Small bowel transplant combined with a reduced auxiliary liver graft.
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Animals↗
Biomedical subjects
E Alvarez
Publications and source records attributed to E Alvarez.
Predicting outcome of lithium added to antidepressants in resistant depression.
This study was conducted to assess the predictive value of different variables including the response to dexamethasone suppression test (DST), in 105 patients with resistant depression after the addition of lithium (600 to 800 mg/day) for 4 weeks to antidepressant medication. Clinical remission was observed in 57 patients and no improvement in 48. A dramatic and rapid relief of depression occurred in 12 patients. Variables with significant or marginally significant differences between responders and non-responders were included in a stepwise logistic regression model. Weight loss (P = 0.0013) and depressive psychomotor activity (P = 0.045) in the Newcastle diagnostic index (NDI) scale, and overall score of the Hamilton Rating Scale for Depression (HRSD) before adding the lithium (P = 0.0039) were significantly associated with clinical remission. The difference in post-DST cortisol plasma levels between both groups was marginally significant. The logistic equation resulted in a sensitivity of 78% and a specificity of 65% and total correct classification of the lithium-added response of 72%. The clinical profile of patients who improve with the addition of lithium may include significant weight loss, psychomotor retardation and possibly, poor control of cortisol secretion. Partial remission before adding lithium as well as endogenomorphic traits according to NDI may also be considered additional criteria for response.
Adolescent↗
Interleukin 2 exerts autocrine stimulation on murine T-cell leukaemia growth.
As it has been suggested that an autocrine mechanism may control tumour cell growth, in this work cells from a spontaneous murine T lymphocyte leukaemia (LB) expressing the interleukin-2 receptor (IL-2R) (CD25) were evaluated in vitro for IL-2-mediated autocrine growth. Cells grew readily in culture and proliferation was enhanced by the addition of recombinant IL-2 but inhibited by monoclonal antibodies against either IL-2 or IL-2 receptor, in the absence of exogenous IL-2. Cyclosporin A also inhibited LB cell growth. However, when exogenous IL-2 was added together with cyclosporin A, cell proliferation proved similar to controls. Using reverse transcription polymerase chain reaction (PCR), mRNA for IL-2 was found to be present in tumour cells. Our findings support the hypothesis that LB tumour cell proliferation is mediated by an autocrine pathway involving endogenous IL-2 generation, despite the fact that these cells are not dependent on exogenous IL-2 to grow in culture.
Animals↗
Cutaneous leishmaniasis in the Peruvian Andes: factors associated with variability in clinical symptoms, response to treatment, and parasite isolation rate.
The severity of cutaneous leishmaniasis may be determined by host immunity, parasite virulence, and host or vector behavior. We performed a multivariate analysis to identify the main causes of the variability in clinical symptoms, response to treatment, and parasite isolation rate among Peruvian patients. The effect of host immunity was demonstrated first by the finding that secondary infections induced smaller lesions associated with a lower parasite isolation rate than did primary infections and, second, by the finding of fewer lesions in older patients. Phenotypic differences between parasite populations were suggested by the observation that the mean scar size and number varied between villages: patients had more scars in villages where the transmission rates were higher. Human behavior probably determined the site of lesions on the body, since most lesions in the cooler South were on the head, whereas in the North, lesions were equally frequent on the extremities. In addition, older patients, who were more likely infected through occupational exposure, had fewer head lesions. Geographic variation in the pattern of exposure to sandflies indicates that uta control strategies should be region specific.
Adolescent↗
Influence of dietary sulfur level on growth performance and digestive function in feedlot cattle.
Using ammonium sulfate, three levels of dietary S (.15, .20, and .25%, DM basis) were evaluated in a finishing trial with 108 yearling crossbred heifers (384 kg). The basal diet contained (DM basis) 4% alfalfa hay, 6% sudangrass hay, 74% steam-flaked corn, 4% yellow grease, 6% cane molasses, and 6% protein-mineral supplement. Increasing dietary S decreased ADG (quadratic effect, P < .10), DMI (linear effect, P < .10), feed efficiency (quadratic effect, P < .10), diet NE (quadratic effect, P < .10), and longissimus muscle area (linear effect, P < .05). Six Holstein steers (218 kg) with cannulas in the rumen and proximal duodenum were used to evaluate treatment effects on characteristics of digestion. Treatment effects on ruminal and total tract digestion of OM and N were small (P > .10). However, ruminal digestion of ADF and starch was slightly lower (quadratic effect, P < .10), and postruminal digestion of ADF and starch was correspondingly greater (quadratic effect, P < .05) with supplemental S. Dietary S level did not influence (P > .10) ruminal synthesis of microbial N. Increasing dietary S did not influence (P > .10) ruminal pH or lactic acid. Increasing S decreased molar proportions of acetate (quadratic effect, P < .10) and increased molar proportions of propionate (linear effect, P < .10). We conclude that S in excess of .20% of dietary DM may have detrimental effects on growth performance and dietary NE. Excessive dietary S may also compromise carcass merit by decreasing longissimus muscle area.
