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Biomedical subjects

A Perez

Publications and source records attributed to A Perez.

At least 37 records · Page 2Linked to original sources

What is the value of telerobotic technology in gastrointestinal surgery?

BACKGROUND: Although telerobotic technology has entered clinical application, its value for gastrointestinal surgery is unclear. Our objective was to evaluate the performance characteristics of telerobotically assisted laparoscopic cholecystectomy (TALC). METHODS: All TALCs performed using the da Vinci Surgical System between January 2000 and September 2001 at a tertiary academic medical center were analyzed. RESULTS: For this study, 20 patients (80% female) with a mean age of 47 +/- 4 years underwent TALC. All had symptomatic cholelithiasis, and all had successful TALC results without complications or need for conversion to conventional laparoscopic cholecystectomy (CLP). The mean procedure time was 152 +/- 8 min. The procedures were performed by one of three staff surgeons experienced in laparoscopic surgery who had training in telerobotic surgery. The perceived advantages of TALC over CLP included easier tissue dissection, enhanced dexterity, and stimulated interest in biliary surgery. The disadvantages included increased operating time and lack of tactile feedback. CONCLUSIONS: The TALC procedure is effective and safe when performed by appropriately trained surgeons. Telerobotic technology has the potential to reinvigorate gastrointestinal surgery.

Academic Medical Centers↗

Expression of nuclear receptors and apo E secretion during the differentiation of monocytic THP-1 cells into macrophages.

The human monocytic THP-1 cell line differentiates into macrophage-like cells that secrete apo E after addition of PMA. Using this model, we studied the time course of apo E transcriptional activation and secretion in relation with the expression of nuclear receptors. Upon treatment with PMA, apo E mRNA and protein secretion were triggered with the concomitant increase of LXRalpha, PPARgamma, and PPARbeta mRNA expression levels. PPARalpha was downregulated, RXRalpha expression was unchanged, and RARalpha and VDR showed only transient increases. FXR and SXR transcripts were not detectable. Specific agonists were used to investigate the functional role of these nuclear receptors upon apo E secretion. The LXRalpha ligands T0901317 and 22(R)-hydroxycholesterol were the most potent apo E inducers, followed by the PPARgamma agonist BRL49653. The PPARalpha agonist Wy14,643 was inactive and 1alpha,25-dihydroxyvitamin D3, 9-cis-retinoic acid and all-trans-retinoic acid decreased apo E secretion. Thus, during PMA-induced THP-1 differentiation, there is a sequential and coordinate regulation of apo E and nuclear receptor transcription.

Apolipoproteins E↗

Communication in general practice: differences between European countries.

BACKGROUND: Based on differences in national health care system characteristics such as the gatekeeping role of GPs (at the macrolevel) and on diverging GP and patient characteristics (at the microlevel), communication may differ between countries. Knowledge of the influence of these characteristics on doctor-patient communication will be important for setting European health care policies. OBJECTIVES: Our objectives were (i) to compare doctor-patient communication in general practice between European countries; and (ii) to investigate the influence of the gatekeeping system and GP and patient characteristics on doctor-patient communication in general practice. METHODS: Fifteen patients per GP (in total 2825 patients) of 190 GPs in six European countries were included. Participating countries were The Netherlands, Spain, the UK (gatekeeping countries), Belgium, Germany and Switzerland (non-gatekeeping countries). Data were collected by means of patient and GP questionnaires and observation of videotaped consultations, and analysed by one-way and multilevel, multivariate analysis. RESULTS: Differences in communication between countries were found in: affective and instrumental behaviour; biomedical and psychosocial talk; GPs' patient-directed gaze; and consultation length. The study showed that GPs' gatekeeping role (with registered patients) was less important for doctor-patient communication than was expected. Patient characteristics such as gender, age, having psychosocial problems, and familiarity between the doctor and the patient were the most important in explaining differences in communication. CONCLUSION: The gatekeeping role of GPs is hardly important in explaining doctor-patient communication. The relationship is more complex than expected. Patient and GP characteristics are more important. Cultural factors should be included in future studies.

