Impact of using marginal cadaver donors and long cold ischemia time in renal transplant survival.
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Biomedical subjects
Publications and source records attributed to V Garcia.
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OBJECTIVE: To evaluate the efficacy, safety, and predictability of hyperopic laser in situ keratomileusis (H-LASIK) using modified software. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The first 72 consecutive eyes of 44 patients with up to +5.00 diopters (D) hyperopia. INTERVENTION: Hyperopic LASIK using the Automatic Corneal Shaper (ACS; Chiron Vision, Claremont, CA) and the Nidek EC-5000 excimer laser (Nidek, Tokyo, Japan). MAIN OUTCOME MEASURES: Uncorrected visual acuity, manifest spherical equivalent (MSE), best-corrected visual acuity (BCVA), and complications were studied. RESULTS: At 6 months, in the low hyperopia group (<3.00 D), mean MSE was +0.30 +/- 0.71 D, with 88.9% eyes within 1 D of emmetropia compared with +1.09 +/- 0.92 D and 51.8% within 1 D of emmetropia in the moderate hyperopia group (> or =3.00 D; P = 0.003). Uncorrected visual acuity was 20/40 or better in 43 of 45 eyes (95.6%) and in 21 of 27 (77.8%) eyes in the low and moderate hyperopia groups, respectively. Only one eye (1.4%) from the moderate hyperopia group lost two lines of BCVA. Eighteen eyes (25%) required retreatment to correct residual hyperopia, 9 eyes (20.0%) in the low hyperopia group and 9 eyes (33.3%) in the moderate hyperopia group. Retreatments resulted in an MSE of +0.02 +/- 0.45 D and +0.04 +/- 0.73 D in the low and moderate hyperopia groups, respectively. No flap-related complications were seen. CONCLUSIONS: Hyperopic LASIK with the ACS and the Nidek EC-5000 excimer laser using our modified software is a safe, effective, and predictable procedure for low hyperopia. Results are satisfactory up to moderate hyperopia. Significant regression can occur for low and moderate hyperopia. Retreatment can be performed safely and effectively to improve the visual and refractive results.
The possibility that the sphingomyelin (SM)-ceramide pathway is activated by CD40, a transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily and that plays a critical role in the regulation of immune responses has been investigated. We demonstrate that incubation of Epstein-Barr virus-transformed lymphoid cells with an anti-CD40 antibody acting as an agonist results in the stimulation of a neutral sphingomyelinase, hydrolysis of cellular SM, and concomitant ceramide generation. In addition, SM degradation was observed in acid sphingomyelinase-deficient cells, as well as after ligation by soluble CD40 ligand. The anti-CD40 antibody, as well as the soluble CD40 ligand induced a decrease in thymidine incorporation and morphological features of apoptosis, which were mimicked by cell-permeant or bacterial sphingomyelinase-produced ceramides. Stable expression of a dominant-negative form of the FAN protein (factor associated with neutral sphingomyelinase activation), which has been reported to mediate tumor necrosis factor-induced activation of neutral sphingomyelinase, significantly inhibited CD40 ligand-induced sphingomyelinase stimulation and apoptosis of transformed human fibroblasts. Transformed fibroblasts from FAN knockout mice were also protected from CD40-mediated cell death. Finally, anti-CD40 antibodies were able to co-immunoprecipitate FAN in control fibroblasts but not in cells expressing the dominant-negative form of FAN, indicating interaction between CD40 and FAN. Altogether, these results strongly suggest that CD40 ligation can activate via FAN a neutral sphingomyelinase-mediated ceramide pathway that is involved in the cell growth inhibitory effects of CD40.
Farber disease is a rare severe lysosomal storage disorder due to a deficient activity of the enzyme acid ceramidase (AC). Patients have granulomas along with lipid-laden macrophages that accumulate in a number of tissues, leading to multiple diverse clinical symptoms. There is no therapy for the disorder and most patients succumb to the disease in early childhood. The severity of the disease progression seems to correlate with the amount of the accumulated ceramide substrate. Since the cDNA for human AC has been elucidated we sought to establish if genetic transfer of this sequence would lead to enzymatic and, especially, functional correction of the catabolic defect in Farber patient cells. To do this, a novel amphotropic recombinant retrovirus was constructed that engineers transfer of the human AC cDNA. On infection of patient fibroblasts, AC enzyme activity in cell extracts was completely restored. Further, substrate-loading assays of intact living cells showed a fully normalized catabolism of lysosomal ceramide. Lastly, as reported for some other corrected enzymatic defects of lysosomes, metabolic cooperativity was seen, in that functionally corrected patient fibroblasts secreted AC that was taken up through the mannose 6-phosphate receptor and used by uncorrected fibroblasts as well as recipient Farber lymphoblastoid cells. This overall transduction and uptake scenario for Farber disease allows future treatment of this severe disorder to be envisioned using gene transfer approaches.
