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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 19 recordsLinked to original sources

Stigma and social barriers to medication adherence with urban youth living with HIV.

Youth adherence to highly active anti-retroviral therapy (HAART) is poor, and little research exists that identifies the reasons youth have difficulty adhering to medications. Given that complete adherence is necessary for favourable health outcomes, it is essential to examine the obstacles youth face in adhering to HAART. The present investigation sought to identify these barriers and to systematically examine the experiences and attitudes youth have towards medications. Twenty-five adolescents and young adults presenting to a public primary care facility for treatment of HIV infection were asked to participate in focus groups which explored their attitudes and experiences around medication adherence. Participants provided richly detailed descriptions of the challenges of managing HIV stigma and their efforts to hide their status from friends, family, doctors, and even themselves. Fifty percent of respondents indicated that they skipped doses because they feared family or friends would discover their status. These results suggest that HIV stigma impacts treatment for youth on several levels, from the accuracy of communication with medical providers to medication adherence, subsequent health outcomes, and the emergence of treatment resistant strains.

Adolescent↗

Theoretical study of adsorption of sarin and soman on tetrahedral edge clay mineral fragments.

This study provides details of the structure and interactions of Sarin and Soman with edge tetrahedral fragments of clay minerals. The adsorption mechanism of Sarin and Soman on these mineral fragments containing the Si(4+) and Al(3+) central cations was investigated. The calculations were performed using the B3LYP and MP2 levels of theory in conjunction with the 6-31G(d) basis set. The studied systems were fully optimized. Optimized geometries, adsorption energies, and Gibbs free energies of Sarin and Soman adsorption complexes were computed. The number and strength of formed intermolecular interactions have been analyzed using the AIM theory. The charge of the systems and a termination of the mineral fragment are the main contributing factors on the formation of intermolecular interactions in the studied systems. In the neutral complexes, Sarin and Soman is physisorbed on these mineral fragments due to the formation of C-H...O, and O-H...O hydrogen bonds. The chemical bond is formed between a phosphorus atom of Sarin and Soman and an oxygen atom of the -2 charged clusters containing an Al(3+) central cation and -1 charged complex containing a Si(4+) central cation (chemisorption). Sarin and Soman interact mostly in the same way with the same terminated edge mineral fragments containing different central cations. However, the interaction energies of the complexes with an Al(3+) central cation are larger than these values for the Si(4+) complexes. The interaction enthalpies of all studied systems corrected for the basis set superposition error were found to be negative. However, on the basis of the Gibbs free energy values, only strongly interacting complexes containing a charged edge mineral fragment with an Al(3+) central cation are stable at room temperature. We can conclude that Sarin and Soman will be adsorbed preferably on this type of edge mineral surfaces. Moreover, on the basis of the character of these edge surfaces, a tetrahedral edge mineral fragment can provide effective centers for the dissociation.

Journal Article↗

Long term fate of slurry derived nitrogen in soil: a case study with a macro-lysimeter experiment having received high loads of pig slurry (Solepur).

In intensive livestock production areas, land application remains the traditional management of manure and slurries for nutrient recycling. For sustainable agriculture there is fear, however, that this practice may have detrimental effects, particularly on the depletion of Soil Organic Matter associated with pig slurry applications. We investigated the long-term fate of nitrogen in a reconstituted soil having received high doses of pig slurry during 5 years (1991-1995). After 5 years of intensive application rates (nearly 1000 m(3)yr(-1)), the N and C content of the soil profile (0-20 cm) had increased by about 60% and 50%, respectively. These results confirm previous findings although it seems that the particularly high rates of application may explain, in part, the relatively important N incorporation in soil. Pig slurry applications ceased in 1995 and nitrogen content in soil and drainage water have been monitored. Apparent mineralization rates were calculated from the decrease in N content of the soil. This analysis indicated that more than 50% of the added N stored in the soil at the end of the applications would eventually be mineralized, leaving nearly 50% of the stored N to be immobilized in the soil. These results are the first published of their kinds, as most reports never examine the fate of applied pig slurry N after halting applications. In addition the few reports on long-term experiments suggest that Soil Organic Matter following pig slurry applications may be unstable. Our analysis tends to show the contrary. However, this conclusion must be tempered because data on nitrate leachate patterns suggest that soil management such as ploughing and sowing may actually trigger mineralization that could eventually deplete nitrogen stored following applications.

