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Biomedical subjects

M Mendez

Publications and source records attributed to M Mendez.

At least 19 recordsLinked to original sources
PubMed2006

Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program.

Although a rare cause of invasive candidiasis, Candida guilliermondii has been reported to exhibit decreased susceptibility to antifungal agents. Aside from case reports and small surveys, there is little information regarding the epidemiology and antifungal susceptibility profile of C. guilliermondii. We report geographic and temporal trends in the isolation and antifungal susceptibilities of 1,029 C. guilliermondii clinical isolates collected from 127 medical centers as part of the ARTEMIS DISK Antifungal Surveillance Program. In addition, we report the in vitro susceptibility of 132 bloodstream isolates of C. guilliermondii to caspofungin. C. guilliermondii represented 1.4% of the 75,761 isolates collected from 2001 to 2003 and was most common among isolates from Latin America (3.7% versus 0.6 to 1.1%). Decreased susceptibility to fluconazole was noted (75% susceptible; range, 68 to 77% across regions), and voriconazole was more active in vitro against C. guilliermondii than fluconazole (91% susceptible; range, 88 to 93% across regions). Fluconazole was least active against isolates from dermatology (58%) and surgical (69%) services and against isolates associated with skin and soft tissue infection (68%, compared to 85% susceptible for bloodstream isolates). There was no evidence of increasing azole resistance over time among C. guilliermondii isolates tested from 2001 to 2003. Of 132 bloodstream isolates of C. guilliermondii tested against caspofungin, most were inhibited by < or =2 microg/ml (96%; MIC50/MIC90, 0.5/1.0 microg/ml). C. guilliermondii, a species that exhibits reduced susceptibility to fluconazole, is the sixth most frequently isolated Candida species from this large survey and may be an emerging pathogen in Latin America.

Candida↗
PubMed2005

A knock-in mouse model of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a recessive autosomal disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment except for allogeneic bone marrow transplantation, and the knowledge of the molecular lesions are strong arguments for gene therapy. An animal model of CEP has been designed to evaluate the feasibility of retroviral gene transfer in hematopoietic stem cells. We have previously demonstrated that the knockout of the Uros gene is lethal in mice (Uros(del) model). This work describes the achievement of a knock-in model, which reproduces a mutation of the UROS gene responsible for a severe UROS deficiency in humans (P248Q missense mutant). Homozygous mice display erythrodontia, moderate photosensitivity, hepatosplenomegaly, and hemolytic anemia. Uroporphyrin (99% type I isomer) accumulates in urine. Total porphyrins are increased in erythrocytes and feces, while Uros enzymatic activity is below 1% of the normal level in the different tissues analyzed. These pathological findings closely mimic the CEP disease in humans and demonstrate that the Uros(mut248) mouse represents a suitable model of the human disease for pathophysiological, pharmaceutical, and therapeutic purposes.

Amino Acid Substitution↗
PubMed2003

Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG.

This study examined the frequency of epilepsy in a consecutive series of patients who received a definitive diagnosis of psychogenic nonepileptic seizures (PNES) after completing inpatient video-EEG (VEEG) monitoring. Of the 1,590 patients receiving definitive diagnosis, 514 (32.3%) were diagnosed with PNES. Twenty-nine (5.3%) of these patients were found to have both PNES and epilepsy. When strict diagnostic criteria are applied, there is little overlap between epileptic seizures and PNES among patients referred for VEEG monitoring.

Alabama↗
PubMed2003

Neurotoxicity following addition of intravenous valproate to lamotrigine therapy.

Reversible neurotoxic symptoms were observed in three adult patients with absence status epilepticus on lamotrigine (LTG) therapy after administration of an IV bolus followed by oral valproic acid (VPA). Neurotoxicity was likely related to elevated serum LTG levels, as improvement correlated with discontinuing or reducing LTG dosage.

Administration, Oral↗
PubMed2003

Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy.

