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Biomedical subjects

J A Sanchez

Publications and source records attributed to J A Sanchez.

At least 73 records · Page 4Linked to original sources
PubMed1990

Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study.

Previous studies in animals have demonstrated liposome-encapsulated doxorubicin (LED) has substantially less cardiac toxicity than free doxorubicin but retains antitumor activity. In a phase I clinical study of LED, the maximum tolerated dose was 90 mg/m2 and dose-limiting toxicity was considered to have been reached when granulocytopenia was produced. We used LED to treat 20 patients with advanced, measurable breast cancer. LED was given at doses of 60-75 mg/m2 every 3 weeks as an intravenous infusion. Regression of disease was objectively measured in nine patients; in five of these patients, complete regression of the index lesion occurred. The mean duration of the responses was 7 months. Hematologic toxicity consisted of grade 1-2 leukopenia in some patients. Gastrointestinal toxicity and mucositis were generally mild and tolerable. Alopecia occurred in all patients and usually was complete. Twelve patients received cumulative doses of LED of greater than 400 mg/m2 and were evaluated with radionuclide ventriculograms. In eight patients, the cumulative dose was greater than 500 mg/m2, and five had endomyocardial biopsies. Four of these biopsy results were Billingham grade 0, while one (cumulative LED dose, 750 mg/m2) showed grade 1 changes with mild myofibrillar loss and dilatation of the sarcoplasmic reticulum involving less than 5% of cardiac myocytes. Two patients had decreases in left ventricular ejection fraction. One of these patients had received a total dose of LED of 630 mg/m2 and had a decline of 13% in left ventricular ejection fraction, but had no clinical evidence of congestive heart failure and had a Billingham grade 0 endomyocardial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity.

The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases.

Adolescent↗
PubMed1990

The effects of lyotropic anions on charge movement, calcium currents and calcium signals in frog skeletal muscle fibres.

1. Intramembrane charge movement and Ca2+ currents were monitored in voltage-clamped segments of frog skeletal muscle fibres using the triple-Vaseline-gap technique. Calcium signals were measured in current-clamped fibres using either of the indicators Arsenazo III or Antipyrylazo III. 2. Non-linear capacitative currents (charge 1) were obtained using a subtraction procedure which employed either a -20 mV control pulse from a holding potential of -100 mV or alternatively a control pulse to +80 mV in depolarized fibres. The amount of charge mobilized depended on voltage according to a two-state Boltzmann function. The total charge (Qmax) was increased by ca 100% and the steepness parameter (k) by ca 70% when a +80 mV control pulse was used. 3. Thiocyanate (SCN-) and other lyotropic anions reversibly shifted the voltage dependence of mobilized charge towards negative potentials. Qmax was not significantly affected. 'Off' charge tails were greatly prolonged by lyotropic anions. 4. Extracellularly applied lyotropic anions affected the dihydropyridine-sensitive Ca2+ current by shifting the I-V relation toward more negative voltages and delaying deactivation of the tail currents. 5. The effects of lyotropic anions did not depend on whether the anion was introduced intracellularly or extracellularly. 6. Extracellular SCN- reversibly increased the peak amplitude and rate of rise of Ca signals, and decreased the latent period between stimulation and onset of the Ca signal. 7. It is concluded that lyotropic anions have similar effects on Ca2+ currents and on charge movement.

Animals↗
PubMed1990

Anti-CD3 monoclonal antibody induction therapy. Immunological equivalency with triple-drug therapy in heart transplantation.

