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Biomedical subjects

E Gomez

Publications and source records attributed to E Gomez.

At least 73 records · Page 4Linked to original sources
PubMed1998

Bioequivalence evaluation of 2 different oral formulations of ciprofloxacin in healthy volunteers.

A bioequivalence study of 2 oral formulations of 500 mg tablets of ciprofloxacin was carried out in 24 healthy volunteers according to a single dose, two-sequence, crossover randomized design. Blood samples were taken prior to each administration and at 13 points within 32 hours after the dose, and plasma concentrations of ciprofloxacin were determined by HPLC. The pharmacokinetic parameters Cmax and tmax were obtained directly from plasma data, ke was estimated by log-linear regression, and AUC was calculated by the trapezoidal rule. The pharmacokinetic parameters AUC and Cmax were tested for bioequivalence after log-transformation of data, differences of tmax were evaluated nonparametrically. The 90% standard confidence intervals of the mean values for the test/reference ratios were 0.87-0.97 for AUC and 0.91-1.05 for Cmax, within the bioequivalence acceptable range of 0.80-1.25 limits. So, we conclude that both formulations were found bioequivalent and, therefore, interchangeable.

Administration, Oral↗
PubMed1997

Sertoli cell-germ cell interactions and TGF beta 1 expression and secretion in vitro.

Transforming growth factor beta 1 (TGF beta 1) has been reported to be secreted and to act within the somatic cells of the testis. We examined whether the TGF beta 1 expression is present at mRNA and protein levels in purified rat Sertoli cells (SC), purified pachytene spermatocytes (SPC), and early spermatids (SPT) cultured alone or together. SC expressed a single TGF beta 1 transcript of 2.5 kb, but no TGF beta 1 protein could be detected in SC conditioned medium indicating that, if at all, SC secreted less than 10 pg/10(6) cells/24 h. Neither TGF beta 1 mRNA nor protein could be detected in either SPC or SPT. Coculture of SC with either SPC or SPT resulted in a 2-fold increase of TGF beta 1 mRNA and more importantly in the secretion of TGF beta 1 protein. These findings demonstrate that Sertoli cell-germ cell interactions regulate TGF beta 1 expression and secretion and indicate that TGF beta 1 may be involved in spermatogenesis.

Animals↗
PubMed1997

Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine.

Human spermatozoa possess a specialized capacity to generate reactive oxygen species (ROS) that is thought to be of significance in the redox regulation of sperm capacitation (De Lamirande and Gagnon, 1993; Aitken et al., 1995). However, the mechanisms by which ROS are generated by these cells are not understood. In this study we have examined the possible significance of NADPH as a substrate for ROS production by human spermatozoa. Addition of NADPH to viable populations of motile spermatozoa induced a sudden dose-dependent increase in the rate of superoxide generation via mechanisms that could not be disrupted by inhibitors of the mitochondrial electron transport chain (antimycin A, rotenone, carbonyl cyanide m-chlorophenylhydrazone [CCCP], and sodium azide), diaphorase (dicoumarol) xanthine oxidase (allopurinol), or lactic acid dehydrogenase (sodium oxamate). However, NADPH-induced ROS generation could be stimulated by permeabilization and was negatively correlated with sperm function. Both NADH and NADPH were active electron donors in this system, while NAD+ and NADP+ exhibited little activity. Stereo-specificity was evident in the response in that only the beta-isomer of NADPH supported superoxide production. The involvement of a flavoprotein in the electron transfer process was indicated by the high sensitivity of the oxidase to inhibition by diphenylene iodonium and quinacrine. These results indicate that NAD(P)H can serve as an electron donor for superoxide generation by human spermatozoa and present a simple strategy for the production of motile populations of free radical generating cells with which to study the significance of these molecules in the control of normal and pathological sperm function.

Acridines↗
PubMed1997

HLA-DQA, -DQB and -DRB allele contribution to narcolepsy susceptibility.

The association of narcolepsy with HLA class I antigens and HLA class II alleles was studies in a series of Spanish narcoleptic patients. The haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was found to be significantly associated with the disease, while the haplotype DRB1*0701-DRB4*01-DQA1*0201-DQB1*02 might confer a slight protective effect against narcolepsy. Gene dose-effect was not seen in any of the involved alleles, and linkage disequilibrium between the positively associated alleles was found to be stronger in patients than in controls. Statistical analysis applied to identify the HLA allele truly responsible for the association did not clearly discriminate between the contribution of DRB1*1501 and that of DQB1*0602, but it proved that the association with DQA1*0102 is secondary to that with DRB1*1501/DQB1*0602. Analysis of the diagnostic value of typing for the narcolepsy-associated alleles demonstrated a very high negative predictive value and revealed that this test can be convenient for exclusion of narcolepsy in cases when the diagnosis is not evident after clinical evaluation and the marker haplotype is absent. Finally, a family study indicated that narcolepsy is a multifactorial disorder that involves HLA genes under an incomplete penetrance model, with possible influences from environmental factors or other genes different to HLA genes.

