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Biomedical subjects

M Marquez

Publications and source records attributed to M Marquez.

At least 19 recordsLinked to original sources

Neuronal intranuclear inclusion disease in a horse.

Neuronal intranuclear inclusion disease (NIID) is reported in a 16-year-old Pure Spanish breed female horse suffering from progressive ataxia and motor deficiencies. The neuropathological study revealed NIIs throughout the central nervous system, although mainly in the brain stem and spinal cord. This distribution did not correlate with neuron loss, which was marked in the hippocampus and moderate in the neocortex, particularly in the occipital cortex. As in humans, NIIs in the horse were hyaline autofluorescent inclusions composed of non-membrane-bound aggregates of filaments and fine granules. NIIs were stained with anti-ubiquitin and anti-clusterin antibodies. In addition, NIIs were stained with antibodies raised against subunits of the 19S and PA28, but not of the 20S, components of the proteasome. These observations indicate similarities between NIID in humans and horses, and suggest that clusterin and abnormal ubiquitin-proteasomal expression participate in NII formation.

Animals↗

A randomized study investigating the efficacy and safety of amprenavir in combination with low-dose ritonavir in protease inhibitor-experienced HIV-infected adults.

OBJECTIVES: To compare the safety and efficacy of amprenavir [APV/j Agenerase trade mark; GlaxoSmithKline, [Ware, UK; 600 mg twice a day (bid)] boosted with low-dose ritonavir (RTV, 100 mg bid) with those of other protease inhibitors (PIs) in PI-experienced HIV-infected patients. STUDY DESIGN: Parallel-group, randomized, open-label, multicentre study. METHODS: One hundred and sixty-three patients with HIV predicted to be sensitive to APV, another PI and a nucleoside reverse transcriptase inhibitor (NRTI) were randomly assigned to receive either APV boosted with low-dose RTV (APV/r) or a standard of care (SOC) PI with or without low-dose RTV. The non-inferiority of APV/r to the SOC PIs was assessed by time-weighted average change from baseline (AAUCMB) in plasma viral load (vRNA) at week 16. RESULTS: The antiviral response for APV/r bid was non-inferior to that for the SOC PI group: the vRNA AAUCMB mean treatment difference was 0.043 log(10) HIV-1 RNA copies/mL [95% confidence interval (CI)-0.250, 0.335]. APV/r bid was generally well tolerated. CONCLUSIONS: Results confirm the antiviral activity, short-term safety and tolerability of APV/r bid in PI-experienced patients.

Adolescent↗

Micro/nano encapsulation via electrified coaxial liquid jets.

We report a method to generate steady coaxial jets of immiscible liquids with diameters in the range of micrometer/nanometer size. This compound jet is generated by the action of electro-hydrodynamic (EHD) forces with a diameter that ranges from tens of nanometers to tens of micrometers. The eventual jet breakup results in an aerosol of monodisperse compound droplets with the outer liquid surrounding or encapsulating the inner one. Following this approach, we have produced monodisperse capsules with diameters varying between 10 and 0.15 micrometers, depending on the running parameters.

Aerosols↗

Assessing coronary blood flow dynamics with the TIMI frame count method: comparison with simultaneous intracoronary Doppler and ultrasound.

This study compared the TIMI frame count (TFC), which has been proposed as a method for quantifying coronary blood flow, with coronary flow and microvascular function measured with intracoronary Doppler and intracoronary ultrasound. Coronary blood flow volume was calculated from coronary blood velocity (by intracoronary Doppler) and lumen area (by intracoronary ultrasound) in the LAD in 46 post-heart transplant patients at baseline and after intracoronary adenosine. TFC correlated significantly with average peak coronary blood velocity (r = -0.42; P = 0.004) and coronary lumen area (r = 0.39; P = 0.008), but not with coronary blood flow volume (r = -0.01; P = 0.96) or the coronary flow reserve response to adenosine (r = 0.09; P = 0.58). In conclusion, TFC is a simple method of assessing coronary blood velocity but not volumetric flow. While TFC does not predict coronary flow reserve, as a measure of velocity it does provide an assessment of basal microvascular tone, information that is complementary to that afforded by flow reserve measurements.

Adult↗

Technetium-99m labelling of glycosylated somatostatin-14.