This study examines the hypothesis that induction immunosuppressive therapy with murine anti-CD3 monoclonal antibodies (OKT3) reduces the frequency of rejection episodes in heart transplant recipients receiving 3-drug maintenance therapy with cyclosporine, azathioprine, and steroids. A group of 26 adult heart transplant recipients requiring preoperative intravenous inotropic drugs or with elevated serum creatinine received OKT3 induction as well as long-term triple drug therapy. Cyclosporine was withheld for the first 4 postoperative days allowing for resolution of cardiogenic renal dysfunction. A corresponding group of 26 heart transplant recipients received triple drug therapy alone started immediately before transplantation. Both groups were comparable in age, sex distribution, and follow-up period. The frequency of rejection episodes was identical for the two groups (0.003 episodes per patient month). Time to first rejection episode in the induction group, however, was delayed twofold as compared with the noninduction group (42 versus 21 days, p less than 0.01). Actuarial survival at 6, 12, and 18 months was 88%, 81%, and 81% for the induction group and 92%, 92%, and 87% for the noninduction group (p = NS). Treatment for rejection was not required in 35% of the induction group and 38% of the noninduction group (p = NS). OKT3 provides satisfactory immunosuppression in heart transplant recipients with hemodynamic or renal compromise, yet it does not reduce the frequency of rejection episodes compared with patients receiving triple drug therapy alone. Although the time to first rejection may be delayed, routine adjuvant use of OKT3 for induction in all heart transplant recipients may incur needless expense without providing an important immunological advantage as compared with triple drug immunosuppression alone.

Antibodies, Monoclonal↗
PubMed1990

Immunohistochemical study of fibronectin in experimental myocardial infarction.

Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing.

Animals↗
PubMed1990

High-risk reparative surgery. A neglected alternative to heart transplantation.

The selection of patients for either high-risk reparative operations on the heart or for transplantation has become increasingly difficult as a result of improved results with both modalities. A retrospective review was done of patients referred for heart transplantation who were not considered candidates for conventional cardiac surgery, yet instead underwent reparative procedures rather than transplantation. Of 23 adult patients referred during a 7-year period, 18 had coronary artery disease, and five had valvular heart disease. All had New York Heart Association class IV symptoms. Preoperative left ventricular ejection fractions were in the range 0.08-0.63 (mean, 0.28). Ten of 18 patients with coronary artery disease required insertion of an intra-aortic balloon pump for hemodynamic support perioperatively. Seven patients had primary coronary artery bypass grafts, and 10 had reoperative coronary bypass procedures. One patient had a left ventricular aneurysmectomy, and one had endocardial stripping in addition to myocardial revascularization procedures. Of the patients with valvular disease, three had aortic valve replacement, of which two were reoperations, and two others had mitral valve replacements with tricuspid annuloplasties. With a mean follow-up of 25 months, 1-, 3-, 12-, and 24-month actuarial survival rates were 91%, 87%, 82%, and 76%, respectively. One patient who underwent aortic valve replacement in this study successfully received heart transplantation 19 months postoperatively. These results compare favorably with the current results for patients undergoing first-graft heart transplantation. All survivors enjoy New York Heart Association class I or II functional capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1988

Microsomal enzyme induction by permethrin in rats.

The synthetic pyrethroid, permethrin, was evaluated for its ability to alter hepatic microsomal drug-metabolizing function. The influence of permethrin (25:75 cis-trans) on plasma antipyrine kinetics and gamma-glutamyl transpeptidase (gamma-GTP) activity were studied in rats. After 3 days of administration of 90 mg permethrin/kg/day, there was no significant change in the antipyrine half-life and the area under the curve, while the apparent volume of distribution and clearance were significantly increased. Treatment with 190 mg permethrin/kg/day for 3 days decreased antipyrine half-life and the area under the curve, and increased the apparent volume of distribution and the clearance significantly. The gamma-GTP activity was significantly increased within 21 days and 14 days after the start of permethrin administration, at doses of 90 and 190 mg permethrin/kg/day, respectively. The antipyrine kinetics results indicate that permethrin is capable of producing a dose-dependent marked enzyme-inducing effect.

Animals↗
PubMed1987

Paget's disease of the breast.

