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Biomedical subjects

D Hernández

Publications and source records attributed to D Hernández.

At least 19 recordsLinked to original sources
PubMed1998

Drug-photosensitized protein modification: identification of the reactive sites and elucidation of the reaction mechanisms with tiaprofenic acid/albumin as model system.

Certain drugs can photosensitive the formation of protein modifications, which are thought to be responsible for the occurrence of photoallergy. In the present work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has been studied as a model system for drug-photosensitized protein modifications. The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the protein. The experimental results strongly suggest that formal hydrogen abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key photochemical process. Competition between cage escape and in cage recombination of the resulting radical pairs governs the final outcome: protein photo-cross-linking versus drug-protein adduct formation. These findings are highly relevant to understand the process of photohapten formation, the first event in the onset of photoallergy.

Amino Acids↗
PubMed1998

Is it possible to control hyperphosphataemia with diet, without inducing protein malnutrition?

Dietary intervention, phosphate (P) removal during dialysis and, especially, phosphate binders are current methods for the management of hyperphosphataemia. Ideally, the amount of P absorbed from the diet should equal the amount of P removed during dialysis, and this must occur in the context of an adequate protein intake. We evaluated the relationship between P intake and protein intake in 60 stable chronic uraemic patients (mean age 55+/-15 years, 25% diabetics, 68% males) on standard 4 h haemodialysis. The dietary counselling was relatively free for protein and calories. Nutrient intake was recorded during a 5 day period, and average daily ingestion of P and proteins was calculated using a computerized diet analysis system. A highly significant correlation was observed between protein and P intake. The mean daily ingestion of P and proteins was 998+/-316 mg and 64+/-19 g (1+/-0.4 g/kg/day), respectively. For an optimal protein diet of 1-1.2 g/kg/day, the P intake was 778-1444 mg. The amount of P removed by haemodialysis, extrapolated to an average week, is 250-300 mg/day. Since approximately 40% of P ingested is absorbed from the gut by uraemic patients treated with intestinal P binders, 750 mg of P intake should be the critical value above which a positive balance of P may occur. This value corresponds to a protein intake of 45-50 g per day (>0.8 g/kg body weight/day for a 60 kg patient). In patients undergoing standard chronic haemodialysis, a neutral P balance is difficult to achieve, despite phosphate binder therapy, when protein intake is >50 g. Additional protein restriction, in order to obtain a neutral balance, may impose the risk of protein malnutrition.

Adult↗
PubMed1998

Parathyroid function in long-term renal transplant patients: importance of pre-transplant PTH concentrations.

Lack of resolution of hyperparathyroidism after long-term renal transplantation is common. The relative roles of the graft function attained and the degree of pre-transplant hyperparathyroidism have not been established. Intact parathyroid hormone (iPTH) and several clinical parameters were studied before and 68.6+/-26.8 months (range: 30-124) after renal transplantation in 62 patients (20 females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal range, and values greater than twice the upper normal limit were not uncommon (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre-transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre-transplant PTH emerged as the more important predictor of post-transplant PTH (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism after renal transplantation is uncommon. In addition, the magnitude of pre-transplant hyperparathyroidism and the renal function determine the long-term post-transplant parathyroid function.

Adult↗
PubMed1998

Subclavian vascular access stenosis in dialysis patients: natural history and risk factors.

Stenosis of the subclavian vein (SVS) after cannulation occurs in 15 to 50% of chronic hemodialysis patients, and impedes the placement of an arteriovenous fistula in the ipsilateral arm. Its natural history and pathogenic mechanisms are not well established. This study examined 42 consecutive chronic renal failure patients (28 men and 14 women; 46+/-19 yr) in whom subclavian catheters had been placed as the initial vascular access for hemodialysis. All patients underwent sequential venography studies: at baseline (24 to 48 h after removal of the catheter) and 1, 3, and 6 mo thereafter. Venograms were considered abnormal when there was evidence of unequivocal strictures (more than 30% narrowing), with or without collateral circulation. At baseline, 52.4% (n=22) of patients showed stenotic vein lesions (n=19) or total thrombosis (n=3), and identical lesions were also observed after 1 mo. Surprisingly, 10 of 22 patients with initial SVS (45.4%) showed spontaneous recanalization of venous lesions in the venographies performed 3 mo after removal. The patients with normal baseline venograms (n=20) showed no change during follow-up. Patients with definitive stenosis at 6 mo (n=12) had a higher number of inserted catheters (1.58+/-0.6 versus 1.2+/-0.48; P < 0.05), longer time in place (49.08+/-32.2 versus 29.03+/-26.6 d; P < 0.05), and higher number of dialysis sessions (21+/-13.8 versus 12.4+/-11.4; P < 0.05) than those without SVS or with spontaneous recanalization of venous lesions during follow-up. Furthermore, a higher number of catheter-related infections were observed in patients with definitive SVS (66.6% versus 33.3%; P < 0.05). In summary, SVS is observed in more than half of patients 24 to 48 h after catheter removal and 1 mo later. Even when recanalization occurs in many cases, a definitive stenosis is seen in 28% of patients by the third month. Thus, the creation of an ipsilateral vascular access is possible provided that venography is normal at this time. Finally, mechanical factors and catheter-related infections are the major risk factors for the development of late SVS.