Animals↗
Feeding value of cottonseed meal for feedlot cattle.
One hundred twenty crossbred steers (294 kg, initially) were used in a 141-d finishing trial. Four concentrations (8, 16, 24, and 32% of diet DM) of cottonseed meal (CSM, prepressed solvent-extracted) replaced steam-flaked corn in a corn-based finishing diet. Increasing level of CSM decreased ADG (linear component, P < .10), feed efficiency (linear component, P < .01), and dietary NE (linear component, P < .01). Observed dietary NE was 99% of expected at 8 and 16% CSM but 95% of expected at higher levels of inclusion (linear component, P < .05). Level of CSM did not influence (P > .10) dressing percentage, longissimus area, fat thickness, or retail yield. Eight Holstein steers (285 kg) were used in a replicated 4 x 4 Latin square design to evaluate treatment effects on characteristics of digestion. Ruminal digestibility of OM decreased (linear component, P < .05) as CSM increased, although ruminal digestibility of starch and feed N were not affected (P > .10). Ruminal escape protein from CSM was 58%. Total tract starch digestion was not altered (P > .10), but total tract digestibility of OM and GE decreased (linear component, P < .05) and digestion of N increased (linear component, P < .01) as CSM replaced steam-flaked corn. The ratio of observed to expected DE value of the diets was similar across CSM levels, averaging .99. Thus, comparative DE value of CSM was not affected by level of inclusion, averaging 3.32 Mcal/kg. We conclude that the NEm and NEg values of CSM are 1.88 and 1.24 Mcal/kg, respectively, and in close agreement with tabular values. However, CSM should not exceed 16% of DMI, because higher levels may depress cattle performance and replacement value of CSM.
Animals↗
Combined small bowel and reduced liver transplantation in pigs.
PURPOSE: Small bowel transplantation is a last resort treatment for intestinal insufficiency. Although the disorder is occasionally associated with chronic hepatopathy of variable severity, it may require simultaneous liver transplantation. We present a new model of heterotopic small bowel and reduced partial liver transplantation to an infrahepatic site. SUBJECTS AND METHODS: "Mini-pig" breed pigs weighing 28 to 35 kg were divided into four experimental transplant groups: intestine only (IO) without immunosuppression (group 1A, n = 11); IO with immunosuppression (group 1B, n = 10); intestine + reduced liver (IRL) without immunosuppression (group 2A, n = 12); IRL with immunosuppression (group 2B, n = 10). RESULTS: Overall mortality from technical causes (first 3 days) was 23/43 animals (53.4%). All animals in group 1A displayed rejection, which was the main cause of death. Rejection occurred in 1 animal in each of the other three groups. CONCLUSIONS: Heterotopic small bowel-reduced liver transplant is a multivisceral model that has the technical advantage of not requiring hepatectomy, and the immunological advantages of delayed appearance of acute rejection and the possibility of reducing immunosuppression during the first postoperative days.
Animals↗
Synthesis and evaluation of new Reissert analogs as HIV-1 RT inhibitors. 2. Benzo[f]quinoline and pyridine derivatives.
The synthesis and preliminary evaluation of new benzo[f]quinoline and pyridine derivatives, obtained by application of the Reissert method and its modifications, as HIV-1 RT inhibitors and anti-infectives are presented. The most active products against HIV-1 RT wild type are the ethyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2b, propyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2c, and 2-cyano-1-(2'-furoyl)-1,2-dihydrobenzo[f]quinoline 2n, which maintain their activity against the mutant type P236L, resulting inactive against the Y181C type. Using the data previously obtained by our research team for analogous series derived from quinoline as reference, the compounds which have now been obtained present an increase in the cytotoxic character attributable to the introduction of a benzene ring fused with the quinoline base nucleus, as well as a decrease of the activity as HIV-1 RT inhibitors when the quinoline benzenic ring is eliminated.
Anti-HIV Agents↗
Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives.
