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Biomedical subjects

J Morales

Publications and source records attributed to J Morales.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of daunomycin implants on filtering surgery outcomes in rabbits.

PURPOSE: To evaluate the effects of a novel daunomycin (DM) implant on intraocular pressure (IOP), bleb survival, and anterior segment complications when administered during filtering surgery on New Zealand White rabbits. METHODS: Implants were prepared by covalent coupling of DM to a high molecular weight hyaluronic acid (HA) and fabricated into solid implants containing 250, 65, and 25 microg of DM. Full thickness sclerostomies were performed, and rabbits received no implant (control), placebo implant containing HA, or an implant containing HA-DM conjugate at the time of surgery. Rabbits were then followed for 30 days to assess change in IOP, bleb survival, and anterior segment associated complications. RESULTS: In vitro, the release of DM from the implants was a first order process with a half-life of 51 h. In control rabbits, rabbits receiving placebo implant, and rabbits receiving HADM (250 microg) implants, the mean IOPs on day 3 were 11.1 +/-1.6, 10.8 +/- 2.7, and 14 +/- 0.98 mm of Hg, respectively. On days 5 through 9, IOP in the control and placebo-implanted groups returned to preoperative levels. However, in rabbits receiving 250 microg of conjugated DM, mean IOP on day 7 was reduced from preoperative levels by 11.8 +/- 3.2 mm of Hg (P < 0.05). This reduction in IOP was significantly different (P < 0.05) from both control and placebo implant groups, and IOPs remained at these levels until studies were terminated on day 30. In control and placebo-implanted rabbits, bleb size started decreasing on day 1, and by day 7, no blebs were observed. In rabbits receiving 250 microg HA-DM implants, mean bleb survival time was greater than 30 days. The DM-induced reduction in IOP and enhanced bleb survival was dose-dependent. In rabbits receiving 65 microg of conjugated DM, lOPs were significantly reduced through day 30; however, at times beyond day 19 there was a gradual rise in mean IOP as filtering procedures in individual animals began to fail. Mean bleb survival time was greater than 30 days for implants containing 65 microg of conjugated DM. In rabbits receiving HA-DM implant containing 25 microg of DM, IOPs were not significantly different from preoperative levels beyond day 9, and no significant enhancement in bleb survival was observed in these animals. Comparison of HA-DM conjugated implants to those containing equal doses of free DM demonstrated that the mean IOP change at 30 days were similar; however, there was a reduction in anterior segment complications associated with the use of HA-DM conjugated implants. CONCLUSIONS: This study provides evidence that the controlled release of DM when conjugated to HA can significantly improve the success of filtering procedures. The maintenance of ocular hypotension and bleb survival along with the reduction in anterior segment complications supports the idea that HA-DM conjugate will be more efficacious than the use of free DM in improving the success rate of filtering surgery.

Animals↗
PubMed1997

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing.

BACKGROUND: Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor ("squamous intraepithelial lesion," or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. METHODS: Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer, PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. RESULTS: The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). CONCLUSIONS: A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective.

Carcinoma↗
PubMed1997

Nonsense mutation in exon 3 of the proteolipid protein gene (PLP) in a family with an unusual form of Pelizaeus-Merzbacher disease.

We report a G-->A transition at nucleotide 431 of the proteolipid protein gene (PLP) results in a nonsense codon in a family with an unusual form of Pelizaeus-Merzbacher disease (PMD). The mutation, which creates a second AluI restriction site, results in a nonsense mutation in PLP. The clinical picture resembles somewhat that of X-linked spastic paraplegia (SPG). It differs from this and both the classical and connatal forms of PMD in that it is relatively mild in form, onset is delayed beyond age 2 years, nystagmus is absent, tremors are prominent, mental retardation is not severe, some patients show dementia or personality disorders, the disease is progressive rather than static in some, and several females show signs of disease. The nonsense mutation, which is in exon 3B, should block the synthesis of normal PLP but spare DM20, the isoform whose persistence has been associated with mild forms of PLP-associated disease in both humans and mice.

Adolescent↗
PubMed1997

Destabilization of human alpha-globin mRNA by translation anti-termination is controlled during erythroid differentiation and is paralleled by phased shortening of the poly(A) tail.