Animals↗

New data on epizootiology and genetics of piroplasms based on sequences of small ribosomal subunit and cytochrome b genes.

As a continuation of our studies on molecular epizootiology of piroplasmosis in Spain and other countries, we present in this contribution the finding of new hosts for some piroplasms, as well as information on their 18S rRNA gene sequences. Genetic data were complemented with sequences of apocytochrome b gene (whenever possible). The following conclusions were drawn from these molecular studies: Theileria annulata is capable of infecting dogs, since it was diagnosed in a symptomatic animal. According to cytochrome b sequences, isolates from cows and dog present slight differences. The same isolates showed, however, identical sequence in the 18S rRNA gene. This exemplifies well the usefulness of the mitochondrial gene for examining infra-specific variation. Babesia bovis is an occasional parasite of equines, since it was detected in two symptomatic horses. We found evidence of genetic polymorphism occurring in the 18S rRNA gene of Spanish T. equi-like and B. ovis isolates. B. bennetti from Spanish seagull is loosely related to B. ovis, and might represent a genetically distinct branch of babesids. A partial sequence of a cytochrome b pseudogene was obtained for the first time in Babesia canis rossi from South Africa. The pseudogene is distantly related to B. bigemina cytochrome b gene. These new findings confirm the ability of some piroplasms to infect multiple hosts, as well as the existence of a relatively wide genetic polymorphisms with respect to the cytochrome b gene. On the other hand, the existence of mtDNA-like pseudogenes of possible nuclear location in piroplasms is interesting due to their possible impact on molecular phylogeny studies.

Animals↗

Endoscopic retrograde cholangiopancreatography and gastroduodenoscopy after Roux-en-Y gastric bypass.

BACKGROUND: The use of Roux-en-Y gastric bypass (RYGB) for morbid obesity has raised concern that subsequent endoscopic evaluation of the gastric remnant and duodenum is difficult. By gaining percutaneous access to the gastric remnant, however, both gastroduodenoscopy and endoscopic retrograde cholangiopancreatography (ERCP) can be performed easily. This report describes the results of a novel technique for performing "transgastrostomy" gastroduodenoscopy and ERCP. METHODS: Six patients with a RYGB for morbid obesity underwent transgastric remnant endoscopic evaluations. If a gastric remnant tube had not been placed during prior surgery, one was placed percutaneously by an interventional radiologist. The tube tract then was dilated to either 20- or 24-Fr. At the time of endoscopy, the gastrostomy tube was removed and the skin anesthetized. Then either a pediatric duodenoscope (outer diameter, 7.5 mm) or a slim gastroscope (outer diameter, 5.9 mm) was inserted through the gastrostomy tube tract. RESULTS: Percutaneous gastroduodenoscopy was successfully performed for all six patients. The findings included two patients with prepyloric ulcers identified and assessed with a biopsy, one patient with intestinal metaplasia and a benign gastric polyp, and three patients with a normal gastric remnant and duodenum. A nonstrictured enteroenterostomy was noted in one of the three patients with a normal endoscopic evaluation. Percutaneous transgastrostomy ERCP was performed for three of the six patients who underwent gastroduodenoscopy. The findings included one patient who had papillary fibrosis treated with a sphincterotomy, a second patient with a normal biliary tree, and a third patient with a normal pancreatic duct. Selective cannulation of the common bile duct was not successful in the third patient. CONCLUSION: The transgastrostomy endoscopic route ensures access to the excluded stomach and proximal small bowel after RYGB. This route is safe and effective, allowing the use of a duodenoscope to improve the cannulation success rate for ERCPs in this patient population.

Anastomosis, Roux-en-Y↗

Uncinaria stenocephala: assessment of antigens for the immunodiagnosis of canine uncinariosis.

