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J Mas

Publications and source records attributed to J Mas.

At least 19 recordsLinked to original sources
PubMed1998

Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.

Metrifonate is converted nonenzymatically to 2.2, dimethyl dichlorovinyl phosphate (DDVP), an inhibitor of acetylcholinesterase (AChE). This 21-day, randomized, double-blind, placebo-controlled trial of metrifonate in patients with Alzheimer's disease (n = 27) evaluated four doses, each administered orally once daily. All patients received a loading dose (LD) for 6 days followed by a maintenance dose (MD) for 15 days. The treatment groups were: panel 1, LD = 1.5 mg/kg (75-135 mg), MD = 0.25 mg/kg (12.5-25 mg); panel 2, LD = 2.5 mg/kg (125-225 mg), MD = 0.40 mg/kg (20-35 mg); panel 3, LD = 4.0 mg/kg (200-335 mg), MD = 0.65 mg/kg (30-60 mg); and panel 4, LD = 4.0 mg/kg (200-335 mg), MD = 1.0 mg/kg (50-90 mg). All metrifonate doses were well tolerated. Most adverse events were mild to moderate in intensity, gastrointestinal in nature, and transient. Mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) for both metrifonate and DDVP increased in relation to dose. Metrifonate and DDVP had similar, largely dose-independent mean values for time to Cmax (tmax) and half-life (t1/2). There was little or no accumulation of either metrifonate or DDVP with long-term administration. After 21 days of treatment, mean percent erythrocyte AChE inhibition was 14%, 35%, 66%, 77%, and 82% for placebo and panels 1 through 4, respectively. Cognitive improvement was observed with the two highest metrifonate doses. These results reflect favorable safety and pharmacokinetic profiles for the use of metrifonate in the treatment of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1998

Metrifonate treatment of the cognitive deficits of Alzheimer's disease. Metrifonate Study Group.

The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was evaluated clinically in patients diagnosed with mild to moderate Alzheimer's disease (AD). This was a prospective, 30-week, multicenter, double-blind, randomized, parallel group, dose-finding study, which included a 2-week screening period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients received a loading dose of 0.5 mg/kg (25 to 45 mg), 0.9 mg/kg (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg (15 to 25 mg), or 0.65 mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifonate significantly improved cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). At 3 months, in the intent-to-treat patients, the treatment difference for the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI, 1.61 to 4.27; p = 0.0001). These patients also exhibited a 0.35-point improvement on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p = 0.0007). Patients receiving lower drug doses had scores intermediate to those of the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The drug was well tolerated; side effects were predominantly gastrointestinal in nature, and no hepatic toxicity was observed. Therefore, in this study, metrifonate safely improved the cognitive deficits and benefited the global function of AD patients.

Aged↗
PubMed1998

Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease (AD) of mild to moderate severity. METHODS: A prospective, 36-week, multicenter, double-blind, randomized, parallel group study of metrifonate in probable AD patients, including a 2-week screening period, a 26-week double-blind treatment period, and a follow-up visit at 8 weeks post-treatment. A total of 24 ambulatory clinics in the United States in a variety of settings, including contract research organizations, public health facilities, and universities. Patients met diagnostic criteria for probable AD as defined by the work group of the National Institute for Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association. Patients had Mini-Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen Modification) of <4. A total of 408 patients were enrolled. Percentages of patients completing double-blind treatment were 88% and 79% in the placebo and metrifonate groups, respectively. Rates of discontinuation due to adverse events were 4% in the placebo group and 12% in the metrifonate group. Placebo or metrifonate was administered once daily. Metrifonate-treated patients received a loading dose of 100 to 180 mg based on weight (2.0 mg/kg) for 2 weeks, followed by a maintenance dose of 30 to 60 mg based on weight (0.65 mg/kg) for 24 weeks. Primary efficacy variables were the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-plus). Secondary efficacy variables included the Neuropsychiatric Inventory (NPI), the Disability Assessment in Dementia, the Global Deterioration Scale (GDS), the ADAS-Noncognitive subscale (ADAS-Noncog), the MMSE, and the Clinician's Interview-Based Impression of Severity with Caregiver Input (CIBIS-plus). Outcome measures reflected changes from baseline at week 26 for all variables. Safety was assessed with incidences of premature termination, treatment-emergent events and mortality, and routine safety evaluations. RESULTS: After 26 weeks of metrifonate therapy, a 2.86-point treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the intent-to-treat AD patients. The treatment difference in the mean CIBIC-plus score at this time was 0.28 points (p = 0.0071). At week 26, treatment differences also were observed in the mean NPI total score (p = 0.0161). Analysis of the remaining secondary efficacy variables showed treatment differences that favored metrifonate but did not reach statistical significance. Metrifonate adverse events were predominantly mild in intensity. No hepatotoxicity was observed. CONCLUSIONS: Metrifonate was safe and well-tolerated. It enhanced not only the cognitive and global function, but also the behavioral function of patients diagnosed with mild to moderate AD. Therefore, metrifonate appears to be useful in the symptomatic treatment of AD.

