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C Gonzales

Publications and source records attributed to C Gonzales.

At least 19 recordsLinked to original sources
PubMed2006

Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.

LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.

Alanine↗
PubMed2005

Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of single-dose duloxetine in cirrhotic and healthy subjects. METHODS: An open-label inpatient study compared duloxetine pharmacokinetics in six subjects with moderate liver cirrhosis (Child-Pugh class B) to those in six healthy subjects. Subjects received a single 20 mg capsule of duloxetine following overnight fasting. Blood samples were collected up to 120 h post dose for determination of plasma concentrations of duloxetine and its major metabolites using a validated LC/MS/MS method. Plasma concentration-time data for duloxetine and its major metabolites were analyzed by noncompartmental methods. Specific pharmacokinetic parameters were assessed statistically using a mixed-effects model. RESULTS: Duloxetine apparent clearance was significantly lower (24 vs 160 l/h, p < 0.05) and AUC values were substantially higher (775 vs 268 ng x (h/ml) in cirrhotic compared to healthy subjects. The half-life of duloxetine was about three times longer (47.8 vs 13.5 h) in cirrhotic than in healthy subjects (p < 0.05). In contrast, there was no significant difference in Cmax or apparent volume of distribution between the two groups. The metabolites exhibited lower levels and longer half-lives in cirrhotic subjects compared to healthy subjects. The lower clearance and slower elimination of duloxetine in cirrhotic individuals is likely attributable to impaired duloxetine metabolism. CONCLUSIONS: The rate of duloxetine elimination is reduced for cirrhotic subjects, making dosage adjustments appropriate. Based on simulations, the duloxetine dose for at least an initial treatment period may need to be reduced and/or less frequently administered for patients with moderate cirrhosis.

Administration, Oral↗
PubMed2004

Estimating dose equivalence for new routes of drug administration.

For patient's convenience, dose administration of insulin via oral inhalation is often considered as an alternative to subcutaneous administration. An important statistical problem is to estimate dose equivalence, which is the amount of drug needed to be delivered by inhalation to generate an equivalent pharmacokinetic (PK) response produced by a therapeutic dose of subcutaneous insulin. Because of high intersubject variability, a crossover design clinical trial is typically used where data from both routes of administration are obtained from the same subject. A linear mixed effects model is proposed to describe the relationship between AK response and insulin dose for the two routes of administration. Estimation of dose equivalence in this setting has not been discussed in the statistical literature. Several competing methods for estimating dose equivalence are proposed and contrasted. A formula for calculating an approximate sample size necessary to estimate dose equivalence with a desired precision for the new route of administration is also provided.

Administration, Inhalation↗
PubMed2004

Inhaled micronized crystalline human insulin using a dry powder inhaler: dose-response and time-action profiles.

AIM: The aim of this euglycaemic glucose clamp study was to investigate the pharmacokinetics, glucodynamics, safety and tolerability of micronized crystalline human insulin inhalation powder delivered by a Spiros dry powder inhaler system in healthy volunteers. METHODS: Thirteen healthy, non-smoking, male and female volunteers [age 30 +/- 7 years; BMI 23.5 +/- 2.7 kg/m(2); (mean +/- sd)] with normal pulmonary function participated in an open-label, randomised, 6-period crossover trial. Each volunteer received four single doses of inhaled insulin (60, 90, 120, 150 U) on separate occasions. For comparison, each volunteer also received two of three possible doses of subcutaneous (s.c.) injected regular human insulin (8, 14, or 20 U). RESULTS: Serum immunoreactive insulin following inhalation of insulin peaked an average of 60 min earlier compared with s.c. injected insulin (P < 0.0001). Following inhalation, the time to maximum glucose infusion rate occurred an average of 70 min earlier than with s.c. insulin: 187, 129, 161 and 162 min vs. 227, 241 and 241 min (P < 0.0001). The dose-response relationships for serum insulin pharmacokinetics and glucodynamics were linear for both inhaled and s.c. insulin. Relative bioavailability (based on serum insulin levels) ranged from 11.5 to 12.2% for the four doses of inhaled insulin and relative biopotency (based on glucose infusion rates) was 10.0 to 16.5%, respectively. Dosing was well tolerated by all volunteers. CONCLUSION: This study demonstrates that inhalation of human insulin via a dry powder inhaler system provides a promising alternative route for administration of insulin.