Although Uncinaria stenocephala is the most frequent hookworm in the intestine of dogs from Northern, Central and Southern Europe, little is known about its host-parasite relationship. Three groups of sera from dogs (Group 1: dogs naturally infected only by U. stenocephala; Group 2: helminth-free dogs at necropsy, and Group 3: dogs parasitized by other helminths) were analyzed by ELISA using U. stenocephala antigens from adult worms (somatic and excretory-secretory antigens) and from L3 larvae (somatic antigens). All three sources of antigens were found to be suitable for immunodiagnosis of canine uncinariosis with up to 90% efficacy. However, an analysis to assess the diagnostic value of the different antigens demonstrated that the adult excretory-secretory antigens had a higher diagnostic efficacy (96.7%), indicating that this is the best antigen source for the diagnosis of Uncinaria infection.

Ancylostomatoidea↗

Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients.

The main objective of this study was to evaluate the role of the recent World Health Organization (WHO) classification for assessing prognosis in patients with myelodysplastic syndromes (MDS). To this effect, we analyzed the prognostic impact of the WHO and French-American-British (FAB) morphologic classifications and of four different scoring systems in a series of 311 patients with primary MDS diagnosed between October 1990 and June 2001. Both the FAB and WHO classifications identified groups with different prognoses (p<0.0001), those presenting refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) showing the best prognosis. The WHO classification subdivided RA into RA with only red cell dysplasia, and refractory cytopenia with multilineage dysplasia (RCMD), and RARS into RARS plus refractory cytopenia with multilineage dysplasia and ringed sideroblast (RCMD-RS). In our population, we have shown that the two subtypes characterized by dysplasia affecting exclusively the erythroid population (RA and RARS) have a better prognosis, with a median survival of 122.2 and 81.9 months, respectively, than those with multilineage dysplasia (RCMD and RCMD-RS) with a median survival of 32.3 and 43.2 months, respectively. There were no significant differences in median survival comparing RA with RAS (p<0.95), or comparing RCMD with RSCMD (p<0.97). Besides, the four scoring systems discriminated our MDS patients in terms of survival, and an increase in prognostic capacity was achieved on adding the score to the morphological classifications. Risk scoring had a greater prognostic impact than the FAB and WHO classifications. Prognostic scoring systems may be an important tool for risk stratification in hematological practice, and add significance to morphological classification. Combined application of the WHO classification and score system is useful for improving the identification of patients with a poorer prognosis. The WHO classification establishes more homogeneous subcategories than the FAB classification and is also able to identify groups with different prognoses.

Adult↗

A randomized trial comparing two corticosteroid regimens combined with mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.

INTRODUCTION: The launching of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection episodes. We sought to evaluate the efficacy of decreasing the steroid dose. MATERIALS AND METHODS: This was a quasiexperimental, randomized, prospective trial. We enrolled 150 patients who received de novo renal transplantations from living or cadaveric donors, fulfilling the screening criteria. Patients were randomized to one of the following two arms: (A) MMF at a 2 g/d dose, cyclosporine (CsA) at a dose necessary to achieve target levels, and corticosteroids at the usual doses; (B) MMF at a 2 g/d dose, CsA at a dose necessary to achieve target levels, and corticosteroids at doses 50% lower than those of group A. RESULTS: Group A included 72 (48%) and group B, 78 patients (52%). There were no differences among the variables: leukopenia occurred in 11 patients in group A, and five patients in group B. Complications occurred in 67.4% (56) of group A, but only 32.6% (27) were related to infections. One case of urinary infection occurred in group B, while six occurred in group A. There was one case of acute rejection in group A, and none in group B. One graft loss occurred in group A. There were no differences in the remaining variables under study. DISCUSSION: The results showed an increased complication rate related to receiving usual steroid doses. There was no increase in acute rejection episodes among patients receiving 50% of the usual steroid dose.

Adrenal Cortex Hormones↗

Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device.