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OBJECTIVE: To evaluate the safety and efficacy of retreatment after myopic laser in situ keratomileusis (LASIK). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: A total of 962 eyes of 566 patients underwent LASIK for up to -20.0 diopters (D) of myopia, of which 53 eyes (5.5%) were retreated. INTERVENTION: Retreatments were performed by lifting the original flap and using the Nidek EC-5000 excimer laser (Nidek Inc., Tokyo, Japan). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), fogged manifest refraction, and complications were evaluated 6 months after retreatment. RESULTS: Overall, 53 (5.5%) of 962 eyes underwent LASIK retreatment. Before retreatment, the mean spherical equivalent (MSE) was -1.7 +/- 1.1 D (range, +0.3 to -5.0 D), UCVA ranged from 20/25 to 20/400, and BCVA ranged from 20/20 to 20/50. Six months after retreatment, the MSE was -0.09 +/- 0.29 D, 48 (90.6%) eyes were within +/-0.5 D, and all eyes were within +/-1.0 D of the attempted correction. The UCVA improved to 20/20 or better in 21 (39.6%) eyes and 20/40 or better in 51 (96.2%) eyes. The BCVA was maintained in 33 eyes (62.3%), 15 eyes (28.3%) gained 1 line or more of vision, whereas 5 eyes (9.4%) lost 1 line. All eyes had a BCVA of 20/50 or better. No retreated eye lost two or more lines of BCVA. No complications were observed. CONCLUSION: Retreatment for low amounts of residual myopia performed by lifting the original flap within the first year after surgery after myopic LASIK is safe, effective, and predictable.
Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cultured vascular cells but their possible toxic action on T lymphocytes has not been described. Peripheral blood lymphocytes from healthy individuals were stimulated in vitro with the polyclonal activator phytohemagglutinin and treated with various doses of native and mildly oxidized LDLs. Low doses of oxLDLs inhibited cell growth and DNA synthesis after 48 h culture and at 200 microg apoB/ml we observed a loss of cell viability. Dead cells did not exhibit significant increase of alteration of membrane integrity (i.e., necrosis) but showed chromatin fragmentation evaluated by DNA staining with 4', 6-diamidino-2-phenylindole and propidium iodide. This fragmentation increased with TBARS and hydroperoxide levels. The expression of early apoptosis marker Apo2.7 rose among the CD3(+) T-cell population. In addition, morphological analysis showed apoptotic features (cell shrinking, nucleus condensation, and fragmentation). Study of phosphatidylserine expression using Annexin V confirmed that oxLDLs induced apoptosis in activated lymphocytes. In the Jurkat T-cell line cultured with oxLDLs, apoptotic morphological changes (condensation and nucleus fragmentation) were observed and they were accompanied by DNA fragmentation visualized by propidium iodide staining and electrophoresis showing apoptotic ladder. These results demonstrate that mildly oxidized LDLs induce apoptosis in a part of activated and proliferating T cells. T-lymphocyte apoptosis induction in atherosclerotic lesions might contribute to the development of an inappropriate local T cell response.
Vertical transmission of HIV-1 can occur at three different stages: during gestation, delivery and breast feeding. To determine the role of cytokines in vertical transmission of HIV during gestation, we studied the secretion of IL-1beta, TNF-alpha and IL-6 from in vitro infected and Mock-infected placental macrophages (Hofbauer cells) in comparison to blood monocyte derived macrophages (MDM). Hofbauer cells stimulated with lipopolysaccharide (LPS) secreted lower levels of HIV stimulatory cytokines (6-8 ng/ml) in the supernatants than MDM (26 ng/ml, p<0.005). Cytokine levels in MDM decreased upon HIV infection to 7 ng/ml. IL-6 was the major cytokine produced after LPS stimulation by the two cell populations (p<0.005), being MDM the major cytokine producer. In vitro infection studies with a M-tropic virus (HIV-BaL) indicated that MDM were 10x more susceptible to HIV than placental macrophages (p=0.001). Our results indicate that although macrophages from term placenta secrete lower amount of HIV stimulatory cytokines than MDM, there was no correlation between the levels of cytokines and HIV production by both cells.
All hospitals should set policies that require the discharge of every newborn in a car safety seat that is appropriate for the infant's maturity and medical condition. Discharge policies for newborns should include a parent education component, regular review of educational materials, and periodic in-service education for responsible staff. Appropriate child restraint systems should become a benefit of coverage by Medicaid, managed care organizations, and other third-party insurers.
Children with special health care needs should have access to proper resources for safe transportation. This statement reviews important considerations for transporting children with special health care needs and provides current guidelines for the protection of children with specific health care needs, including those with a tracheostomy, a spica cast, challenging behaviors, or muscle tone abnormalities as well as those transported in wheelchairs.
