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Biomedical subjects

L Martinez

Publications and source records attributed to L Martinez.

At least 55 records · Page 3Linked to original sources

T1 GIII bladder cancer. Management with transurethral resection only.

OBJECTIVE: Transurethral resection (TUR) is the elective procedure in the treatment of superficial bladder tumor. The association of intravesical chemotherapy has no influence on survival and cause specific survival. This study was carried out to determine the evolution of T1 GIII bladder carcinoma treated with TUR only. PATIENTS AND METHODS: We retrospectively reviewed the records of 42 consecutive patients with T1 GIII bladder carcinoma. Follow-up was available for 34 patients. No patient received either adjuvant or neoadjuvant therapy. All the patients were treated with TUR only and followed for a median of 40 months. They were followed by cystoscopy, urinary cytology and intravenous urography. RESULTS: Forty-seven percent of patients had a solitary tumor while 53% had multiple tumors. Tumor recurrence occurred in 50% with a disease-free interval until the first relapse of 9.6 months. Progression of the primary tumor was observed in 23.5% of patients. The overall survival rate was 73.6% and the cancer-specific survival estimate was 88.2% at mean 36 months of follow-up. CONCLUSIONS: T1 GIII bladder carcinoma may be treated initially with transurethral resection only with acceptable recurrence and progression rates. This would avoid costs and complications of the adjuvant/neoadjuvant therapies.

Adult↗

Long-term follow-up of patients with biliary atresia successfully treated with hepatic portoenterostomy. The importance of sequential treatment.

The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range 10.7-22.5 years; mean 15.4+/-0.7 years) treated with hepatic portoenterostomy (HPE) and jaundice-free for more than 10 years without liver transplantation (LT) is analyzed retrospectively. Eight of these patients subsequently required LT (age at LT 12. 8+/-0.5 years, range 10.5-15.2 years); 3 children (aged 11.6, 13.2 and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding associated with other signs of severe disease and are now candidates for LT; and among the 7 asymptomatic patients (age range 11.2-22.5 years; mean 15.9+/-2.1 years), 5 had sonographic and biochemical signs of moderate portal hypertension (PH). In order to analyze whether the age at transplantation influences the survival of children transplanted for BA, we also reviewed the outcome of 71 BA patients transplanted at our hospital between 1986 and 1996. All the children older than 10 years at the time of LT were alive; only patients younger than 10 years died following LT (n = 15). We conclude that the natural outcome of extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases successfully treated with HPE. In our experience, the results of sequential treatment with HPE and LT were excellent.

Adolescent↗

Tonic and bursting activity in the cuneate nucleus of the chloralose-anesthetized cat.

Whole-cell recordings were obtained from cuneate neurons in anesthetized, paralysed cats. Stimulation of the contralateral medial lemniscus permitted us to separate projection cells from presumed interneurons. Pericruciate motor cortex electrical stimulation inhibited postsynaptically all the projection cells (n=57) and excited all the presumed interneurons (n=29). The cuneothalamic cells showed an oscillatory and a tonic mode of activity. Membrane depolarization and primary afferent stimulation converted the oscillatory to the tonic mode. Hyperpolarizing current steps applied to projection neurons induced a depolarizing sag and bursts of conventional spikes in current-clamp records. This indicates the probable existence of low-threshold and hyperpolarization-activated inward currents. Also, the hyperpolarization induced on projection cells by motor cortex stimulation deinactivated a low-threshold conductance that led to bursting activity. The presumed cuneate interneurons had larger and more proximally located peripheral receptive fields than the cuneothalamic cells. Finally, experiments specifically designed to test whether motor cortex-induced presynaptic inhibition could be postsynaptically detected gave negative results. These results demonstrate, for the first time, that the cuneothalamic cells possess both bursting and tonic firing modes, and that membrane depolarization, whether produced by injection of positive current or by primary afferent stimulation, converts the oscillatory into the tonic mode.