This study presents a technetium-99m labelling method based on organometallic chemistry. It describes the simple mixing of a 99mTc(I)-carbonyl compound [99mTc(OH2)3(CO)3]+ with a histidine-tagged somatostatin-dextran (SMS-Dx-His) conjugate. Somatostatin and histidine was coupled to periodate activated dextran. The linkage was stabilised by reductive amination. The conjugate was then radiolabelled with 99mTc by using the 99mTc(CO)3 core. The labelling efficiency was 65-80% and the radiochemical purity > 95%. In the in vitro cysteine challenge, the result showed that 25% of the radiolabel was released after 1 h incubation at 37 degrees C (cysteine-conjugate at 1000:1 molar ratio). The radiolabelled SMS-Dx-His showed similar HPLC profile as the unlabelled conjugate. This labelling method, employing non reducing conditions, is useful for the labelling of peptides containing disulphide bonds. It should be possible to be used also for labelling with rhenium-188 for therapeutic applications.

Chromatography, High Pressure Liquid↗

The effect of handgrip position on upper extremity neuromuscular responses to arm cranking exercise.

The purpose of this study was to determine if handgrip position during arm cranking exercise influences the neuromuscular activity of muscles biceps brachii (BB), lateral head of triceps brachii (TB), middle deltoid (DT), infraspinatus (IS) and brachioradialis (BR). Fifteen participants cranked an arm ergometer using three different handgrip positions (supinated, pronated, and neutral). Electromyographic (EMG) data were recorded from the aforementioned muscles, and relative duration of EMG activation and amplitude were quantified for the first and second 180 degrees of crank angle. EMG measures were analyzed with MANOVA and follow-up univariate procedures; alpha was set at 0.01. The relative durations of EMG activation did not differ between handgrip positions. Muscle IS exhibited 36% less amplitude in the supinated versus neutral handgrip position (second half-cycle), and muscle BR displayed 63% greater amplitude across cycles in the neutral versus supinated and pronated handgrip positions. The greater BR activity displayed in the neutral handgrip position may reflect its anatomical advantage as an elbow flexor when the forearm is in neutral position. Muscle IS exhibited less activity in the supinated position and may be clinically relevant if it allows arm cranking to occur without subsequent shoulder pain, which is often the aim of shoulder rehabilitation.

Adult↗

Radiolabeling of dextran with rhenium-188.

This study describes a method for the radiolabeling of dextran with rhenium-188 (188Re). In nuclear oncology 188Re is very useful for therapeutic applications. Its nuclear characteristics allow radiotherapy and in situ monitoring of tumor uptake as well as dosimetry calculations. Consequently new compounds with this radiolabel are of general interest. Dextran was oxidized with sodium periodate yielding reactive aldehyde groups and subsequently reacted with cysteine. The linkage was stabilized by reducing the Schiff bases with sodium cyanoborohydride. The conjugate was then radiolabeled with 188Re by using 188Re-gluconate as the transchelator, labeling the free thiols. Synthesis and radiolabeling were done in the absence of oxygen. The labeling efficiency was 60-70% and the radiochemical purity > 95%. The in vitro stability study, using "cysteine challenge" demonstrated that 50% of the radiolabel was transcomplexed to the 100 mM cysteine solution (after 1 h incubation at 37 degrees C). However, at physiologic conditions and presence of an antioxidant good stability was achieved. The 188Re labeled dextran presented in this study provides a template with therapeutic and diagnostic potential in nuclear oncology, either alone for local treatment or as a backbone in a tumor specific conjugate for systemic treatment.

Dextrans↗

[Single extramedullary plasmacytoma of the nose].

A new solitary extramedullary plasmacytoma of nasal localization meeting the conditions for definition is reported. The patient was treated with surgery and irradiation, which controlled the disease and produced excellent cosmetic results. The bibliography is reviewed and the pathologic, clinical, and evolutive characteristics are discussed.

Antibodies, Monoclonal↗

Prevention of corticosteroid-induced osteoporosis: results of a patient survey.

OBJECTIVE: To evaluate the current use of bone densitometry and agents to prevent bone loss among long-term corticosteroid users. METHODS: A telephone survey of patients receiving long-term oral corticosteroid treatment. RESULTS: One hundred forty-seven patients receiving a mean prednisone dose of 10 mg per day for an average of 1-2 years were surveyed. Twenty-nine percent reported having a bone density test, 29% were taking calcium supplements, and 45% were receiving vitamin D. Forty percent of postmenopausal (PMP) women were receiving hormone replacement therapy and 14%, bisphosphonate treatment. Forty-two percent of PMP women were receiving no preventive treatment. Patients who were evaluated by primary care physicians and rheumatologists were more likely to have undergone bone density testing and to have received preventive treatments than were patients of other specialists. CONCLUSION: Many patients receive inadequate treatment to prevent corticosteroid-induced osteoporosis, and physician specialty is an important predictor of bone density testing and treatment. A broad educational effort directed to physicians of varied specialties is needed to ensure that osteoporosis prevention becomes the standard of care for patients receiving long-term corticosteroid treatment.