BACKGROUND: In the face of availability of newer antiepileptic drugs (AEDs) such as lamotrigine and topiramate, there is need to reassess the role of older AEDs in the treatment of juvenile myoclonic epilepsy (JME). OBJECTIVES: To explore whether lamotrigine and topiramate monotherapy or polytherapy can be effective options in the treatment of JME, and to determine whether older AEDs, such as phenytoin and carbamazepine, have a role in the treatment of JME. DESIGN: A retrospective cohort study. SETTING: A large academic teaching hospital. PATIENTS: Seventy-two consecutive JME patients treated with valproic acid, lamotrigine, topiramate, phenytoin, or carbamazepine between April 1, 1991, and March 31, 2001. METHODS: We compared the efficacy of valproic acid, lamotrigine, and topiramate monotherapy or polytherapy in the control of different seizure types of JME, and compared their efficacy and tolerability with the efficacy and tolerability of phenytoin and carbamazepine. RESULTS: Seizure outcome did not differ when patients receiving valproic acid monotherapy (n = 36) were compared with those receiving lamotrigine monotherapy (n = 14), and when patients receiving valproic acid polytherapy (n = 22) were compared with those receiving lamotrigine polytherapy (n = 21) or topiramate polytherapy (n = 15) (P>.05 for all). The combined data of myoclonic seizure control by all 3 AEDs were poorer when compared with the combined data of generalized tonic-clonic seizure control by all 3 AEDs (P =.03), but not when compared with the combined data of absence seizure control by all 3 AEDs (P =.43). Valproic acid, lamotrigine, and topiramate, when compared with phenytoin or carbamazepine, demonstrated significantly better control of myoclonic seizures (P<.01 for all), but not of generalized tonic-clonic seizures (P>.11 for all). CONCLUSIONS: Lamotrigine and topiramate are effective alternative options to valproic acid in the treatment of JME. Lamotrigine is an effective option as monotherapy and polytherapy. Topiramate is an effective option as polytherapy, but more data are needed to determine if it is an effective option as monotherapy. More effective therapy is needed to improve myoclonic seizure control. Older AEDs, such as phenytoin and carbamazepine, may not be indicated in JME patients.

Adult↗
PubMed2002

Gravitationally redshifted absorption lines in the X-ray burst spectra of a neutron star.

The fundamental properties of neutron stars provide a direct test of the equation of state of cold nuclear matter, a relationship between pressure and density that is determined by the physics of the strong interactions between the particles that constitute the star. The most straightforward method of determining these properties is by measuring the gravitational redshift of spectral lines produced in the neutron star photosphere. The equation of state implies a mass-radius relation, while a measurement of the gravitational redshift at the surface of a neutron star provides a direct constraint on the mass-to-radius ratio. Here we report the discovery of significant absorption lines in the spectra of 28 bursts of the low-mass X-ray binary EXO0748-676. We identify the most significant features with the Fe XXVI and XXV n = 2-3 and O VIII n = 1-2 transitions, all with a redshift of z = 0.35, identical within small uncertainties for the respective transitions. For an astrophysically plausible range of masses (M approximately 1.3-2.0 solar masses; refs 2-5), this value is completely consistent with models of neutron stars composed of normal nuclear matter, while it excludes some models in which the neutron stars are made of more exotic matter.

Journal Article↗
PubMed2002

Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus.

BACKGROUND: Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. The disease is the result of a profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait, whereas familial porphyria cutanea tarda is dominant. At least 30 different mutations of the UROD gene have been identified in patients with HEP and familial porphyria cutanea tarda, with 1 predominant missense mutation (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with HEP. OBSERVATION: A 5-year-old patient with first-degree-related parents presented with HEP and mild symptomatology. We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were healthy carriers of the mutation. The mother had reduced UROD activity (50% of normal), whereas the father had normal UROD activity. Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. When the mother started a new pregnancy, a prenatal study showed the absence of F46L mutation in the fetus and no accumulation of porphyrins in the amniotic fluid. CONCLUSIONS: A new mutation in the UROD gene causes a mild HEP phenotype. A normal UROD enzymatic activity was observed in the father, despite the presence of the heterozygous mutation. To our knowledge, this observation is the first description of a prenatal exclusion of HEP.