Afferent Pathways↗

Coexistence of multiple periodic and chaotic regimes in biochemical oscillations with phase shifts.

The numerical study of a glycolytic model formed by a system of three delay differential equations reveals a multiplicity of stable coexisting states: birhythmicity, trirhythmicity, hard excitation and quasiperiodic with chaotic regimes. For different initial functions in the phase space one may observe the coexistence of two different quasiperiodic motions, the existence of a stable steady state with a stable torus, and the existence of a strange attractor with different stable regimes (chaos with torus, chaos with bursting motion, and chaos with different periodic regimes). For a single range of the control parameter values our system may exhibit different bifurcation diagrams: in one case a Feigenbaum route to chaos coexists with a finite number of successive periodic bifurcations, in other conditions it is possible to observe the coexistence of two quasiperiodicity routes to chaos. These studies were obtained both at constant input flux and under forcing conditions.

Animals↗

The effect of hepatic vascular exclusion on hepatic blood flow and oxygen supply--uptake ratio in the pig.

The hemodynamic disturbances produced by total hepatic vascular exclusion (THVE) for 40 minutes were studied in 7 pigs (19-22 kg). THVE was produced by clamping the hepatic pedicle and inferior vena cava, above and below the liver, for a 40-minutes period, followed by unclamping. Compared to baseline values, 30 minutes after onset of THVE, there was a decrease in cardiac output (3.86 +/- 0.55 vs 1.23 +/- 0.23 L x min-1), systemic arterial pressure (97.54 +/- 13.58 vs 43.43 +/- 11.38 mm Hg), and pulmonary artery pressure (16.57 +/- 6.38 vs 12.57 +/- 3.58) and an increase in systemic and pulmonary vascular resistance (1772 +/- 198 vs 2351 +/- 462, and 182 +/- 66 vs 361 +/- 124 dyn x s x cm-5 respectively). As a result of diminished cardiac output, the systemic oxygen supply decreased (461 +/- 131 vs 101 +/- 46 ml x min-1), but the systemic oxygen extraction rate rose from 17.3% t0 31.2%. Thirty minutes after unclamping, the changes had reversed and all the parameters tended to normalize. Total hepatic blood flow 30 minutes after unclamping was higher than at baseline (5.08 +/- 1.2 vs 6.66 +/- 0.67 ml x min-1 x 100 g-1), because of the increase in portal blood flow (4.52 +/- 1.21 vs 6.07 +/- 0.70 ml x min-1 x 100 g-1). There were no significant differences in hepatic oxygen supply and uptake at baseline and after unclamping (152.6 +/- 23.0 vs 187.0 +/- 34.7 and 22.7 +/- 4.9 vs 28.7 +/- 8.4 ml O2 respectively). AST rose (29 +/- 7 vs 136 +/- 91 U/l), but there was no change in the remaining liver enzymes, glucose, creatinine and serum electrolytes, so we conclude that the hemodynamic disturbances produced by 40 minutes of THVE are manageable and spontaneously reversible. Liver metabolism was not greatly disturbed, so THVE was judged to be a viable technique to be added to the surgeon's range of options.

Analysis of Variance↗

Coupled slow and delta oscillations between cuneothalamic and thalamocortical neurons in the chloralose anesthetized cat.

Simultaneous recordings were obtained from cuneothalamic (extracellular) and thalamocortical (intracellular) cells in chloralose anesthetized cats. It was found that cuneothalamic neurons present slow rhythmicity (0.1-1 Hz) tightly coupled to slow oscillations of thalamocortical neurons. This coupling was not due to a direct synaptic linkage but rather produced by other (s) structure (s) probably the cortex. Furthermore, the cuneothalamic neurons also showed delta rhythms (1-4 Hz) coherently oscillating with the delta rhythms of thalamocortical cells which suggests that these rhythms are more widespread than previously thought, and may be a general phenomenon characterizing quiet sleep in multiple structures.