The synthesis and preliminary evaluation of new quinoline and quinoxaline derivatives (obtained by applying the original Reissert method, conveniently modified) as HIV-1 Reverse Transcriptase (RT) inhibitors are presented in this paper; likewise, the first structure-activity relationships are also proposed. Propyl 2-cyano-1(2H)-quinolin-carboxylate 2e, isopropyl 2-cyano-1 (2H)-quinolincarboxylate 2f, butyl 2-cyano-1 (2H)-quinolincarboxylate 2g and isobutyl 2-cyano-1 (2H)-quinolincarboxylate 2h have been selected as lead compounds. These compounds are active against the HIV-1 RT mutant type P236L (2f, IC50 = 1.2 microM) and present activity as anti-infective agents in HLT41acZ-1IIIB cells, showing no cytotoxicity at the active concentrations.
Anti-HIV Agents↗
[Role of liver biopsy in hepatitis C].
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Biopsy↗
Olanzapine in treatment-refractory schizophrenia: results of an open-label study. The Spanish Group for the Study of Olanzapine in Treatment-Refractory Schizophrenia.
BACKGROUND: Clozapine is currently the treatment of choice for neuroleptic-resistant schizophrenia. Olanzapine is a new antipsychotic drug that has shown efficacy against positive and negative symptoms of schizophrenia, with minimal extrapyramidal side effects. However, the effectiveness of olanzapine has not yet been reported among treatment-refractory schizophrenic patients. METHOD: A total of 25 schizophrenic patients (DSM-IV criteria) with documented lack of response to two conventional antipsychotic drugs entered this 6-week prospective, open-label treatment trial with olanzapine 15 to 25 mg/day. An optional extension up to 6 months was provided. RESULTS: As a group, the olanzapine-treated patients showed statistically significant improvement (p < .05) in both positive and negative symptoms by the end of 6 weeks of therapy. Overall, 9 of the patients (36%) met the a priori criteria for treatment-response (> or = 35% decrease in Brief Psychiatric Rating Scale [BPRS] total score, plus posttreatment Clinical Global Impression-Severity < or = 3 or BPRS total < 18). Only one patient discontinued treatment because of an adverse event during the study. Despite the relatively high dosages of olanzapine used, there were no reports of parkinsonism, akathisia, or dystonia, and no patients required anticholinergic medication. CONCLUSION: This open study suggests that olanzapine may be effective and well tolerated for a substantial number of neuroleptic-resistant schizophrenic patients. Further blinded, controlled trials are needed to confirm our results.
Adult↗
Influence of the age and sex on respiratory burst of human monocytes.
The respiratory burst reaction has been studied in monocytes from men and women of different age. Phorbol myristate acetate (PMA) was used to stimulate NADPH oxidase. Superoxide anion production was found to be dependent on age and sex (it decreased 45% in men and 70% in women during aging).
Adult↗
Nitric oxide and superoxide anion production decrease with age in resident and activated rat peritoneal macrophages.
Superoxide anion and nitric oxide production have been studied in resident and activated peritoneal macrophages of 3-, 12-, and 24-month-old rats. Some key enzymes involved in the metabolism of glucose were also studied in relation to aging. Production of O2 and NO was reduced in all cases in middle-aged (12 months) and old (24 months) animals. Malic enzyme and citrate synthase activity shows a progressive reduction with age. Hexoquinase, pyruvate quinase, and lactate dehydrogenase activities decrease sharply from 3 to 12 months with no significant change between 12 and 24 months. Taken as a whole, the results of enzyme activity suggest that aging may reduce the capacity for glucose utilization in macrophages.
Aging↗
Autonomic profile of subjects prone to fainting.
Syncope is the most common form of fainting that may occur at least once during a life-time in up to one-third of the general population. In 50% of patients the cause remains unknown. In an attempt to identify subtle disturbances of the autonomic nervous system, we examined 70 subjects, aged from 14 to 39 years, who suffered from recurrent neurally mediated syncope. We performed a battery of non-invasive tests assessing cardiovagal, sympathetic cholinergic and sympathetic adrenergic function. We compared the results with a group of 30 healthy, non-fainting subjects matched for age and sex. Basal records were similar in both groups. Patients had preserved cardiovagal function. The multivariate cluster analysis allowed us to find a homogeneous group of cases (46%) that simultaneously presented: greater fall in systolic and diastolic blood pressure after standing, increased 15:30 ratio, exaggerated absolute heart rate rise in response to standing and subclinical reduced sudomotor function in the foot. The results suggest the existence of a subclinical autonomic profile, with subtle sympathetic postganglionic impairment, evident in lower limbs. These findings may contribute to proving the existence of different types of neurally mediated syncope, all different in their onset and mechanism but with a common final manifestation: syncopal loss of consciousness.