Adult↗
PubMed1998

Dengue virus in the brain of a fatal case of hemorrhagic dengue fever.

Neurologic complications associated with dengue fever are in general unusual. However, recent reports evidence more frequent neurologic alterations. In Mexico, neurologic involvement has not been reported in dengue cases. This report demonstrates the detection of dengue virus in the brain of a fatal case of dengue hemorrhagic fever. Serotype 4 was detected by immunohistochemistry and by RT-PCR in the inferior olivary nucleus of medulla and in the granular layer of cerebellum. Immunoreactivity was observed in neurons, astrocytes, microglia and endothelial cells. Our results emphasize the importance of neurologic manifestations in patients with dengue fever.

Adolescent↗
PubMed1997

Antibody levels against alpha-galactosyl epitopes in sera of patients with squamous intraepithelial lesions and early invasive cervical carcinoma.

We measured serum levels of anti-Gal(alpha 1-->3)Gal and anti-Gal(alpha 1-->2)Gal antibodies in 89 and 91 women, respectively, by using ELISA. These patients had cervical intraepithelial neoplasia (CIN) grades 1 to 3 and early invasive cervical carcinoma (ICC). Our objective was to compare anti-alpha-galactosyl antibody levels among them and with those of normal controls. High levels of anti-Gal(alpha 1-->2)Gal antibodies were detected in 22% of patients (P = 0.006). The mean level was 1.6 times greater than that of controls, without difference among subgroups. Thirty percent of patients had abnormally high anti-Gal levels (P = 0.001). Mean levels were twofold greater than the mean control value. Subsets with human papillomavirus/CIN 1 and CIN 2-3 had high immunoreactivity (P = 0.004). Both antibodies showed a significant correlation (r = 0.53, P < 0.00001). We conclude that 22 to 30% of patients with CIN 1-3 showed significantly high levels of anti-alpha-galactosyl antibodies. This seroreactivity might be related to the abnormal expression of alpha-galactosyl residues at some point of the natural history of human papillomavirus infection of the uterine cervix, suggesting an active immune response by natural antibodies against this virus. Further studies are needed to determine whether anti-alpha-galactosyl antibodies confer protection in human papillomavirus infection.

Adult↗
PubMed1997

Prediction of left ventricular mass changes after renal transplantation by polymorphism of the angiotensin-converting-enzyme gene.

Cardiac complications are the main cause of death in renal transplant patients and left ventricular hypertrophy (LVH) may play a determinant role. An association between the insertion-deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and LVH has been reported in adults. However, little is known about the genetic influence on left ventricular mass changes after renal transplantation, where unique environmental factors, such as cyclosporine A (CsA) and prednisone treatment concur. In fact, CsA treatment has recently been associated with the development of LVH. We prospectively determined the changes on cardiac structure and function, assessed by echocardiographic criteria, in 38 consecutive nondiabetic adults who received a cadaveric renal allograft. They were treated with cyclosporine and prednisone and maintained a good renal function during the follow-up. Echocardiographic studies (M-mode, 2-B and color flow Doppler) were performed without previous knowledge of the genetic typing, at the time of transplantation, and 6 and 12 months later. ACE alleles were typed using a PCR-based assay developed to ascertain the presence of an insertion (I)-deletion (D) polymorphism in intron 16 of the ACE gene. Patients with the so-called "unfavorable" DD genotype (N = 16) were compared with the ID or II genotypes (N = 22). The baseline left ventricular mass index was similar in patients with or without the unfavorable DD genotype (X +/- SE; 166.6 +/- 10.4 vs. 181.3 +/- 9 g/m2, respectively) and a similar proportion fulfilled the criteria of LVH (88% vs. 82%, respectively). The mean percent increase of the left ventricular mass index 12 months after renal transplantation was significantly higher in patients with the DD genotype compared to those with other genotypes (21.3 +/- 7.9 vs. -0.08 +/- 4.9%, respectively; P < 0.05). As a result, 94% of DD patients showed LVH at the end of the follow-up, while 68% of the ID or II patients had LVH (P < 0.05). In addition, the left ventricular ejection fraction significantly increased only in ID or II patients 12 months after transplantation with respect to baseline (ID/II patients, 70.4 +/- 1.5 vs. 63.7 +/- 1.8%; P < 0.05; DD patients, 68.3 +/- 2.1 vs. 63.3 +/- 2.9%). The deleterious effect of the DD genotype was independent of blood pressure, biochemical parameters, weight gain, and cumulative steroids dosages or cyclosporine levels. In conclusion, genetic factors determine the changes on cardiac structure and function after renal transplantation. The presence of the DD genotype of the ACE gene is a marker associated with an elevated risk of LVH in this population.

