized study using a control group. Gadodiamide injection at a dosage of 0.1 mmol/kg body weight was administered to 39 children; 20 received no contrast. The mean age was 10.6 weeks in the contrast group and 9.3 weeks in the control group. MR examinations, blood (serum creatinine, S-ASAT, S-ALAT, S-bilirubin, alkaline phosphatase) and urine (proteins, blood, others) sampling before sedation and after examination, heart rate (electrocardiography) and oxygen saturation (pulse oximetry) during examination, adverse events, and efficacy parameters were analyzed. RESULTS: In the contrast group, 18 (51.4%) children had 31 abnormal changes in one or more of the safety parameters and vital signs. In the control group there were 16 (80.0%) children with 19 abnormal changes. Gadodiamide injection had no negative influence on the safety parameters. No serious adverse events occurred, and only three clinically relevant adverse events (elevation of S-ALAT and S-ASAT, elevation of bilirubin) in two patients in the contrast group and one event (vomiting) in one patient in the control group were documented. The benefit of the contrast medium was clearly shown for all evaluated parameters. CONCLUSIONS: Gadodiamide injection is safe, well tolerated, and effective in infants younger than 6 months of age.
OBJECTIVE: It has been suggested that ascites is a risk factor for variceal bleeding. Recently, it has been demonstrated that total paracentesis decreases variceal pressure. However, no data are available showing the basal variceal pressure in patients with and without ascites. METHODS: We studied 76 cirrhotic patients, 49 with and 27 without ascites. Variceal pressure was measured by direct puncture. Variceal size, variceal pressure gradient, and variceal wall tension were also obtained. RESULTS: No demographic differences were observed between the groups. Child score was higher (9.7+/-1.5 vs 7.8+/-2.1, p < 0.001) and serum albumin lower (2.6+/-0.6 vs 3.0+/-0.7 mg %, p < 0.02) in ascitic than in nonascitic patients, respectively. Variceal pressure and variceal pressure gradient were significantly higher in patients with ascites than in those without ascites (25.0+/-6 vs 20.4+/-4.6 mm Hg, p < 0.001 and 18.75+/-4.7 vs 13.70+/-4.1 mm Hg, p < 0.0001, respectively). The variceal wall tension was significantly higher in patients with ascites (71.0+/-25.1 mm Hg/mm) than in those without ascites (55.1+/-22.1 mm Hg/mm, p < 0.03). No relationship was observed between variceal pressure gradient and liver function. Ascites patients included in Child-Pugh grade A+B presented a similar variceal pressure to Child C patients (18.5+/-4.2 vs 19.3+/-5.7 mm Hg, respectively, p = ns). In addition, no relationship was observed between variceal pressure gradient and etiology of cirrhosis. CONCLUSION: Our results demonstrate that patients with ascites have significantly higher variceal pressure and wall tension than patients without ascites. These results suggest that patients with ascites may be at risk for variceal bleeding.
A study was undertaken to implement the quality criteria proposed by the European Commission for brain general and lumbar spine (disc herniation) CT examinations. The proposed criteria were evaluated for samples including 93 brain and 86 lumbar spine CT examinations, with special emphasis on the diagnostic and radiation dose requirements. The extent to which the image criteria had been achieved was evaluated after two independent observers had each read the images twice. Dose measurements were conducted in parallel to estimate the proposed dose quantities needed to obtain the images. For brain examinations, we found that a group of image criteria were largely met, and met uniformly in all sites. One criterion (1.2.5) was frequently fulfilled but had intermediate values for two sites; the remaining criteria were fulfilled to different extents, although for criteria 1.2.1 and 1.2.2, scores were lower than 50% and 70%, respectively. The mean percentage image quality score had values between 57% and 78%, with variation coefficients in the range 30-68%. Mean values of the dose quantities were in the ranges 44-74 mGy for weighted CT dose index (CTDIw), 497-1018 mGy cm for dose-length product (DLP) and 1.1-2.2 mSv for effective dose (E). CTDIw and DLP were not correlated because of significant variations in the scanned length, whereas DLP and E were strongly correlated. A weak relationship between image quality score and DLP was found for the sample as a whole. For lumbar spine examinations, none of the critical reproduction image criteria was systematically achieved. One group of criteria (1.2.7, 1.2.8 and 1.2.9) was fulfilled to a large extent in many departments, but fulfilment of the remainder varied widely. The mean score fluctuated in the range 39-88%, with three groups of differences: low (39-51%), intermediate (67-71%) and high (85-88%). Mean values of the CTDIw varied between sites in the range 27-48 mGy. Mean DLP values varied between 188 mGy cm and 333 mGy cm, and the mean effective dose ranged between 3 mSv and 5 mSv. There were significant differences in effective dose between men and women. By sites, there was no relationship between DLP and mean score, with the highest image score associated with intermediate dose values. The percentage disagreement among the observers about a given criterion ranged between 2% and 22% for brain, and between 3% and 46% for lumbar spine.
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Percutaneous vertebroplasty is an effective treatment for many focal vertebral lesions. Methyl methacrylate is too viscous to be handled without difficulty in the conventional way because injection time is short. The operator is left with little time and must fumble with multiple syringes. We describe a special screw-system syringe that decreases the effort needed to inject the cement. In addition, it can standardize the injection pressures and control the injected volume because the threaded plunger affords greater control of injection pressure and volume delivered than does the conventional method.
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UNLABELLED: Stunning of thyroid remnants after diagnostic scanning with 131I may limit 131I therapy. The follow-up scans and serum thyroglobulin levels of such patients have been studied. METHODS: Three-hundred seventy-eight patients who underwent thyroidectomy for differentiated thyroid carcinoma were studied. Diagnostic scans were obtained with 185 MBq 131I; 7.2 wk afterward, the patients received 489 ablative treatments with 4 GBq 131I. A total of 1575 scans were obtained (pre- and posttreatment scans and 615 follow-up scans). The evolution of serum thyroglobulin levels was determined. RESULTS: In all patients, the thyroid-stimulating hormone level was more than 30 microIU/mL. Posttherapy scans showed less uptake than did diagnostic scans or even showed negative findings in 99 patients (21%). In these patients, the mean time between diagnostic scanning and therapy was 7.9 wk. In 61 of these 99 patients (61.6%), follow-up scans have shown negative findings, serum thyroglobulin was less than 3 ng/mL, and antithyroglobulin antibodies were not present. Twenty-three patients (23.2%) have not undergone follow-up scanning yet. In 8 patients (8.1%), follow-up scans showed negative findings but serum thyroglobulin was more than 3 ng/mL. In 7 patients (7.1%), follow-up scans showed less uptake than posttherapy scans, but the findings were not yet negative and thyroglobulin was less than 3 ng/mL. CONCLUSION: Our data suggest that a stunning effect does not exist for doses of 185 MBq 131I for diagnostic scans. However, a therapeutic effect may exist.