Adolescent↗
PubMed1997

Type I and type II interleukin-1 receptor expression in rat, mouse, and human testes.

Despite clear indications of interleukin-1 (IL-1) action on Sertoli and germ cells, previous studies failed to detect IL-1 receptors (IL-1R) within the seminiferous tubules. Here, we investigated the existence of the type I signaling receptor (IL-1RI) and the type II decoy receptor (IL-1RII) mRNAs within the testis. Polymerase chain reaction analysis showed the presence of both receptor mRNAs in isolated rat, mouse, and human somatic testicular cells (macrophages, Leydig, Sertoli, and peritubular cells). While also present in rat and mouse isolated pachytene spermatocytes and early spermatids, these receptor mRNAs were not found in human germ cells. The distribution of both IL-1R mRNAs was then examined in adult rat and mouse testis using light and electron microscopic in situ hybridization. No IL-1RI signal was detected in rat testis. In mouse testis, we did not find any signal for IL-1RII. In contrast, IL-1RI mRNA was detected in a wide variety of mouse testicular cells. Strong expression was observed in the rete testis area and high expression was seen over the epithelium of the epididymal duct and in interstitial cells, while lower labeling was detected in peritubular and Sertoli cells and in all germ cell types from spermatogonia to early spermatids; no signal was seen in late spermatids. That the IL-IR was also strongly expressed in the interstitium, the rete testis and efferent duct areas, and the epididymis was established using an autoradiography technique. Overall, our study strongly supports the hypothesis that IL-1 is a regulator of testicular function of prime importance.

Aged↗
PubMed1997

Management of paroxysmal atrioventricular nodal reentrant tachycardia in the critically ill surgical patient.

OBJECTIVES: Paroxysmal atrioventricular nodal reentrant tachycardia is an infrequently encountered supraventricular arrhythmia that continues to present difficult management problems in the critically ill surgical patient. The purpose of this study was to evaluate the efficacy of a new treatment algorithm involving the sequential administration of different classes of antiarrhythmic agents until conversion to sinus rhythm was achieved. DESIGN: Nonrandomized, consecutive, protocol-driven descriptive cohort. SETTING: University hospital surgical and trauma intensive care unit (ICU). PATIENTS: During an 11-month period, we prospectively evaluated all hemodynamically stable patients who sustained new-onset atrioventricular nodal reentrant tachycardia. INTERVENTIONS: Vagal maneuver, followed by the rapid, sequential infusion of antiarrhythmic agents (i.e., adenosine, verapamil, and esmolol, respectively) until the arrhythmia was terminated. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (4% of all admissions) were evaluated, including 16 trauma patients (injury Severity Score of 20 +/- 8) and 11 general surgical patients (Acute Physiology and Chronic Health Evaluation II score of 17 +/- 7). Time from ICU admission to onset of atrioventricular nodal reentrant tachycardia was 4.5 +/- 5 days (median 2.5). Arrhythmia termination was achieved in all patients within minutes (mean 13 +/- 10 [SD]). Incremental sequential adenosine administration alone, however, was successful in affecting conversion to sinus rhythm in only 44% of initial episodes of atrioventricular nodal reentrant tachycardia (95% confidence interval 21% to 67%). A total of 14 (52%) patients developed 38 relapses of paroxysmal supraventricular tachycardia in the ICU after initial conversion to sinus rhythm. These relapses required additional antiarrhythmic therapy. Adenosine was only effective in 34% of the relapses (95% confidence interval 17% to 53%). Seven (50%) of these 14 patients developed multiple relapses. However, only two patients were receiving suppressive calcium-channel or beta-adrenergic receptor blockade at the time of relapse. CONCLUSIONS: The use of a multiagent algorithm was effective for the initial conversion of new-onset atrioventricular nodal reentrant tachycardia to sinus rhythm in critically ill surgical and trauma patients. This preliminary report suggests that adenosine has marginal efficacy in the critically ill surgical or trauma patient. Given the high frequency of relapses, regardless of the agents used to achieve initial control, suppression therapy for the arrhythmia during the period of maximal cardiovascular stress is essential.

