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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 91 records · Page 5Linked to original sources

Time to first shock in implantable cardioverter defibrillator (ICD) patients with Chagas cardiomyopathy.

UNLABELLED: The time to first ICD shock has been extensively studied in patients with coronary artery disease (CAD). However, there are no published data on ICD shocks in patients with Chagas cardiomyopathy (ChC). The occurrence of the first appropriate ICD shock during the first 6 months of follow-up in 20 patients with ChC (group 1) and 35 CAD patients (group 2) was analyzed retrospectively. All patients had received a third-generation pectoral ICD for ventricular tachycardia or fibrillation (VT/VF). Indications for ICD implantation were refractoriness to drug therapy or noninducibility of VT/VF at EPS in cardiac arrest survivors. RESULTS: The mean age, left ventricular ejection fraction (LVEF), and sex in groups I and II were 57.4 +/- 7 years versus 64 +/- 9 (P < 0.01), 30.9% +/- 10% versus 32.9% +/- 10% (P = NS), and 10 men versus 31 women (P < 0.005), respectively. Six months after ICD implantation, 85% (17/20) group I patients received appropriate ICD shocks versus 51% (18/35) in group 2, a statistically significant difference (P < 0.02, RR: 1.65, OR: 5.35). CONCLUSIONS: The incidence of appropriate ICD shocks within the first 6 months postimplantation was significantly higher in ChC patients than in CAD patients. ChC patients were younger and more often women than CAD patients.

Adult↗

The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome.

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. To gain further insight into the mechanisms leading to dysregulation of the GH-IGF-1 axis in these patients, we assessed 24-h spontaneous GH secretion, GH responses to GHRH, and IGF-1 and IGF binding protein (BP)-3 levels before and after 4 days treatment with human (h)GH. We found that, in comparison with controls, patients with FM exhibited a marked decrease in spontaneous GH secretion as assessed by mean GH secretion (2.5 +/- 0.4 microg/L in controls vs. 1.2 +/- 0.1 microg/L in FM, P < 0.05), pulse height (4.7 +/- 0.8 microg/L in controls vs. 2.5 +/- 0.3 microg/L in FM, P < 0.05), and pulse area (4.7 +/- 1 min/mg x L in controls vs. 2.3 +/- 0.3 min/mg x L in FM, P < 0.05). In contrast, GH responses to GHRH (100 microg, i.v.) were similar in controls (mean peak, 13.5 +/- 2.5 microg/L) and in patients with FM (12.2 +/- 3 microg/L). Finally, treatment with hGH (2 IU, s.c. daily), over 4 days, led to a clear-cut increase in plasma IGF-1 and IGFBP-3 levels in patients with FM. In conclusion, our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM.

Adult↗

The flow cytometric pattern of CD34, CD15 and CD13 expression in acute myeloblastic leukemia is highly characteristic of the presence of PML-RARalpha gene rearrangements.

BACKGROUND AND OBJECTIVE: Rapid identification of AML patients carrying the t(15;17) translocation for treatment decision-making is currently made on the basis of morphologic screening. However, the existence of both false positives and negatives highlights the need for more objective methods of screening AML cases and further molecular confirmation of the t(15;17) translocation. DESIGN AND METHODS: In the present study we analyzed a total of 111 AML cases in order to investigate whether immunophenotyping based on the assessment of multiple-stainings analyzed at flow cytometry could improve the sensitivity and specificity of morphologic identification of acute promyelocytic leukemia (APL) carrying the t(15;17) translocation. FISH analysis was used as a complementary technique for cases in which morphology and molecular biology yielded discrepant results. RESULTS: Concordant results between morphology and RT-PCR were found in 102/111 (91.8%) cases: 34 patients had M3/PML-RARalpha+ and 68 non-M3/PML-RARalpha- disease. Nine cases showed discrepants results. Multivariate analysis showed that the best combination of immunologic markers for discriminating between M3/PML-RARalpha+ and non-M3/PML-RARalpha- cases was that of the presence of heterogeneous expression of CD13, the existence of a single major blast cell population, and a characteristic CD34/CD15 phenotypic pattern (p<0.02). A score system based on these parameters was designed, and the 34 M3/PML-RARalpha+ cases showed a score of 3 (presence of the 3 phenotypic characteristics). In contrast, only 1 out of the 68 (1.3%) non-M3/PML-RARalpha- cases had this score, most o these latter cases (53/68, 78%) scoring either 0 or 1. Therefore, among these cases, immunophenotyping showed a sensitivity of 100% and a specificity of 99% for predicting PML/RARalpha gene rearrangements. Of the 9 cases in which morphology and molecular biology results were discrepant, four cases displayed M3 morphology without PML/RARalpha rearrangements by RT-PCR. In only one of these 4 cases did the immunophenotype score 3, this being the only FISH positive case. From the remaining five discrepant cases (non-M3 morphology while positive for PML/RARalpha) two cases had a phenotypic score of 3 and were FISH positive while the other three were negative by FISH. Upon repeating RT-PCR studies, two of these latter three cases became negative. INTERPRETATION AND CONCLUSIONS: Our results show that immunophenotyping may be of great value for quick screening of APL with PML/RARalpha rearrangements.

