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Biomedical subjects

Jesús Villar

Publications and source records attributed to Jesús Villar.

At least 19 recordsLinked to original sources
PubMed2006

Year in review 2005: Critical Care--respirology: mechanical ventilation, infection, monitoring, and education.

We summarize all original research in the field of respiratory intensive care medicine published in 2005 in Critical Care. Twenty-seven articles were grouped into the following categories and subcategories to facilitate rapid overview: mechanical ventilation (physiology, spontaneous breathing during mechanical ventilation, high frequency oscillatory ventilation, side effects of mechanical ventilation, sedation, and prone positioning); infection (pneumonia and sepsis); monitoring (ventilatory monitoring, pulmonary artery catheter and pulse oxymeter); and education (training and health outcome).

Critical Care↗
PubMed2006

Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two Spanish families.

Bartter syndrome (BS) is a heterogeneous group of autosomal recessive hypokalaemic salt-losing tubulopathies. Five types of BS caused by different genetic defects have been identified, and one of them is associated with sensorineural deafness (BSND). Mutations in the recently described BSND gene, mapped in chromosome 1p31, have been reported to be associated with BSND. This gene encodes barttin, an essential beta-subunit subunit for ClC-Ka and ClC-Kb channels. Both subunits are co-expressed in basolateral membranes of renal tubules, in the ascending limb of the loop of Henle, and in the stria vascularis of the inner ear. We studied two apparently unrelated Spanish families from the Canary Islands, with five members showing this pathology. Sequence analysis of the BSND gene showed that the affected members were homozygous for a C-to-T transition in exon 1, while their parents were heterozygous. This alteration results in a missense mutation, G47R, which has been previously shown to abolish the stimulatory effect on the subunit barttin of the ClC-Kb channel. Our results indicate that families with the G47R mutation indeed present polyhydramnios, premature birth and salt loss. Nevertheless, glomerular filtration rate was normal in all patients. Clinical manifestations are moderate in patients with the G47R mutation compared to other published data form patients with BSND. This constitutes the first report of BSND cases in Spain.

Adolescent↗
PubMed2006

Prins-type synthesis and SAR study of cytotoxic alkyl chloro dihydropyrans.

A series of functionalized tetrahydropyran and dihydropyran derivatives was synthesized by means of a Prins-type cyclization between unsaturated alcohols and several aldehydes. An unprecedented dimer bearing two 4-chloro-5,6-dihydro-2H-pyran scaffolds was obtained in high yield. A panel of three representative human solid tumor cells from diverse origin was used to assess the cytotoxicity of the compounds. Overall, the results show the relevance of the chlorovinyl group in the biological activity, and 2-alkyl-4-chloro-5,6-dihydro-2H-pyrans represent interesting leads for further chemical modifications and biological studies.

Antineoplastic Agents↗
PubMed2006

Tyrosine phosphatase SHP-2 regulates IL-1 signaling in fibroblasts through focal adhesions.

Interleukin-1beta (IL-1beta) mediates destruction of matrix collagens in diverse inflammatory diseases including arthritis, periodontitis, and pulmonary fibrosis by activating fibroblasts, cells that interact with matrix proteins through integrin-based adhesions. In vitro, IL-1beta signaling is modulated by focal adhesions, supramolecular protein complexes that are enriched with tyrosine kinases and phosphatases. We assessed the importance of tyrosine phosphatases in regulating cell-matrix interactions and IL-1beta signaling. In human gingival fibroblasts plated on fibronectin, IL-1beta enhanced the maturation of focal adhesions as defined by morphology and enrichment with paxillin and alpha-actinin. IL-1beta also induced activation of ERK and recruitment of phospho-ERK to focal complexes/adhesions. Treatment with the potent tyrosine phosphatase inhibitor pervanadate, in the absence of IL-1beta, recapitulated many of these responses indicating the importance of tyrosine phosphatases. Immunoblotting of collagen bead-associated complexes revealed that the tyrosine phosphatase, SHP-2, was also enriched in focal complexes/adhesions. Depletion of SHP-2 by siRNA or by homologous recombination markedly altered IL-1beta-induced ERK activation and maturation of focal adhesions. IL-1beta-induced tyrosine phosphorylation of SHP-2 on residue Y542 promoted focal adhesion maturation. Association of Gab1 with SHP-2 in focal adhesions correlated temporally with activation of ERK and was abrogated in cells expressing mutant (Y542F) SHP-2. We conclude that IL-1beta mediated maturation of focal adhesions is dependent on tyrosine phosphorylation of SHP-2 at Y542, leading to recruitment of Gab1, a process that may influence the downstream activation of ERK.