Amino Acid Substitution↗
PubMed2001

Gene therapy of a mouse model of protoporphyria with a self-inactivating erythroid-specific lentiviral vector without preselection.

Successful treatment of blood disorders by gene therapy has several complications, one of which is the frequent lack of selective advantage of genetically corrected cells. Erythropoietic protoporphyria (EPP), caused by a ferrochelatase deficiency, is a good model of hematological genetic disorders with a lack of spontaneous in vivo selection. This disease is characterized by accumulation of protoporphyrin in red blood cells, bone marrow, and other organs, resulting in severe skin photosensitivity. Here we develop a self-inactivating lentiviral vector containing human ferrochelatase cDNA driven by the human ankyrin-1/beta-globin HS-40 chimeric erythroid promoter/enhancer. We collected bone marrow cells from EPP male donor mice for lentiviral transduction and injected them into lethally irradiated female EPP recipient mice. We observed a high transduction efficiency of hematopoietic stem cells resulting in effective gene therapy of primary and secondary recipient EPP mice without any selectable system. Skin photosensitivity was corrected for all secondary engrafted mice and was associated with specific ferrochelatase expression in the erythroid lineage. An erythroid-specific expression was sufficient to reverse most of the clinical and biological manifestations of the disease. This improvement in the efficiency of gene transfer with lentiviruses may contribute to the development of successful clinical protocols for erythropoietic diseases.

Animals↗
PubMed2001

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells.

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FACS from deficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hematopoiesis. This selection system represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.

Animals↗
PubMed2001

Detection and quantification of snow algae with an airborne imaging spectrometer.

We describe spectral reflectance measurements of snow containing the snow alga Chlamydomonas nivalis and a model to retrieve snow algal concentrations from airborne imaging spectrometer data. Because cells of C. nivalis absorb at specific wavelengths in regions indicative of carotenoids (astaxanthin esters, lutein, beta-carotene) and chlorophylls a and b, the spectral signature of snow containing C. nivalis is distinct from that of snow without algae. The spectral reflectance of snow containing C. nivalis is separable from that of snow without algae due to carotenoid absorption in the wavelength range from 0.4 to 0.58 microm and chlorophyll a and b absorption in the wavelength range from 0.6 to 0.7 microm. The integral of the scaled chlorophyll a and b absorption feature (I(0.68)) varies with algal concentration (C(a)). Using the relationship C(a) = 81019.2 I(0.68) + 845.2, we inverted Airborne Visible Infrared Imaging Spectrometer reflectance data collected in the Tioga Pass region of the Sierra Nevada in California to determine algal concentration. For the 5.5-km(2) region imaged, the mean algal concentration was 1,306 cells ml(-1), the standard deviation was 1,740 cells ml(-1), and the coefficient of variation was 1.33. The retrieved spatial distribution was consistent with observations made in the field. From the spatial estimates of algal concentration, we calculated a total imaged algal biomass of 16.55 kg for the 0.495-km(2) snow-covered area, which gave an areal biomass concentration of 0.033 g/m(2).

Aircraft↗
PubMed2001

Intractable epilepsy following radiosurgery for arteriovenous malformation.