Administration, Inhalation↗
PubMed2001

Cavernous angioma of the brain stem simulating diffuse pontine glioma.

Brainstem vascular malformations can sometimes simulate other conditions such as multiple sclerosis and pontine glioma. We report a case of brainstem cavernous angioma for which clinical course and radiologic appearance were suggestive of a pontine glioma. The diagnosis was uncertain until the clinical and radiologic evolution made it clear that the patient had a cavernous angioma. We suggest that brainstem angioma be considered as a differential diagnosis for pontine glioma.

Adolescent↗
PubMed2001

Branded versus generic clozapine: bioavailability comparison and interchangeability issues.

Clozapine has been the treatment of choice for patients with refractory schizophrenia. Generic clozapine has recently become available, because of a waiver of the usual criteria for establishing bioequivalence. However, there are biopharmaceutical, bioavailability, and clinical concerns related to the generic formulation raised by both clinicians and academic researchers. We conducted a prospective, randomized, crossover study to evaluate steady-state pharmacokinetics, pharmacodynamics, and tolerability of generic clozapine (Zenith Goldline Pharmaceuticals) versus Clozaril (Novartis Pharmaceuticals) in schizophrenic patients. A preliminary report of the pertinent bioavailability results is presented here. Despite comparable mean plasma concentration-time curves, significant differences were found in the primary pharmacokinetic parameters of the 2 formulations in almost 40% of patients. Such intraindividual differences raise the issue of average bioequivalence versus individual bioequivalence and the implication for interchangeability of different clozapine formulations. The decision to switch a patient from branded to generic clozapine should be made on an individual basis with special emphasis on clinical outcome, and patients should be monitored closely during the transition.

Adult↗
PubMed2001

Effect of Lepidium meyenii (maca) roots on spermatogenesis of male rats.

AIM: To determine the effect of oral administration of an aqueous extract from the roots of Lepidium meyenii (maca) on spermatogenesis in adult male rats. METHODS: Male rats received an aqueous extract of the root (66.7 mg in one mL) twice a day for 14 consecutive days. RESULTS: Treatment with Lepidium meyenii resulted in an increase in the weights of testis and epididymis but not the seminal vesicle weight. The length and frequency of stages IX-XIV seminiferous tubules, where mitosis occurred, were increased and stages I-VI were reduced in rats treated with Lepidium meyenii. CONCLUSION: The Lepidium meyenii root invigorates spermatogenesis in male rats by acting on its initial stages (IX-XIV).

Administration, Oral↗
PubMed2001

Education and training in hyperbaric medicine. The Icelandic experience. An example of international scientific cooperation.

The authors describe their experience in the practice, education and learning in the field of hyperbaric medicine, following a project of international scientific cooperation, first in history, between Italy and Iceland. As a result of this project, the first hyperbaric facility came into use in Iceland in March 1993, initially entirely run and economically supported by the Italian side. Since 1997 the activity has been entirely financed by Icelandic National Health System with a special budget established each year according to an agreement between Icelandic and Italian Health Authorities, leaving the medical and the economical management of the Service to Italian personnel. Hyperbaric medicine is now a reality in the Icelandic medical practice. Moreover, since 1994 young Italian doctors from the University of Trieste, Italy, enrolled in the School of Specialization in Anesthesia, Intensive Care, have received training at the Service of Hyperbaric Medicine of the University of Reykjavik City Hospital, as part of their training. The educational activity, endorsed by the Italian Ministry of University and Research, consists of a theoretical part and of a practical part of operational assistance. At the end of his or her training, the resident has a full knowledge of the indications for hyperbaric oxygen therapy (HBOT) and of the related diagnostic and therapeutic procedures, is autonomous and is able to safely operate an hyperbaric chamber. An analytical report of the activity in year 2000 is also included.

Hyperbaric Oxygenation↗
PubMed2001

Altitude decompression sickness. Case presentation.