BACKGROUND: The goal of this study was to determine the optimal treatment parameters for the ablation of human esophageal epithelium using a balloon-based bipolar radiofrequency (RF) energy electrode. METHODS: Immediately prior to esophagectomy, subjects underwent esophagoscopy and ablation of two separate, 3-cm long, circumferential segments of non-tumor-bearing esophageal epithelium using a balloon-based bipolar RF energy electrode (BARRX Medical, Inc., Sunnyvale, CA, USA). Subjects were randomized to one of three energy density groups: 8, 10, or 12 J/cm2. RF energy was applied one time (1x) proximally and two times (2x) distally. Following resection, sections from each ablation zone were evaluated using H&E and diaphorase. Histological endpoints were complete epithelial ablation (yes/no), maximum ablation depth, and residual ablation thickness after tissue slough. Outcomes were compared according to energy density group and 1x vs 2x treatment. RESULTS: Thirteen male subjects (age, 49-85 years) with esophageal adenocarcinoma underwent the ablation procedure followed by total esophagectomy. Complete epithelial removal occurred in the following zones: 10 J/cm2 (2x) and 12 J/cm2 (1x and 2x). The maximum depth of injury was the muscularis mucosae: 10 and 12 J/cm2 (both 2x). A second treatment (2x) did not significantly increase the depth of injury. Maximum thickness of residual ablation after tissue slough was only 35 microm. CONCLUSIONS: Complete removal of the esophageal epithelium without injury to the submucosa or muscularis propria is possible using this balloon-based RF electrode at 10 J/cm2 (2x) or 12 J/cm2 (1x or 2x). A second application (2x) does not significantly increase ablation depth. These data have been used to select the appropriate settings for treating intestinal metaplasia in trials currently under way.

Adenocarcinoma↗

HIV infection does not influence clinical outcomes in hospitalized patients with bacterial community-acquired pneumonia: results from the CAPO international cohort study.

In a case-control study, outcomes for 58 human immunodeficiency virus (HIV)-positive patients with community-acquired pneumonia (CAP) were compared with outcomes for 174 HIV-negative patients with CAP. No differences were found in the time to clinical stability, the length of hospitalization, and mortality. Clinical outcomes for hospitalized patients with CAP may not be influenced by HIV infection.

Adult↗

Doppler ultrasonography for the assessment of tumor necrosis after percutaneous ethanol injection prior to liver transplantation as adjuvant therapy of hepatocellular carcinoma.

INTRODUCTION: Percutaneous ethanol injection (PEI) is considered to be a curative treatment for hepatocellular carcinoma (HCC). The imaging technique of choice for the assessment of local response after PEI has not been well defined, but helical computerized tomography (hCT) has been recommended. The aim of this study was to assess the accuracy of Doppler ultrasonography (US) for evaluation of tumor necrosis after PEI. PATIENTS AND METHODS: Twenty-one patients with single HCC listed for liver transplantation underwent multisession US-guided PEI. Liver Doppler US was done at the 4th week after PEI. Complete response was defined as the absence of any intratumoral Doppler signal. The liver was analyzed in transplant recipients during the follow-up. Complete pathological response was defined as necrosis > or = 90% of total tumor volume. Histological and sonographic findings were compared. RESULTS: Twelve patients underwent transplantation (9 men, mean age 60 +/- 5.2 years). Nine of these (75%) showed a complete ultrasonographic response. In the explanted liver, complete necrosis was present in 6 nodules, and incomplete necrosis was seen in the remaining 6 cases. In comparison with histology, Doppler US showed values of sensitivity, specificity, positive predictive values, and negative predictive values of 50%, 100%, 100%, and 60%, respectively. Overall accuracy was 75%. CONCLUSIONS: In our series, Doppler US showed low sensitivity but high specificity in the assessment of HCC necrosis after PEI. The ultrasonographic finding of complete response requires hCT for confirmation, but the presence in Doppler US of neoplastic viable tissue is enough to indicate a further cycle of PEI.

Administration, Cutaneous↗

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis.

BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Adolescent↗

JLK inhibitors: isocoumarin compounds as putative probes to selectively target the gamma-secretase pathway.