Aged↗
PubMed1996

Cellular content of storage inclusions in purple sulfur bacteria determined by ultrathin sections.

Phototrophic sulfur bacteria accumulate storage inclusions as a mechanism to adapt to several types of environmental stress. We compare the content of elemental sulfur and poly-beta-hydroxybutyrate (PHB) found in cultures growing under laboratory conditions with the content found in microorganisms in natural environments. Since natural communities are extremely heterogeneous in composition (they do not contain only phototrophic sulfur bacteria) and physiological state, it was not possible to apply conventional chemical analyses for the determination of the contents of sulfur and PHB. The study was performed by means of transmission electron microscopy, which turned out to be an excellent tool for this purpose. The results indicate that, in natural environments, cells have an extremely high content of storage inclusions, much higher than their laboratory grown counterparts, probably as a consequence of less favorable environmental conditions.

3-Hydroxybutyric Acid↗
PubMed1995

Prevalence, geographical distribution and clinical manifestations of onchocerciasis on the Island of Bioko (Equatorial Guinea).

A survey for the prevalence, geographical distribution and clinical manifestations of onchocerciasis was conducted on the Island of Bioko (formerly Fernando Póo), Equatorial Guinea, between 1987-89. The whole population (1799 inhabitants) of thirteen villages distributed around the island was surveyed. Identification data, physical examination and Snellen "E" test for visual acuity were performed. Skin snips were taken from both iliac crests and right scapula and calf. Differential diagnosis between Onchocerca volvulus and Mansonella streptocerca was carried out in both fresh and Giemsa stained preparations. The overall prevalence (+ skin snips) and mean microfilarial density were 75.2% (range 51.9% to 87.1%) and 32.2 mf/snip respectively. Skin snips showed a higher microfilarial density from iliac crests. The following clinical manifestations were found: 560 (31.2%) with nodules; 518 (28.8%) with dermatitis, pigmentation changes and cutaneous atrophy; 753 (41.9%) with lymphoadenopathy and lymphoedema. Blindness due to different causes was registered in 13 cases (0.8%). The results showed that onchocerciasis is hyperendemic and widespread over the island. It is estimated that almost the whole population (62,000) is at risk of infection.

Adolescent↗
PubMed1994

7-azetidinylquinolones as antibacterial agents. 2. Synthesis and biological activity of 7-(2,3-disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids. Properties and structure-activity relationships of quinolones with an azetidine moiety.

A series of 7-(2,3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria, and the in vivo efficacy of selected derivatives was determined using a mouse infection model. The X-ray crystal structures of 6b, 6c, and 6d were found to be in reasonable agreement with the corresponding AM1 calculated geometries. Correlations between antibacterial potency of all the synthesized 7-azetidinylquinolones and naphthyridines and their calculated electronic properties and experimental capacity factors were established. Antibacterial efficacy and pharmacokinetic and physicochemical properties of selected derivatives were compared to the relevant 7-(3-amino-1-azetidinyl) and 7-(3-amino-3-methyl-1-azetidinyl) analogues (for Part 1, see: J. Med. Chem. 1993, 36, 801-810). A combination of a cyclopropyl or a substituted phenyl group at N-1 and a trans-3-amino-2-methyl-1-azetidinyl group at C-7 conferred the best overall antibacterial, pharmacokinetic, and physicochemical properties to the azetidinylquinolones studied.

4-Quinolones↗
PubMed1993

[Treatment of peritumoral cerebral edema with tetracosactide].