Adult↗

Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities.

Inoculation of Trypanosoma cruzi, Tulahuén strain, into C57BL/6 and BALB/c mice led to an acute infection characterized by marked parasitaemia, myocardial inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and lethal disease, BALB/c mice partly recovered. To characterize these murine models more effectively, we studied the parasite burden, serum levels of major infection outcome-related cytokines, the in vitro features of T. cruzi infection in peritoneal macrophages and the immunophenotype of thymic cells. The greater disease severity of T. cruzi-infected C57BL/6 mice was not linked to an increased parasite load, as parasitaemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were not different from those in BALB/c mice. Cortical thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.) revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group displayed higher levels of TNF-alpha on days 14 and 21 p.i., in the presence of lower IL-1beta and IL-10 concentrations by days 14 and 21, and days 7 and 14 p.i., respectively. Day-21 evaluation showed higher concentrations of nitrate and TNF-alpha soluble receptors in C57BL/6 mice with no differences in IFN-gamma levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi-infected mice does not seem to result from an aggravated infection but from an unbalanced relationship between pro- and anti-inflammatory mediators.

Acute Disease↗

Angiotensin AT(1) receptor stimulates heat shock protein 27 phosphorylation in vitro and in vivo.

The angiotensin type 1 receptor (AT(1)) exerts a variety of its signaling and cellular actions through its effects on protein phosphorylation. Phosphoproteomic analysis of angiotensin (Ang) II-stimulated aortic smooth muscle cells revealed that heat shock protein 27 (HSP27) represents a major protein phosphorylation target of the AT(1) signaling pathway. Stimulation of cells with Ang II resulted in 1.7-fold (P<0.05) and 5.5-fold (P<0.001) increases in HSP27 phosphoisoforms at pI 5.7 and pI 5.4, respectively. This was accompanied by a 54% (P<0.01) decrease in the nonphosphorylated HSP27 isoform, located at pI 6.4. Treatment of samples with alkaline phosphatase reversed this redistribution of HSP27 phosphoisoforms. Ang II-stimulated HSP27 phosphorylation was completely blocked by pretreatment of cells with the AT(1) antagonist CV11974. Phosphoamino acid analysis demonstrated that Ang II-induced phosphorylation of both HSP27 phosphoisoforms occurred exclusively on serine. Protein kinase C inhibition completely blocked phorbol ester-induced HSP27 phosphorylation but did not impair Ang II-stimulated phosphorylation of HSP27, suggesting that AT(1) increased HSP27 phosphorylation by a protein kinase C-independent pathway. Intrajugular infusion of Ang II in rats increased HSP27 in aorta by 1.7-fold (P<0.02), and this response was inhibited by CV11974. These results suggest that Ang II-induced HSP27 phosphorylation is a physiologically relevant AT(1) signaling event. Because serine phosphorylation of HSP27 blocks its ability to cap F-actin, Ang II/AT(1)-induced HSP27 phosphorylation may play a key role in actin filament remodeling required for smooth muscle cell migration and contraction.

Angiotensins↗

Abdominal zippers for temporary abdominal closure in planned relaparotomies for peripancreatic sepsis: experience in a developing country.

BACKGROUND: Planned relaparotomies have generated renewed interest because of the high mortality rates associated with conventional management techniques in severe intraabdominal sepsis. The use of abdominal zippers for temporary abdominal closure was devised to facilitate repeated explorations, allowing daily cleansing of the peritoneal cavity and the detection and management of septic complications. METHODS: In our institution, eight patients were managed in a 4-year period, using abdominal zippers for peripancreatic sepsis. RESULTS: In all eight patients, subsequent laparotomies allowed the detection of progressive necrosis. Repeated explorations successfully controlled the sepsis in five patients. In three patients, the condition deteriorated, and they died of multiple organ failure. CONCLUSIONS: The technique warrants further prospective controlled trials in the local setting to ascertain its role in the management of severe intraabdominal sepsis, and in other patients who may require "second-look" operations.