Actinin↗
PubMed2006

[Hepatocarcinoma in noncirrhotic liver].

Hepatocellular carcinoma (HCC) usually develops in patients with liver cirrhosis or chronic liver disease. These tumors are highly infrequent in patients without precipitating factors. We present a series of four patients with nonfibrolamellar HCC arising in healthy liver. None of the patients had viral infection, or showed alcohol abuse and/or hemochromatosis. Three patients underwent surgery. The clinical characteristics, therapeutic options, and survival and recurrence rates in this type of tumor are discussed.

Adult↗
PubMed2006

A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.

OBJECTIVE: It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). DESIGN: Randomized, controlled clinical trial. SETTING: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study). PATIENTS: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV. INTERVENTIONS: In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). CONCLUSIONS: A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.

Adult↗
PubMed2005

The tert-butyl dimethyl silyl group as an enhancer of drug cytotoxicity against human tumor cells.

In this study, we synthesized a series of enantiomerically pure (2R,3S)-disubstituted tetrahydropyranes with diverse functional groups using known methodologies. In addition to the tert-butyl dimethyl silyl group, other common protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were used to obtain appropriate derivatives. Pure compounds were evaluated in vitro against HL60 human leukemia cells and MCF7 human breast cancer cells. From the growth inhibition data a structure-activity relationship was obtained. Overall the results point to the relevant role of the tert-butyl dimethyl silyl group in the modulation of cytotoxic activity.

Acetates↗
PubMed2005

Antiproliferative activity in HL60 cells by tetrasubstituted pyrroles: a structure-activity relationship study.

A number of tetrasubstituted pyrrole derivatives have been synthesized and evaluated for their in vitro antiproliferative activities using the human promyelocytic leukemia cell line HL60. Tetrasubstituted pyrroles are obtained by irradiation of a silica gel absorbed mixture of a conjugated alkynoate and a primary amine. Active compounds exhibited GI50 values in the range 4-45 microM, and only six products showed TGI values within the evaluation range. A structure-activity relationship is also discussed.

Cell Division↗
PubMed2005

[Distal pancreatectomy: one technique with several indications].

INTRODUCTION: Distal pancreatectomy (DP) is performed for various pancreatic processes. This procedure has become less frequent since it ceased to be systematically used in oncologic gastric surgery and it is now performed mainly in patients with chronic pancreatitis. We present a series of patients who underwent DP and discuss technical features and surgical indications. PATIENTS AND METHODS: We performed a retrospective study of patients who underwent classical DP with associated splenectomy (CIE: 52.52) in our service from 1998-2003. Fourteen DP were performed during the study period. RESULTS: The mean age was 52.6 years. Thirty-six percent of the patients were male (5/14). Diagnosis was mucinous cystic tumor of the pancreas (5), neuroendocrine tumor (3), focal chronic pancreatitis (2), pancreatic cancer (2), pancreatic injury due to a sharp instrument wound (1), and pancreatic metastases from renal cancer (1). The most frequently used diagnostic procedure was abdominal computerized axial tomography (13/14). Surgery was elective in 86%. The technique used to close the distal stump was manual suture (29%), mechanical stapling (64%) and suture plus stapling (7%). No statistically significant relationship was observed between closure of the stump and the development of pancreatic fistula. Morbidity was 35% and mortality was 0%. The mean length of hospital stay was 18 days. CONCLUSIONS: DP can be performed without mortality but morbidity is not inconsiderable and is usually associated with the development of pancreatic fistulas. The indications for DP have changed and currently this procedure is performed for several pancreatic processes that are becoming increasingly frequent.