The extraordinary stability of globin mRNAs permits their accumulation to over 95% of total cellular mRNA during erythroid differentiation. The stability of human alpha-globin mRNA correlates with assembly of a sequence-specific ribonucleoprotein complex at its 3'-untranslated region. A naturally occurring anti-termination mutation, Constant Spring (CS), which permits ribosomes to enter the 3'-untranslated region of the alpha-globin mRNA, results in accelerated mRNA decay. To study the mechanism of this destabilization in vivo, we established transgenic mouse lines carrying the human alphaCS gene. Relative to wild-type human alpha-globin mRNA (alphawt), alphaCS mRNA is destabilized in marrow erythroid cells. The poly(A) tails of both the alphaCS and alphawt mRNAs show a periodicity of 20-25 nucleotides consistent with phased binding of poly(A) binding proteins. However, the mean size of poly(A) tails of the unstable alphaCS mRNA is significantly shorter than that of the alphawt mRNA. Unexpectedly, the alphawt and alphaCS mRNAs are of equal stability in peripheral reticulocytes, where their respective poly(A) tails shorten coordinately. These findings demonstrate a characteristic organization of the poly(A) tail on alpha-globin mRNA which is maintained during normal and accelerated decay, a correlation between poly(A) metabolism and anti-termination-mediated accelerated mRNA turnover, and a switch in the mechanism of mRNA decay during erythroid terminal differentiation.

Animals↗
PubMed1997

Exfoliation syndrome in a 17-year-old girl.

A 17-year-old girl with unilateral congenital glaucoma who had undergone trabeculectomy and peripheral iridectomy in infancy developed apparent exfoliation syndrome (XFS) in the eye that underwent the surgical procedures. A conjunctival biopsy was performed and the specimen was fixed in 2.5% glutaraldehyde, embedded in epoxy resin (Epon-Araldite, Electron Microscopy Sciences, Fort Washington, Pa), and processed for routine electron microscopy and immunostaining for elastin. Results of ultrastructural study showed scattered fibrillar aggregates compatible with those of XFS in an older adult, differing chiefly in sparsity of granular interfibrillar matrix. The XFS fibers were closely associated with elastic fibers and microfibrils. Elastosis of the actinic-aging type was somewhat greater than expected for age. To our knowledge, this is the youngest patient described with characteristic ocular findings of XFS to date, supporting others who have suggested an association between iris surgery in youth and early onset XFS. Electron microscopy was essential in ruling out the possibility of a clinically similar entity caused by ultrastructurally different material.

Adolescent↗
PubMed1997

Clinical review 91: Female sex hormones and cardiovascular disease in women.

Cardiovascular disease is the leading cause of mortality in women, a fact that is underappreciated by women and physicians. Clinical and experimental data underscore the cardioprotective effects of female sex hormones, particularly estrogen. Indeed, the loss of female sex hormones after menopause contributes to the striking increase in the incidence of cardiovascular morbidity and mortality after menopause. Estrogen replacement therapy improved lipoprotein profiles in the postmenopausal women, but this accounts for less than half of the cardioprotective effects of estrogen replacement therapy. Addition of progestins to estrogen therapy in women appears not to significantly attenuate the cardioprotective effects of estrogen replacement therapy despite experimental data suggesting otherwise. This review addresses potential mechanisms, other than influences on lipoproteins, by which estrogen and progesterone exert their cardiovascular protective effects. Particular emphasis is directed to genomic and nongenomic effects of estrogen and progesterone that are exerted directly on cardiovascular tissue.

Blood Vessels↗
PubMed1997

Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project.

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

Adolescent↗
PubMed1997

Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes.