Adrenal Cortex Hormones↗

Inter-clinician agreement on clinical data abstracted from patients' medical charts.

PURPOSE: The purpose of this study was to determine the inter-observer repeatability of retrospective chart reviews. METHODS: Retrospective abstraction of corneal transplant patients' medical records by two independent observers was performed at the University of California, Davis, Department of Ophthalmology, Sacramento, CA. The sample consisted of 100 consecutive patients who underwent penetrating keratoplasty, and the primary outcome measure was the degree of agreement between the 2 independent observers on clinical ocular data abstracted from patients' medical charts. RESULTS: Even when given specific criteria for abstraction of data from patients' medical charts, inexperienced but trained observers exhibited a small degree of disagreement (range 0 to 12%) on patient demographic variables (e.g., gender, age, and date of birth) to be used for data analysis. Larger amounts of disagreement (range 3 to 26%) were found on frequently occurring variables (e.g., predisposing ocular conditions, surgical complications, and classification of corneal staining). CONCLUSIONS: Based on these data, inter-observer repeatability for retrospective chart review studies is good, but investigators using this study methodology must be quite specific about the data to be collected and should be aware of standardization techniques to enhance observer repeatability.

Abstracting and Indexing↗

Variations in physicians' judgments about corticosteroid induced osteoporosis by physician specialty.

OBJECTIVE: Longterm corticosteroid use is associated with an increased risk of osteoporosis and fractures. Calcium and vitamin D supplementation and estrogen replacement therapy can decrease this risk, but the majority of patients receiving longterm corticosteroid treatment do not receive treatments to prevent bone loss. We assess whether this is due to variations in physicians' judgments about risks and efficacy of treatments to prevent corticosteroid-induced osteoporosis. METHODS: Questionnaires were mailed to 425 physicians, who were sampled so that half were generalists and half were specialists. Physicians were given hypothetical clinical scenarios involving patients taking corticosteroids and asked to judge the importance of osteoporosis as a risk of corticosteroid treatment, the importance of discussing this side effect with patients, and to indicate how often they would use calcium with vitamin D and estrogen for a hypothetical postmenopausal patient receiving longterm corticosteroid treatment. RESULTS: In total 198 physicians (50%) responded to this survey. Most physicians rated osteoporosis as one of the 3 most significant side effects of corticosteroid treatment for postmenopausal women, but there was significant variation in physician judgments about the importance of corticosteroid induced osteoporosis for premenopausal women (p=0.03) and men (p=0.001). There was also significant variation in physician judgments about the importance of discussing osteoporosis as a side effect with patients (p=0.001), and their use of both calcium and vitamin D (p=0.002) and estrogen replacement therapy (p=0.001) for a hypothetical postmenopausal patient. The physician characteristics most associated with these differences were physician specialty and experience with corticosteroid use. Primary care physicians and physicians who more commonly prescribe corticosteroids were more likely to report that they would use estrogen and calcium to prevent corticosteroid induced bone loss. Physician age, sex, and university affiliation had no association with physician assessments. CONCLUSION: Physicians' judgments varied significantly by physician specialty and experience with corticosteroid use. These data suggest that patients cared for by physicians in different specialties will get varying advice about osteoporosis risk and preventive treatments when receiving longterm corticosteroid treatment.

Adrenal Cortex Hormones↗

Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother.

This report describes an infant with multiple congenital anomalies born to a 20-year-old mother with juvenile rheumatoid arthritis who had been taking weekly low-dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low-dose MTX treatment.

Abnormalities, Drug-Induced↗

Modulation of organ uptake of 11C-labelled L-DOPA.

The present study was undertaken to investigate if pretreatment with pharmacological agents could change the organ uptake of 11C-labelled L-DOPA, and especially if the urinary excretion could be decreased. L-[beta-11C]DOPA was injected IV into unanesthetized Sprague-Dawley rats. After 20 min the rats were decapitated and organs taken out for radioactivity measurements. The uptake in the organs was investigated in animals only given the tracer, and in animals pretreated with drugs such as decarboxylase inhibitors carbidopa and benserazide as well as the monoamine oxidase inhibitors deprenyl, clorgyline, and the COMT inhibitor OR-486. A marked decrease in the urinary radioactivity was observed after carbidopa and benserazide administration. HPLC analysis revealed that under native conditions the major part of urinary radioactivity existed as dopamine, which was eliminated by the decarboxylase inhibitors. After pretreatment with the COMT inhibitor OR-486, the radioactivity uptake in the pancreas increased fourfold as compared to non-treated animals. HPLC analysis showed that this correlated with a marked increase in radiolabelled DOPAC. In the other organs and with the other drugs, only small effects were observed. With L-[beta-11C]fluoroDOPA as a tracer, similar results were observed although the increase in the pancreas by OR-486 had a lower magnitude. These studies suggest that it might be possible to improve the diagnostic ratio of L-[beta-11C]DOPA or L-[18F]fluoroDOPA in whole-body PET studies by pretreating the patient with decarboxylase inhibitor for reducing the urinary excretion and potentially increase the target organ uptake by COMT inhibition.