Adult↗
PubMed2005

[Duodenal adenocarcinoma].

INTRODUCTION: Duodenal adenocarcinoma is an infrequent neoplasm. Consequently, there are no large series that would allow conclusions to be reached on its diagnosis and treatment. PATIENTS AND METHOD: A retrospective study (1999-2003) of five patients diagnosed with duodenal adenocarcinoma in our service was performed. RESULTS: The mean age was 54 years. Eighty percent were male. All patients showed weight loss and abdominal pain. The tumors were localized in the second portion in three patients and in the third portion in two patients. All patients underwent gastrointestinal endoscopy with biopsy, which revealed adenocarcinoma. The most effective diagnostic test was computed tomography. In all patients, the preoperative diagnosis was correct. The technique performed was cephalic duodenopancreatectomy in three patients and duodenectomy with atypical pancreatic resection and right hemicolectomy in one patient. A decision not to perform surgery was made in one patient with liver metastases. Two patients who underwent surgery showed no complications. The remaining two patients showed slow gastric emptying in one patient and pancreatitis of the stump leading to fatal systemic inflammatory response syndrome in the other. Patient survival was 60, 13 and 1 month respectively. There were no recurrences. The patient who did not undergo surgery died at 4 months. CONCLUSION: Duodenal adenocarcinoma is an infrequent tumor that is associated with various diseases. Surgical treatment is usually cephalic duodenopancreatectomy. Survival in resected patients is better than that obtained in primary pancreatic tumors.

Adenocarcinoma↗
PubMed2005

[Benign solid liver tumors].

Benign solid liver tumors are a heterogeneous group of lesions (adenoma, focal nodular hyperplasia, hemangioma, etc.) with highly varied epidemiological characteristics. Advances in diagnostic methods have improved preoperative diagnosis. Magnetic resonance imaging has become the key test, but there is still a percentage of cases in which definitive preoperative diagnosis is not feasible. The most frequent symptom is abdominal pain, although patients are frequently asymptomatic. Surgery is indicated when diagnosis is uncertain or there are complications (rupture, hemorrhage, etc.). Because of the risk of malignant transformation, adenomas should always be resected. Morbidity and mortality after resection of these tumors is very low since excision is limited, performed in young people without concomitant disease, and in healthy liver.

Adenoma↗
PubMed2005

[Surgical treatment of liver metastases from breast cancer].

INTRODUCTION: A small number of patients with breast cancer develop liver metastases (LM) as the sole site of regional dissemination. In these patients, surgical resection seems to be the best therapeutic option. We present our experience of LM from breast cancer and discuss the indications for resection. MATERIAL AND METHODS: Between July 2003 and March 2005, we performed five hepatectomies for LM from breast cancer. The mean age was 51 years (range: 38-66). Patients received diverse combinations of chemotherapy, hormone therapy and radiotherapy after mastectomy. The disease-free interval between mastectomy and diagnosis of LM was 61 months (range: 36-80). The number of LM was 1.83 (range: 1-6) with a median of one LM. The mean size was 4.1 cm (range: 1.5-6). RESULTS: Surgery consisted of segmentectomy (three patients), bisegmentectomy (one patient), right hepatectomy associated with isolated metasectomies of the left lobe and hilar lymphadenectomy (one patient). Operative mortality was 0%. Morbidity was 20% (one patient). The mean length of hospital stay was 8 days. The mean length of follow-up was 11.4 months (range: 3-21). The mean survival was 11.4 months (range: 3-21). Disease-free survival was 9.6 months (range: 3-21). Two patients have had recurrence (one local and one regional). CONCLUSIONS: Given its characteristics, LM from breast cancer is an infrequent indication for liver resection and should be performed whenever technically feasible, whenever R0 resection can be achieved, and when there is low operative risk. Postoperative survival is better with resection than with any other therapeutic modality, even though the period of disease-free survival is short.