Paget's disease of the breast is often an important early warning sign of underlying breast carcinoma, usually arising from the major mammary ducts. Because the conditions may be confused with benign diseases of the nipple, treatment is frequently delayed. If Paget's disease is the sole indication for surgery, the likelihood of cure is high. When evaluating nipple lesions, physicians should maintain a high index of suspicion for Paget's disease of the breast.

Breast Neoplasms↗
PubMed1986

Slow permeation of organic cations in acetylcholine receptor channels.

Block, permeation, and agonist action of small organic amine compounds were studied in acetylcholine receptor (AChR) channels. Single channel conductances were calculated from fluctuation analysis at the frog neuromuscular junction and measured by patch clamp of cultured rat myotubes. The conductance was depressed by a few millimolar external dimethylammonium, arginine, dimethyldiethanolammonium, and Tris. Except with dimethylammonium, the block was intensified with hyperpolarization. A two-barrier Eyring model describes the slowed permeation and voltage dependence well for the three less permeant test cations. The cations were assumed to pause at a site halfway across the electric field of the channel while passing through it. For the voltage-independent action of highly permeant dimethylammonium, a more appropriate model might be a superficial binding site that did not prevent the flow of other ions, but depressed it. Solutions of several amine compounds were found to have agonist activity at millimolar concentrations, inducing brief openings of AChR channels on rat myotubes in the absence of ACh.

Animals↗
PubMed1985

Single-channel activity of bilayers derived from sea urchin sperm plasma membranes at the tip of a patch-clamp electrode.

Changes in the plasma membrane permeability of echinoderm sperm play a fundamental role in the acrosome reaction. During the reaction there is an increase in intracellular Ca2+ and Na+ and an efflux of H+ and K+. We have formed bilayers at the tip of patch pipets from a mixture of lipid vesicles and sea urchin sperm plasma membranes (12-50 microgram protein/ml). We observed three types of K+ channels (conductances: 22, 46, and 82 pS), two of which are partially blocked by TEA, and one Cl- channel (148 pS). The presence of K+ channels in sperm plasma membranes is consistent with the inhibition by TEA of the acrosome reaction in whole sperm and the membrane potential change that occurs during the reaction.

Acrosome↗
PubMed1983

Lyotropic anions. Na channel gating and Ca electrode response.

The effects of external anions on gating of Na channels of frog skeletal muscle were studied under voltage clamp. Anions reversibly shift the voltage dependence of peak sodium permeability and of steady state sodium inactivation towards more negative potentials in the sequence: methanesulfonate less than or equal to Cl- less than or equal to acetate less than Br- less than or equal to NO-3 less than or equal to SO2-4 less than benzenesulfonate less than SCN- less than ClO-4; approximately the lyotropic sequence. Voltage shifts are graded with mole fraction in mixtures and are roughly additive to calcium shifts. The peak PNa is not greatly affected. Except for SO2-4, these anions did not change the Ca++ activity of the solutions as measured with the dye murexide. Shifts of gating can be explained as the electrostatic effect of anion adsorption to the Na channel or to nearby lipid. Such adsorption is expected to follow the lyotropic series. Anions also interfere significantly with the response of a Ca-sensitive membrane electrode following the same sequence of effectiveness as the shifts of gating. The lyotropic anions decrease the Ca++ sensitivity and cause anomalously negative responses of the Ca electrode because these anions are somewhat permeant in the hydrophobic detector membrane.

Aged↗
PubMed1980

Effect of calcium withdrawal on mechanical threshold in skeletal muscle fibres of the frog.