OBJECTIVE: To assess the insulin antibody (IA) response to human insulin (HI) therapy in women with gestational diabetes. RESEARCH DESIGN AND METHODS: IAs were measured by a competitive radiobinding assay in 50 women with gestational diabetes before and during treatment with HI and after delivery. At delivery, 15 maternal-cord blood sample pairs were analyzed for IA. As a reference, we searched for IA in 25 new-onset type I diabetic patients, before and at 3, 6, and 12 months after insulin therapy. RESULTS: Insulin autoantibodies (IAAs) were detected in 1 of 50 women with gestational diabetes and 4 of 16 type I diabetic patients (P < 0.05). At the end of pregnancy after 9.3 +/- 6.8 weeks on insulin therapy, 22 of 50 (44%) women with gestational diabetes became IA+ and 4 additional women were found to be positive 2 months postpartum. After 3 months on insulin, type I diabetic patients showed a higher rate of IA positivity (92%, P < 0.001). IA titers at the end of pregnancy were associated with the cumulative insulin dose (r = 0.29, P < 0.05). Postpartum, IA disappeared slowly in most IA+ women, but two women still showed IA 2 years after delivery Titers in cord blood were strongly related to those in maternal blood (r = 0.74, P < 0.01). The rate of adverse fetal outcome did not differ in IA and IA- mothers (27 vs. 40%, NS). CONCLUSIONS: HI is immunogenic, and a short course of HI therapy induces IA in approximately 50% of women with gestational diabetes and 92% of type I diabetic patients. In women with gestational diabetes, insulin dose is slightly associated with IA titers. These IAs apparently cross the placenta. Fetal outcome does not differ according to the maternal IA status, and IAs disappear gradually after delivery but may remain positive for 2 years after delivery.

Adolescent↗
PubMed1997

Identification of developmentally regulated sea urchin U5 snRNA genes.

A PCR approach was used to isolate repeated U5 small nuclear RNA (snRNA) genes from the sea urchin Lytechinus variegatus. A 1.3 kb repeat, LvU5.0, and three other variants, LvU5.1-U5.3, that differ in the coding region and in the proximal sequence element (PSE) region were isolated. Southern Blot analysis indicate that the U5 snRNA genes, unlike other embryonically expressed snRNA genes (U1, U2 and U6), are not found in a simple tandem repeat, but instead, exist in several heterogeneous clusters each with a small number of genes. The U5 PSE has limited sequence similarity with the other sea urchin PSEs. However, when used in a mobility shift assay the U5 PSE forms a protein/DNA complex that is very similar to the complex formed with the U6 PSE. An RNase protection assay used to monitor the accumulation of U5 snRNA during development shows that at least two U5 variants are coordinately expressed during embryogenesis.

Animals↗
PubMed1997

[Primary stent treatment in the acute phase of myocardial infaction].

INTRODUCTION: Although direct balloon angioplasty has emerged as an alternative to thrombolytic therapy in patients with acute myocardial infarction, reocclusion and restenosis rates are limiting factors. We postulated that these limitations could be partly overcome by primary stenting of the responsible lesion. MATERIAL AND METHODS: Since January/94 we have studied 59 patients with acute myocardial infarction who were treated in the early phase (3.1 +/- 2 hours since the onset of symptoms) by elective Palmaz-Schatz stent implantation. No adjunctive thrombolytic therapy was associated. Two patients were in cardiogenic shock and were treated under percutaneous cardiopulmonary support. At cardiac catheterization a left ventriculography and coronary angiograms were obtained. Then, mechanical recanalization of the responsible lesion was performed. If the angiographic anatomy was considered suitable, a stent was implanted at the lesion. RESULTS: The infarct related artery was the left anterior descending in 29 patients, the circumflex in 14 and the right coronary artery in 16. At baseline conditions, 40 patients had a totally occluded artery and 19 showed a TIMI-grande 1 antegrade flow. One patient had an early clinical recurrence 4 days later, which required an additional divided Palmaz-Schatz stent at the distal portion of the lesion, in order to seal a residual dissection. All remaining patients had a favourable clinical course without major complications. Immediately after treatment the minimal lumen diameter was 3.2 +/- 0.4 mm and no residual stenosis was detectable at the treated segment. Six-month angiographic reevaluation was performed in all 29 (49%) eligible patients. Restenosis (> 50% stenosis) was detected in 6 out of the 29 evaluated patients (21%). CONCLUSIONS: Primary stent implantation in selected patients with an evolving myocardial infarction provides good initial and 6-month results.

Acute Disease↗
PubMed1996

Antimyeloperoxidase antibodies in individuals with occupational exposure to silica.

