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Biomedical subjects

R Lopez

Publications and source records attributed to R Lopez.

At least 37 records · Page 2Linked to original sources

[Improvement of transfusion safety in a health care service through the implementation of a quality program].

The quality policy brings with it an efficient method as well as relevant tools to improve transfusion safety in health care services. This article illustrates the details of the approach through the presentation of a project developed in the East Picardie region throughout several hospitals. It underlines the importance of the choice of a good reference system, of a pertinent method and the necessity of a real project management. Furthermore, the follow-up of the project has enabled us to identify a certain number of success criteria in the steering of the changing process.

France

Changes in vancomycin pharmacokinetics during treatment.

Using data gathered in routine monitoring, the pharmacokinetics of vancomycin during the first 10 days of treatment were compared with the pharmacokinetics after 10 days of treatment in 46 adult patients with normal renal function, ages 17-85 years old (mean +/- SD: 50.8 +/- 17.5). The mean time from initiation of treatment to the first sample determination was 5.5 days, and the mean time to the second determination was 13.4 days. Statistical differences between the two periods were observed for all pharmacokinetic parameters, except for the steady-state distribution volume. After 10 days of treatment, the mean +/- SD of the vancomycin clearance and elimination rate constant decreased from 1.31 +/- 0.82 to 1.13 +/- 0.72 ml/kg/min (p = 0.0044) and from 0.13 +/- 0.08 to 0.10 +/- 0.06 h-1 (p = 0.091), respectively. The half-life (t1/2) increased from 8.01 +/- 6.82 to 10.02 +/- 8.00 h (p = 0.012). The median percentage of the increment of t1/2 was 9.4%. The increase in t1/2 was > 50% in 12 patients and > 100% in nine cases. No association was found between the increment of t1/2 and the cumulative vancomycin dose. Frequent monitoring of serum vancomycin seems indicated, given the risk of decreased elimination during prolonged treatment.

Adolescent

Antinuclear antibodies in dogs with leishmaniasis.

An indirect immunofluorescence method using rat liver as material was developed to determine the incidence of antinuclear antibodies in serum from 44 adult dogs naturally infected with leishmaniasis and, for comparative purposes, in a control group of 30 healthy dogs. Animals in both groups were of different breeds with a similar age distribution. Antinuclear antibodies were not detected in the healthy dogs and only 15.9% of the diseased dogs, 12.0% males and 21.1% females, were positive. The results indicate that in contrast to previously reported figures, the incidence of antinuclear antibodies is low in canine leishmaniasis at least when diagnosis is first made. In order to investigate whether antinuclear antibodies may play a role in the development of the renal damage observed in canine leishmaniasis, the concentrations of serum creatinine were related to the presence of antinuclear antibodies. Only 28.5% of the antinuclear antibodies positive infected dogs showed hypercreatininemia as did 32.4% of the antinuclear antibodies negative infected dogs. Thus, antinuclear antibodies are not significantly cause-effect related to the development of the renal lesions seen in canine leishmaniasis.

Animals

Circulating immune complexes and renal function in canine leishmaniasis.

A third component of complement (C3) capture enzyme-linked immunosorbent assay was used to determine the concentration of IgG circulating immune complexes (CIC) in 91 dogs with naturally acquired leishmania infection and in a control group of 24 healthy dogs. Results were expressed as a percentage of a reference standard. Mean concentrations of CIC were significantly (P < 0.001) higher in leishmania-infected dogs (228.725 +/- 14.283%) than in controls (74.542 +/- 12.614%). An increase in CIC concentration was found in 57.1% of the leishmania-infected dogs. No significant differences could be recorded in CIC levels between males and females in either group. Infected dogs showing hypercreatininemia rendered a statistically significant (P < 0.030) higher serum CIC concentration than sick dogs with normal creatininemia. When hypercreatininemia (> or = 1.30 mg/dl) was used as an indicator for CIC increase, the positive predictive value obtained was 0.9 indicating that renal function impairment was associated with high serum CIC concentration in 90% of the infected dogs.

Animals

Inhibition of apoptotic cell death in B-CLL by interferon gamma correlates with clinical stage.

Apoptosis was evaluated in B cells from 41 patients with B-CLL and 20 healthy aged-matched controls. B cells were cultured with and without gamma-IFN and other cytokines; apoptosis was quantified at regular intervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eight as high risk. In vitro, purified B cells from B-CLL patients were evaluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IFN to the culture media prevented apoptosis in a dose-dependent manner. Maximal inhibition of apoptosis was achieved with 100 IU/ml of gamma-IFN. The degree of inhibition of apoptosis by gamma-IFN was greater in cells from the high-risk group patients than in those from the intermediate and good prognosis group (P < 0.0001). The expression of gamma-IFN receptors in B-CLL cells was evaluated using a MnAb against the extracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups showed an increase in the density of gamma-IFN receptors (P < 0.001). gamma-IFN was not detected in the sera of our study patients. However gamma-IFN was detectable in the media from both normal B cells and B-CLL cells in culture; there was no difference in the amount of gamma-IFN released by cells from the three groups of patients studied. Our results show that in vivo gamma-IFN inhibits apoptosis of B cells from B-CLL patients. The inhibitory effect of gamma-IFN on apoptosis correlates directly with the severity of the disease and this is likely explained by a marked upregulation of gamma-IFN receptors in cells from patients in the high-risk group.