Adult↗
PubMed1997

Adenovirus-mediated gene transfer into human hepatocytes: analysis of the biochemical functionality of transduced cells.

The use of replication-defective adenoviruses to deliver transgenes into hepatocytes seems to be a promising approach to human liver gene therapy. However, the effects that the adenovirus-mediated expression of a foreign gene could have on the expression of other hepatic characteristic genes have not yet been properly examined. We have investigated this problem by using human hepatocytes infected with a recombinant E-1 defective adenovirus that carried a modified lacZ gene. The analysis of the biochemical functionality of transduced cells showed that the use of adenovirus: (1) was a very efficient way to introduce a foreign gene into human hepatocytes (80% transduced cells after 1 h contact, at an MOI of 15; approximately 100% transduced cells at an MOI of 20); (2) allowed the expression of the transgene to levels that enabled cells effectively to use lactose as an energy source; (3) does not affect urea synthesis, plasma protein synthesis and xenobiotic biotransformation activities (1A2, 2A1, 2B6, 3A3/5). Glycolysis was moderately increased (approximately 20%), while gluconeogenesis decreased (approximately 20%) in transduced hepatocyte; moreover, (4) the expression of inducible genes (acute-phase plasma proteins, CYPs) was not impaired in transduced human hepatocytes upon stimulation with IL-6 or methylcholantrene. The results of this research support the idea that efficient expression of transgenes can be achieved in human hepatocytes by means of adenoviral transduction, without altering these characteristic hepatic biochemical functions.

Adenoviridae↗
PubMed1997

Codon 89 polymorphism of the human 5alpha-steroid reductase type 2 gene.

The existence of a genetic polymorphism within the coding region of the human 5alpha-steroid reductase type 2 (5alpha-SR2) gene is reported in a Mexican population. Genotypic variation was assessed in 100 unrelated, healthy volunteers (50 males; 50 females), using single-stranded conformational polymorphism and direct sequencing analysis. Examination of exon 1 DNAs disclosed the presence of sequences encoding for valine (GTA) or leucine (CTA) at codon 89 of the gene. Of the subjects screened, 45% were homozygous for GTA (89Val), 50% had a heterozygous pattern GTA/CTA (89Val/89Leu) and the remaining 5% were homozygous for CTA (89Leu). These data support the view that the G/C condition at codon 89 of the 5alpha-SR2 gene represents a silent polymorphism which does not alter phenotypical development in the human.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Validity of colposcopy to identify and grade squamous intraepithelial lesions among Venezuelan women.

To assess the validity of colposcopy to correctly detect and grade squamous intraepithelial lesions (SIL) in Venezuelan women, we did a prospective, nonrandomized and cross sectional study on patients referred with low-grade and high-grade SIL. After a second cervical smear, they were colposcopically evaluated and biopsied. The outcome measures were interobserver variation, sensitivity, specificity, and predictive values. Ninety-nine patients were evaluable. Colposcopy had poor agreement with repeat cervical smears, and moderate to good agreement with conization biopsy (kappa = 0.55; 95% C.I.: 0.45 to 0.65), with a sensitivity of 0.87, a specificity of 0.69, a positive predictive value of 0.85 and a negative predictive value of 0.71 for high-grade SIL. The criterion of colposcopic vascular atypias was accurate enough to detect and grade SIL, showing good agreement with histopathology. Because of the disparity of results in previous reports, only a carefully designed, randomized study will settle this question.

Adult↗
PubMed1996

Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco.

The geographic origin of Mexican patients with phenylketonuria (PKU) in Mexico City and in southern California was studied. Compared to patients with other metabolic disorders, patients with PKU were significantly more likely to have originated from the Los Altos region of the state of Jalisco and its environs. The incidence of PKU among mentally retarded students attending special education schools was found to be significantly higher in Jalisco (particularly the Los Altos region) than in the neighboring state of Guanajuato (1.09% vs 0.3%). These results strongly suggest a "population of origin" effect, the mutant allele(s) having been introduced by the Spanish ancestors of the current population. Our findings also support the addition of PKU to the neonatal screening program for this region of Mexico.