Adult↗
PubMed1997

Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6.

Interleukins (IL)-1 and -6 have been shown to be produced by several categories of cells in the rat testis and involved in the paracrine control of testicular function. Evidence of high amounts of IL-1 have been shown in the human testis, but nothing is known about its cellular origin. Furthermore, to our knowledge, the presence of IL-6 in the human testis has not yet been investigated. Therefore, the present study was aimed at identifying IL-1 and -6 expression and production within the human testis, using RT-PCR, bioassays, and enzyme linked immunosorbent assays. We demonstrated that IL-1 and -6 messenger RNA and proteins were produced constitutively in vitro by human Leydig cell- and Sertoli cell-enriched preparations. FSH only stimulated IL-6 production by Sertoli cell-enriched preparations, but increased the release of both IL-1 and -6 in germ cell-depleted Sertoli cell cultures. In addition, lipopolysaccharides and latex beads enhanced the production of both cytokines by Sertoli cell cultures, whereas human chorionic gonadotropin and lipopolysaccharides enhanced the release of both cytokines by Leydig cells. Enzyme linked immunosorbent assays and neutralization experiments revealed that human Sertoli cells produce essentially the alpha form of IL-1, whereas both forms, alpha and beta, are present in Leydig cells. The demonstration that human Leydig and Sertoli cells produce IL-1 and -6 under the control of gonadotropin hormones and exogenous factors, opens the possibility to study the involvement of these cytokines in the control of testis function, in normal and pathological conditions in men.

Adult↗
PubMed1996

Impact of in vitro fertilization culture media on peroxidative damage to human spermatozoa.

OBJECTIVE: To compare different culture media for their effects on sperm motility and lipid peroxidation. DESIGN: The ability of four different culture media to sustain the motility of human spermatozoa during an overnight incubation was examined in relation to the induction of lipid peroxidation. The role of transition metals in the genesis of peroxidative damage was investigated in experiments involving the addition of iron or the chelating reagent ethylenediamine tetra acetic acid (EDTA). SETTING: Academic research institute. MAIN OUTCOME MEASURES: The generation of malondialdehyde and 4-hydroxyalkenals after the addition of a ferrous ion promoter and the measurement of sperm motility. RESULTS: Spermatozoa incubated in Ham's F-10 medium (GIBCO, Paisley, Scotland) exhibited a marked loss of motility in association with a significant increase in peroxidative damage. Addition of EDTA to Ham's F-10 medium significantly reduced the degree of lipid peroxidation and induced a simultaneous increase in sperm motility. CONCLUSIONS: Ham's F-10 medium is a suboptimal medium for the long-term culture of human spermatozoa because it induces peroxidative damage and a concomitant decline of sperm motility.

Chelating Agents↗
PubMed1996

Tertiary telemedicine support during global military humanitarian missions.

OBJECTIVE: The U.S. military medical units face the challenge of delivering the latest medical knowledge and advances to remote areas of the world. This study details the tertiary care telemedicine support by Walter Reed Army Medical Center (WRAMC) for these humanitarian missions in several locations worldwide. METHODS: This study encompasses data from all clinical consults received at WRAMC, from the earliest deployment of a satellite-based system in February 1993 through February 1996. The analysis of the consultations include type of consult, medical specialty consulted, response time, and technology used. RESULTS: Two hundred forty consults were received from 12 remote telemedicine sites supporting military medical missions. The consults used a combination of "store-and-forward" technologies and interactive video conferencing systems. Establishment of a telemedicine service at WRAMC, including medical and technical support personnel, facilitated the delivery of telemedicine consultations. Several concurrent missions were supported. The distribution of consults included medicine (40%), surgery (36%), radiology (21%), and dentistry (3%). The most frequently consulted medical subspecialty was dermatology (29%) followed by orthopedic surgery (16%). Most consults were routine (88%). Ninety-four percent of the consults were completed within the predefined telemedicine response criteria (24 hours for routine consults and 3 hours for emergencies). CONCLUSION: The study illustrates the importance of a responsive telemedicine service at a tertiary facility supporting simultaneous medical missions. Access to the complete spectrum of medical and surgical specialties was essential to enhancing the delivery of medical care. The critical analysis and evaluation of this experience will assist in designing future prospective studies for evaluation of telemedicine.

Humans↗
PubMed1996

Expression of HLA class I genes in meiotic and post-meiotic human spermatogenic cells.

