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Biomedical subjects

R Perez

Publications and source records attributed to R Perez.

At least 73 records · Page 4Linked to original sources
PubMed1998

Characterization of nanostructured materials using SEM and HREM techniques.

A microstructural characterization based on analytical scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HREM) was carried out on nanostructured M50-type steel and also on nanometer-sized gold particles. Both nanostructured materials were prepared with different chemical methods recently reported in the literature. The obtained nanostructured steel powders were subsequently consolidated into bulk samples. The SEM studies of the M50 compound probes show the presence of pores of different sizes. The composition of the specimens indicates small differences with the M50-type steel alloy, with strong variations of the vanadium amount in the cavities of the compound. The HREM images show the presence of small precipitates in the range of a few nanometers in size. The structural characteristics of the grain boundaries between the nanometric crystallites were also explored. The geometrical relationships between adjacent alpha-Fe grains were obtained for some particular boundary arrangements. The nanometric gold particles show diameters which vary from 4 to 11 nm. Some of these particles display twin boundary arrangements. The nature of these twin arrangements was also explored. Theoretical simulations based on the multislice theory of the electron diffraction dynamical theory were carried out mainly to explore the nature of the twin boundaries obtained in the gold particles. Comparisons between the simulated images and the experimental results are presented.

Gold↗
PubMed1998

Outpatient ultrasound-guided palladium 103 brachytherapy for localized adenocarcinoma of the prostate: a preliminary report of 434 patients.

OBJECTIVES: To assess the effectiveness of palladium 103 (Pd-103) brachytherapy in Stage T1 and T2 adenocarcinoma of the prostate. METHODS: Charts of 474 patients treated between 1991 and 1996 with transperineal real-time ultrasound-guided Pd-103 implants were reviewed to assess post-treatment prostate-specific antigen (PSA) levels and follow-up biopsy results. Of 474 patients, 434 had sufficient data for this report. The implant technique used allows precise placement of seeds and accurate dose delivery of the entire prostate. Preoperative neoadjuvant leuprolide (Lupron) and flutamide (Eulexin) were given selectively to reduce prostate size greater than 50 cc and for Gleason grade lesions greater than 7. RESULTS: Of 434 patients, successful cancer control was demonstrated in 81% of patients by a decrease in PSA levels to less than 1.5 ng/mL at 1 year. Biopsies were negative in 88% of patients 1 year after the procedure and in 89% at 2 years. Analysis of the data suggests that patients with pretreatment PSA levels less than 10 ng/mL had the best outcomes. There were no disease-related deaths; the predominant morbidity was short-term bladder and bowel irritation without permanent sequelae. Incontinence occurred in less than 5% of patients who had undergone prior transurethral resection of the prostate. Impotence occurred in less than 15% of patients. CONCLUSIONS: The technique used in this study proved effective in reducing PSA levels to less than 1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. Results are comparable to external-beam radiation therapy, demonstrating a significant reduction in morbidity.

Adenocarcinoma↗
PubMed1998

Neural mechanisms underlying stereoscopic vision.

The progressive frontalization of both eyes in mammals causes overlap of the left and right visual fields, having as a consequence a region of binocular field with single vision and stereopsis. The horizontal separation of the eyes makes the retinal images of the objects lying in this binocular field have slight horizontal and vertical differences, termed disparities. Horizontal disparities are the main cue for stereopsis. In the past decades numerous physiological studies made on monkeys, which have in many aspects a similar visual system to humans, showed that a population of visual cells are capable of encoding the amplitude and sign of horizontal disparity. Such disparity detectors were found in cortical visual areas V1, V2, V3, V3A, VP, MT (V5) and MST of monkeys and in the superior colliculus of the cat and opossum. According to their disparity tuning function, these cells were first grouped into tuned excitatory, tuned inhibitory, near and far sub-groups. Subsequent studies added two more categories, tuned near and tuned far cells. Asymmetries between left and right receptive field position, on and off regions, and intra-receptive field wiring are believed to be the neural mechanisms of disparity detection. Because horizontal disparity alone is insufficient to compute reliable stereopsis, additional information about fixation distance and angle of gaze is required. Thus, while there is unequivocal evidence of cells capable of detecting horizontal disparities, it is not known how horizontal disparity is calibrated. Sensitivity to vertical disparity and information about the vergence angle or eye position may be the source of this additional information.