Alzheimer's disease is characterized by the extracellular deposition of the amyloid beta-peptide that derives from its precursor betaAPP by sequential actions of beta- and gamma- secretases, respectively. Recent studies aimed at identifying these enzymes have been reported as it is thougth that their inhibition should hopefully lead to reduce Abeta load in the AD brains. beta-secretase seems to be due to BACE1, a novel membrane-bound aspartyl protease. gamma-secretase identification is still a matter of controversy. Invalidation of presenilin genes was reported to impair both gamma-secretase-mediated Abeta production and Notch cleavage leading to NICD production. This observation together with another biochemical and pharmacological evidences led to suggest that presenilins could be the genuine long-searched gamma-secretase that would be responsible for both APP and Notch cleavages. We have designed novel non peptidic potential inhibitors of gamma-secretase (referred to as JLK inhibitors) and examined their ability to prevent Abeta40 and Abeta42 secretions as well as NICD production. Three out of a series of these agents drastically lower the recoveries of both Abeta40 and Abeta42 produced by betaAPP-expressing cell lines and concomitantly protect intracellular C99 and C83 recoveries. These inhibitors also prevent Abeta40/42 productions by C99-expressing cells. Interestingly, these inhibitors were totally unable to affect the DeltaENotch cleavage leading to NICD generation. Here, we also further characterize the pharmacological properties and specificity of these JLK inhibitors.

Amyloid Precursor Protein Secretases↗

Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation.

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.

Acute Disease↗

Heat shock protein synthesis over time in infective Trichinella spiralis larvae raised in suboptimal culture conditions.

Changes in the viability, infectivity and heat shock protein (Hsp) levels are reported in Trichinella spiralis first stage larvae (L1) stored in 199 medium for up to seven days at 37 degrees C. These conditions induce stress that the larvae, eventually, cannot overcome. After three days of storage, the infectivity and viability were unchanged, although higher Hsp70 levels were observed. After this time, larvae gradually lost viability and infectivity, coinciding with a decrease in Hsp70 and Hsp90 and an increase in actin (a housekeeping protein). In addition, a possibly inducible heat shock protein, Hsp90i, appeared as constitutive Hsp90 disappeared. No significant changes in Hsp60 levels were detected at any time. These results suggest that heat shock proteins initially try to maintain homeostasis, but on failing, may be involved in cell death.

Animals↗

Biological activity of silylated amino acid containing substance P analogues.

The need to replace natural amino acids in peptides with nonproteinogenic counterparts to obtain new medicinal agents has stimulated a great deal of innovation on synthetic methods. Here, we report the incorporation of non-natural silylated amino acids in substance P (SP), the binding affinity for the two hNK-1 binding sites and, the potency to stimulate phospholipase C (PLC) and adenylate cyclase of the resulting peptide. We also assess the improvement of their stability towards enzyme degradation. Altogether, we found that replacing glycine with silaproline (Sip) in position 9 of SP leads to a potent analogue exhibiting an increased resistance to angiotensin-converting enzyme hydrolysis.

Adenylyl Cyclases↗

JLK isocoumarin inhibitors: selective gamma-secretase inhibitors that do not interfere with notch pathway in vitro or in vivo.

gamma-Secretase activity is involved in the generation of Abeta and therefore likely contributes to the pathology of Alzheimer's disease. Blocking this activity was seen as a major therapeutic target to slow down or arrest Abeta-related AD progression. This strategy seemed more doubtful when it was established that gamma-secretase also targets other substrates including Notch, a particularly important transmembrane protein involved in vital functions, at both embryonic and adulthood stages. We have described previously new non-peptidic inhibitors able to selectively inhibit Abeta cellular production in vitro without altering Notch pathway. We show here that in vivo, these inhibitors do not alter the Notch pathway responsible for somitogenesis in the zebrafish embryo. In addition, we document further the selectivity of JLK inhibitors by showing that, unlike other described gamma-secretase inhibitors, these agents do not affect E-cadherin processing. Finally, we establish that JLKs do not inhibit beta-site APP cleaving enzymes (BACE) 1 and BACE2, alpha-secretase, the proteasome, and GSK3beta kinase. Altogether, JLK inhibitors are the sole agents to date that are able to prevent Abeta production without triggering unwanted cleavages of other proteins.

Amyloid Precursor Protein Secretases↗