1. Voltage-clamp experiments were performed on frog skeletal muscle fibres using two intracellular micro-electrodes. The threshold for the Na current and the strength-duration curve for mechanical threshold were determined. 2. The change in threshold for the Na current was studied as a function of the external Ca and Mg concentrations which ranged from 0.1 to 50 mM. 3. The resting potential, effective resistance and threshold for the Na current were unchanged when 1.8 mM-Ca was replaced by 3 mM-Mg, indicating that the surface potential and the electrical properties of the fibres were not modified. The additon of 5 mM-EGTA did not affect these parameters. 4. In Ca-free saline (3 mM-Mg and 5 mM-EGTA) the mechanical threshold was significantly increased for short pulses (less than or equal to 20 msec.). In isolated single muscle fibres this effect was observed shortly after applying the Ca-free saline, and was rapidly reversed upon the return to control saline. 5. In isotonic EGTA (85 mM-EGTA) the muscle fibres were depolarized and were unable to contract even if they were hyperpolarized to --90 mV for 12 min prior to stimulation. If 3 mM-Mg was added, most fibres contracted locally. 6. In single muscle fibres caffeine contractures were unmodified after a 30 min exposure to Ca-free saline. 7. It can be concluded that external Ca withdrawal impairs Ca release from the sarcoplasmic reticulum and that external Ca is not essential for triggering contraction.

Animals↗
PubMed1978

Inward calcium current in twitch muscle fibres of the frog.

1. Voltage clamp experiments using the three micro-electrode voltage clamp technique were performed on sartorius muscles of the frog. 2. By blocking potassium currents with tetraethylammonium and replacing chloride ions with sulphate a slow inward current was detected. 3. The slow inward current is mainly carried by calcium, since it is abolished by cobalt and D-600, it depends on external calcium, and is not affected by removing external sodium or by tetrodotoxin (TTX). 4. The slow inward current has a mean threshold of -40 mV, reaches a mean maximum value at ca. 0 mV of 81 microamperemetercm-2 and has a mean reversal potential of +38 mV. 5. The calcium current is inactivated by the application of 2 sec conditioning prepulses according to a sigmoid curve with V(h) = -42 mV and k = 6.2 mV. 6. The slow time course of this calcium current makes it rather unlikely that it participates in contraction during a twitch, but it might be activated during long depolarizations as potassium contractures.

Action Potentials↗
PubMedDate not supplied

Epidural vs. intramuscular oxymorphone analgesia after thoracotomy in dogs.

Oxymorphone was administered epidurally (0.1 mg/kg) or intramuscularly (IM) (0.2 mg/kg) to 16 dogs undergoing thoracotomy, to compare the analgesic effectiveness. Heart rate, respiratory rate, systolic and diastolic blood pressure, and pain score were measured hourly. Arterial blood gases were measured at hour 1. A single dose of oxymorphone injected epidurally provided analgesia for up to 10 hours, whereas the IM route provided a comparable effect for less than 2 hours. There were statistically significant increases in heart rate, and systolic and diastolic blood pressures at hour 2 in the dogs treated IM over the dogs treated epidurally. We conclude that epidurally administered oxymorphone is highly effective in alleviating pain after thoracotomy in dogs and provides longer lasting analgesia than the IM route.

Analgesia, Epidural↗
PubMedDate not supplied

Articulatory representation and speech technology.

In this paper we demonstrate the feasibility and usefulness of articulation-based approaches in two major areas of speech technology: speech recognition and speech synthesis. Our articulatory recognition model estimates probabilities of categories of manner and place of articulation, which establish the articulatory feature vector. The transformation from the articulatory level to the symbolic level is performed by hidden Markov models or multi-layer perceptions. Evaluations show that the articulatory approach is a good basis for speaker-independent and speaker-adaptive speech recognition. We are now working on a more realistic articulatory model for speech recognition. An algorithm based on an analysis by synthesis model maps the acoustic signal to 10 articulatory parameters which describe the position of the articulators. EMA (electro-magnetic articulograph) measurements recorded at the University of Munich provide good initial estimates of tongue coordinates. In order to improve articulatory speech synthesis we investigated an accurate physical model for the generation of the glottal source with the aid of a numerical simulation. This model takes into account nonlinear vortical flow and its interaction with sound-waves. The simulation results can be used to improve the articulatory synthesis model developed by Ishizaka and Flanagan (1972).

Equipment Design↗