Biomedical subjects

A Tobar

Publications and source records attributed to A Tobar.

8 recordsLinked to original sources

PubMed2002

Replicative senescence in organ transplantation-mechanisms and significance.

In the past two decades, transplantation has become a preferred modality of treatment of end-stage failure of vital organs. Currently, with the significant improvement in short-term graft survival rates, the main effort is concentrated on prolonging the functional life span of transplanted organs. One of the theories which were put forward to explain the progressive deterioration of transplant function was that of replicative senescence. Senescence of an organ or tissue results from age and/or environmental stress-dependant modification of cellular function. With time, the accumulation of cellular alterations may lead to deleterious effects in various organs and tissues and adversely affect transplants. In this article we are reviewing the candidate mechanisms of senescence such as telomere shortening, genetic regulation and environmental-'toxic' factors and are examining the implications of the theory of replicative senescence for organ allograft. We are also presenting our experiments with renal ischemia/reperfusion in rat serving as a model of kidney transplantation, where baseline kidney telomere length and novel marker of cellular senescence--senescence associated beta-Galactosidase (SA-Gal) expression in tissue served as markers. For the first time in vivo, we were able to show that with aging of the animals the amount of senescent cells in kidney tissue was increasing, while the average renal tissue telomere length was decreasing. The degree of tissue senescence, as determined by amount of SA-Gal positively stained cells, was inversely correlated with the recovery of the kidney function after ischemia/reperfusion injury. These results confirm the theory of replicative senescence in organ ischemia for the first time in vivo, and quantitatively validate the direct correlation between the amount of senescent cells in the organ and its susceptibility to ischemic injury. We conclude that recent advances in study of the cellular basis of senescence, in vitro and especially in vivo, may hold clues to the understanding of events which could be implicated in the damage or protection of organ allografts.

Animals↗

PubMed2001

Phenotypic expression of tissue mosaicism in a 45,X/46,X,dicY(q11.2) female.

We describe a girl who presented at the age of 11 years with short stature. She had female external genitalia and some clinical features of Turner syndrome. At laparotomy a uterus and Fallopian tubes and small gonad-like tissue masses in the region of the Fallopian fimbria were found. The tissue masses were removed and histological examination revealed no organized testicular or ovarian morphology. Remnants of Fallopian tubes, epididymis, and clusters of Leydig cells were seen but no Sertoli cells were found. Endocrine studies showed levels of sex hormones consistent with primary gonadal failure. G-banding analysis of 16 blood lymphocytes revealed the karyotype 46,X,dicY(q11.2) in all cells. Varying proportions of X and Y centromeres in blood lymphocytes, skin fibroblasts, and in the incompletely formed Wolffian and Müllerian duct derivatives were demonstrated by FISH. Molecular studies confirmed the absence of most of the long arm of the Y chromosome and an intact short arm. The SRY gene was shown to be present, but we presume that due to the mosaicism the dose was insufficient to allow normal testicular development.

Child↗

PubMed2001

Caseous calcification of the mitral annulus: a neglected, unrecognized diagnosis.

BACKGROUND: Mitral annular calcification is a common echocardiographic finding. Caseous calcification is a rare variant seen as a large mass with echolucencies that resembles a tumor, occasionally resulting in exploratory cardiotomy. The aim of this study was to assess the prevalence of caseous calcification of the mitral annulus, to evaluate patient characteristics and the echocardiographic variables for diagnosing this entity, and to describe the clinical outcome on follow-up of such patients. METHODS: Caseous calcification was defined as a large, round, echo-dense mass with smooth borders situated in the periannular region, with no acoustic shadowing artifacts and containing central areas of echolucencies resembling liquefaction. Eighteen patients were diagnosed by 2-dimensional echocardiography as having caseous calcification of the mitral annulus. One had calcification of the tricuspid annulus. Nine patients underwent transesophageal echocardiographic studies. RESULTS: A typical finding of a round, sometimes semilunar, large, echo-dense, soft mass with central echolucencies seen on both transthoracic and in particular transesophageal echocardiography, resembling a periannular mass, was demonstrated. The mass was posteriorly located in all mitral patients. Transesophageal echocardiography added limited information. Three patients underwent mitral valve replacement. The operative findings were a solid mass adherent to the posterior portion of the mitral valve. Sectioning revealed a toothpaste-like, white, caseous material. Sixteen (84%) patients were treated conservatively. On follow-up of 3.8 +/- 2.4 years, 4 patients died of unrelated causes. CONCLUSION: The characteristic appearance of a large, soft, echo-dense mass containing central areas of echolucencies resembling liquefaction at the posterior periannular region of the mitral valve on 2D echocardiography is compatible with the diagnosis of caseous abscess. Such a finding should not be confused with a tumor. Transesophageal echocardiography does not appear to contribute to the diagnosis. This rather impressive lesion appears to carry a benign prognosis.

Aged↗

PubMed2001

The digital pulp as a presenting site of metastatic esophageal carcinoma.