Adolescent↗

Lon-mediated proteolysis of the Escherichia coli UmuD mutagenesis protein: in vitro degradation and identification of residues required for proteolysis.

Most SOS mutagenesis in Escherichia coli is dependent on the UmuD and UmuC proteins. Perhaps as a consequence, the activity of these proteins is exquisitely regulated. The intracellular level of UmuD and UmuC is normally quite low but increases dramatically in lon- strains, suggesting that both proteins are substrates of the Lon protease. We report here that the highly purified UmuD protein is specifically degraded in vitro by Lon in an ATP-dependent manner. To identify the regions of UmuD necessary for Lon-mediated proteolysis, we performed 'alanine-stretch' mutagenesis on umuD and followed the stability of the mutant protein in vivo. Such an approach allowed us to localize the site(s) within UmuD responsible for Lon-mediated proteolysis. The primary signal is located between residues 15 and 18 (FPLF), with an auxiliary site between residues 26 and 29 (FPSP), of the amino terminus of UmuD. Transfer of the amino terminus of UmuD (residues 1-40) to an otherwise stable protein imparts Lon-mediated proteolysis, thereby indicating that the amino terminus of UmuD is sufficient for Lon recognition and the ensuing degradation of the protein.

ATP-Dependent Proteases↗

Caprine testicular hypoplasia associated with sexual reversion decreases the expression of insulin-like growth factor II (IGF-II) mRNA in testes.

The genetic expression of insulin-like growth factor II (IGF-II) mRNA was studied in healthy adult testes and in hypoplastic testes of polled Murciano-Granadina goats by means of in situ hybridization. A positive reaction in spermatogonia, pachytene spermatocytes and a few peritubular myoid cells was observed using the ovine antisense oligonucleotide in healthy testes. The hypoplastic testes displayed a loss of germinal epithelium and a slight thickening of the basement membranes. A limited number of immature germinal cells displayed a lesser hybridization reaction, while the expression of IGF-II mRNA observed in the peritubular myoid cells was similar to that seen in healthy testes. In hypoplastic testes, IGF-II mRNA expression within germinal cells decreased with increasing hypoplasia within the seminiferous epithelium and there was no hybridization within the tubules in cases of severely disrupted spermatogenesis. These results suggest that testicular hypoplasia is associated with changes in the expression of IGF-II mRNA.

Animals↗

The sequential role of lymphotoxin and B cells in the development of splenic follicles.

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-beta receptor (LT-betaR), since blocking ligand-receptor interaction in recipient SCID mice ablates the capacity of the transferred cells to segregate. A week after lymphocyte transfer, host-derived FDCs appeared in the reconstituted SCID mice. This induction of FDCs is dependent on LT-betaR signaling by B cells since LT-alpha-/- B cells are incapable of inducing development of FDCs in SCID mice, even after cotransfer of LT-alpha+/+ T cells. Therefore, LT plays at least two discrete roles in splenic organization. First, it appears that LT induces the differentiation of the white pulp to create sites for lymphocyte segregation. Second, LT expression by B cells drives the maturation of FDCs and the organization of B cell follicles.

Animals↗

Increased acquired dyschromatopsia among solvent-exposed workers: an epidemiology study on 249 employees of an aluminum-foil printing factory.