Tetracosactide is known to be used in brain tumours, but its action is difficult to evaluate clearly. Tetracosactide exerts analgesic, anti-emetic and anti-inflammatory effects and it reduces the oedema surrounding brain tumours. It is this latter effect which we have studied. We used a technetium-labelled cerebral marker, 99mTc HMPAO (Ceretec), and found that this functional exploration not only detects the presence of a brain tumour, but also measures regional cerebral blood flow. This marker is mainly used in intracerebral vascular diseases. Since february 1990, eighteen patients suffering from malignant brain tumour with pronounced perilesional oedema were selected and treated with tetracosactide for two days. With the help of 99mTc HMPAO scintigraphy the oedema was quantified, and the results obtained were interpreted. The initial results of this clinical experiment indicate that the phenomena observed were due to improved vascularization of the healthy peritumoral areas with resorption of oedema. This was a consequence of the direct tetracosactide action, and the higher the dose of this compound, the clearer its action.

Adult↗
PubMed1992

[Paragonimiasis and pulmonary tuberculosis].

Paragonimiasis (infestation by the Paragonimus species) in Spain is a very infrequent entity within the group of imported infectious diseases. A native, resident of Equatorial Guinea who was affected by pulmonary and probably extrapulmonary paragonimiasis together with active pulmonary tuberculosis is described. This association is relatively common and may complicate the diagnostic process. The identification of the parasite was established from samples of pulmonary secretion obtained by natural expulsion and by fiber bronchoscopy in which Kinyoun carbonfucsine dye, Giemsa dye and argentic impregnation were used. The possibility of neurological disease existing (medullar and cerebral) produced by the same parasite is also discussed. Antituberculous treatment and the use of praziquantel satisfactorily control both infections.

Adult↗
PubMed1991

Introducing simultaneous spatial resolution and attenuation correction after scatter removal in SPECT imaging.

A new approach to simultaneous spatial resolution and attenuation correction in SPECT imaging is presented. Before these corrections, scatter is removed on the projections. This removal is performed by spectral constrained factor analysis. The innovation reported here is the use of the different impulse responses of the system, according to the source-detector distance, and their integration in a generalized version of the Chang attenuation correction method. This novel algorithm is evaluated on computed and physical phantoms. In the computer-simulated phantom, the count rates after full-processing are very close to the initial values. In the physical phantom, the contrast is increased by 1.8 after full processing. The activity profiles drawn both on raw projections and reconstructed slices demonstrate the effectiveness of the algorithm for the restoration of spatial resolution. Furthermore, the method improves the quality of the images greatly. A clinical study is also presented. When the whole procedure is applied, the resulting slice matches the corresponding computed tomographic scan very well, which is not the case with the usual back-projected images. The process is fully automatic and the computing time performance allows its daily use for single photon emission tomographic examinations.

Algorithms↗
PubMed1991

[Automatic reading of ABO and Rh groups on microplates using FMC medium and an IBG Systems reader].

We present in this paper our experience in the routine use of an automatic reader for microtiter plates (IBG Systems). A total of 2044 samples from blood donors have been tested for ABO (haematic and seric) and Rh (D antigen) blood group typing. The red blood cell samples have been tested against monoclonal anti-A, anti-B, anti-AB and anti-Rh 1 (D) sera (using two different anti-D reagents). As a negative control, 3% albumin solution was employed. In order to determine the seric groups, the plasma samples were tested against A1, A2, B and 0 cells. In all cases the red cells were suspended in Ficoll 400R-Methyl cellulose (FMC), and 0.01 Bromelin was added to red blood cell samples to be typed. The obstacles in the automatic readings were mainly solved by visual reading of the microplates. In the 2,044 samples analysed with the automatic reader, 19 discrepancies (0.94%) were found in ABO typing. In all cases the error was in the seric blood group. Three false positive reactions were found with 0 red cells. Two false negative with B red cells, interpreted by the automatic reader as doubtful results. Three positive readings were detected, in one case the positivity was due to alloantibodies (C + D specificities), the other two cases were autoagglutinations. False negative reactions were found, in 11 cases, 8 of them due to lipaemia and the remaining three were haemolysed plasma samples. It should be stressed that out of 19 cases of discrepancy, only 5 (0.24%) were due to the automatic reader while the remaining were due, to sample troubles.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1990

Scatter correction in planar imaging and SPECT by constrained factor analysis of dynamic structures (FADS).

The removal of Compton scattered photons included within the pulse height window is recognized as one of the most difficult noise problems in the restoration of nuclear medicine images. A new approach to Compton scatter correction based on factor analysis of dynamic structures (FADS) is presented in this study. The method requires all of the energy information. Acquisition of data can be performed either by list-mode or frame-mode. While the former presents some theoretical advantages, the latter is actually used in this work. Two factors are extracted by FADS, unfortunately no pure photopeak factor can be found by the algorithm. These rough factors lead to incorrect factor images. The innovation reported here is the use of a constrained photopeak factor. This novel algorithm is evaluated both on planar imaging and SPECT data using Monte Carlo simulations and real phantoms. A comparison with the modified method of Jaszczak is also presented. Different parameters are significantly improved with our recombination method in SPECT studies, particularly after attenuation compensation by the iterative method of Chang. Compared with the subtraction method the contrast is increased by 1.5 for planar Monte Carlo simulations and the scatter fraction is reduced four times with our recombination method.