The in-flight altitude-related decompression sickness (DCS) is not as common as DCS occurring after working or recreational diving, or, at least, it is not commonly described in the medical literature. Though modern aircraft are safer and more reliable, occupants are still subject to the stress of high altitude flight, and altitude DCS still represents a risk to the occupants, mostly if they are exposed to altitudes of 25,000 ft or higher. The authors report their experience about two different accidents involving a US Air Force pilot and a navigator, treated at the Service of Hyperbaric Medicine at Landspitallin Fossvogur, the University of Reykjavik City Hospital, Iceland, because of occurrence of type II altitude-related DCS. A US Navy Oxygen Treatment Table 6 was successfully applied in both cases. Also considered are some aspects related to physiopathology, clinical presentation and therapy of DCS, with particular regard to the occurrence of DCS during flight.

Adult↗
PubMed2001

HBO and gas gangrene. A case report.

A 58-year old man, in a mediocre health condition, was admitted into Landspitallin Fossvogur, the University of Reykjavik City Hospital, Iceland, because of fever, chills, local pain and swelling due to the presence of a big old wound in his left heel. The first clinical appearance showed a gas gangrene of the area. The patient immediately underwent a surgical debridement and a fasciotomy, and antibiotic intravenous therapy and hyperbaric oxygen therapy (HBOT) were started. During the treatment the patient suffered for a multi-organ failure syndrome (MOFS), was admitted in ICU and survived. A total of 52 HBO sessions were performed and one month since the admission into the hospital the patient received a skin transplant. He achieved a complete restitutio ad integrum after 78 days of hospitalization. Gas gangrene is a fulminating infection caused by the genus of Clostridia. If not treated, it leads to the death of the host. The actual treatment for gas gangrene includes surgery, antibiotics, general resuscitative measures and HBOT.

Combined Modality Therapy↗
PubMed2001

Lepidium meyenii (Maca) improved semen parameters in adult men.

AIM: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24-44 years old. METHODS: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment. RESULTS: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treatment. Increase of sperm count was not related to dose of Maca. CONCLUSION: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.

Adult↗
PubMed2000

Two Factor Additive Conjoint Measurement with One Solvable Component.

This paper addresses conditions for the existence of additive separable utilities. It considers mainly two-dimensional Cartesian products in which restricted solvability holds w.r.t. one component, but some results are extended to n-dimensional spaces. The main result shows that, in general, cancellation axioms of any order are required to ensure additive representability. More precisely, a generic family of counterexamples is provided, proving that the (m+1)st order cancellation axiom cannot be derived from the mth order cancellation axiom when m is even. However, a special case is considered in which the existence of additive representations can be derived from the independence axiom alone. Unlike the classical representation theorems, these representations are not unique up to strictly positive affine transformations, but follow Fishburn's (1981) uniqueness property. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Frequent occurrence of paralytic shellfish poisoning toxins as dominant toxins in marine puffer from tropical water.

Considerably high toxicity was detected in marine puffers collected from Masinloc Bay, Philippines. The toxicity was detected in the liver, intestine, muscle and skin. Noteworthy, the specimens, the muscle of which showed high toxicity, appeared in high frequency, indicating that puffers from this area is not safe for human consumption. These puffer specimens contained paralytic shellfish poisoning (PSP) toxins, often as major toxin components, the profile of which was similar to that of freshwater puffers reported from tropical areas. These results indicate that PSP toxins are common in tropical puffers both from marine and freshwater.

Animals↗
PubMed2000

Characterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate in spontaneously hypertensive rats.

