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Biomedical subjects

C Suarez

Publications and source records attributed to C Suarez.

At least 19 recordsLinked to original sources

Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient?

Timely diagnosis and effective, safe treatment are essential to reduce transmission and improve outcomes for patients with tuberculosis. Aside from laboratory methods, many programmatic factors influence the overall turnaround time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured each step in the overall TAT required for MDR-TB in two of five health districts of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and appropriate treatment, was 5 months, almost twice as long as the bacteriological procedures per se. Expensive investments in laboratory technology may yield low returns unless the programmatic aspects of the diagnostic process are streamlined at the same time.

Antibiotics, Antitubercular↗

The outcome after treatment of venous thromboembolism is different in surgical and acutely ill medical patients. Findings from the RIETE registry.

BACKGROUND: The history of venous thromboembolism (VTE), and the rationale for thromboprophylaxis in surgical patients are well understood. The situation is less clear for acutely ill medical patients. OBJECTIVES: To compare the clinical presentation of VTE and clinical outcomes of immobile acutely ill medical patients with surgical patients. PATIENTS: RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) is a Spanish registry of consecutively enrolled patients with objectively confirmed, symptomatic acute VTE. In this analysis, clinical characteristics of patients, details of anticoagulant therapy, and outcomes of all enrolled acutely ill medical patients with immobility >/= 4 days, and surgical patients are included. RESULTS: Of 6160 patients enrolled up to December 2003, 756 (12%) were acutely ill medical patients with immobility >/= 4 days, and 884 (14%) were surgical patients who developed VTE within 2 months of surgical intervention. Only 28% of acutely ill medical patients had received thromboprophylaxis, compared with 67% of surgical patients. During the 3-month follow-up period, both fatal pulmonary embolism (PE) and fatal bleeding occurred more frequently in acutely ill medical patients. Immobility in acutely ill medical patients, cancer, and PE were associated with a significantly higher risk of fatal PE or bleeding. CONCLUSIONS: In patients treated for VTE, the incidences of fatal PE, fatal bleeding, and major bleeding were significantly higher in acutely ill medical patients compared with surgical patients. Given the low percentage of acutely ill medical patients who had received thromboprophylaxis, increasing its use appropriately may reduce the incidence of VTE and associated complications.

Acute Disease↗

The Fcgamma receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians.

OBJECTIVE: To determine whether inheritance of Fcgamma receptor (FcgammaR) alleles conferring lower affinity for IgG binding increases the risk of developing lupus nephritis. METHODS: We compared the frequency of low-affinity alleles of two FcgammaR polymorphisms (FcgammaRIIA and FcgammaRIIIA) among 235 patients with systemic lupus erythematosus (SLE) and proven nephritis (nephritis patients) and among 352 SLE patients with no evidence of renal disease (non-nephritis control subjects). The ethnic distribution of patients in the study was 49% Caucasian, 20% Hispanic, 17% Asian/Pacific Islander, 12% African American, and 2% from other ethnic groups. All patients were genotyped for the FcgammaRIIA-131R/H and FcgammaRIIIA-158V/F polymorphisms. We used contingency table analysis to compare allele and genotype distributions for nephritis patients and nonnephritis control subjects, including ethnic-specific strata. Multivariate logistic regression analyses included sex and disease duration as covariates. RESULTS: Univariate and multivariate analyses demonstrated a striking association between the low-affinity FcgammaRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017). This association was even stronger among Caucasians with severe nephritis (OR 4.4, P < 0.0001). In contrast, inheritance of the low-affinity FcgammaRIIA-131R allele (and RR genotype) was not associated with an increased risk of lupus nephritis among any of the ethnic groups examined. CONCLUSION: The FcgammaRIIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians, but not among non-Caucasians. These results suggest that ethnic variation is critical in defining the specific genetic factors underlying the pathogenesis of SLE, and they have important prognostic and therapeutic implications as well.

Adolescent↗

Langerhans cell histiocytosis following childhood acute lymphoblastic leukemia.

Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells of unknown etiology that results in a range of clinical manifestations. LCH has been known to be associated with a variety of malignant diseases. A 7-year-old boy was treated for standard-risk acute lymphoblastic leukemia (ALL) at age 2 years, on a Children's Cancer Group chemotherapy protocol for 3 years and developed LCH 2 years after completion of chemotherapy. The case and a review of literature on the association of LCH and ALL are presented.

Antineoplastic Combined Chemotherapy Protocols↗

CD81 regulates neuron-induced astrocyte cell-cycle exit.

Astrocytes respond to contact with neurons by cell-cycle arrest and complex process formation. In our effort to discover the molecular mechanisms that underlie this phenomenon we have identified a known tetraspanin, CD81, as a critical component of astrocyte responses to neuronal differentiation signals. Here we show that CD81 is expressed on the surface of the astrocyte and that its expression level can be modulated by contact with neurons. Further, using three separate antibodies, 2F7, Eat1, and Eat2, which recognize unique epitopes in the extracellular domains of the CD81 protein, we show that there is a unique domain, recognized by Eat1, that is required for astrocyte cell-cycle withdrawal in response to neurons. This is likely due to conformational changes in the CD81 molecule, as inclusion of 2F7 actually augments neuron-induced astrocyte growth arrest. The critical nature of CD81 in normal astrocyte-neuron biology was confirmed by using mice in which CD81 had been deleted by homologous recombination. Astrocytes null at the CD81 locus were blind to the proliferative arrest encoded on the neuronal cell surface. Taken together, these data strongly suggest that CD81 is a critical regulator of neuron-induced astrocytic differentiation.

Animals↗

Postnatal disappearance of type A intercalated cells in carbonic anhydrase II-deficient mice.

Despite chronic acidosis, collecting ducts in adult carbonic anhydrase II-deficient (CAD mice) are depleted of intercalated cells, including those of type A, which are acid-secreting cells. We hypothesized that this depletion could occur during postnatal development. Principal cells were identified by immunofluorescence using an antibody to rat aquaporin-2 (AQP-2), and type A intercalated cells using an antibody specific for anion exchanger (AE1). In CAD mice the proportion of AQP2-positive cells, normal at 11 days, increased progressively in the cortical (CCD) and outer medullary collecting duct (OMCD), to reach almost 100% in the OMCD in adults. The percentage of AE1-positive cells in the OMCD of CAD mice decreased by half by 6 weeks of age and further by adulthood. In controls, however, the proportion of AQP2-positive cells and that of AE1-positive cells in the OMCD remained stable after 10 days of age. AE1-positive cells accounted for the majority of intercalated cells in the OMCD. The mechanisms leading to selective postnatal cell depletion in the collecting duct in CAD mice remain to be determined.

Aging↗

Expression of carbonic anhydrase IV in mouse placenta.

Carbonic anhydrase (CA) facilitates acid-base transport in several tissues. Acidosis upregulates membrane-bound SDS-resistant hydratase activity in various tissues and CA IV mRNA in rabbit kidney. This study was designed to assess whether the expression of membrane-bound CA IV isozyme in mouse placenta is regulated developmentally and by maternal ammonium chloride loading at the end of pregnancy. For this purpose we used Northern blot analysis, Western blots of microsomal membranes, and immunocytochemistry. The expression of CA IV mRNA on Northern blots tripled from day 11 to day 15 and then remained stable until the end of pregnancy. Expression of CA IV immunoreactive protein on Western blot tripled from day 11 to day 15 and decreased almost to baseline by day 19. Strong staining for CA IV was detected by immunocytochemistry in labyrinthine trophoblast, in the endodermal layer of the yolk sac (both intra- and extraplacental) and in the uterine epithelium. Weak staining was observed in most fetal endothelial cells at 11 days but not later in gestation. Maternal acidosis did not upregulate the expression of CA IV mRNA or CA IV immunoreactive protein. Thus CA IV expression in mouse placenta is developmentally regulated. Maternal acidosis during the last quarter of pregnancy does not upregulate CA IV mRNA or CA IV immunoreactive protein.

