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Biomedical subjects

M Diaz

Publications and source records attributed to M Diaz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?

OBJECTIVE: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. DESIGN: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. SETTING: Referral centers, including university, county, and veterans' hospitals and clinics. PATIENTS: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. MAIN OUTCOME MEASURES: Clinical and cerebrospinal fluid relapse. RESULTS: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. CONCLUSION: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.

Administration, Oral↗
PubMed1996

Characterization of cwl1+, a gene from Schizosaccharomyces pombe whose overexpression causes cell lysis.

From a Schizosaccharomyces pombe genomic library we have isolated the gene cwl1+ that causes cell lysis when it is overexpressed in the absence of an osmotic stabilizer. Southern hybridization showed that cwl1+ exists as a single copy in the S. pombe genome. The cwl1+ gene nucleotide sequence revealed a putative open reading frame of 924 bp encoding a polypeptide of 308 amino acids with a calculated Mt of 27000. The cwl1+ DNA hybridizes to a major RNA transcript of 1.5 kb whose 5' end maps at a position 452 bp upstream from the predicted translation start. Comparison of the amino acid sequence with those included in the current databases, showed no significant similarity to any known sequences. Cells overexpressing the cwl1+ gene under the control of the S. pombe nmt inducible promoter displayed a reduced cell wall content, were unable to separate after division and lysed drastically in the absence of osmotic stabilizer. Disruption of the cwl1+ gene caused no noticeable phenotype.

Amino Acid Sequence↗
PubMed1996

Bleeding complaints during the first year of norplant implants use and their impact on removal rate.

The frequency of bleeding complaints during the first year of use and their influence on removal rate were analyzed in a retrospective cohort study of 491 Norplant implants acceptors. Removal rates were significantly higher in women having menstrual complaints (1.98% and 29.23% in the first and fourth trimester) than in those who did not mention them (0.79 and 5.07% in the same periods). In all periods of observation, most women who mentioned menstrual problems decided to continue using the method. Two possible explanations for this are that 1) the complaints did not persist for very long, and 2) the most frequent complaint mentioned was bleeding irregularity, which was not as strongly associated with removals as increased or decreased bleeding. The authors conclude that bleeding problems are the most important factor limiting the acceptability of Norplant implants, either being the main reason for removal (3.9 per 100 women) or influencing the rate of removal for other reasons. Adequate counseling appears to be critical for reducing the impact of bleeding problems on removal rates, and thereby increasing the acceptability of the method. The importance of research aimed at preventing or treating menstrual problems to improve the acceptability of the method is emphasized.

Adult↗
PubMed1996

Deferoxamine interferes with adhesive functions of activated human neutrophils.

Deferoxamine is a potent chelator of ferric iron. Past studies have shown that deferoxamine interferes with acute inflammatory tissue injury in a number of animal models. In cell culture, it inhibits neutrophil-medicated killing of endothelial cells. Both the animal model and cell culture data are thought to reflect the capacity of deferoxamine to interfere with the superoxide anion- and and ferric iron-dependent reduction of hydrogen peroxide to the hydroxyl radical (Fenton Reaction). The present study describes a second mechanism by which deferoxamine may interfere with the acute inflammatory response. Here it is shown that deferoxamine has the capacity to inhibit neutrophil adhesion to lung epithelial cells and vascular endothelial cells. Adhesion of phorbol ester-stimulated neutrophils to both cell types is reduced by 70-80%. The inhibitory effects are reversible and are overcome when ferric iron is present along with deferoxamine in a 2:1 molar ratio. Concentrations of deferoxamine that prevent neutrophil adhesion also prevent neutrophil-mediated killing of the same target cells. In contrast, deferoxamine does not significantly inhibit activation-induced up-regulation of neutrophil surface adhesion structures (CD11b/CD18) and does not prevent binding of a monoclonal antibody that recognizes beta 2 integrins in the high-affinity state. Release of proteolytic enzymes from activated cells is also not significantly inhibited by deferoxamine. Taken together, these data indicate that deferoxamine modulates neutrophil adhesive functions associated with the activated state. The ability of deferoxamine to interfere with neutrophil binding to target cells may contribute to its anti-inflammatory activity.

Adult↗
PubMed1996

Development of monoclonal antibodies against a riboflavin-tryptophan photoinduced adduct: reactivity to eye lens proteins.