Radiosurgery is often used to treat arteriovenous malformations (AVMs) located in deep brain locations. Most of these procedures are successful not only in obliterating the AVM but also in decreasing the frequency and severity of associated seizures. Although radiosurgery is occasionally associated with the development of easy-to-control seizures immediately postoperatively, there have been no reports of intractable epilepsy developing after radiosurgery. In this report, however, a case is presented in which a patient underwent gamma knife surgery (GKS) for an AVM, after which intractable epilepsy and mesial temporal sclerosis (MTS) gradually developed. A 37-year-old right-handed woman underwent GKS for a right mesial parietotemporooccipital AVM. One year later, the AVM had reduced in size, but the patient began to experience complex partial seizures (CPSs). These CPSs initially occurred at a frequency of one per month, but 6 months later they were occurring every other week. She also started having secondarily generalized tonic-clonic seizures (GTCSs) once per month. Over the next year the frequency of her seizures gradually increased to several CPSs per day and two to three GTCSs per week, despite treatment with various combinations of antiepileptic drugs. By this time her AVM had decreased to one half of its original size. Video-electroencephalography monitoring demonstrated that both the CPSs and GTCSs were arising from the right posterior quadrant. Magnetic resonance imaging revealed not only the presence of the right-sided AVM, but also right-sided MTS. The patient underwent surgical resection of the AVM and right temporal lobectomy. She has been free from seizure for longer than 1 year. Radiosurgery may be associated with intractable epilepsy and MTS.

Adult↗
PubMed2000

Mutations in familial porphyria cutanea tarda: two novel and two previously described for hepatoerythropoietic porphyria.

Uroporphyrinogen decarboxylase (URO-D) deficiency is responsible for two forms of genetic cutaneous porphyria: familial porphyria cutanea tarda (f-PCT) and hepatoerythropoietic porphyria (HEP). The f-PCT transmitted as an autosomal dominant trait, is characterized by photosensitive cutaneous lesions frequently associated to hepatic dysfunction and is precipitated by various ecogenic factors. The HEP, transmitted as a recessive trait, is more severe than f-PCT and would be considered as the homozygous form of f-PCT. For the mutational analysis of f-PCT patients, the entire URO-D gene was amplified and each exon, intron-exon boundaries and the promoter region were cycle sequenced. Five mutations were found in 6 unrelated families studied, of these, two were new: a nonsense mutation in exon 6 (W159X) and a splice defect in intron 9 (IVS9(-1)G-->C). The other two missense mutations, P62L and A80G, had been previously reported in the homozygous state in HEP families. The g10insA, reported in our laboratory, was again identified in other two unrelated families. In addition 3 novel URO-D polymorphisms in non-coding regions were found. The reverse transcription-PCR and sequencing of the splice mutation carrier's RNA did not reveal the presence of an abnormal mRNA, suggesting that no stable transcript from the mutated allele is synthesized. These results increase to 39 the number of mutations identified in the URO-D gene; 4 of them causing both HEP and f-PCT.

Adult↗
PubMed2000

The p53-independent tumoricidal activity of an adenoviral vector encoding a p27-p16 fusion tumor suppressor gene.

We describe here that DE1-adenovirus vectors (AV) expressing a p27-p16 fusion molecule, termed W9, induce tumor cell apoptosis when overexpressed in a wide range of tumor cell types. However, in primary human cells derived from a variety of normal tissues, AV-W9 induced minimal apoptosis. In tumor cells AV-W9 demonstrated 5- to 50-fold greater tumoricidal activity than either of the parental molecules p16 and p27. In these studies, AV-W9 elicited apoptosis independent of the p53 and Rb status of the tumor cells. In several murine tumor models AV-W9 demonstrated p53-independent antitumor activity. It completely prevented tumor formation in two ex vivo models, whereas the parental molecules resulted in partial protection. Furthermore, AV-W9 induced tumor regression or suppressed tumor growth when introduced intratumorally into preestablished tumors in mice. This effect may be mediated through tumor cell apoptosis or antiangiogenic activity of AV-W9. Thus, this novel chimeric molecule is more potent and capable of killing a broader spectrum of tumors than the parental p16 and p27 molecules independent of the tumor cell p53 and phenotype and represents a powerful new therapeutic agent for cancer gene therapy.

Adenoviridae↗
PubMed1999

Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T).