Aged

Autosomal dominant congenital epiphyseal dysplasia limited to the femoral heads.

A father and son with unusual congenital skeletal symptoms, mainly characterized by short stature and epiphyseal dysplasia limited to the femoral heads are described. The comparative analysis with other spondyloepiphyseal dysplasias supports the notion that the syndrome reported here is a distinct autosomal dominant connective tissue disorder.

Adult

Differential expression of DNA topoisomerases in non-small cell lung cancer and normal lung.

UNLABELLED: DNA topoisomerases are ubiquitous nuclear enzymes, and important targets of cancer chemotherapy. Expression of topoisomerase genes is often correlated with in vitro chemosensitivity. We investigated the expression of the topoisomerase genes in normal lung and non-small cell lung cancer. Expression of topoisomerase II-alpha, topoisomerase II-beta, and topoisomerase I genes has been assessed in tumor samples of 60 patients who underwent operation for a non-small cell lung carcinoma, by RNase protection assay, and by immunohistochemistry. The expression of topoisomerase II-alpha gene was either undetectable or very low in normal lung, while most NSCLC expressed readily quantifiable levels of this gene. No alteration of the topoisomerase II-alpha gene was found by Southern blotting in the NSCLC samples. In contrast to topoisomerase II-alpha, topoisomerase II-beta was expressed in most normal as well as in tumor tissue samples, at a similar level. The levels of expression of both topoisomerase II isoforms was lower than that of human lung cancer cell lines. The results of the topoisomerase II mRNA expression were confirmed by immunohistochemistry. Whereas topoisomerase II-alpha staining was mainly limited to the nucleus, staining with topoisomerase II-beta antibody was exclusively observed in nucleoli. Topoisomerase I was localized in the nuclei and expression was mainly limited to tumor cells. By RNase protection, topoisomerase I expression in NSCLC samples was in the range of that of human lung cancer cell lines. The expression of the topoisomerase genes did not seem to be coordinated. In tumor cells, there was a positive association between expression of topoisomerase II-alpha and Ki-67, a marker of cell proliferation, as assessed by immunohistochemistry, but not with topoisomerase II-beta or topoisomerase I. Clinical characteristics of the patients, and their survival did not appear to be correlated to the level of expression of any of the topoisomerase genes, although a trend towards a shorter survival was observed in patients whose tumors expressed relatively high topoisomerase II-alpha mRNA levels. IN CONCLUSION: (1) the two isoforms of topoisomerase II are differentially expressed in normal lung and NSCLC cells; (2) higher topoisomerase II-alpha expression is associated with higher cell proliferation in NSCLC; (3) the expression of topoisomerase II-alpha and topoisomerase I, but not of topoisomerase II-beta, was higher in tumor cells compared to normal lung. Given the differential expression of topoisomerases in normal lung and tumors, research of more potent and specific topoisomerase inhibitors might prove beneficial in non-small cell lung cancer. Immunohistochemistry may be indicated in prospectively investigating the correlation between expression of topoisomerases and results of chemotherapy treatment.

Aged

Parathyroid hormone stimulates electrogenic sodium transport in A6 cells.

The effects of parathyroid hormone (PTH) on sodium homeostasis in the distal tubule are not well defined. Using A6 cells as a model for distal tubular epithelium we measured equivalent short circuit current (leq), as an estimate of net sodium transport. We found that PTH increased leq in a dose-dependent manner. DDA, an agent which inhibits adenylate cyclase, decreased PTH-activated sodium transport, suggesting a role for cAMP elevation in PTH effects. Moreover, addition of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, partially blocked the PTH-stimulated leq. PTH also elicited a sustained increase in [Ca2+]i in A6 cells. This elevation in [Ca2+]i was abolished by removal of calcium from the extracellular medium, suggesting the involvement of calcium influx pathways. In fact, addition of the calcium channel blocker nitrendipine to PTH-stimulated leq partially blocked PTH-activated sodium transport. Taken together these data demonstrate that PTH stimulates electrogenic sodium transport in A6 cells and that this effect may be mediated through a rise in both intracellular calcium and cellular cAMP.

Adenylyl Cyclase Inhibitors

Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative.

An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the epsilon 4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD.

Age Factors

Durability of the Carpentier-Edwards porcine bioprosthesis: role of age and valve position.