We describe here the development of monoclonal antibodies to the hapten tryptophan-riboflavin, generated by irradiation of a solution of bovine serum albumin in the presence of riboflavin. The specificity of the three obtained monoclonal antibodies, named 1E6, 5H5, 5A8 all belonging to the IgG1 isotype, was assessed by a competitive enzyme-linked immunosorbent assay in the presence of an increasing concentration of the tryptophan-riboflavin adduct, obtained from an irradiated riboflavin-sensitized tryptophan solution. It was demonstrated that the tryptophan-riboflavin antibodies react with the soluble proteins of the eye lens; this reaction was more intense in the old rat lenses as compared to the young ones, and a maximum binding of the antibodies was obtained with the soluble protein fraction from the human cataractous lens. By indirect immunofluorescence, a reactivity associated with the protein matrix, localized in the lens central zone, was observed. In the peripheral zone of the lens, where the younger cells are found, a marked immunofluorescent emission was observed on structures preferentially localized in the nuclei.

Animals↗
PubMed1996

Use of PCR-RFLP assays to detect genetic variation at single-copy nuclear loci in striped bass (Morone saxatilis).

We developed three assays that detect genetic variation at single-copy nuclear loci in striped bass (Morone saxatilis). Because these assays are based on restriction enzyme digests of DNA amplified by the polymerase chain reaction (PCR-RFLP), they are easy to perform on large numbers of samples. Breeding trials demonstrated that the alleles identified in each of the three assays are inherited in a Mendelian fashion as codominant alleles at single-copy loci. To demonstrate the utility of these PCR-RFLP assays, we compared the genetic composition of striped bass populations from the Congaree River in South Carolina and from the Choptank River in Maryland. Allele frequencies were significantly different at the SB14 locus, suggesting that the two populations may be genetically distinct. Furthermore, during the development of the PCR-RFLP assays, we demonstrated that the GT(n) microsatellite-associated DNA regions (MSA regions) contained RFLPs at a frequency 9-fold higher than that observed for randomly chosen segments of DNA. If MSA regions proved to be variable in other organisms as well, they could provide a valuable source of intraspecific variation.

Animals↗
PubMed1995

Molecular study of the interferon genes in chronic myeloid leukemia.

The interferons alpha, beta, and w (IFNA, IFNB, IFNW), are a family of genes that have been mapped on the short arm of chromosome 9 (9p21-22). Deletions of genetic material on 9p are frequently observed in hematological diseases, particularly in lymphoid neoplasias. In this paper we have performed the molecular studies of IFNA and IFNB genes in chronic myeloid leukemia (CML) in order to determine if the deletions of these genes are prevalent in this pathology. Forty CML patients, Philadelphia positive or with BCR/ABL rearrangement, were studied at diagnosis. The analysis of IFNA and IFNB genes was performed by Southern and dot blot techniques. Homozygous or hemizygous deletions of IFNA and IFNB genes could not be detected, indicating that deletions of these genes would not be present or would be a very infrequent event in the chronic phase of the CML patients.

Adult↗
PubMed1995

Hering-Breüer reflexes in high-altitude infants.

1. Pulmonary ventilation was found to be similar in high-altitude and low-altitude newborn infants, but the breathing pattern was deeper and slower at high altitude (Mortola, J.P., Frappell, P.B., Frappell, D.E., Villena-Cabrera, N., Villena-Cabrera, M., Peña, F., Am Rev Respir Dis 1992, 46: 1206-9). We questioned the contribution of vagal reflexes to these differences in breathing pattern. 2. Measurements were performed on high-altitude (La Paz, Bolivia, 3600-4050 m, inspired O2 pressure approximately 92 mmHg, n = 34) and low-altitude infants (Santa Cruz, Bolivia, 400 m, PIO2 approximately 141 mmHg, n = 26). The strength of the Hering-Breüer inspiratory inhibitory reflex was estimated from the inspiratory time during a respiratory effort against airways closed at end-expiration (Tloccl). The strength of the Hering-Breüer expiratory facilitatory reflex was estimated from the expiratory duration when airways were occluded during expiration (TEoccl). 3. Tloccl was significantly longer than the open-airways TI at both low and high altitude, but significantly more so (approximately 14%) at high altitude. TEoccl was longer than open-airways TE in both groups of infants, but significantly less so at high altitude, whether TEoccl was compared between occlusions of similar tidal volume (on average, TEoccl at high altitude was 79% of that at low altitude) or similar airway pressure (87%). 4. The results suggest that at high altitude the contribution of the phasic volume-dependent vagal input to the inspiratory off-switch threshold is higher, and that the tonic vagal expiratory facilitation is lower, than at low altitude, presumably because of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude↗
PubMed1995

Role of octreoscan and correlation with MR imaging in Graves' ophthalmopathy.