Ammonium Chloride↗

Ultra-short pulse (femtosecond) laser surgery: initial use in LASIK flap creation.

The highly localized tissue effects of low energy femtosecond duration (ultrashort) laser pulses may be used to create three-dimensional intrastromal resections with micron precision and minimized collateral tissue damage. A surgical laser system that produces and delivers such pulses has been developed and tested clinically for creation of a corneal flap in LASIK. Expanded evaluation of this technology in this and additional keratorefractive applications is currently underway.

Corneal Stroma↗

Interstitial carbonic anhydrase (CA) activity in brain is attributable to membrane-bound CA type IV.

We tested the hypothesis that extracellular membrane-bound carbonic anhydrase (CA) type IV is responsible for the regulation of interstitial pH (pH(o)) transients in brain. Rat hippocampal slices were incubated in phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves the link of CA IV to the external face of plasma membranes. Then evoked alkaline pH(o) shifts were studied in a recording chamber, using pH microelectrodes. Incubation fluid was saved for later analysis. The ability to buffer a rapid alkaline load was reduced markedly in PI-PLC-treated tissue as compared with adjacent, paired control slices. The effect of benzolamide (a poorly permeant CA inhibitor) on evoked pH(o) shifts was diminished greatly in the PI-PLC-treated tissue, consistent with the washout of interstitial CA. Treatment of the incubation fluid with SDS abolished nearly all of the CA activity in fluid from controls, whereas an SDS-insensitive component remained in the fluid from PI-PLC-treated slices. These data suggested that CA type II (which is blocked by SDS) leaked from injured glial cells in both slice preparations, whereas CA type IV (which is insensitive to SDS) was liberated selectively into the fluid from PI-PLC-treated tissue. Western blot analysis was consistent with this interpretation, demonstrating a predominance of CA IV in the incubation fluid from PI-PLC-treated tissue and variable amounts of CA II in fluid from PI-PLC-treated and control slices. These results demonstrate that interstitial CA activity brain is attributable principally to membrane-bound CA IV.

Animals↗

Time course of the response to recombinant growth hormone in acidotic mice.

Long-term administration of recombinant growth hormone (GH) increases growth, despite persistent acidosis, in mice with carbonic anhydrase II deficiency (CAD). In contrast, short-term administration of GH to acidotic rats fails to improve growth. To determine the factors affecting the rate of growth response to GH in acidosis, we analyzed serial measurements obtained during a randomized trial of GH in CAD mice and healthy controls. Administration of GH increased standardized growth progressively up to 5-9 weeks. These data suggest that assessment of the response to GH in rodents requires prolonged administration.

Acidosis↗

Sexual isolation between Drosophila melanogaster, D. simulans and D. mauritiana: sex and species specific discrimination.

The sexual isolation among the related species Drosophila melanogaster, D. simulans and D. mauritiana is asymmetrical. While D. mauritiana males mate well with both D. melanogaster and D. simulans females, females of D. mauritiana discriminate strongly against males of these two species. Similarly, D. simulans males mate with D. melanogaster females but the reciprocal cross is difficult. Interspecific crosses between several populations of the three species were performed to determine if (i) males and females of the same species share a common sexual isolation genetic system, and (ii) males (or females) use the same genetic system to discriminate against females (or males) of the other two species. Results indicate that although differences in male and female isolation depend on the populations tested, the isolation behaviour between a pair of species is highly correlated despite the variations. However, the rank order of the isolation level along the populations was not correlated in both sexes, which suggests that different genes act in male and female sexual isolation. Neither for males nor for females, the isolation behaviour of one species was paralleled in the other two species, which indicates that the genetic systems involved in this trait are species-pair specific. The implications of these results are discussed.

Animals↗

Amplification of herpes simplex virus type 1 DNA in human geniculate ganglia from formalin-fixed, nonembedded temporal bones.