OBJECTIVE: To determine the prevalence of autoantibodies to myeloperoxidase (MPO) in a series of patients exposed to silica. METHODS: The study included 52 patients with occupational exposure to silica (mean exposure time seven years) and a control group comprising seven patients with progressive systemic sclerosis (PSS), six patients with systemic lupus erythematosus (SLE), and 15 healthy individuals. Antibodies to MPO were detected using commercial enzyme linked immunosorbent assay (ELISA) plates coated with MPO. Indirect immunoflurescence studies for antineutrophil cytoplasmic antibodies were performed using ethanol and formol fixed neutrophils. Clinical and biological data of individuals exposed to silica were recorded (published previously). RESULTS: Antibodies to MPO were detected in 14 individuals exposed to silica (27%). There was a statistically significant difference in anti-MPO ELISA units between the healthy subjects and patients (SLE, PSS, silica exposed individuals) (p < 0.01), but no difference between the different disease groups. CONCLUSIONS: Individuals chronically exposed to silica, whether or not they have a connective tissue disease, have levels of antibodies to MPO (as detected by ELISA) that are greater than those found in the normal population, but similar to those in patients with systemic diseases not induced by silica (SLE/PSS).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

[Directional coronary atherectomy in ostial lesions of the anterior descending coronary artery].

INTRODUCTION AND OBJECTIVES: Coronary stenoses at ostial level, when treated by balloon angioplasty, show a primary success rate much lower than those located in other parts of the coronary tree. Balloon dilation of lesions located at the left anterior descending ostium is associated with a high degree of restenosis, elastic recoil and the possibility of retrograde dissection to the left main coronary artery. Simpson atherectomy may be considered a percutaneous alternative in this particular location, since this technique produces fewer incidents of elastic recoil than balloon dilation. The purpose of the present study is to evaluate directional atherectomy in the treatment of patients with symptoms deriving from severe to stenosis at the origin of the left anterior descending artery. MATERIAL AND METHODS: From a total number of 302 patients treated by Simpson atherectomy, we have analyzed 45 with severe stenosis at the left anterior descending ostium (less than 3 mm from its origin). The mean age was 54 +/- 12 years. Eighty two percent of the patients were male. The clinical condition was stable in unstable in 34; eleven had had a previous myocardial infarction. Six had multivessel coronary disease, all of them underwent combined balloon angioplasty of other segments. The treated lesion was native in 41 patients and previously dilated by balloon (restenosis) in 4. Two patients needed balloon predilation with 2 and 2.5 mm to facilitate the pass of the atherocatheter. The size of the Simpson atherocatheter was mainly 7F (78%). The weight of the resected arteriosclerotic material was 11 +/- 7 mg. RESULTS: Primary success (residual stenosis < 40% without major complications) was obtained in 42 out of 45 patients (93%); 3 patients (7%) had major complications (1 death, 1 emergency surgery, and 1 non-Q wave myocardial infarction). A follow-up angiography study was available in 31 patients 7 +/- 8 months later. Restenosis was evidenced in 12 (39%). CONCLUSIONS: Simpson atherectomy for left anterior descending artery ostial lesions is an effective transluminal alternative in selected patients providing a high rate of primary success (93%) and an acceptable restenosis rate (39%).

Adult↗
PubMed1996

[Experience of a single center in liver transplantation in adults and children].

Orthotopic liver transplantation (THO) is the treatment of choice for a variety of liver diseases. The national experience before 1993 has been scarce. In November 1993 we started our experience in THO at Clínica Las Condes, as part of a multiorgan transplant program (liver, kidney, pancreas). Until January 1995 we have performed 14 THO in 13 recipients (one retransplantation), of which 5 were in pediatric cases. The recipients range of age fluctuated between 1 and 61 years. In two pediatric cases a liver allograft reduction was performed. Six recipients (46%) required treatment for acute cellular rejection. One recipient had an hepatic artery thrombosis and had to be retransplanted. There was no operative mortality up to 30 days in cases of primary liver transplants. The retransplanted adult recipient, and another pediatric recipient that died from a late recurrence of a hepatoblastoma, accounted for the mortality of this experience. After an average follow up of 10 months, the actual patient survival in 85%. Of the 11 surviving recipients, 9 are in excellent conditions with a very good quality of life. This experience shows that an active liver transplant program in our country can be successful in obtaining results comparable to those published by very experienced foreign transplant centers.

Adolescent↗