The durability (structural deterioration-free interval) after valve implantation with the first-generation Carpentier-Edwards porcine bioprosthesis has been investigated. From 1978 through 1984, 420 patients (175 male, 245 female) underwent valve replacement with the Carpentier-Edwards standard bioprosthesis. Mean age was 50.6 years (range, 13 to 77 years). Isolated mitral valve replacement (MVR) was performed in 198 patients (47.1%), aortic valve replacement (AVR) in 136 (32.4%), and double valve replacement (DVR) in 86 (20.5%). Hospital mortality was 32 patients (7.6%), 7.5% for MVR, 5.1% for AVR, and 11.6% for DVR. Mean follow-up was 10.8 years (range, 9 to 15 years) and is 96.2% completed. Reoperation for structural deterioration was required in 143 patients. Actuarial curve free from structural deterioration at 15 years is 33.0% +/- 6.5% for MVR, 62.0% +/- 5.1% for AVR, and 44.2% +/- 8.2% for DVR (p < 0.03). Durability of the CE bioprosthesis for MVR was 101.6 +/- 34.5 months, 92.9 +/- 26.4 for AVR, and 84.3 +/- 25.3 for DVR (p = not significant). The regression logistic analysis between age at the time of surgery and durability of the bioprosthesis showed no correlation for the MVR group, but with the following predictive formula for AVR and DVR groups of patients older than 30 years" durability = 46.05 + 0.818 x age, for AVR (r2 = 0.43); durability = 15.81 + 1.122 x age, for DVR (r2 = 0.52). In conclusion, we have found a significant difference in the behavior of the CE porcine bioprosthesis between the mitral and aortic position.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

The focal cone electroretinogram.

The focal cone electroretinogram (ERG) in monkey retina has been examined with a 3 deg pulse of laser light (544 and 633 nm) centered on a 25 deg steady white rod saturating field. The stimuli were viewed simultaneously through a slit lamp and corneal contact lens. Cone ERGs were studied at different eccentricities from the fovea and compared with full-field corneal and intraretinal ERGs. The cone ERG is maximum at the fovea. There are two components to the on- (b-wave) and off- (d-wave) response, one slower, more long wavelength sensitive and more foveally oriented than the faster response. This makes the foveal cone ERG slower and more longer wavelength sensitive than the perifoveal ERG. This difference disappears at high rates (> 20 Hz) of stimulation. The foveal cone ERG is larger and slower than that of more peripheral retina. The slowness appears to be due to a subcomponent of the response which is especially prominent in the fovea and has a slightly greater long wavelength sensitivity than the more peripherally generated ERG. It may depend on a unique difference in L-M cone bipolar systems or in L-M cone interactions that are more prominent near the fovea.

Animals

Retroviral gene transfer into retinal pigment epithelial cells followed by transplantation into rat retina.

In this preliminary report, we describe a technique for gene transfer into the retina using a retrovirus vector. We transferred the bacterial LacZ gene and the neomycin-resistance gene into pigmented wild-type rat retinal pigment epithelial (RPE) cells in culture. The RPE culture was exposed to retrovirus, and infected cells were selected with a neomycin analog (G418). The LacZ gene product was detected by X-Gal histochemistry in 95-100% of drug-resistant cells. These genetically labeled cells were transplanted into the subretinal space of two 15- to 25-day-old albino RCS rats, which have an inherited retinal degeneration syndrome. The retinas were fixed and stained with X-Gal at 3 and 6 weeks after transplantation. At both time points, pigmented, LacZ-containing cells were seen in the subretinal space. Further, there were several rows of photoreceptor nuclei in the transplant area of the approximately 2-month-old rats, while in the control contralateral eye the photoreceptor nuclei were virtually absent, as for untreated animals, suggesting that the transplanted LacZ-marked, wild-type RPE cells may have helped preserve photoreceptors. The technique for gene transfer into RPEs followed by transplantation thus provides a means for gene therapy in organisms with a genetic defect in RPE cells.

Animals

A standard water provocative test for dogs anaesthetized with acepromazine-ketamine.

Administration of 60 ml/kg of water to anaesthetized dogs increased intraocular pressure; this reached its maximum at 15 min after ingestion, except in young dogs, whose maximum was attained at 10 min. Pressure fell back close to original levels by 60 min. Pressure increases in females and young dogs were greater than those of males and adults, respectively.

Acepromazine

Portal vein patency in candidates for liver transplantation: MR angiographic analysis.