In human spermatogenic cells, in contrast to somatic cells, expression of major histocompatibility complex (MHC) class I molecules is undetectable. This lack of expression may contribute to the absence of female immune reaction against spermatozoa and may be necessary for gamete fusion. Among the molecular repressor mechanisms that may be used at the DNA level, we investigated 5' CpG methylation of the different class Ia and class Ib loci in meiotic pachytene spermatocytes and postmeiotic round spermatids, which had been purified from human testes by centrifugal elutriation. These results were compared with those obtained with mature spermatozoa and peripheral blood mononuclear cells. Using methylation-sensitive restriction enzymes and DNA locus-specific probes, we found that HLA-A, HLA-B/C, and HLA-E loci were similarly unmethylated in the germ and somatic cells tested, whereas HLA-F and HLA-G were even less methylated in the former cells. Together with the observation that spermatozoon DNA contains class I genes that are transfectable and able to direct transcription and protein synthesis in murine L cells, these data suggest that HLA class I genes are in an active conformation in male germ cells. We indeed found that both spermatocytes and spermatids contained low levels of class Ia and class Ib mRNA. Using reverse transcriptase-polymerase chain reaction, followed by DNA sequencing, we also detected three HLA-G transcriptional isoforms, resulting from alternative splicings, which suggested that this class Ib gene may have a potential function in these germ cells. Although intracellular expression of beta2-microglobulin (the light chain that associates with HLA class I heavy chains) was found in spermatocytes but not in round spermatids, no membrane-bound nor intracellular translated HLA class I heavy chain was detected in either germ cell type, when monomorphic anti-HLA class I monoclonal antibodies were used. Thus, lack of expression of HLA class I proteins in the male germ line is likely to involve post-transcriptional mechanisms of regulation.

Alternative Splicing↗
PubMed1996

Influence of plasma-protein binding on analgesic effect of methadone in rats with spontaneous withdrawal.

The effect of spontaneous withdrawal on alpha 1-acid glycoprotein (AAG) levels and methadone protein binding has been studied in the rat. Animals were made physically dependent on morphine by providing morphine HCl in drinking water for three weeks. The natural opiate withdrawal was induced in rats by substituting the morphine solution with drinking water. The severity of the abstinence syndrome was assessed at various time intervals. After 12 h of withdrawal, the animals showing abstinence signs and low morphine levels were injected with intravenous methadone (0.35 mg kg-1) and the analgesic effect was measured by the tail-flick method and compared with animals receiving water. The oral administration of morphine produced an increase in AAG levels from 0.64 +/- 0.05 g L-1 in control animals to 1.47 +/- 0.92 g L-1 in experimental animals at the point of withdrawal and 1.21 +/- 0.09 g L-1 24 h after withdrawal. The percentage of methadone unbound was significantly lower in morphine-treated than in control animals. A significant correlation between AAG levels and percentage of methadone bound was observed. A parallel analgesic effect after intravenous methadone, as measured by AUC in the tail-flick test, was less in abstinence animals than in control (287.6 +/- 24.8 compared with 401.0 +/- 37.06s min). We suggest that in the withdrawal syndrome an adjustment of methadone dose may be necessary because of changes in protein binding.

Analgesics, Opioid↗
PubMed1996

Physical and psychosocial functioning of 117 survivors of bone marrow transplantation.

All surviving patients receiving a BMT at our center since 1976 were surveyed. Among 163 eligible patients, 145 were contacted and 117 (81%) responded. Their median follow-up was 55 months (range 6-154). The research instruments consisted of a demographic questionnaire, a current medical status form, a quality of life questionnaire (Nottingham Health Profile), and a screening instrument for psychiatric morbidity (the 28-item version of the General Health Questionnaire). Current functioning varied considerably across patients. They reported a high use of medical services (37%) and varied ongoing medical problems within the last 6 months. Most of them (93%) received Karnofsky ratings of 80 or above. Eight percent had current chronic GVHD. Comparing our patients' quality of life with a British reference population, most important differences were found for physical mobility, work, and sex life. Psychiatric morbidity in BMT survivors was higher than in a Spanish general population. Multivariate analyses revealed that a higher systemic symptomatology score, a lower educational level, an older age at BMT, a shorter time post-BMT, a female gender, and impotence were significant predictors of an impaired overall quality of life. Similarly, a higher systemic symptomatology score, a shorter time post-BMT, a higher number of major infections, and a lower educational level were predictive factors of a higher psychosocial distress. No differences in quality of life or psychosocial status between allogeneic and autologous transplants were found. Quality of life and psychosocial distress improved with the passage of time, specially within the first 3 years.

Adolescent↗