Depth Perception↗
PubMed1998

The clinical development of paclitaxel and the paclitaxel/carboplatin combination.

Paclitaxel and carboplatin have nonoverlapping toxicities with a broad range of clinical activity. The combination of escalating dose paclitaxel and carboplatin dosed to a fixed area under the curve (AUC) was explored in a series of phase I studies. 76 patients were treated with paclitaxel over three hours followed by a 30 min carboplatin infusion, dosed by the Calvert formula to a target AUC of 4.0 or 4.5 mg/min/ml-1. The maximum tolerated dose of paclitaxel was 270 to 290 mg/m2, with a dose limiting toxicity of peripheral sensory neuropathy. Activity was seen in lung cancer, with a paclitaxel dose at or above 230 mg/m2. Neuropathy correlated with paclitaxel AUC due to nonlinear pharmacokinetics at higher doses. Ongoing studies include the use of amifostine as a neuroprotectant and phase II studies of the paclitaxel/carboplatin regimen in head and neck cancer, small cell lung cancer and sarcomas.

Adult↗
PubMed1998

Indocyanine green angiography in isolated primary retinal arterial macroaneurysms.

PURPOSE: The study was carried out to describe the indocyanine green angiographic findings in isolated primary retinal arterial macroaneurysms and their contribution to the diagnosis of this condition. METHODS: Fluorescein and indocyanine green angiography examination techniques were used to study isolated primary retinal arterial macroaneurysms in 8 consecutive patients with retinal or preretinal haemorrhage over a period of 12 months. RESULTS: The fluorescein angiography examination showed the macroaneurysm in four cases; pulsatility was not observed in any case. Indocyanine green angiography disclosed the macroaneurysm in six cases; pulsatility was observed in two cases. CONCLUSION: Indocyanine green angiography allows better visualization of arterial macroaneurisms in the first examination and therefore facilitates the diagnosis, follow-up and laser treatment of this vascular abnormality.

Aged↗
PubMed1998

Depth perception in random dot stereograms is not affected by changes in either vergence or accommodation.

PURPOSE: To test the hypothesis that extraretinal cues related to vergence angle and lens accommodation are used to scale horizontal disparities for fixation distance. METHODS: Depth perception of random dot stereograms was studied in 10 healthy adult subjects with normal visual acuity by modifying retinal disparity, fixation distance, vergence angle, and accommodation. Statistical analysis was used to compare the data. RESULTS: Depth perception increased with fixation distance. The increment of depth perception persisted even when horizontal retinal disparity was kept constant. The magnitude of depth perception was independent of vergence angle. Depth perception did not vary with changes in accommodation. CONCLUSIONS: Extraretinal cues related to vergence angle and accommodation seem to be not necessary to scale horizontal disparities for viewing distance.

Accommodation, Ocular↗
PubMed1998

Use of a focussed teen prenatal clinic at a military teaching hospital: model for improved outcomes of unmarried mothers.

We evaluated the utility of a focussed, multidisciplinary adolescent clinic in improving perinatal outcomes. The study population included all delivering unmarried teenagers (13-19 years) from January 1, 1993 to December 31, 1995 attending the focussed adolescent obstetrical clinic compared to a similar cohort of married teenagers (13-19 years), married 20-24 year-old patients, and unmarried 20-24 year-old patients. There were no statistical differences in chorioamnionitis, intrauterine growth retardation (IUGR), postpartum haemorrhage, maternal weight gain, mean gestational age at delivery, preterm delivery rates (<37 weeks), low birth-weight (<2,500 g), Caesarean delivery, postterm delivery rates (>41 weeks), macrosomia (>4,000 g), placental abruption, chronic hypertension, alcohol use, Apgar scores or stillbirth rates or neonatal death rates among the 4 groups studied. Statistical differences were noted in mean delivery weights (p<0.05), preeclampsia (p<0.004), gestational diabetes (p<0.01), history of substance abuse (p<0.0001), tobacco use (p<0.0001), and forceps delivery rates (p<0.004). However, in the teen cohort none of these differences appeared to adversely affect perinatal outcomes in our patients. The focussed, adolescent obstetrical clinic appears to provide perinatal morbidities equal to a low-risk, general population generating better than expected outcomes for pregnant teenagers.