Child↗
PubMed1996

Influence of vitamin D receptor genotype on bone mass changes after renal transplantation.

Renal transplant patients immunosuppressed with cyclosporine A (CsA) exhibit both a significant bone loss and an increased rate of bone fractures. An association between common allelic variants of the the vitamin D receptor (VDR) gene and bone mineral density and turnover has been reported in adults. However, the genetic influence on the rate of bone loss after renal transplantation has not been explored. We prospectively determined the changes in spinal mineral density in 34 consecutive nondiabetic adults who received a cadaveric renal allograft. Serum biochemical markers of bone metabolism and the vertebral mineral density (VMD) assessed by quantitative computed tomography were determined at the time of transplantation and three and twelve months later. In fifteen patients the histomorphometric features of iliac bone were analyzed at baseline and twelve months after transplantation. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. Patients with the so-called "favorable" bb genotype (N = 12) were compared with those with the Bb or BB genotype (N = 22). Baseline VMD was similar in patients with or without the favorable bb genotype. Three months after transplantation the mean (+/- SD) VMD decreased 14 +/- 13.3 percent in all patients (16.5 +/- 13.1% in patients homozygous for the b allele and 13.77 +/- 13.9% in those with Bb or BB genotypes). The rate of VMD loss at this time inversely correlated with pretransplant PTH levels (r = -0.40; P < 0.05). Between 3 and 12 months after transplantation, patients with the favorable bb genotype recovered more VMD than those with Bb or BB types and showed a significantly higher Z score at the end of the follow-up (-0.37 +/- 1.16 vs. -1.10 +/- 1.20, respectively; P < 0.05). The beneficial effect of bb genotype was independent of the prevailing PTH levels and was also observed in those patients with a baseline PTH level < 250 pg/ml (final Z score: bb, -0.42 +/- 1.3, N = 11; Bb/BB, -1.35 +/- 0.8, N = 11, P < 0.05). At the end of follow-up, the histomorphometric studies showed a higher bone formation rate adjusted for PTH levels in patients with the Bb or BB genotype than in those with the favorable bb genotype (0.29 +/- 0.06 vs. 0.21 +/- 0.08 micron3/micron2/day respectively; P < 0.05). In conclusion, high pretransplant PTH levels enhance the early trabecular bone loss after renal transplantation, and functionally different alleles of the vitamin D receptor gene may condition the bone turnover and the degree of recovery of the bone mass.

Adult↗
PubMed1996

Abnormal expression of galactosyl(alpha 1-->3) galactose epitopes in squamous cells of the uterine cervix infected by human papillomavirus.

This study describes the presence of alpha-galactosyl epitopes on 12 cervical biopsy samples with features of human papillomavirus infection (HPV) and different stages of cervical intraepithelial neoplasia. An avidin-biotin-peroxidase assay with a monoclonal antibody recognizing gal(alpha 1-->3)gal residues was strongly positive in 5 of 12 cases. None of the controls stained (p = 0.02). Immunostaining was intense in the areas with the highest viral load (koilocytes and keratinocytes) and absent in malignant foci. Immunostaining was also absent in normal exo- and endocervical epithelium of 12 controls with no features of HPV infection. A faint background staining in cases and controls was evident, but similar. These initial findings suggest that alpha-galactosyl epitopes are expressed in cervical squamous cells infected with HPV, turning them vulnerable to lysis by natural anti-alpha-galactosyl antibodies.

Adolescent↗
PubMed1996

Renal infarction in a severely hypertensive patient with lupus erythematosus and antiphospholipid antibodies.

Systemic lupus erythematosus (SLE) patients, specially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations. However, renal infarction has been rarely reported in these patients. The case of a young female with renal infarction, diagnosed by renal arteriography and scintigraphy, and arterial hypertension (AH) is described. In subsequent years she also suffered several cerebrovascular accidents with important neurological sequelae. No evidence of systemic disease was observed at this time. Fourteen years after the renal infarction a diagnosis of SLE was established. Despite therapy with prednisone, acetylsalicylic acid, azathioprine and antihypertensive drugs the progression of the neurological disease led to death. The sudden appearance of severe AH in a young woman with a renal infarction should alert the clinician about a possible underlying renal artery thrombosis in association with SLE and antiphospholipid antibodies.

Adult↗
PubMed1995

Bone disease in predialysis, hemodialysis, and CAPD patients: evidence of a better bone response to PTH.

The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