Abdomen, Acute↗

Muc4/sialomucin complex in the mammary gland and breast cancer.

MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, characterized by mucin tandem repeat domains and a transmembrane domain which associates it with the cell plasma membrane. Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protective mechanism(s) may be highjacked by some carcinomas, such as those of the breast, to increase tumor progression. Two mechanisms are proposed to contribute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-recognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-beta, which are relieved during pregnancy to permit secretion of MUC4 into milk. These mechanisms are also abrogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.

Animals↗

Value of a dipstick based on recombinant RK39 antigen for differential diagnosis of American visceral leishmaniasis from other sympatric endemic diseases in Venezuela.

A laboratory trial using recombinant rK39 dipsticks for differential diagnosis of American visceral leishmaniasis (AVL) from other sympatric endemic diseases which share similar clinic features (Chagas disease, malaria, schistosomiasis and toxoplasmosis) was conducted in Venezuela. The 100% specificity of the test previously obtained in other countries was confirmed. The use of this test at the primary health care level in Venezuela for a rapid diagnosis of active AVL cases, which may avoid deaths, is recommended.

Antigens, Protozoan↗

The effects of food restriction in man on hepatic metabolism of acetaminophen.

BACKGROUND: Recent reports have suggested that food deprivation may contribute to acetaminophen hepatotoxicity by shunting drug detoxification from the conjugative to the potentially toxic oxidative pathways. METHODS: This study assessed this concept in a prospective study of food restriction of 500 calories/day over 5 days and also of 1000 calories/day over 13 days. Obese, otherwise normal, individuals received 2 g acetaminophen orally at the start and again after food restriction. Sequential liver tests, as well as serum and urine acetaminophen and its derivatives were measured. RESULTS: In both food-restricted groups there was no evidence of any change in the elimination or in the metabolic pattern of acetaminophen removal. Liver tests remained normal. The average weight loss was about 6 pounds. CONCLUSIONS: Our data, with this brief, but major degree of food restriction, and this load of acetaminophen (half-maximal daily dose), do not demonstrate an effect of caloric restriction on acetaminophen disposition.

Acetaminophen↗

Diving after stapedectomy: clinical experience and recommendations.

OBJECTIVES: Much controversy exists concerning the risk of inner ear barotrauma after stapes surgery in scuba and sky divers. Uniform consensus has not been established regarding poststapedectomy barorestrictions. The purpose of this study was (1) to determine the prevalence of adverse auditory and/or vestibular sequelae in patients after stapedectomy related to scuba and sky diving, and (2) to offer recommendations on barometric exposure after stapes surgery. STUDY DESIGN: Survey questionnaires were mailed to 2222 patients who had undergone stapedectomies at a single tertiary otologic referral center between 1987 and 1998. Two hundred eight of the initial 917 respondents (22.7%) had snorkeled, scuba, or sky dived after stapes surgery, and 140 of these responded to a second questionnaire detailing dive protocols, otologic symptoms, and their relationship to the diving activities. Of the 140, 28 had scuba or sky dived. Their survey data were analyzed and their medical records were reviewed. RESULTS: Four of the 22 scuba divers (18.1%) experienced otologic symptoms at the time of diving. These included otalgia on descent (3/22; 13.6%), tinnitus (1/22; 4.5%), and transient vertigo on initial submersion (1/22; 4.5%). One patient had sudden sensorineural hearing loss and vertigo develop 3 months after scuba diving, which he related to noise exposure. He was subsequently found to have a perilymph fistula, which was successfully repaired. Of the 9 patients who sky dived, 2 patients (22.2%) reported otologic symptoms during the dive. No significant diving-related long-term effects indicative of labyrinthine injury were seen in any of the 28 patients. CONCLUSIONS: Stapedectomy does not appear to increase the risk of inner ear barotrauma in scuba and sky divers. These activities may be pursued with relative safety after stapes surgery, provided adequate eustachian tube function has been established.