Adolescent↗
PubMed1998

The plasma beta-carotene response to a single meal of carrots in Guatemalan schoolchildren.

Plasma samples were obtained before, and 8 and 24 h after the ingestion of an ad libitum amount of cooked carrots by 23 school children from a peri-urban community in Guatemala City. The single-meal consumption of cooked carrots ranged from a low 122 g to a high of 961 g (mean: 370.5 +/- 237.2 g; median: 268.4 g). The measured beta-carotene content of the carrots was 10.1 mg per 100 g of edible portion; therefore, the range of intake of beta-carotene was 12.4 to 97.0 mg (mean: 37.4 +/- 24 mg; median: 27.1 mg). Changes in plasma beta-carotene levels at 8 h ranged from a decrement of -0.32 mumol/l (-16.98 micrograms/dl) to an increment of 0.79 mumol/l (42.44 micrograms/dl), with a mean of 0.11 +/- 0.24 mumol/l (5.97 +/- 12.82 micrograms/dl). Changes at 24 h were less dramatic than those at 8 h. A regression of the 8-h changes in plasma beta-carotene on the amount of carrot carotene consumed (corrected by body weight) had an r-value of 0.12. Baseline levels of plasma retinol were poor predictors of the plasma beta-carotene response with this sample size (r = 0.10). The magnitude of the plasma response to beta-carotene from carrots appears to be lower than that observed with pure, powdered, crystalline carotenes; moreover, the variability of the post-carrot response seems to be greater--and its association to dosage appears to be weaker--than with the pharmacological beta-carotene.

Biological Availability↗
PubMed1998

Ambulatory urodynamics of female soldiers.

The purpose of this study was to assess the accuracy of ambulatory urodynamic monitoring compared with conventional urodynamic studies for the detection of exercise-induced urinary incontinence in the female soldier. Fifty active duty female soldiers with exercise-induced urinary incontinence and 10 asymptomatic control soldiers underwent conventional multichannel cystometry and then ambulatory monitoring during work or exercise. Ambulatory monitoring detected a greater number of abnormalities than conventional multichannel urodynamic studies in exercise-induced urinary incontinence. This greater sensitivity is valuable in formulating more effective treatment. Behavioral interventions were effective in treating exercise-induced urinary incontinence in this population. Test results normalized after behavioral intervention. It is neither cost-effective nor efficacious to require sophisticated urodynamic testing before instituting behavioral interventions.

Adult↗
PubMed1997

Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease.

Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes increase the production of the highly amyloidogenic 42-residue form of amyloid beta-protein (Abeta42) in a variety of cell lines and transgenic mice. To elucidate the molecular mechanism of this effect, wild-type (wt) or mutant PS1 and PS2 genes were stably transfected into Chinese hamster ovary cells expressing endogenous or transfected beta-amyloid precursor protein (APP). By immunoprecipitation/Western blot analysis, APP was consistently found to coimmunoprecipitate with PS1 or PS2 proteins. Several distinct PS1, PS2, or APP antibodies precipitated PS-APP complexes that were detectable by blotting with either APP or PS antibodies. Importantly, complex formation could be detected at endogenous protein levels in nontransfected cells. In various Chinese hamster ovary cell lines, the amounts of APP coprecipitated by PS antibodies were proportional to the expression levels of both APP and PS. APP-PS complexes also were recovered from human 293 and HS683 cells. Full maturation of APP was not required for the interaction; most APP molecules complexed with PS were solely N-glycosylated. Treatment of cells with brefeldin A or incubation at 20 degrees C did not block complex formation, suggesting that the association between APP and PS occurs in part in the endoplasmic reticulum. Complex formation was detected for both wt and mutant PS and APP proteins. Deletion of the APP C-terminal domain did not abrogate complex formation, suggesting that the interaction does not occur in the cytoplasmic domains of the proteins. Our results demonstrate that wt and mutant PS1 and PS2 proteins form complexes with APP in living cells, strongly supporting the hypothesis that mutant PS interacts with APP in a way that enhances the intramembranous proteolysis of the latter by a gamma-secretase cleaving at Abeta42.