Animals↗

Preoperative risk factors for surface disease after penetrating keratoplasty.

We sought to identify the types of, prevalence of, and predisposing factors for the development of surface keratopathy after penetrating keratoplasty. We reviewed the records of 120 corneal grafts performed over a 15-month period. Twenty patients were excluded from the study. Fifty-three men and 47 women composed the group studied. All transplants were performed by the same surgeon. Retrospective data from patients' records were gathered preoperatively and from postoperative visits at 1 week and at 1, 2, 3, and 4 months. Data included preoperative medical and demographic data, operative time, postoperative medication regimens, assessment of the presence and degree, if present, of punctate epithelial keratopathy (PEK), hurricane keratopathy, macroepithelial defects, microcystic edema, bullous edema, and filamentary keratitis. In addition, information on the donor material was recorded. Surface disease and normal groups were compared to identify risk factors for the occurrence of surface abnormalities. Thirty-three of the patients demonstrated persistent surface abnormalities. Coarse PEK was the most common surface abnormality in the sample studied and was most prominent in the first week after surgery. Postoperative surface keratopathy was not statistically associated with preoperative diagnosis, donor age, death-to-preservation time, preservation-to-surgery time, or donor epithelial status. However, corneal recipients in the group with surface keratopathy were significantly older (mean, 68.7 years) than patients in the group with no surface abnormalities (mean, 52.6 years; Mann-Whitney U test, p < 0.001). Although many factors may contribute to the normal integrity of the corneal surface after keratoplasty, recipient age is of key importance in the development of surface disease.

Aged↗

Catechol-O-methyltransferase inhibition increases the uptake of 11C-3-(3,4-dihydroxyphenyl)-L-alanine in the rat pancreas.

BACKGROUND: The objective of the present investigation was to evaluate the uptake and metabolism of 3-(3,4-dihydroxyphenyl-L-alanine) (L-DOPA) in the rat pancreas. METHODS: The procedure included intravenous injection of the positron-emitting radiotracer L-[beta-11C] DOPA (DOP) into unanaesthetized male Sprague-Dawley rats and evaluation of uptake of radioactivity in organs in animals only given the tracer and in animals given therapeutic doses of three different catechol-O-methyltransferase (COMT) inhibitors, OR-486, OR-611, or Ro 41-0960. Selected pancreati were homogenized, and the chemical form bearing the radioactivity was analysed with high-performance liquid chromatography (HPLC). RESULTS: The main finding was that the tracer uptake in the pancreas increased fourfold when the rats were pretreated with COMT inhibitors. Half maximum effect of OR-486 was found at a dose of 0.2 mg/kg. HPLC analysis showed that with COMT inhibitor, the radioactivity in the pancreas consisted of 90% DOPAC. When administering MAO-A and COMT inhibitor together, the pancreas radioactivity corresponded to dopamine. Also in the pig pancreas a significant increase of DOP was observed after COMT inhibition. CONCLUSIONS: This study has shown a high turnover of L-DOPA in the rat pancreas, which can be modulated to give enhanced levels of DOPAC or dopamine by COMT and MAO inhibition.

Analysis of Variance↗

Labeling of polypeptides with technetium-99m using a dextran spacer.

Radioimmunoscintigraphy and other forms of scintigraphy are becoming increasingly important as tools in detection and evaluation of cancer diseases. Several radionuclides can be considered as radiolabel; however, 99mTc may be the most suitable because of easy availability and near ideal physical properties. This study describes how dextran is coupled to a monoclonal anticytokeratin antibody, epidermal growth factor, and somatostatin through stable amine bonds. The dextran moiety could then be labeled with 40-62 MBq of 99mTc. The labeling efficiency was 60-94%, determined by gel filtration or TLC. The specific binding could be considerably preserved after the dextranation, the antibody retained > 90% of its activity, epidermal growth factor bound with > 90% specificity to receptor-expressing tumor cells, and somatostatin showed approximately 40% specific binding to rat adrenal homogenates. Because somatostatin only has a transient half-like in vivo, the in vivo plasma half-life of somatostatin-dextran was tested in normal female Sprague-Dawley rats. The result showed a strong enhancement of the plasma half-life that was dependent on two compartments, 4 and 8 h.

Animals↗