Algorithms↗
PubMed1989

Variations in cell size and buoyant density of Escherichia coli K12 during glycogen accumulation.

The effect of glycogen accumulation on buoyant density and volume of Escherichia coli K12 was studied. A procedure consisting of three linear equations is presented. This requires measurement only of three parameters: cell buoyant density, cell volume and specific content of the polymer. Experimental values are then used to calculate intercepts and slopes of the equations by linear regression. From the estimated values of such parameters the in vivo values of several variables of interest can be calculated. These include in vivo density and volume of the glycogen inclusion, as well as density and volume of the structural material in the cell. The results are consistent with the glycogen inclusions being hydrated.

Escherichia coli↗
PubMed1989

Improvement of quantification in SPECT studies by scatter and attenuation compensation.

The filtered backprojection images obtained from classical SPECT studies are not adequate for evaluation of volumes or parameters of clinical interest. Noise, scattering, boundary accuracy and attenuation are the main problems of SPECT quantification. It is the aim of the following study to overcome these difficulties. The first step of all correction algorithm is the contour detection of the attenuation medium. A new procedure, previously described by the authors, accurately and automatically found the boundaries of the surrounding body. The Compton scattering elimination is carried out by a modified version of Jaszczak's method. This alteration is essential to implement the iterative attenuation correction algorithm derived from Chang's method. Results obtained using computer simulation and real phantoms or clinical studies demonstrate the high improvement of contrast and count levels in the corrected slices. The process is fully automatic and the efficiency of the procedures allow fast processing of the daily SPECT examination.

Algorithms↗
PubMed1989

[Prevalence of antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus in pregnant women of Catalonia].

A seroepidemiological survey was carried out to evaluate the prevalence of antibodies against toxoplasma, rubella virus, cytomegalovirus (CMV) and herpes simplex virus in pregnant women from Catalonia during 1985. The study was carried out in a representative sample of the pregnant women cared for in public and private hospitals from Catalonia, which was selected in maternal clinics by random sampling. Antibody measurements were carried out with the following techniques: toxoplasma, IFI (positive values greater than or equal to 1:10); rubella virus, Iha (greater than or equal to 1:10); CMV and herpes simplex virus, CF (greater than or equal to 1:10). 50.21% of pregnant women had antibodies against toxoplasma, 97.48% against rubella virus, 73.31% against CMV, and 80.93% against herpes simplex virus. The presence of antibodies against CMV and herpes simplex virus were significantly associated ( less than 0.00001). The demographic and socioeconomic variables associated with the prevalence of antibodies were analyzed, and they were compared with other results from the literature.

Animals↗
PubMed1989

[Serum beta 2-microglobulin and ankylosing spondylitis].

The serum beta-2-microglobulin (B2-m) was evaluated by radio-immunoassay in 28 patients with ankylosing spondylarthritis. The mean B2-m level is within normal limits. There is no overall correlation with other biological or immunological parameters (Sed Rate, IgA, CD3+, CD4+, CD8+, Leu 7, NK activity). There is no difference between treated and untreated patients, between patients with recent or old disease. On the contrary, the mean the mean B2-m level is significantly lower in patients B27 positive, as compared with B27 negative. The possible role of anti-B2-m antibodies interfering with the serum B2-m assay discussed.

Adult↗
PubMed1988

Narcotic alkylating agents: synthesis, structure and biological activities.

The synthesis, structure and biological activities of a series of derivatives of normorphine, noracetylmethadol (IV a), 6-amino-4,4-diphenyl-3-heptanol acetate (V a), and norpropoxyphene (VI a), in which the corresponding nitrogen supports an alkylating group (chloroethyl or fumaroyl) are reported. Structural identification was achieved spectroscopically. 13C Nuclear Magnetic Resonance proved the most useful tool in this task. N-Chloroethylnoracetylmethadol (IV c), acted as a potent long-lasting analgesic. Although some compounds (IV c), (V c) and (V d) showed substantial cytostatic activity, no antineoplastic activity in mice with P388 leukaemia was detected in the series.

Alkylating Agents↗