Alzheimer Disease↗
PubMed1997

Effect of glutathione depletion on the cytotoxicity of cisplatin and iproplatin in a human melanoma cell line.

Previous studies from our laboratory have indicated that glutathione (GSH) may affect the cytotoxicity of iproplatin to a greater extent than four other platinum agents tested including cisplatin. Therefore we studied the effect of GSH depletion by buthionine sulfoximine (BSO) on the cytotoxicity of iproplatin and cisplatin in a human melanoma cell line SK-MEL-2. Depletion of GSH was dependent on the concentration and time of incubation with BSO. BSO (100 microM) depleted GSH by 85% at 24 h and by 91% at 48 h. BSO (10 to 100 microM) by itself was not cytotoxic to SK-MEL-2 cells. At 85% depletion of GSH, cytotoxicity of iproplatin was increased by a factor of > 7 and that of cisplatin by < 2. These results confirm the previous finding that GSH interferes with the cytotoxicity of iproplatin to a significantly greater extent than that of cisplatin. Equitoxic IC65 and IC90 values of cisplatin (2 microM and 5 microM) or iproplatin (25 microM and 50 microM) had no effect on the intracellular GSH levels in SK-MEL-2 cells. Also, depletion of GSH by BSO had no effect on the accumulation of platinum from either cisplatin or iproplatin in this cell line. Our results suggest that the effect of GSH on the cytotoxicity of cisplatin and iproplatin in this cell line was not a consequence either of differences in GSH-Pt conjugate formation, or of differences in platinum accumulation induced by GSH depletion. GSH may have modulated the cytotoxicity of these platinum complexes by other means such as effects on DNA repair, apoptosis, free radical scavenging or through other yet unidentified mechanisms.

Antineoplastic Agents↗
PubMed1997

Electrophysiology and pharmacology of outward potassium currents in semicircular canal hair cells of toadfish, Opsanus tau.

Outward currents from hair cells from the horizontal semicircular canal (HSCC) of the toadfish were investigated using whole cell patch clamp methods. Two classes of hair cells are found. One class (approx. 10% of cells) showed only a non-inactivating current (IKCa) which was blocked by 2 mM TEA. A second class had both inactivating and non-inactivating currents. The former (IA) was blocked by 4-AP (1 mM) and the latter (IKCa) by TEA (2-20 mM) . While the majority of the cells expressed both these outward currents, due to IA inactivation both currents are functionally present in the same cell only between -60 and -40 mV. At more depolarized membrane potentials, IA was inactivated, suggesting that a single hair cell may have two distinct signalling modes, one dominated by IA at more hyperpolarized membrane potentials and the other by IKCa at depolarized values where ICa is beginning to grow, increasing both amplitude and activation rate of IKCa. The switch between modes will be determined by the amplitude and frequency characteristics of the stimulus and possibly also by actions of efferent transmitters. In current clamp mode, 10% of the HSCC hair cells showed high Q and high frequency resonance, from 44 to 360 Hz at 12 degrees C. These cells expressed only one outward calcium dependent, non-inactivating, TEA sensitive current, characteristic of IKCa. A suggested role for high frequency resonance is as positive feedback to produce a high frequency updating of the stereociliary compliance to most faithfully transduce angular acceleration.

4-Aminopyridine↗
PubMed1997

Unusual central nervous system toxicity in a phase I study of N1N11 diethylnorspermine in patients with advanced malignancy.