Since the identification of somatostatin receptors on lymphocytes, orbital infiltration with mononuclear cells in Graves' ophthalmopathy has provided a rationale for receptor imaging with the radiolabeled somatostatin analog Octreotide. In 40 patients with Graves' ophthalmopathy and 10 controls, 110 MBq indium-Octreotide were administered i.v., and scans were performed at 4 and 24 h after injection. An uptake ratio between the orbits and the brain was determined. In 20 ophthalmophathy patients, magnetic resonance imaging (MRI) of the orbits was performed and the T2 relaxation time was measured within the rectus muscles. Compared to controls (4 h Octreotide uptake: median 6.0 counts/pixel/MBq, orbit/brain ratio 5.6), ophthalmopathy patients showed a 2- to 3-fold increased uptake (15.8 counts/pixel/MBq vs controls p = 0.0032; ratio 12.6, vs controls p = 0.003). When considering patients with active disease only, a higher uptake was registered (16.8 counts/pixel/MBq vs controls p 0.0048, ratio 15.6 vs controls p = 0.0006). Untreated patients showed a markedly higher uptake (23 counts/pixel/MBq) compared to patients receiving steroid therapy (12.6, p = 0.001). MRI of the orbit revealed a correlation between T2 relaxation time of the eye muscles and orbital uptake of Octreotide (p < 0.001).

Adult↗
PubMed1995

Electron microscopy of cerebral cortex in Arnold-Chiari type II malformation: report of two cases.

Two samples of cerebral cortex of patients with clinical diagnosis of Arnold-Chiari type II malformation were studied with conventional transmission electron microscopy. Pyramidal and non-pyramidal nerve cells of layers II to V exhibited moderate and severe swelling of intraneuronal compartment. The cerebral cortex neuropile showed hydrocephalic edema featured by remarkable enlargement of the extracellular space, degenerated synaptic contacts and swollen dendrites. Interfascicular oligodendrocytes appeared extremely swollen with widened nuclear pores, apparent nucleo-cytoplasmic transfer of chromatinic substance and areas of focal necrosis. Swollen astrocytes displayed lamellar bodies, microfilaments and monogranular glycogen granules. The vacuolated astrocytes showed images suggestive of hydrocephalic edema resolution characterized by deep invaginations of the plasma membrane and formation of numerous cytoplasmic vacuoles. The cortical capillaries exhibited signs of increased cerebrovascular permeability, such as augmented endothelial vacuolar transport, open endothelial junctions and nodular thickening, thinnings and discontinuities of the basement membrane. A transparenchymal route for cerebrospinal fluid absorption through the cortical capillaries, as a means of hydrocephalic edema resolution, is proposed.

Arnold-Chiari Malformation↗
PubMed1995

Indium-111-pentetreotide scintigraphy in Graves' ophthalmopathy.

UNLABELLED: The radiolabeled somatostatin analog 111In-pentetreotide can sensitively demonstrate somatostatin receptor-positive localizations in diseases where activated lymphocytes play a role. Lymphocyte infiltration of retrobulbar tissue in Graves' ophthalmopathy is the rationale of receptor imaging with radionuclide-coupled 111In-pentetreotide. METHODS: Forty patients with Graves' ophthalmopathy, 5 patients with orbital myositis and 10 control subjects were included in this prospective study. Indium-111-pentetreotide (110 MBq) was intravenously injected and SPECT images were obtained at 4 and 24 hr after injection. The scans were analyzed by a region of interest technique. An uptake ratio between the orbits and the brain was determined. RESULTS: Compared to controls (4-hr 111In-pentetreotide uptake: median 6.0 counts/voxel/MBq, orbit-to-brain ratio 5.6), ophthalmopathy patients showed two- to threefold increased uptake (15.8 counts/voxel/MBq versus controls p = 0.0032; ratio 12.6 versus controls p = 0.003). When considering patients with active disease only, even higher uptake was registered (16.8 counts/voxel/MBq versus controls p = 0.0048, ratio 15.6 versus controls p = 0.0006). Untreated patients showed markedly higher uptake (23 counts/voxel/MBq) compared to patients under steroid therapy (12.6, p = 0.001). In myositis, high uptake (20 counts/voxel/MBq) was also registered. CONCLUSION: In contrast to controls, ophthalmopathy patients showed markedly increased orbital accumulation of labeled 111In-pentetreotide. This sensitive nuclear medicine technique could possibly select those patients who might benefit from treatment with immunosuppressive agents and/or octreotide.

