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Biomedical subjects

A Gomez

Publications and source records attributed to A Gomez.

At least 73 records · Page 4Linked to original sources

Renal TGF-beta regulation in spontaneously diabetic NOD mice with correlations in mesangial cells.

Diabetic nephropathy is characterized by excessive glomerular matrix accumulation, basement membrane thickening and sclerosis. Although it is clear that systemic metabolic disturbances precipitate such renal changes, the signals and pathways involved in this process are not fully elucidated. Recent evidence suggests that growth factors/cytokines are intimately involved in the pathogenesis of diabetic nephropathy. Because of its prosclerotic properties, transforming growth factor-beta (TGF-beta) is a prime candidate mediator of diabetic nephrosclerosis. We examined perfused kidney tissues isolated from spontaneously diabetic, non-obese diabetic mice (NOD) for TGF-beta content. By using murine isotype specific TGF-beta probes, we demonstrate that within 5 to 10 days of hyperglycuria renal TGF-beta 2 mRNA and protein content increases. By immunohistochemical analysis, de novo TGF-beta immunoreactivity was detected within both glomeruli and the interstitium. In order to determine the signals involved in promoting kidney TGF-beta content in vivo, TGF-beta regulation was examined in renal mesangial cells in vitro. Murine mesangial cells stimulated with glycosylated protein secrete bioactive TGF-beta and demonstrate a disproportionate increase in the steady state levels of TGF-beta 2 mRNA. These data suggest that a major early renal response in NOD mice to hyperglycemia or to glycosylated proteins is characterized by increases in TGF-beta.

Animals↗

Proliferative responses of lymphocytes from malaria patients and healthy controls to isolated, Plasmodium falciparum schizont antigens.

The specificity of lymphocyte proliferative responses of malaria patients and healthy control subjects was analysed using antigen fractions from soluble extracts of purified Plasmodium falciparum schizonts. Fractions of 14-250 kDa were separated by SDS-PAGE, blotted to nitrocellulose membranes and eluted for use in lymphocyte stimulation studies. Lymphocyte proliferation following stimulation with the separated protein fractions demonstrated that the fractions were recognized only by patients' T cells. Moreover, only the fractions including proteins of 36-250 kDa were immunogenic to the T cells. The pattern of response against each fraction differed between patients, indicating an HLA-dependent genetic restriction in the T cell activation.

Animals↗

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, both in continuous 96-hour infusion, in the treatment of locally advanced head and neck cancer.

In this study, 79 patients with locally advanced head and neck cancer were treated with induction chemotherapy. Cisplatin, 25 mg/m2, and 5-fluorouracil (5-FU), 1000 mg/m2, were employed, both of them in 24-hour continuous infusion over 96 hours, four cycles. The patients later underwent surgery and/or radiation therapy. The response to chemotherapy was 49%: of the complete responses (CR), 56% were histological; 29% were partial responses (PR). With the administration of the fourth cycle, CR increased from 30% to 49%. Once the complete treatment had been finished, 75% of CR and 5% PR were achieved. With a maximum follow-up period of 44 months, overall survival stands at 50%.

Antineoplastic Combined Chemotherapy Protocols↗

Left ventricular systolic performance is depressed in chronic pulmonary emphysema in dogs.

The effect of chronic right ventricular (RV) pressure overload on left ventricular (LV) systolic function in chronic obstructive lung disease is unclear. To examine LV systolic performance in pulmonary emphysema, a chronic canine model was developed in which pulmonary artery pressure could be elevated to a level found in human disease. Severe emphysema was produced by the repeated instillations of the enzyme papain into the lung. Sonomicrometry was used to assess LV dimensions along the septal-lateral, apex-base, and anterior-posterior orthogonal axes of the LV. With the animal conscious, measurements of LV systolic function were obtained over a wide range of LV circumferential end-ejection stresses at baseline and after 1 yr of emphysema (post-1-yr study). In the emphysema group (n = 5), the results showed that at the post-1-yr study, measurements of LV ejection fraction, mean velocity of circumferential shortening, and rate of anterior-posterior dimensional shortening were reduced compared with those obtained at the baseline study. In the emphysema group, end-systolic volume was increased for a given end-systolic pressure or stress at the post-1-yr study compared with baseline values, while fractional shortening measured along the three axes was decreased. There were no similar changes in systolic parameters in control groups. We conclude that chronic RV pressure overload may cause an impairment in LV systolic performance in chronic emphysema.

Analysis of Variance↗

Factors determining lobar emptying during maximal and partial forced deflations in nonhomogeneous airway obstruction in dogs.