Adolescent↗

Biochemical and histochemical analysis of 71 kDa dystrophin isoform (Dp71f) in rat brain.

Dp71 is a member of the dystrophin family and the most abundant dmd gene product in the brain. In the present study, we focused on a short dystrophin transcript named Dp71f, which is alternatively spliced when exon 78 is absent The topographic localization of this protein in the encephalon has not been properly described yet, nor its cellular or subcellular localization, and even less its functions. Dp71f was found to be a cytoplasmic 70 kDa protein and localized in all encephalon regions studied. Double labeling using specific markers for various cell types confirmed Dp71f distribution in the cytoplasm of all cell types studied. Labeling was more conspicuous near the nucleus and diminished towards the periphery of cells. In some cases, we observed cells that were positive for actin and Dp71f in regions corresponding to lamellipodia-like structures. Dp71f and Dp71d isoforms were differently distributed. Our study is the first specific and unambiguous description of the topography and cellular localization patterns of Dp71f in brain, suggesting that Dp71f is a ubiquitous protein.

Animals↗

Immunogenetic analysis of variable regions encoding AB1 and gamma-type AB2 antibodies from the NeuGc-containing ganglioside family.

The variable regions from P3, a murine monoclonal antibody (MAb) against NeuGc-containing gangliosides, and two anti-idiotype MAbs directed to P3 MAb were cloned and sequenced. Comparisons with previously reported sequences showed that P3 is a germline antibody encoded by genes from the V(H)Q52 and V(kappa)19 families. Analysis of nucleotides at the heavy chain CDR3 (H-CDR3) showed the presence of an extensive 3' N region that contains almost 50% of the nucleotides of this CDR. In addition, amino acid sequence analysis of the H-CDRs of this MAb revealed the presence of three arginines, two of which are present in the H-CDR3, that could be involved in the interaction of P3 MAb with its electronegative epitope on gangliosides. Anti-idiotype 1E10, which seems to define a "regulatory" idiotope on P3 MAb (it induces Id+ Ab3), represents a germline Ab2 that belongs to the V(H)J558 and V(kappa)10 gene families. By contrary, the anti-idiotype 3B11 is an extensively mutated antibody that belongs to the V(H)3660 and V(kappa)4/5 gene families, defining a "private" idiotope on P3 MAb. Even when different V genes contribute to the variable regions of 1E10 and 3B11 MAbs, they share an acidic motif E/D-D-Y/D-Y-D in H-CDR3, suggesting that both Ab2s recognize paratope positive residues on the Ab1. Therefore, complementary electrostatic interactions involving H-CDR3 from both Ab1 and Ab2, might provide a clue to understand the molecular basis for the generation of gamma-type anti-idiotype antibodies to V regions recognizing glycolylated ganglioside antigens.

Amino Acid Sequence↗

Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress.