OBJECTIVE: To analyze the effects on color vision of chronic exposure to mixtures of solvents including ethyl acetate, ethanol, and ketones among the workers of a large factory specializing in the manufacture of photoengraved aluminum packaging. METHODS: We analyzed a group of 129 subjects who had been exposed to solvents for more than 3 years (mean age 40 years, range 25 59 years) and a nonexposed group of 120 subjects (mean age 41 years, range 21-57 years). The two groups had a similar length of service (17 and 19 years on average, respectively). The exposed subjects consumed more tobacco and alcohol than the nonexposed workers. The study involved administration of the Lanthony D-15 desaturated test. The subjects were classified as having or not having dyschromatopsia on the basis of Lanthony's criteria and the chromatic confusion index (CCI) was calculated according to Bowman's method. After observation of the work stations and analysis of an occupational questionnaire the findings were used to construct a cumulative exposure index covering the whole of each subject's working life. Air samples were taken at each work station and in each production sector to determine current exposure. RESULTS: The average cumulative exposure index was 194 (median 174, range 27-513). The average hygienic effect index (according to ACGIH recommendations), regularly used for atmospheres containing mixtures of products, varied between 12% and 27% of the occupational limit values permitted under French legislation. As regards color vision, 23% of the exposed group had dyschromatopsia, as did 13% of the nonexposed group, with the odds ratio (OR) adjusted for age and consumption of tobacco and alcohol being 1.99 (1.02, 3.89). The analysis of the dose-response relationship according to the cumulative exposure index showed an OR of 1.59 for the lowly exposed group (index < 174) and an OR of 2.40 for the highly exposed group (index > 174) as compared with the nonexposed group. Subjects with complex color vision loss (n=23) had a significantly higher cumulative exposure index than those with blue-yellow loss (n=23; 232 versus 155; P=0.04). The CCI was on average higher in the exposed group, but the difference between the two groups was not significant. CONCLUSION: The results of this study are in favor of an increased risk for impairment of chromatic discrimination among workers exposed to mixtures of solvents including mainly ethyl acetate, ethanol, and ketones.

Adult↗

Evidence of a strong interaction of 2,4-dichlorophenoxyacetic acid herbicide with human serum albumin.

The interaction of 2,4-dichlorophenoxyacetic acid herbicide (2,4-D) with human serum albumin (HSA) was studied using fluorescence and differential scanning calorimetry (DSC). Fluorescence displacement of 1-anilino-8-naphtalenesulfonate (ANS) bound to HSA was used to evaluate the binding affinity of 2,4-D to HSA. The binding is associated to a high affinity site of HSA located in the IIIA subdomain. The association constant (Kass) of the herbicide was about 5 microM(-1), several times higher than the affinity found for pharmaceutical compounds. This relatively strong interaction with HSA was evidenced by the increase in HSA protein thermostability induced as consequence of herbicide interaction. 2,4-D induces an increase in the midpoint of thermal denaturation temperature from 60.1 degrees C in herbicide free solution to 75.6 degrees C in full ligand saturating condition. The calorimetric enthalpy and the excess heat capacity also increased upon 2,4-D binding. To investigate the possibility of other/s system/s of 2,4-D transport in blood, besides of HSA, the interaction of the herbicide with lipid monolayers was explored. No interaction was detected with any of the lipids tested. The overall results provided evidence that high affinity 2,4-D-HSA complex exhibits enhanced thermal stability and that HSA is the unique transport system for 2,4-D in blood.

2,4-Dichlorophenoxyacetic Acid↗

Study of the behavioral effects of bilateral nucleus accumbens lesions on amphetamine and apomorphine in adult cats.

The aim of the present work was to study the effects of three different types of bilateral lesions performed on the nucleus accumbens, upon the behaviors elicited in adult cats by parenteral administration of amphetamine and apomorphine, and to obtain an understanding of the functional role played by the cited structure. To this end, 10 cats received bilateral injections of 6-OHDA, 18 microg in each accumbens; 8 cats received a similar treatment with ibotenic acid (20 microg), and 11 cats were submitted to bilateral electrolytic damage. Before and after performing these lesions, in separate sessions, amphetamine (2.5 mg/kg SC) and apomorphine (2.0 mg/kg SC) were administered and their respective behaviors were compared. Besides, in a group of 10 cats, 6 of them were bilaterally injected with the above cited dose of 6-OHDA into the accumbens to determine dopamine concentration and the other four served as control. In three cats, ibotenic acid (20 microg) was unilaterally injected into the accumbens for histological analysis. The contralateral structure served as control. Finally, four cats were sham operated. The results obtained show that the accumbens in cats participates in locomotion, in stereotyped motor behaviors, and in emotional fear-like behavior. Its role in the production of motor behaviors apparently is not as important as has been reported in rodents.