Eye↗
PubMed1995

Studies of natural killer cell activity in a drug-free, healthy population. Response to a challenge with taxol, estramustine and lipopolysaccharide.

Preincubation of peripheral blood lymphocytes with the microtubule disturbing agents estramustine (ETMN; n = 7, final conc. 20 microM) or taxol (TX; n = 13, final conc. 10 microM), resulted in a statistically significant inhibition of natural killer cell activity [(NKCA); baseline (x +/- SD; expressed as percentage of specific chromium release) of 32.2 +/- 30.5 and 34.4 +/- 27.7 and drug treated samples of 13.9 +/- 19.9 and 12.5 +/- 20.8, respectively; Student's paired t-test p < 0.005]. Furthermore, most individual values for NKCA in the drug preincubated samples were at least 20% below the same subject baseline lytic function (except for TX sample No.1), and NKCA was non detectable in 4 out of 7 and 5 out of 13 samples (pretreatment with either ETMN or TX< respectively). The use of other concentrations and different preincubation times for these chemotherapeutic agents also produced NKCA inhibition, which was time and dose dependent. Preincubation with lipopolysaccharide (LPS; n = 16, final conc. 50 micrograms/ml), an endotoxin prominently involved in the etiology of septic shock, resulted in a statistically significant enhancement of NKCA [baseline (x +/- SD; expressed as percentage of specific chromium release) of 25.4 +/- 20.4 and LPS treated sample of 36.6 +/- 17.4, respectively; Student's t paired t-test p < 0.005]. At least a 20% increase in NKC lytic function over its own baseline value was recorded for each and everyone of the samples tested with LPS.2+ the pathophysiology associated with septic shock.

Adult↗
PubMed1994

[Somatostatin receptor scintigraphy in endocrine orbitopathy].

Somatostatin receptor scintigraphy with 111In-labeled octreotide proves to be a very sensitive diagnostic tool for evaluation of inflammative activity in endocrine ophthalmopathy (EO). The results of somatostatin receptor scintigraphy (SRS) in 40 patients with EO show a high orbital accumulation of 111In-octreotide in clinically active EO (4 h-median/orbit-brain-ratio: 12.6; controls 4 h-median: 5.8) Patients with clinically inactive EO (4 h-median: 7.1) show a similar orbital accumulation of radioactivity compared to controls. 5 patients with active orbital myositis also revealed an even higher orbital accumulation of radioactivity (4 h-median: 42.3). The diagnostic value of SRS lies in its ability to act as a measure of inflammation and can be useful as an activity parameter when planning therapeutic procedure as well as for EO follow-up. The results in patients with orbital myositis nevertheless do not permit a differential diagnosis with this method. The therapeutic value of 111In-octreotide in Graves' disease has yet to be established.

Adult↗
PubMed1994

Ultrastructural alterations of Golgi apparatus in the nerve cells of cerebral cortex in human hydrocephalus. A qualitative study using cortical biopsies.

Cortical biopsies of 17 patients with clinical diagnosis of hydrocephalus and associated pathology were examined in the transmission electron microscope. Moderately and severely edematous neurons showed relevant structural changes of the Golgi apparatus consisting of either discrete or marked dilation, fragmentation, and partial disappearance of Golgi stacked cisternae. In Arnold-Chiari malformation small Golgi complexes of vesicular type and atrophic changes were observed in severely edematous neurons. The microtubules appeared intact, suggesting differential response between Golgi complex and microtubules. Atrophic changes of the Golgi complex coexisted with degenerated presynaptic endings.

Adult↗
PubMed1994

[Scintigraphic display of an ectopic parathyroid adenoma using 99mTc-MIBI--2 case reports].

Radionuclide imaging of the parathyroid gland is used in the preoperative localization of parathyroid adenoma. Until recently radionuclide imaging of parathyroid tumors was performed using a dual-tracer subtraction technique with 201TI and 99mTcO4-. As an alternative radionuclide imaging with 99mTc-sestamibi (MIBI) has been introduced some years ago. The utility of preoperative parathyroid localization lies in its ability to direct surgical exploration, particularly of ectopic localizations. We present two cases of parathyroid adenoma in which radionuclide imaging with 99mTc-MIBI was successful in detecting atypical locations. In the first case remaining primary hyperparathyroidism was caused by a mediastinal gland. The second case suffered from a recurrence of secondary hyperparathyroidism caused by hyperplasia of the autotransplanted gland after removal of all four parathyroid glands.

Adenoma↗