A partial deficiency of Porphobilinogen deaminase (PBG-D) is responsible for acute intermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion, and the prevalence in the Argentinean population is about 1:125,000. Here, two new mutations and three previously reported were found in the PBG-D gene in 12 Argentinean AIP patients corresponding to 5 different families. To screen for AIP mutations in symptomatic patients, genomic DNA isolated was amplified in 2 Multiplex PCR reactions, then all coding exons and flanking intronic regions were sequenced. The new mutations are 453-455delAGC in exon 9 which results in the loss of an alanine residue at position 152, and one new point mutation in the splicing aceptor site in the last position of intron 8 (IVS8-1G>T) which leds to a 15 bp deletion because a cryptic site (first AG upstream) is used. Both mutations produce amino acid deletion without frameshift effect. To further characterize the 453-455delAGC mutation, the pKK-PBGD construct for the mutant allele was expressed in E. coli, the enzymatic activity of the recombinant protein was 1.3% of the mean level expressed by the normal allele. Finally, three missense mutations, previously reported, were identified in three unrelated families.

Adolescent↗
PubMed1999

Acute intermittent porphyria: biochemical and clinical analysis in the Argentinean population.

Acute intermittent porphyria (AIP) is the most common type of hepatic acute porphyria. In this work, we have analyzed the biochemical data of all Argentinean AIP families studied in the Porphyrins and Porphyrias Research Centre (CIPYP). We have shown that: (i) the prevalence for this population is about 1:125,000; (ii) the disease is more frequent in women than in men (7:3); (iii) about 60% are latent carriers; (iv) 15% of patients with symptomatic AIP died during an acute attack; (v) the most important precipitating factors of acute attacks in our population were the ingestion of therapeutic drugs (25%), anesthetics in surgical interventions (25%) and infections (20%); (vi) the initial symptom in Argentinean AIP individuals is severe abdominal pain (100%), and it is often accompanied by constipation (37%), anorexia (37%) and tachycardia (30%); and (vii) the percentage of recurrence of the acute attacks is high (81%).

Adult↗
PubMed1999

Effect of ventilator flow rate on respiratory timing in normal humans.

Respiratory rate (RR) increases as a function of ventilator flow rate (V). We wished to determine whether this is due to a decrease in neural inspiratory time (T In), neural expiratory time (TEn), or both. To accomplish this, we ventilated 15 normal subjects in the assist, volume cycled mode. Ventilator flow rate was varied at random, at four breaths with each step, over the flow range from 0.8 (Vmin) to 2.5 (Vmax) L/s. V T was kept constant. The pressure developed by respiratory muscles (Pmus) was calculated with the equation of motion (Pmus = V. R + V. E - Paw, where R = resistance, V = volume, E = elastance, and Paw = airway pressure). Electromyography of the diaphragm (Edi) was also done in five subjects. TIn and TEn were determined from the Pmus or Edi waveform. TIn decreased progressively as a function of V, from 1.44 +/- 0.34 s at Vmin to 0.62 +/- 0.26 s at Vmax (p < 0.00001). Changes in TEn were inconsistent and not significant. TIn/Ttot decreased significantly (0.30 +/- 0.06 at Vmin to 0.18 +/- 0.09 at Vmax; p < 0. 00001). We conclude that TI is highly sensitive to ventilator flow, and that the RR response to V is primarily related to this T In response. Because an increase in V progressively reduces T In/Ttot, and this variable is an important determinant of inspiratory muscle energetics, we further conclude that inspiratory muscle energy expenditure is quite sensitive to V over the range from 0.8 to 2.5 L/s.

Adult↗
PubMed1999

Personality disorders among medically refractory epileptic patients.

DSM-III-R personality disorders were assessed in 52 medically refractory epileptic patients. Twenty-one percent of patients met threshold criteria for an Axis II disorder. Dependent and avoidant personality disorders were the most common diagnoses. Epileptic aura was positively correlated with the presence of personality disorders. These results support previous studies that have demonstrated an increased rate of dependency and social isolation in epileptic patients. This increase may be related to disrupted psychosocial functioning as a consequence of having epilepsy, to disrupted neuronal function in central nervous system structures as a consequence of repeated epileptiform discharge or to some combination of the two.

Adult↗