Using middle cerebral artery occlusion (MCAO) and in vivo microdialysis, we have evaluated the changes in extracellular concentrations of the excitatory amino acids (EAA) glutamate and aspartate during varying periods of MCAO (0, 30, 60 min) in the striatum of spontaneously hypertensive rats (SHR). A positive correlation between occlusion time-dependent elevations in EAAs and the resulting ischemic injury was observed. This is the first demonstration of the temporal profile of EAA efflux during transient focal ischemia in SHRs. Possible sources and mechanisms of ischemia-induced EAA efflux were examined during 60 min of MCAO. Removal of Ca(2+) from the microdialysis infusion media significantly attenuated ischemia-induced increases in both glutamate (from ischemic peak of 4892 +/- 1298 to 1144 +/- 666% of preischemic values) and aspartate (from 2703 +/- 682 to 2090 +/- 599% of preischemic values). Similarly, infusion of the voltage dependent Na(+) channel blocker tetrodotoxin (TTX; 10 microM) significantly attenuated MCAO-induced increases in glutamate (to 1313 +/- 648%) and aspartate (to 359 +/- 114%). Infusion of the GLT-1 selective nontransportable inhibitor, dihydrokainate (DHK; 1 mM) also significantly attenuated the ischemia-induced increases in both EAAs (1285 +/- 508 and 1366 +/- 741% of the preischemic levels, respectively). These results indicate that during transient focal ischemia the increase in extracellular EAAs originates from both the neuronal pool, via conventional exocytotic release, and glial sources via the reversal of the GLT-1 transporter.

ATP-Binding Cassette Transporters↗
PubMed2000

The moderating effect of trivial triggering provocation on displaced aggression.

Two studies examined the interaction between the presence or absence of (a) an initial provocation and (b) a subsequent minor triggering action on the part of the target of displaced aggression. Consistent with the triggering event being seen by participants as indeed trivial when administered by itself without prior provocation, exposure to it literally had no impact on aggression toward its source. When previously provoked, however, this subsequent triggering event strongly increased displaced aggression, causing it to reliably exceed both that displayed when there was no antecedent provocation and that elicited by provocation alone. Mediation analyses showed that for participants who had been provoked, subjective feelings of displeasure concerning the triggering event mediated the effect of the trigger on aggression.

Adolescent↗
PubMed2000

Evaluation of a digital camera for acquiring radiographic images for telemedicine applications.

Many rural sites cannot afford a digitizer to digitize radiographic films and transmit them via a telemedicine network for review by a radiology specialist. This project tested the feasibility of using a consumer digital still camera to photograph radiographic images and transmit them via a telemedicine network to a consulting hub site. In this study, the feasibility of using a digital camera to photograph plain film radiographs of 40 bone trauma cases from a rural health center in Arizona was tested. The cases were transmitted to the Arizona Telemedicine Program hub site using a private asynchronous transfer mode network based on T1 carriers. Two orthopedic surgeons and two radiologists reviewed the cases on a color monitor and the original film images. The readers also rated image quality. There were no significant differences in diagnostic accuracy between conventional film and telemedicine reading. Diagnostic agreement between film and monitor viewing was quite high, as was agreement in confidence ratings. Image quality was generally rated as excellent to good in both viewing conditions. Cases that did not correlate well were judged to have poor image quality, or diagnoses were based on photographs that had part of the diagnostic region of interest cropped off. It was determined that a digital still camera can be used effectively in many cases to photograph radiographic images for transmission and viewing via a telemedicine network, as long as adequate views, zoomed in regions of interest, and good quality original films are used in the acquisition process.

Arizona↗
PubMed1999

Percent of oxygen saturation of arterial hemoglobin among Bolivian Aymara at 3,900-4,000 m.

A range of variation in percent of oxygen saturation of arterial hemoglobin (SaO2) among healthy individuals at a given high altitude indicates differences in physiological hypoxemia despite uniform ambient hypoxic stress. In populations native to the Tibetan plateau, a significant portion of the variance is attributable to additive genetic factors, and there is a major gene influencing SaO2. To determine whether there is genetic variance in other high-altitude populations, we designed a study to test the hypothesis that additive genetic factors contribute to phenotypic variation in SaO2 among Aymara natives of the Andean plateau, a population geographically distant from the Tibetan plateau and with a long, separate history of high-altitude residence. The average SaO2 of 381 Aymara at 3,900-4,000 m was 92+/-0.15% (SEM) with a range of 84-99%. The average was 2.6% higher than the average SaO2 of a sample of Tibetans at 3,800-4,065 m measured with the same techniques. Quantitative genetic analyses of the Aymara sample detected no significant variance attributable to genetic factors. The presence of genetic variance in SaO2 in the Tibetan sample and its absence in the Aymara sample indicate there is potential for natural selection on this trait in the Tibetan but not the Aymara population.

Adaptation, Physiological↗