Adult↗
PubMed2004

Signet-ring-cell carcinoma of the Vater's ampulla.

CONTEXT: Most tumors affecting Vater's Ampulla are adenocarcinomas and other histological variants are less frequent. A review of the literature revealed only seven previously reported cases of signet ring cell carcinoma of the ampulla of Vater. The presence of this kind of tumor has no clear histological explanation. Two possible theories have been proposed: the presence of gastric heterotopia in the ampulla of Vater or the existence of a perivaterian duodenal heterotopia of ulcerous etiology as the origin of a signet ring cell tumor which secondarily invades the ampulla of Vater. CASE REPORT: We performed a pancreatoduodenectomy in a 67-year-old woman with a T2N0M0 ampulla tumor. A histologic study revealed a signet ring cell neoplasm. CONCLUSION: Etiology and survival of signet ring cell carcinoma of Vater's ampulla is not well-defined in the literature due to the extreme rarity of this disease. Duodenopancreatectomy with pylorus preservation is the treatment of choice.

Adenocarcinoma↗
PubMed2004

Molecular cloning and expression in yeast of caprine prochymosin.

We cloned and characterized a preprochymosin cDNA from the abomasum of milk-fed kid goats. This cDNA contained an open reading frame that predicts a polypeptide of 381 amino acid residues, with a signal peptide and a proenzyme region of 16 and 42 amino acids, respectively. Comparison of the caprine preprochymosin sequence with the corresponding sequences of lamb and calf revealed 99 and 94% identity at the amino acid level. The cDNA fragment encoding the mature portion of caprine prochymosin was fused in frame both to the killer toxin signal sequence and to the alpha-factor signal sequence-FLAG in two different yeast expression vectors. The recombinant plasmids were transformed into Kluyveromyces lactis and Saccharomyces cerevisiae cells, respectively. Culture supernatants of both yeast transformants showed milk-clotting activity after activation at acid pH. The FLAG-prochymosin fusion was purified from S. cerevisiae culture supernatants by affinity chromatography. Proteolytic activity assayed toward casein fractions indicated that the recombinant caprine chymosin specifically hydrolysed kappa-casein.

Amino Acid Sequence↗
PubMed2004

Bench-to-bedside review: understanding genetic predisposition to sepsis.

Sepsis is a complex syndrome that develops when the initial, appropriate host response to an infection becomes amplified, and is then dysregulated. Among other factors, the innate immune system is of central importance to the early containment of infection. Death from infection is strongly heritable in human populations. Hence, genetic variations that disrupt innate immune sensing of infectious organisms could explain the ability of the immune system to respond to infection, the diversity of the clinical presentation of sepsis, the response to current medical treatment, and the genetic predisposition to infection in each individual patient. Such genetic variations may identify patients at high risk for the development of sepsis and organ dysfunction during severe infections. Single base variations, known as single nucleotide polymorphisms (SNPs), are the most commonly used variants. There has been great interest in exploring SNP in those genes involved in the inflammatory cascade resulting from the systemic inflammatory response to micro organisms. The rationale for studying gene SNPs in critical illnesses seeks to identify potential markers of susceptibility, severity, and clinical outcome; seeks to identify potential markers for responders and non-responders in clinical trials, and seeks to identify targets for therapeutic intervention. In this review, we focus on the current state of association studies of those genes governing the powerful bacterial infection-induced inflammation and provide guidelines for future studies describing disease associations with genetic variations based on current recommendations. We envision a time in the near future when genotyping will be include in the standard evaluation of critically ill patients and will help to prioritize a therapeutic option.

Genetic Markers↗