The objectives of this study were to determine the dose limiting toxicity (DLT) and other major toxicities, the maximum tolerated dose (MTD) and the human pharmacokinetics of N1N11 diethylnorspermine (DENSPM), a new polyamine analog which in experimental systems inhibits the biosynthesis of intracellular polyamines and promotes their degradation by inducing the enzyme spermine/spermidine N-acetyl transferase. These objectives were incompletely achieved because of the occurrence of an unusual syndrome of acute central nervous system toxicity which forms the basis of the present report. Fifteen patients with advanced solid tumors were entered into a phase I study of DENSPM given by a 1 h i.v. infusion every 12 h for 5 days (10 doses). The starting dose was 25 mg/m2/day (12.5 mg/m2/dose) with escalation by a modified Fibonacci search. Doses of 25 and 50 mg/m2/day were tolerated with only minor side effects of facial flushing, nausea, headache and dizziness (all grade I). At doses of 83 and 125 mg/m2/day, a symptom complex of headache, nausea and vomiting, unilateral weakness, dysphagia, dysarthria, numbness, paresthesias, and ataxia, was seen in 3 patients, one after 2 courses of 83 and 2 after 1 course of 125 mg/m2/day. This syndrome occurred after drug administration was complete and the patients had returned home. Lesser CNS toxicity was seen in 2 other patients at lower daily doses. Preliminary pharmacokinetics of DESPM measured in plasma by HPLC in 8 patients showed linearity with dose and a rapid plasma decay with a t1/2 of 0.12 h. We conclude that great caution is warranted in administering DENSPM on this schedule at doses of > or = 83 mg/m2/day.

Adenocarcinoma↗
PubMed1997

Growth inhibition of human lung adenocarcinoma cells by antibodies against epidermal growth factor receptor and by ganglioside GM3: involvement of receptor-directed protein tyrosine phosphatase(s).

Growth of the EGF receptor-expressing non-small-cell lung carcinoma cell line H125 seems to be at least partially driven by autocrine activation of the resident EGF receptors. Thus, the possibility of an EGF receptor-directed antiproliferative treatment was investigated in vitro using a monoclonal antibody (alpha EGFR ior egf/r3) against the human EGF receptor and gangliosides which are known to possess antiproliferative and anti-tyrosine kinase activity. The moderate growth-inhibitory effect of alpha EGFR ior egf/r3 was strongly potentiated by the addition of monosialoganglioside GM3. Likewise, the combination of alpha EGFR ior egf/r3 and GM3 inhibited EGF receptor autophosphorylation activity in H125 cells more strongly than either agent alone. A synergistic inhibition of EGF receptor autophosphorylation by alpha EGFR ior egf/r3 and GM3 was also observed in the human epidermoid carcinoma cell line A431. In both cell lines, the inhibition of EGF receptor autophosphorylation by GM3 was prevented by pretreatment of the cells with pervanadate, a potent inhibitor of protein tyrosine phosphatases (PTPases). Also, GM3 accelerated EGF receptor dephosphorylation in isolated A431 cell membranes. These findings indicate that GM3 has the capacity to activate EGF receptor-directed PTPase activity and suggest a novel possible mechanism for the regulation of cellular PTPases.

Adenocarcinoma↗
PubMed1997

Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis.

BACKGROUND & AIMS: Bioavailability of insulin-like growth factor (IGF-I) is reduced in liver cirrhosis. The aim of this study was to analyze the effect of IGF-I on liver histopathology and function in experimental cirrhosis. METHODS: Rats received CCl4 inhalations for 11 or 30 weeks (protocols 1 and 2, respectively) and were treated with 2 microg x 100 g body wt(-1) x day(-1) IGF-I (group CI + IGF) or saline (group CI) on weeks 13 and 14 (protocol 1) or on weeks 28-30 (protocol 2). Normal rats were studied in parallel. RESULTS: Serum albumin and total protein levels were reduced in CI but not in CI + IGF rats compared with normal rats. Clotting factors II, VII, and X were significantly greater in CI + IGF than in CI rats. Liver lipid peroxidation products were significantly increased in CI but not in CI + IGF rats, and liver fibrosis was less pronounced in CI + IGF than in CI animals. The activities of antioxidant enzymes and mitochondrial transmembrane potential were reduced compared with normal animals in CI but not in CI + IGF rats. CONCLUSIONS: IGF-I improves liver function and reduces oxidative liver damage and fibrosis in rats with compensated or advanced liver cirrhosis. Improved mitochondrial function could play a role in the hepatoprotective effect of this hormone.

Animals↗