Adolescent↗
Phase II trial of epirubicin at standard dose in relapsed ovarian cancer.
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Adult↗
Expression of the glucagon-like peptide-1 receptor gene in rat brain.
Evidence that glucagon-like peptide-1 (GLP-1) (7-36) amide functions as a novel neuropeptide prompted us to study the gene expression of its receptor in rat brain. Northern blot analysis showed transcripts of similar size in RINm5F cells, hypothalamus, and brain-stem. First-strand cDNA was prepared by using RNA from hypothalamus, brainstem, and R1Nm5F cells and subsequently amplified by PCR. Southern blot analysis of the PCR products showed a major 1.4-kb band in all these preparations. PCR products amplified from hypothalamus were cloned, and the nucleotide sequence of one strand was identical to that described in rat pancreatic islets. In situ hybridization studies showed specific labeling in both neurons and glia of the thalamus, hypothalamus, hippocampus, primary olfactory cortex, choroid plexus, and pituitary gland. In the hypothalamus, ventromedial nuclei cells were highly labeled. These findings indicate that GLP-1 receptors are actually synthesized in rat brain. In addition, the colocalization of GLP-1 receptors, glucokinase, and GLUT-2 in the same areas supports the idea that these cells play an important role in glucose sensing in the brain.
Animals↗
Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake.
This study was designed to determine the possible role of brain glucagon-like peptide-1 (GLP-1) receptors in feeding behavior. In situ hybridization showed colocalization of the mRNAs for GLP-1 receptors, glucokinase, and GLUT-2 in the third ventricle wall and adjacent arcuate nucleus, median eminence, and supraoptic nucleus. These brain areas are considered to contain glucose-sensitive neurons mediating feeding behavior. Because GLP-1 receptors, GLUT-2, and glucokinase are proteins involved in the multistep process of glucose sensing in pancreatic beta cells, the colocalization of specific GLP-1 receptors and glucose sensing-related proteins in hypothalamic neurons supports a role of this peptide in the hypothalamic regulation of macronutrient and water intake. This hypothesis was confirmed by analyzing the effects of both systemic and central administration of GLP-1 receptor ligands. Acute or subchronic intraperitoneal administration of GLP-1 (7-36) amide did not modify food and water intake, although a dose-dependent loss of body weight gain was observed 24 h after acute administration of the higher dose of the peptide. By contrast, the intracerebroventricular (i.c.v.) administration of GLP-1 (7-36) amide produced a biphasic effect on food intake characterized by an increase in the amount of food intake after acute i.c.v. delivery of 100 ng of the peptide. There was a marked reduction of food ingestion with the 1,000 and 2,000 ng doses of the peptide, which also produced a significant decrease of water intake. These effects seemed to be specific because i.c.v. administration of GLP-1 (1-37), a peptide with lower biological activity than GLP-1 (7-36) amide, did not change feeding behavior in food-deprived animals. Exendin-4, when given by i.c.v. administration in a broad range of doses (0.2, 1, 5, 25, 100, and 500 ng), proved to be a potent agonist of GLP-1 (7-36) amide. It decreased, in a dose-dependent manner, both food and water intake, starting at the dose of 25 ng per injection. Pretreatment with an i.c.v. dose of a GLP-1 receptor antagonist [exendin (9-39); 2,500 ng] reversed the inhibitory effects of GLP-1 (7-36) amide (1,000 ng dose) and exendin-4 (25 ng dose) on food and water ingestion. These findings suggest that GLP-1 (7-36) amide may modulate both food and drink intake in the rat through a central mechanism.
Animals↗
Evaluation of congenital dysautonomia other than Riley-Day syndrome.
We report on four children, from different families, who suffer from a congenital autonomic disorder, presumably inherited. Three of them have a sensory neuropathy but do not fit any described hereditary sensory and autonomic neuropathy. All four were examined along with some of their immediate family members. We assessed the cardiovagal, sympathetic adrenergic and sympathetic cholinergic functions with a battery of non-invasive tests. Results demonstrated that sudomotor and cardiovascular orthostatic regulation exhibited the greatest abnormalities, pointing to a predominant impairment of sympathetic components, both cholinergic and adrenergic. The overall examination showed a heterogeneous group of congenital dysautonomia, exclusive of Riley-Day or other recognized hereditary sensory and autonomic neuropathies. We emphasize the importance of studying whole family groups to diagnose subclinical impairment and to provide correct genetic counselling.
Adolescent↗