An unusual skin lesion may be a primary skin cancer or a sign of internal malignancy. Metastatic lesions to the hand are rare. The authors describe a patient who presented with a nodule of the digital pulp. Workup, including X-ray films and biopsy, revealed a metastatic squamous cell carcinoma invading the distal phalanx. The primary site of the tumor was the esophagus. To the best of their knowledge, this is the second case described in the literature of a metastatic carcinoma of the esophagus presenting as a lesion of the digital pulp.

Aged↗

PubMed2001

Autosomal dominant nephritis with renal failure of non-Alport type: clinical and molecular studies.

BACKGROUND: Familial nephritis is a heterogeneous group of disorders caused by several genetic conditions such as Alport syndrome, glomerulonephritic syndromes, and unclassified nephritis without deafness or ocular defects. OBJECTIVES: To describe a family of Iraqi Jewish origin, several of whose members suffer from non-syndromic renal failure without deafness or ocular defects and where transmission is by autosomal dominant inheritance. We present the case histories of four family members and describe the molecular analysis performed in order to seek a possible linkage to one of the genes causing Alport or Alport-like syndromes. METHODS: We investigated all family members over the age of 18 for evidence of renal failure. We also extracted DNA and carried out molecular linkage analysis with polymorphic markers in each of the known loci involved in Alport and Alport-like syndromes. RESULTS: Histology of the renal biopsy specimens showed non-specific findings. Linkage was excluded for all the Alport and Alport-like syndrome loci. CONCLUSIONS: The condition suffered by several members of this family seems to represent a unique autosomal dominant type of progressive hereditary nephritis, characterized by hypertension and progressive renal failure without significant hematuria or proteinuria. The main histological changes are non-specific in the early stage of the disease. Our study rules out all the currently known genes that cause Alport syndrome as being responsible for the basic defect in this type of nephritis.

Adolescent↗

PubMed2000

Maxillomandibular brown tumor--a rare complication of chronic renal failure.

We report a 17-year-old hemodialysis patient with a rapidly growing maxillary mass diagnosed as a brown tumor. Although successful control of the parathyroid hormone (PTH) levels was achieved by treatment with vitamin D pulse therapy, the lesion progressed, invaded the maxillary sinus, and caused severe eating and speech disabilities. No recurrence was observed following surgical excision. The differential diagnosis and considerations regarding the causes of the disease in a child, therapy options, and review of the literature are presented.

Adolescent↗

PubMed2000

Clinical relevance of molecular diagnosis in childhood rhabdomyosarcoma.

Rhabdomyosarcoma may be divided into three subtypes--embryonal, alveolar, and undifferentiated sarcoma--which can be distinguished by molecular analysis. The authors applied reverse transcriptase-polymerase chain reaction analysis (RT-PCR) to analyze tumor samples from 14 children with rhabdomyosarcoma for the presence of the chimeric PAX3-FKHR transcript resulting from the translocation t(2;13)(q35,q14). Both fresh and paraffin-embedded tissues were used. In only nine specimens was the RNA intact for the analysis. The chimeric transcript was identified in seven samples: four alveolar type, one embryonal type, and two undifferentiated sarcoma. Histologic review was performed in the three samples with discordance between the molecular and histologic findings. A sample from a patient with a diagnosis of embryonal rhabdomyosarcoma on presentation and expression of PAX3-FKHR fusion transcript yielded a small focus of alveolar rhabdomyosarcoma and was reclassified as alveolar rhabdomyosarcoma. One of the samples from a patient with undifferentiated sarcoma was redefined as alveolar subtype; the diagnosis of the second undifferentiated sarcoma remained unchanged, in accordance with the histologic diagnosis. These findings further support the recommendation that molecular analysis be included in the diagnostic workup of childhood small round cell tumors to reach a more accurate diagnosis for tailoring of specific treatment.

Adolescent↗

PubMed1993

A rule-based postoperative pain controller: simulation results.

We describe a system for controlling postoperative pain, a phenomenon that is difficult to treat by conventional control methods due to interpatient variability, interferences, non-linearity and the lack of a plausible, well-defined mathematical model. The system consists of two phases. In Phase 1 a closed-loop fuzzy controller implementing a suitable control strategy brings the patient to a zero-pain state. In Phase 2, an open-loop computer-assisted continuous infusion controller maintains a constant concentration of the analgesic (alfentanil) in plasma, subject to an upper safety limit on infusion rate; the set-point of this controller is periodically revised (either maintained or reduced) on the basis of feedback on the duration of zero pain (set-point reduction is necessary because the open-loop system has no means of knowing whether analgesic is accumulating in the patient). Pain is quantified by the patient on a numerical scale of 1 to 10 at 1.5-min intervals during Phase 1 and 9-min intervals during Phase 2. In simulation trials in which a fixed approximate model was used for the effect of sedation on pain while the pharmacokinetics of alfentanil were varied from one simulated patient to another, zero pain was achieved in under 15 min with minimal overshoot in plasma drug concentration and was maintained, with only minor deviation, by means of low drug concentrations.

Alfentanil↗