The use of naturally occurring botanicals with substantial antioxidant activity to afford protection to human skin against UV damage is receiving increasing attention. The green tea constituent (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant and has shown remarkable preventive effects against photocarcinogenesis and phototoxicity in mouse models. In this study we have investigated the effects of topical application of EGCG, the major polyphenol present in green tea, to human skin before UV irradiation on UV-induced markers of oxidative stress and antioxidant enzymes. Using immunohistochemistry and analytical enzyme assays, we found that application of EGCG (mg/cm(2) skin) before a single UV exposure of 4x minimal erythema dose (MED) markedly decreases UV-induced production of hydrogen peroxide (68-90%, P < 0.025-0.005) and nitric oxide (30-100%, P < 0.025-0.005) in both epidermis and dermis in a time-dependent manner. EGCG pretreatment also inhibits UV-induced infiltration of inflammatory leukocytes, particularly CD11b(+) cells (a surface marker of monocytes/macrophages and neutrophils), into the skin, which are considered to be the major producers of reactive oxygen species. EGCG treatment was also found to inhibit UV-induced epidermal lipid peroxidation at each time point studied (41-84%, P < 0.05). A single UV exposure of 4x MED to human skin was found to increase catalase activity (109-145%) and decrease glutathione peroxidase (GPx) activity (36-54%) and total glutathione (GSH) level (13-36%) at different time points studied. Pretreatment with EGCG was found to restore the UV-induced decrease in GSH level and afforded protection to the antioxidant enzyme GPx. Further studies are warranted to study the preventive effects of EGCG against multiple exposures to UV light of human skin.

Adult↗

Necrotizing pancreatitis: contemporary analysis of 99 consecutive cases.

OBJECTIVE: To analyze the impact of a conservative strategy of management in patients with necrotizing pancreatitis, reserving intervention for patients with documented infection or the late complications of organized necrosis. SUMMARY BACKGROUND DATA: The role of surgery in patients with sterile pancreatic necrosis remains controversial. Although a conservative approach is being increasingly used, few studies have evaluated this strategy when applied to the entire spectrum of patients with necrotizing pancreatitis. METHODS: The authors reviewed 1,110 consecutive patients with acute pancreatitis managed at Brigham and Women's Hospital between January 1, 1995, and January 1, 2000, focusing on those with pancreatic necrosis documented by contrast-enhanced computed tomography. Fine-needle aspiration, the presence of extraintestinal gas on computed tomography, or both were used to identify infection. RESULTS: There were 99 (9%) patients with necrotizing pancreatitis treated, with an overall death rate of 14%. In three patients with underlying medical problems, the decision was made initially not to intervene. Of the other 62 patients without documented infection, all but 3 were managed conservatively; this group's death rate was 11%. Of these seven deaths, all were related to multiorgan failure. Five patients in this group eventually required surgery for organized necrosis, with no deaths. Of the 34 patients with infected necrosis, 31 underwent surgery and 3 underwent percutaneous drainage. Only four (12%) of these patients died, all of multiorgan failure. Of the total 11 patients who died, few if any would have been candidates for earlier surgical intervention. CONCLUSIONS: These results suggest that conservative strategies can be applied successfully to manage most patients with necrotizing pancreatitis, although some will eventually require surgery for symptomatic organized necrosis. Few if any patients seem likely to benefit from a more aggressive strategy.

Adult↗

Terminal sialylation is altered in airway cells with impaired CFTR-mediated chloride transport.

Reduced terminal sialylation at the surface of airway epithelial cells from patients with cystic fibrosis may predispose them to bacterial infection. To determine whether a lack of chloride transport or misprocessing of mutant cystic fibrosis transmembrane conductance regulator (CFTR) is critical for the alterations in glycosylation, we studied a normal human tracheal epithelial cell line (9/HTEo(-)) transfected with the regulatory (R) domain of CFTR, which blocks CFTR-mediated chloride transport; DeltaF508 CFTR, which is misprocessed, wild-type CFTR; or empty vector. Reduced cAMP-stimulated chloride transport is seen in the R domain and DeltaF508 transfectants. These two cell lines had consistent, significantly reduced binding of elderberry bark lectin, which recognizes terminal sialic acid in the alpha-2,6 configuration. Binding of other lectins, including Maakia amurensis lectin, which recognizes sialic acid in the alpha-2,3 configuration, was comparable in all cell lines. Because the cell surface change occurred in R domain-transfected cells, which continue to express wild-type CFTR, it cannot be related entirely to misprocessed or overexpressed CFTR. It is associated most closely with reduced CFTR activity.

Biological Transport↗

Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model.

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 +/- 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72-96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.

Animals↗