Animals↗

Intermittency route to chaos in a biochemical system.

The numerical analysis of a glycolytic model performed through the construction of a system of three differential-delay equations reveals a phenomenon of intermittency route to chaos. In our biochemical system, the consideration of delay time variations under constant input flux as well as frequency variations of the periodic substrate input flux allows us, in both cases, to observe a type of transition to chaos different from the 'Feigenbaum route'.

Biochemical Phenomena↗

Quasiperiodicity route to chaos in a biochemical system.

The numerical study of a glycolytic model formed by a system of three delay differential equations reveals a quasiperiodicity route to chaos. When the delay changes in our biochemical system, we can observe the emergence of a strange attractor that replaces a previous torus. This behavior happens both under a constant input flux and when the frequency of the periodic substrate input flux changes. The results obtained under periodic input flux are in agreement with experimental observations.

Glycolysis↗

Donor vascular grafts for arterial reconstruction in pediatric liver transplantation.

The authors compared the results of 48 orthotopic liver transplantations (OLT) in which revascularization was achieved with a conduit interposed between the receptor aorta and the graft (vascular graft [VG] group) with those obtained for 56 OLT performed during the same period (1991 to 1994) in which end-to-end anastomosis (EEA) of the hepatic arteries or celiac trunk was used (EEA group). In the VG group, the interposed conduits were the cadaveric iliac artery (37) the living-donor saphenous vein (3), or nonthrombosed conduits from previous transplants (8) (7 iliac arteries, 1 saphenous vein). There were significant differences between the two groups with respect to recipient age, recipient weight, the retransplant:first transplant ratio, the number of emergency transplantations, the use of reduced-size grafts, and intraoperative transfusion requirements. Twenty-nine grafts in the VG group (60.4%) and 43 in the EEA group (76.7%) currently are functioning. The actuarial 3-year graft survival rates are 60% and 71.5% for the VG and EEA groups (P < .05), respectively. The rate of arterial thrombosis did not differ between the two groups. The authors conclude that, although EEA of the hepatic artery is still the preferred revascularization technique for OLT, revascularization of the liver graft by conduit interposition is safe when EEA is not possible. Reutilization of the interposed conduit during retransplantation proved to be safe in the absence of hepatic artery thrombosis.

Anastomosis, Surgical↗

Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder: a bridging study.

Lesopitron, a 5-hydroxytryptamine 1A agonist, is a new potential anxiolytic of the azapirone class. It has greater potency in animal models of anxiety than buspirone, gepirone, or ipsapirone, and it lacks the antidopaminergic effects associated with buspirone. Lesopitron has been tolerated at single doses up to 50 mg and repeated dosages of 45 mg/day in healthy volunteers. Forty-two patients with generalized anxiety disorder (GAD) were enrolled in this double-blind bridging study to determine the safety and tolerability of fixed doses of lesopitron (20, 25, 30, 40, 45, 50, and 60 mg two times a day) over a 6 1/2-day inpatient administration period. Each of the seven panels included six patients (four drug/two placebo). One patient in the 25-mg, two-times-a-day panel voluntarily withdrew because of increased anxiety symptoms. One patient experienced severe orthostatic hypotension at 60 mg two times a day, and moderate to severe adverse events (dizziness, lightheadedness, nausea, headache) occurred in two other patients at this dosage. The most commonly reported adverse events in all the panels were headache, dizziness, and nausea. Lesopitron is rapidly absorbed in patients, having a time to maximum concentration (Tmax) ranging from 0.5 to 1 hour, and its elimination half-life ranged from 1.1 to 5.6 hours. Peak plasma concentrations showed high interindividual variability for lesopitron, but increased linearly with dose for the main metabolite, 5-hydroxylesopitron. We defined the maximum tolerated dose in GAD patients as 50 mg two times a day, twice as high as the highest dose tested in healthy volunteers.