Amphetamine↗

The innervation pattern of the radial nerve at the elbow and in the forearm.

Sixty paired cadaver forearms were dissected to examine the distribution of the radial nerve branches to the muscles at the elbow and forearm. Emphasis was placed on the innervation of the extensor carpi radialis brevis and the supinator muscles because of discrepancies in the literature concerning these muscles. The most common branching pattern (from proximal to distal) was to brachioradialis, extensor carpi radialis longus, superficial sensory, extensor carpi radialis brevis, supinator, extensor digitorum/extensor carpi ulnaris, extensor digiti minimi, abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus and extensor indicis. The branch to extensor digitorum and extensor carpi ulnaris came off as a common stem often with the branch to extensor digiti minimi. The branch to the ECRB muscle was noted to arise from the posterior interosseous nerve in 45%, superficial sensory nerve in 25% and at the bifurcation of the posterior interosseous and superficial sensory nerves in 30% of specimens. The supinator had an average of 2.3 branches from the posterior interosseous nerve (range 1-6). The branches to the supinator showed a wide variability proximal to and within the supinator.

Elbow↗

The flexor pollicis longus and its relation to the anterior and posterior interosseous nerves.

Sixty paired cadaver upper extremities were dissected to study the anatomy of the flexor pollicis longus in the forearm and its relation to the median and anterior interosseous nerves. An accessory head was noted in 33 (55%) of 60 specimens. The accessory head was noted to pass anterior to the anterior interosseous nerve in all specimens. The accessory head was noted to pass posterior to the median nerve in 57 specimens, and anterior to the nerve in three. Tendon or muscle anomalies were noted in eight specimens (13%), seven of which involved an anomalous attachment between the FPL and the flexor digitorum profundus of the index.

Forearm↗

Warm ischemic time tolerance after ventilated non-heart-beating lung donation in piglets.

OBJECTIVE: The availability of lungs for transplantation could be ameliorated with the use of organs retrieved from ventilated non-heart-beating donors (VNHBD). The aim of this work is to determine the limit to tolerable in situ warm ischemia time (WIT) for lung grafts after circulation is stopped. METHODS: Twenty piglets underwent left lung allotransplantation. Animals were randomly allocated based on the donor's status before lung harvesting into the following study groups: Sham (n = 5), Heart-beating donors-non-warm ischemia; I-30 (n = 5), I-60 (n = 5) and I-90 (n = 5), VNHBD-WIT of 30, 60 and 90 min, respectively. Right pulmonary artery and bronchus were permanently occluded one hour after transplantation. Assessment of pulmonary function was monitored hourly by hemodynamic, oxygenation and pulmonary mechanic measurements during a period of 6 h after reperfusion. Lung grafts were weighed pre- and post-transplantation. RESULTS: Cold ischemic time was similar for all groups, and averaged 80.1+/-2.7 min. Final mean lung weight was significantly greater in VNHBD (92.5+/-3.1 g vs. Sham values 75.6+/-2.4 g, P < 0.01). After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also modified, with a rise in airway resistance and a fall in compliance. CONCLUSIONS: Post-transplantation lung graft function from VNHBD with up to 90 min of WIT, is equivalent to those achieved by grafts harvested after heart-beating donation. This method may be a promising strategy of increasing the pulmonary donor pool.

Animals↗

Risk factors of stroke after percutaneous transluminal coronary angioplasty.

Objective: to determine possible risk factors of a stroke after percutaneous transluminal coronary angioplasty (PTCA). Design: this is a retrospective evaluation of a consecutive group of 4088 patients undergoing PTCA between 1988 and 1995. We have studied the incidence, clinical characteristics, risk factors, and outcome. Results: seven patients, six males and one female (0.17%) developed a stroke after this procedure. In comparison with the control group, the stroke group did not differ regarding age or gender. The existence of a stroke (six located in the brain, and one in the spinal cord), represented 1.24% of all complications (P < 0.001), and 5% of all deaths (P < 0.01) of PTCA. Three patients developed TIA, two patients developed hemorrhagic strokes (in which they received previous thrombolytic therapy), and the other two patients suffered from an ischemic stroke. The statistically significant risk factors of a stroke after PTCA included: intracoronary thrombolytic therapy (P < 0.01), hypercholesterolemia (P < 0.001) and a prior PTCA (P < 0.05). Conclusions: although these procedural complications are infrequent, they are usually serious and important risk factors which could be identified prior to the procedure. These risk factors would allow identification of patients who are prone to a stroke after PTCA. Intracranial hemorrhage occurred only after thrombolytic therapy, and the factors related to hemorrhagic strokes were probably different from those predisposed to ischemic strokes and TIA. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗

Reduced-size lung transplantation from adult to neonatal swine.

BACKGROUND: Lung donor shortage is a critical factor limiting the expansion of pediatric lung transplantation programs. This report details the surgical technical feasibility of a training model of lobar lung transplantation as well as the perioperative monitoring to evaluate the appropriate pulmonary graft function. METHODS: Ten hybrid Large-White pigs underwent left lower lobe lung allotransplantation; Donors weighed 15 to 20 kg and recipients 5 to 7 kg. The first five animals were used to learn the surgical anatomy and to establish the surgical technique and instrumentation's model (Group A). One hour after transplantation the right lung was excluded. Lung function and hemodynamic data were collected sequentially in the following five animals (Group B). RESULTS: The left inferior pulmonary lobe was found to be the most suitable allograft for transplantation. Usually, bronchial size discrepancy allowed telescoping of the airway anastomosis. Left atrial clamping was well tolerated during the pulmonary vein anastomoses. Preoperative antiaggregation and postoperatively heparinization achieved with ACT values over 200 seconds, prevented left atrial thrombosis. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics were also modified, with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: The neonatal pig tolerates left lobar pulmonary transplantation satisfactorily. Although it is a useful and promising surgical learning model, questions remain regarding the applicability of this experience to clinical pediatric lung transplantation.

Animals↗

Essentiality of copper in humans.

The biochemical basis for the essentiality of copper, the adequacy of the dietary copper supply, factors that condition deficiency, and the special conditions of copper nutriture in early infancy are reviewed. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. Mechanisms responsible for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support the existence of a copper-dependent gene regulatory element. Diets in Western countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption, elevated requirements induced by rapid growth, or increased copper losses. The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerance. A range of safe intakes should be defined for the general population, including a lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population.

Animals↗

Snowblower injuries to the hand.

A retrospective review of 22 patients who sustained snowblower injuries to the hand was performed. There were 17 men and 5 women, ranging in age from 20 to 68 years (average age, 39.7 years). Fifty percent were manual laborers, 25% were unemployed, 15% were office workers, and 10% were not categorized. The dominant hand was involved in 86% of patients. In all patients, injuries occurred during an attempt to unclog manually the snowblower of wet snow. Patients were evaluated initially in the emergency room, where their wounds were irrigated and debrided, subungual hematomas drained, and nail bed lacerations repaired. Patients with more extensive injuries were taken to the operating room for definitive treatment including open or closed reduction of fractures, fingertip replacement as composite grafts or skin grafts, revision amputations, tenorrhaphies, and digital nerve repairs. All injuries occurred distal to the metacarpophalangeal joints. Only 1 patient sustained an injury to the proximal phalanx. Ten patients injured only 1 finger, 6 patients injured 2 fingers, and 6 patients injured 3 fingers. The middle and ring fingers were most commonly injured (39.6% and 33.3% respectively), followed by the index and little fingers (16.7% and 8.3% respectively), and the thumb (2.1%). Phalangeal fractures were the most common type of injury, occurring in 29.2% of patients, and usually involved the distal phalanx. This was followed in frequency by nail bed injuries (22.9%), amputations (22.9%), tendon lacerations (14.6%), soft-tissue avulsions (6.3%), and digital nerve injuries (4.2%). Snowblower injuries can involve bone, soft tissue, nail bed structures, nerves, and tendons, and may even result in amputation of one or several fingers. These injuries are localized to the distal portions of the fingers. The middle and ring fingers are most commonly involved, with relative sparing of the thumb. Fractures are the most frequent injury, followed by nail bed injuries and amputations. Snowblower injuries are often managed as open fractures with intravenous antibiotics; irrigation and debridement; and repair of bone, soft tissue, and nail bed structures.

Adult↗