PURPOSE: To assess the accuracy of magnetic resonance (MR) angiography for evaluating portal vein patency in candidates for liver transplantation. MATERIALS AND METHODS: MR angiography was performed in the main portal vein and proximal confluence of the portal vein in 102 candidates for liver transplantation (64 male patients and 38 female patients aged 8 months to 74 years; mean age, 47 years). The MR angiographic results were compared with the surgical and histologic findings in the explanted liver and excised main portal vein. RESULTS: MR angiography depicted 10 portal vein clots, all of which were confirmed at transplantation. Ninety-two portal veins were patent at MR angiography, a finding that was confirmed at transplantation. One tiny chronic clot in a small, intrahepatic branch of the portal vein was not seen at MR angiography or transplantation. It was identified at histologic analysis of the explanted liver. CONCLUSION: MR angiography is accurate in the evaluation of portal vein patency.

Adolescent

Farm-related fatalities among children in California, 1980 to 1989.

To evaluate farm-related deaths among children in California and to identify specific risk factors, this study used death certificate tapes to identify 40 farm-related deaths among children under age 15 in California for 1980 to 1989. Mortality rates and odds ratios for cause-specific unintentional farm deaths were calculated. While California's farm-related mortality rate was lower than those in the midwestern states studied, the rate for Hispanic boys was 70% higher than that for non-Hispanics. The odds of death from machinery (81.3), animals (10.1), electricity (5.2), and nontraffic motor vehicles (3.4) were significantly greater than those in nonfarm locations; those from drowning were significantly lower (0.2). Specific factors associated with the lower California mortality rate need to be identified.

Accidents

Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina.

PURPOSE: To transplant human fetal retinal pigment epithelium (RPE) into the subretinal space of rabbits and monkeys as an organized monolayer without artificial support. METHODS: The method involves dissecting small patches of cultured RPE monolayers in sheets (1 to 5 mm2), sucking them into a glass pipette and injecting them into the subretinal space after producing a bleb detachment of the neural retina. RESULTS: These patches unfold and survive as a quasi-monolayer under the reattached neural retina intimately associated with the host photoreceptors and phagocytizing host outer segment material. Graft rejection is observed in most rabbits at 1 month but not in monkeys at 3 months after transplantation. CONCLUSIONS: Monolayer patches of cultured human fetal RPE can be transplanted to the subretinal space, where they survive in contiguity with healthy host outer segments. In primates, but not in rabbits, host-graft rejection does not occur for at least 2 to 3 months.

Animals

Evaluation of the exon predictions of the GRAIL software.

Identification of transcribed sequences within genomic regions has been a major rate-limiting step in the pursuit of genes. We have tested the ability of GRAIL 1 and GRAIL 2 to locate coding exons in the 41 longest human genomic sequences available in release 38 of the EMBL database. Of the total annotated exons GRAIL 1 correctly identified 68% of coding exons. GRAIL 2 correctly identified 71%. Of the 686 predictions made by GRAIL 1, 46.4% did not correspond to an annotated exon. The corresponding figures for GRAIL 2 were 556 and 30.5%. The GRAIL 2 software predicted as excellent a significantly higher proportion of the coding exons than did GRAIL 1, and also gave a significantly lower figure for false predictions. GRAIL 2 thus represents a significant improvement over GRAIL 1.

Exons

The role of family history in risk of childhood brain tumors.

BACKGROUND: Although brain tumors are the second most frequent malignancy in children, relatively little is known about the role of family history in risk of these tumors. METHODS: Children under the age of 18 years (n = 361) in whom primary brain tumors were diagnosed were identified from eight United States population-based Surveillance, Epidemiology, and End Results registries and compared to matched controls (n = 1083) identified by random-digit dialing. Information regarding family history of birth defects or tumors was obtained, along with data on other potential risk factors, from interviews with the mothers and fathers of the index children. RESULTS: No significant differences were found in family history of epilepsy. However, moderate elevations in risk were observed for a history of birth defects in maternal relatives, particularly for female propositi. Significantly more mothers (odds ratio [OR] = 1.63, 95% confidence limits [CL] = 1.03, 2.57) and maternal female relatives (OR = 2.15, 95% CL = 1.14, 4.06) of cases than of controls were reported to have had birth defects. History of birth defects in maternal relatives was particularly associated with childhood brain tumors of "other" (not astrocytoma or medulloblastoma) histologic type (OR = 2.37, 95% CL = 1.25, 4.53) and infratentorial tumors (OR = 1.76, 95% CL = 1.06, 2.93). Slight excesses of tumors were observed in paternal relatives of children with astrocytomas (OR = 1.43, 95% CL 0.93, 2.20) or with infratentorial tumors (OR = 1.46, 95% CL 0.97, 2.20). Risk of childhood brain tumors did not increase with the number of relatives affected with brain tumors, breast cancer, leukemia or lymphoma, soft tissue sarcomas, or all of these tumor types combined (the Li-Fraumeni syndrome). CONCLUSIONS: These findings suggest a modest increase in risk of childhood brain tumors associated with maternal family history of birth defects. Family history of tumors does not appear to contribute appreciably to an increased risk of brain tumors in children.

Adolescent