Adolescent↗

Further observations on the role of nitric oxide in the feline lateral geniculate nucleus.

We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L-arginine, but not the biologically inactive isomer, D-arginine. Nitroprusside and S-nitroso-N-acetylpenicillamine (SNAP), nitric oxide donors, but not L-arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.

Afferent Pathways↗

Determination of ventricular vulnerable period and ventricular fibrillation threshold by use of T-wave shocks in patients undergoing implantation of cardioverter/defibrillators.

BACKGROUND: This study was designed to characterize the ventricular vulnerable period (VVP) and ventricular fibrillation (VF) threshold by use of T-wave shocks in patients undergoing implantation of cardioverter/defibrillators. A premature condensed shock applied during the VVP can induce VF. Most studies on the VVP and VF threshold have been conducted in animals rather than in humans. METHODS AND RESULTS: Twenty-one patients undergoing implantation of Medtronic PCD Jewel 7219D cardioverter/defibrillators because of ventricular tachycardia and/or VF were enrolled. All had structural heart disease. Their ages ranged from 42 to 85 years (mean, 69 +/- 11.3 years). Seventeen (80.9%) had atherosclerotic coronary artery disease. The right ventricle (RV) was driven at a cycle length (S1) of 400 ms, and monophasic shocks (S2) of 0.6 J were delivered through an RV apex lead (cathode) and a superior vena cava lead (anode) during the T wave of each cardiac cycle. The longest and shortest S1-S2 intervals that were capable of inducing sustained VF were defined as the outer and inner limits of the VVP at an energy level of 0.6 J, respectively. To determine the VF threshold, a shock of 0.2 J was applied at the midpoint of the VVP at 0.2-J increments until sustained VF was induced. The lowest energy setting capable of inducing sustained VF was defined as the VF threshold. Of the 21 patients, the VVP at an energy level of 0.6 J averaged 53.8 +/- 26.0 ms. Characteristically, the VVP started from the ascending limb of the T wave and ended at or slightly beyond the peak of the T wave, occupying 12.2 +/- 5.8% of the QT interval. The midpoint of the VVP used for determination of the VF threshold measured 0 to 90 ms (mean, 32.9 +/- 26.0 ms) before the peak of the T wave. Of the 21 patients, 16 (76.2%) had a VF threshold at < or = 0.2 J (estimated 57 V), 3 at 0.4 J (estimated 81 V), and 2 at 0.6 J (estimated 99 V). CONCLUSIONS: The VF threshold is low (< or = 0.2 J) in the majority of patients requiring implantation of cardioverter/defibrillators. Further studies are needed to define clinical usefulness of the study technique relative to its potential role for risk stratification and for assessing antifibrillatory properties of antiarrhythmic drugs in this subset group of patients.

Adult↗

Caprylic acid, a medium chain saturated fatty acid, inhibits the sodium inward current in neuroglioma (NG108-15) cells.

The effects of caprylic acid (CA) on ionic currents were investigated, using the whole-cell patch-clamp technique, in differentiated neuroglioma cells. External application of CA reduced the peak amplitude of the inward Na+ current, while outward currents were not affected. CA (1 and 5 mM) reversibly attenuated the peak of the inward Na+ current by 21% (n = 26) and 46% (n = 31), respectively. The inactivation curve in the presence of CA was shifted by 8 mV toward hyperpolarized potentials, with half-inactivation voltage being -47.9 and -55.9 before and after external application of CA (5 mM), respectively. This shift was readily reversed after 5 min wash. The slope remained unchanged (-8.4 and -8.8 mV, respectively, n = 4). The activation process was unaffected (CA 5 mM, n = 8). Under current-clamp conditions, CA 5 mM (but not 1 mM) reversibly reduced the amplitude, and the slope of the rising phase of the action potential. These results agree with the fact that free fatty acids can modulate the activity of ion channels by mechanisms which do not involve enzymatic or membrane disruptive pathways.

Action Potentials↗