The partial expiratory flow-volume (PEFV) maneuver has been proposed as a sensitive test to detect nonuniform airway disease. We tested this hypothesis in seven dogs in an open-chest preparation in which the right upper lobe (RUL) bronchus was partially obstructed. Alveolar capsules were placed on the obstructed RUL and nonobstructed right lower lobe (RLL) to measure respective alveolar pressures (Palv) during PEFV and maximal expiratory flow-volume (MEFV) maneuvers. PEFV curves were initiated at about 75% of the whole-lung vital capacity (VC). A Pitot static tube was placed into the airway to identify sites of flow limitation (choke-points [CP]), frictional pressure losses to CP (Pfr), CP area (A*), and compliance (K*). Results were analyzed at 45% VC, where a central tracheal CP was identified, and at 29% VC, where lobar CP were identified. At both lung volumes, the results showed that during PEFV, Palv and flows of the obstructed RUL decreased, whereas Palv and flows of the RLL increased compared with values obtained during MEFV. However, total maximal expiratory flow (Vmax) did not change between maneuvers. At 45% VC, although Pfr decreased during PEFV, this decrease was not large enough to result in an increase in A* and hence total Vmax because CP were identified in the noncompliant trachea. At 29% VC, offsetting changes in lobar A* and flow occurred between maneuvers: during PEFV, RLL A* and flow relatively increased while RUL A* and flow decreased. This study describes the mechanisms that explain why the PEFV maneuver is not useful in the detection of nonhomogeneous airway obstruction.

Animals↗

Choice making to promote adaptive behavior for students with emotional and behavioral challenges.

Two analyses investigated the effects of choice making on the responding of elementary school students with emotional and behavioral challenges. In the first analysis, 2 participants were given choices from menus of academic tasks, all of which were pertinent to their educational objectives in English and spelling, respectively. Reversal designs showed that the choice-making conditions increased task engagement and reduced disruptive behavior for both students. An additional analysis was performed with a 3rd student in an effort to further distinguish the effects of choice making from preference. In this study, one of the no-choice phases was yoked to a previous choice-making condition. This analysis demonstrated that the choice-making condition was superior to baseline and yoked control phases as determined by levels of task engagement and disruptive behavior. The findings of the two analyses contribute information relevant to students with emotional and behavioral disorders, and to a growing literature on the desirable effects of choice making for students with disabilities and challenging behaviors.

Attention↗

Unresectable nonmetastatic squamous cell carcinoma of the esophagus managed by sequential chemotherapy (cisplatin and bleomycin) and radiation therapy.

BACKGROUND: For patients with unresectable nonmetastatic squamous cell carcinoma of the esophagus (SCCE), the conventional treatment has been radiation therapy (RT). Because RT alone is unsatisfactory, there has been increasing interest in including chemotherapy (CT) in the management of these patients. METHODS: Twenty-five previously untreated patients with unresectable nonmetastatic SCCE were treated with sequential CT and RT. CT consisted of cisplatin 35 mg/m2/day for 3 days plus bleomycin 15 mg/day for 3 days as an 18-hour infusion every 3 weeks. After three courses of CT, RT was administered (dose, 200 rads/day with a planned total dose of 50-60 Gy). RESULTS: Nineteen tumors were T3; six were T2 and larger than 7 cm. Fifteen patients (60%) had severe dysphagia that required placement of nasogastric tubes in 14 and gastrostomy in 1. All patients were evaluable for response. Thirteen patients (52%) had a partial response to CT. After combined treatment, four patients had complete responses (16%), and nine had partial responses (36%; overall response rate, 52%). The median survival was 8 months; 20% were alive at 1 year, and 8% lived more than 4 years. The median survival for responders to CT was 8 months compared with 5 months for nonresponders (P = 0.005). Combined treatment improved dysphagia in 16 patients (64%) with complete resolution in 13. Toxicity was mild. CONCLUSIONS: The use of sequential CT (cisplatin and bleomycin) and RT in this group of patients is feasible; there is little additional toxicity, and good palliative effects can be achieved. The patient's response to CT is a good prognostic factor. The development of more effective combinations that induce more durable responses and higher rates of complete response are required.

Aged↗

Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and apomorphine in adult cats.

1. The aim of the present study was to analyze whether the dopaminergic D1 and D2 receptors are involved in the production of the behaviors evoked by parenteral administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were again injected on different days. The same procedure was carried on with sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two dopaminergic drugs, before and after the receptor blocker administration were respectively compared. The Wilcoxon signed rank test was employed for statistical analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and sulpiride produced per se hypomotility and sedation, effects that were considered when analysing the results. Some of the behaviors produced by amphetamine (pupillary dilation, head movements) were slightly modified by both receptor blockers. SCH 23390 only modified the licking behavior produced by apomorphine. In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine, especially when the 30 mg/kg dose was administered. It is concluded that the behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.

Amphetamine↗

Amoxicillin and clavulanic acid in the treatment of actinomycetoma.

BACKGROUND: Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. METHODS: We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). RESULTS: Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. CONCLUSIONS: We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.

Amoxicillin↗

Altered left ventricular chamber stiffness and isovolumic relaxation in dogs with chronic pulmonary hypertension caused by emphysema.