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BACKGROUND: Atopic dermatitis is an allergic T-cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte-associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response. OBJECTIVE: To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus-related TCR Vbeta segments. METHODS: Peripheral blood T cells were stained with HECA-452 (anti-CLA) and a panel of TCR Vbeta specific monoclonal antibodies and analysed by flow cytometry. RESULTS: Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vbeta2 and Vbeta5.1 segments in the CLA+ but not in the CLA- subset. These TCR Vbetas are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA-DR+ expression by CLA+ Vbeta5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vbeta and HLA-DR phenotype in circulating CLA+ T lymphocytes. CONCLUSION: Our data indicate that circulating skin-homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vbeta segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.
SETTING: The Dominican Republic. OBJECTIVE: To assess the extent of drug-resistant tuberculosis (TB) following the guidelines of the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) new global surveillance project on drug resistance in TB. METHODS: Using a multi-step proportional weighted approach, a sample of 688 sequential cases of smear positive pulmonary TB diagnosed between April 1994 and April 1995 was studied in six of the country's eight health regions. Pre-treatment sputum samples were cultured on Loewenstein-Jensen medium and drug susceptibility tests were performed using the economic variant of the proportion method. RESULTS: Of 420 cases with drug susceptibility results, resistance to one or more drugs was observed in 43.8%; resistance was found in 52.1% of 117 TB cases with a history of previous antituberculosis treatment and in 40.6% of 303 new TB cases. In five of the six health regions surveyed, > or = 41% of strains were resistant to one or more drugs. Multidrug resistance (MDR) to isoniazid and rifampicin with or without resistance to other drugs was found in 43 (10.2%) of 420 cases, including 6.6% of new TB cases. In five of the six health regions > or = 8% of strains were classified as MDR. Independent predictors of MDR-TB included being in the age group 25 to 44 years (odds ratio [OR] = 4.2, 95% confidence interval [Cl] 1.5, 11.6; P = 0.005), being aged 45 years and over (OR = 4.5, 95% CI 1.4, 14.4; P = 0.009), and having a prior history of TB (OR = 3.7, 95% CI 1.9, 7.4; P = 0.0001). CONCLUSION: The proportion of Mycobacterium tuberculosis strains resistant to one or more anti-TB drugs in the Dominican Republic is among the highest observed world-wide. The severity of the problem urgently requires the full implementation of TB control strategies endorsed by the WHO and the IUATID, which include political commitment to a National TB Program, case detection utilizing sputum-smear microscopy, directly observed treatment, regular drug supply, and standardised recording and reporting systems. Also, the sale of TB drugs in the private market should be controlled.
We present six cases of superior vena cava syndrome caused by a malignant tumor that were treated by percutaneous endoprostheses. The technique is described and the results evaluated. In one case there was acute thrombosis of the endoprosthesis that was treated by urokinase. No other complications were observed. A patient died one month later due to progression of the tumor. The remaining cases were asymptomatic for longer than 6 months. It was concluded that endoprostheses for superior vena cava syndrome are efficient, with quick improvement of the symptomatology.
Based on the existence of choline acetyltransferase and acetylcholine in human placenta, we have investigated the presence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta. Radioligand binding assay, using [3H]N-methyl-scopolamine as tracer, showed the existence of acetylcholine muscarinic receptors in brush-border (Kd 0.28 +/- 0.04 nM; Bmax 9.4 +/- 1.6 fmol/mg protein) and basal plasma membranes (Kd 0.24 +/- 0.05 nM; Bmax 34.3 +/- 6.3 fmol/mg protein). In order to perform a pharmacological characterization of these receptors, competition binding experiments were carried out using the muscarinic receptor antagonists pirenzepine, (11(2-diethyl-amino)methyl)-1-piperidinylacetyl-5-11-dihydro-6H-py rido(14) benzodiazepine (AF-DX 116), himbacine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), dicyclomine and hexahydro-sila-difenidol (HHSD). The results obtained showed that the muscarinic receptors in brush-border and basal plasma membranes belong to different subtypes. In brush-border membranes, the receptor found match in terms of affinity for the antagonists with the muscarinic M1 receptor subtype (Ki pirenzepine, 13.6 +/- 8.2 nM; Ki AF-DX 116, 1680 +/- 271 nM; Ki himbacine, 212 +/- 6.5 nM; Ki 4-DAMP. 1.5 +/- 0.4 nM; Ki dicyclomine, 5.1 +/- 0.8 nM; Ki HHSD, 34.3 +/- 7.3 nM), whereas the receptor in basal plasma membrane seems to be of the muscarinic M2 receptor subtype (Ki pirenzepine, 202 +/- 48 nM; Ki AF-DX 116, 124 +/- 60 nM; Ki himbacine, 20.6 +/- 4.8 nM; Ki 4-DAMP, 4.5 +/- 1.2 nM; Ki dicyclomine, 54.6 +/- 22 nM; Ki HHSD, 89.2 +/- 15.8 nM). The results obtained show the existence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta with a different distribution pattern in terms of number of receptors and distribution of different subtypes. The functional significance of these findings is as yet unknown, but these receptors probably mediate different functions as they belong to different subtypes and are coupled to different second messengers.
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