Polymerase chain reaction (PCR) has provided new insights in molecular biology. Recently, some studies have been focused on temporal bone pathology, with amplification of DNA from fixed sections of celloidin-embedded bones. The purpose of our study was to elucidate the utility of PCR in detection of minor concentrations of DNA from nonoptimal stored samples. We obtained geniculate ganglia from 30 temporal bones preserved in formalin for a long time, without any process of embedding. By performing a nested PCR assay, we detected herpes simplex virus type 1 DNA in 13 of 30 ganglia (43%). We conclude therefore that study of temporal bones stored under poor conditions by PCR is possible, although there are some limitations when compared with fresh or optimally archived samples.

Adult↗

NMR study of the metabolic 15N isotopic enrichment of cyanophycin synthesized by the cyanobacterium Synechocystis sp. strain PCC 6308.

1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopy has been used to characterize cyanophycin, a multi-l-arginyl-poly-[l-aspartic acid] polypeptide from the cyanobacterium Synechocystis sp. strain PCC 6308. 1H, 13C and 15N chemical shifts and 1JHN and 1JCN coupling constants were measured in isolated 15N-labeled cyanophycin, and showed chemical shift values and J-couplings consistent with the reported polypeptide structure. 15N enrichment levels were determined from the extent of 1H-15N J-coupling in 1H NMR spectra of cyanophycin. Similar experiments using 13C-15N coupling in 13C NMR spectra were not useful in determining enrichment levels.

Bacterial Proteins↗

Two internal pools of soluble polyphosphate in the cyanobacterium Synechocystis sp. strain PCC 6308: an in vivo 31P NMR spectroscopic study.

Two intracellular pools of soluble polyphosphate were identified by in vivo 31P NMR spectroscopy in the cyanobacterium Synechocystis sp. strain PCC 6308. Polyphosphate was present in the cells after growth in sulfur-limited media containing excess phosphate. The presence of polyphosphate was confirmed by transmission electron microscopy and chemical analysis. 31P NMR spectroscopy of whole cells treated with EDTA revealed two pools of mobile polyphosphate. A downfield shift and narrowing of part of the broad polyphosphate resonance was observed after EDTA treatment, suggesting that EDTA binds metal ions normally associated with some of the polyphosphate. Phosphate, but not polyphosphate, leaked out of the cells after this treatment. Addition of magnesium ions caused the downfield shift in the polyphosphate resonance to move back toward its original value. These data show that only part of the cation-complexed polyphosphate is accessible to the added EDTA and suggest that there are two internal fractions of NMR-visible polyphosphate in the cells, only one of which loses its associated cations to EDTA. Spheroplast formation showed that polyphosphate was not present in the periplasm of the cells.

Cyanobacteria↗

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.

Adult↗

Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis.

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from approximately 5 to approximately 12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.

Acidosis↗

How to stabilize the level of ionized calcium and citrate during plateletpheresis.

BACKGROUND AND OBJECTIVES: Citrate reactions are uncomfortable and potentially dangerous to apheresis donors. Reduction of citrate increases comfort, but may lead to platelet clumping. MATERIALS AND METHODS: We describe a protocol for stepwise reduction of the volume of ACD-A injected during plateletpheresis. This protocol has been carried out in 45 healthy donors with the Cobe 2997 (Cobe) cell separator, and in 35 with the Fenwal-CS 3000 (CS). RESULTS: Using this protocol, during the first hour of platelet collection, ionised calcium decreased on average by 18% for CS and by 18.4% for Cobe. During the second hour, Ca2+ and citrate ion concentration did not change with either Cobe or CS (about 65% of citrate ion load is eliminated). We observed mild signs of neuromuscular hyperexcitability in only 22% and 28% of donors with Cobe and CS, respectively. We also found a significant reduction of phosphate ions (p < 0.0001) at the end of the procedures. CONCLUSIONS: With this stepdown citrate reduction protocol, we obtained a significant reduction of injected citrate without the complication of platelet clumps.

Blood Proteins↗