BACKGROUND: In chronic obstructive lung disease, a right to left ventricular septal shift that occurs as a consequence of right ventricular pressure overload is the usual mechanism given to explain a decrease in left ventricular (LV) diastolic performance. The purpose of the present study was to examine the extent to which this mechanism could account for a decrease in LV diastolic function in a canine model in which pulmonary artery pressure was elevated to a level found in human disease. METHODS AND RESULTS: Severe emphysema was produced in dogs by repeated instillations of the enzyme papain into the lung. To assess LV diastolic function, we used sonomicrometry, in which three pairs of subendocardial crystal transducers were implanted along the three orthogonal axes of the LV. LV end-diastolic dimensions and pressure-strain relations along the three axes, as well as the time constant of LV isovolumic relaxation (T), were measured before (baseline) and after 1 year of emphysema (post-1-year study). The results showed that after 1 year of pulmonary hypertension, LV pressure-strain relations were decreased along the septal-lateral and anterior-posterior axes, but a right to left ventricular septal shift was not detected. The relation of average midwall circumferential stress to midwall circumferential strain was used to describe the intrinsic compliance of the LV. The results showed that myocardial stiffness increased in emphysema but that chamber volume was not reduced. At the post-1-year study, T was abnormally increased in the emphysema group in response to augmented preload and afterload compared with preemphysema measurements. CONCLUSIONS: We conclude that mechanisms other than ventricular interdependence may be operative in leading to altered LV diastolic filling in chronic emphysema.

Analysis of Variance↗

Effects of disulfiram, phenoxybenzamine and propranolol on the behaviors evoked by apomorphine and amphetamine in adult cats.

The aim of this work was to study the role that the noradrenergic system could play in the mechanism of production of the behaviors evoked by parenteral injection of apomorphine and amphetamine in adult cats. Ten cats were injected s.c. with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine in separate sessions. The behaviors were recorded, until control conditions were again attained. In a second stage, disulfiram was administered ip., followed by apomorphine and amphetamine in the same doses as cited above. The effects on behaviors produced by disulfiram and those of apomorphine and amphetamine were recorded by three independent observers. Comparisons of the pre- and post-disulfiram behavioral results were analyzed with the help of the non-parametric Wilcoxon signed rank test. In another group of ten cats a similar procedure was carried on employing the alpha and beta noradrenergic blocking agents, phenoxybenzamine and propranolol. The noradrenergic blocking drugs, especially disulfiram and phenoxybenzamine produced by themselves a decrease in motility, in alertness and an increase in indifference and inappetence. Apomorphine and amphetamine administered after the blocking drugs showed slight behavioural modifications, reflection most of them the changes produced by the three blocking drugs. It is concluded that probably the nor-adrenergic system could be involved in the hypomotility elicited by amphetamine. NA is not involved in the induction of the other behaviors evoked by apomorphine and amphetamine.

Amphetamine↗

Interaction between effects of hypoxia and hypercapnia on altering left ventricular relaxation and chamber stiffness in dogs.

Left ventricular (LV) isovolumic relaxation and chamber stiffness were examined in dogs to see how hypoxemia and hypercapnia occurring during an acute exacerbation of chronic obstructive lung disease could directly affect diastolic performance. Measurements were obtained during baseline (arterial PO2 approximately 200 mm Hg; PCO2 approximately 35 mm Hg; pH approximately 7.35), hypoxia (PO2 approximately 35 mm Hg; PCO2 approximately 35 mm Hg; pH approximately 7.35), and hypoxia-hypercapnia (PO2 approximately 35 mm Hg; PCO2 approximately 60 mm Hg; pH approximately 7.15) in an open-chest, open-pericardium preparation. Changes in LV diastolic performance during hypoxic and hypercapnic interventions were contrasted with those caused by ventricular interdependence in which pulmonary artery occlusion was used to produce a right to left ventricular septal shift. Subendocardial ultrasonic crystal transducers were placed along the three orthogonal axes of the left ventricle to measure dimensions by sonomicrometry. Along each axis, LV end-diastolic dimension-pressure relations were constructed in the various conditions; the slope of this relationship, obtained over a linear portion of the curve, was used as an index of diastolic dimensional distensibility (DD). The results showed that during hypoxia, DD appeared decreased along the three axes, with a reduction in filling primarily along the anterior-posterior and apex-base axes. The addition of hypercapnia to hypoxia completely abolished the hypoxic effect. On the other hand, during pulmonary artery occlusion, LV DD were not changed along the latter two dimensions. We conclude that during respiratory failure, LV diastolic performance may be directly affected by arterial blood gas tensions, which by altering the interaction between the contractile filaments modulate LV filling.

Animals↗

[Cardiac rhabdomyoma in tuberous sclerosis. Presentation of a case].

We report of a case of cardiac tumor in a three months old infant, examined with echocardiography because a murmur was noted on routine examination. Further investigations brought out the diagnosis of tuberous sclerosis. Spontaneous regression of the tumor mass occurred in the following months. No signs of cardiac dysfunction of CNS involvement appeared. The peculiarity of rhabdomyoma as an early manifestation of tuberous sclerosis is emphasized.

Echocardiography↗