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Biomedical subjects

A Rodriguez

Publications and source records attributed to A Rodriguez.

At least 163 records · Page 9Linked to original sources

Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis.

PURPOSE: To describe the authors' approach to the management of patients with recalcitrant, chronic, endogenous uveitis using low-dose Cyclosporin A (CSA) alone or in combination with other immunosuppressive agents with attention to the anti-inflammatory efficacy, visual outcome, and side effects of therapy. METHODS: The authors reviewed the records of 50 patients (92 eyes) with uveitis of various etiologies who had been treated with low-dose CSA (2.5-5.0 mg/kg daily) alone or in combination with prednisone and/or azathioprine (1.5-2.0 mg/kg daily). The median follow-up on low-dose CSA was 16 months (range, 6-64 months). RESULTS: Inflammatory control was achieved in 68 (73.9%) eyes, while persistent inflammatory activity was observed in 14 (15.2%). Thirty-eight (41%) eyes improved two Snellen lines or more, 43 (47.0%) stabilized, and 11 (12.0%) lost two lines or more. The CSA was discontinued because of nephrotoxicity in three patients and in each of two with systemic hypertension and constitutional intolerance to the drug, respectively. Thirteen patients enjoy inflammatory remission with this regimen. CONCLUSION: Low-dose CSA used alone or in combination with other immunosuppressive agents is effective in achieving inflammatory control with a favorable visual outcome and provides a useful steroid-sparing strategy in the management of chronic endogenous uveitis. The CSA-associated toxicity may be reduced by initiating therapy at very low initial doses, with incremental dosage escalation to the desired target range.

Adult↗

Trisomy 12 and p53 deletion in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: association with morphology and resistance to conventional chemotherapy.

The incidence of trisomy 12 and p53 deletion was studied in a group of chronic B-lymphocytic leukemia (B-CLL) patients, using fluorescence in situ hybridization (FISH). Trisomy 12 was detected in eight of 50 patients (16%) and p53 deletion in six of 38 cases analyzed (15.8%). A statistically significant difference was observed between the incidence of trisomy 12 in patients with typical and atypical morphology (3.03% versus 41.18%). No correlation was found between this alteration and the rest of the clinical and biological parameters studied (adenopathies, hepatomegaly, splenomegaly, lymphocyte count, staging, CD11c expression, and resistance to chemotherapy). The p53 deletion was correlated with the presence of hepatomegaly and splenomegaly, advanced stage of disease, and resistance to conventional chemotherapy. The application of FISH to whole blood cell nuclei, without prior manipulation or culture, showed a higher percentage of cells with trisomy 12 than when the method was used following culture. We conclude that 1) FISH is a simple and sensitive technique for the detection of numerical and structural chromosome abnormalities; 2) Its application to uncultured samples obviates the alteration of results originated by the probable growth advantage of the normal or neoplastic cell population in vitro; 3) Trisomy 12 appears to define a B-CLL subgroup of atypical morphology; and 4) The p53 deletion is correlated with advanced stage of disease and resistance to treatment.

Aged↗

Parkinsonism in an HIV-infected patient with hypodense cerebral lesion.

A 49-year-old man presented with fever and parkinsonism. Examination of cerebrospinal fluid confirmed tuberculous meningitis. Cerebral computerized tomography scan revealed hypodense lesions and human immunodeficiency virus tests were positive. The patient's clinical picture and parkinsonism were improved with tuberculosis treatment.

AIDS-Related Opportunistic Infections↗

Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: effect of thyroid hormone therapy.

Cardiac atrial and ventricular parameters were determined by Doppler two-dimensional echocardiography at rest and exercise in 8 patients with subclinical hypothyroidism (SCH) (6 women and 2 men; age range: 28-48 years) before and 3 months after achievement of a euthyroid state with incremental adjustment of L-thyroxine therapy. None of the patients had known heart disease. At 3 months of L-thyroxine therapy, TSH levels decreased from 14.8 +/- 9.4 mIU/L to 3.0 +/- 1.5 mIU/L and FTI increased from 7.1 +/- 1.8 to 8.1 +/- 1.9. The cardiac studies were performed at rest, and during incremental exercise load (50, 100, 150 W workload) on a Quinton exercise bicycle. No significant differences were found between the subclinical hypothyroid and euthyroid states in systolic blood pressure at rest (104.8 +/- 12.3 vs 105 +/- 10.1 mm Hg) and exercise (158 +/- 24.9 vs 158.5 +/- 20.9 mm Hg) or diastolic blood pressure at rest (70 +/- 4.7 vs 69 +/- 5.7 mm Hg) and exercise (86 +/- 11.4 vs 89.2 +/- 7.3 mm Hg). All echocardiographic atrial and ventricular parameters were similar before and during L-thyroxine therapy with the exception of a small but significant change in left ventricular diastolic dimension (4.5 +/- 0.3 vs 4.8 +/- 0.4 cm; p < 0.05). All Doppler parameters were not significantly affected by L-thyroxine therapy with the exception of preejection period at stage III exercise (51 +/- 17 vs 39 +/- 13 msec; p < 0.05). Preejection period at other stages of exercise showed trends toward similar differences between subclinical hypothyroidism and euthyroidism, but the differences were not statistically significant. We conclude that the cardiac structure and function overall remains for practical purposes normal in subclinical hypothyroidism. However, the latter may be responsible for a mild prolongation of the preejection period during exercise and a slightly smaller left ventricular diastolic dimension at rest, changes that may not be of clinical significance in patients without underlying heart disease.

Adult↗

Identification of immune system and response genes, and novel mutations causing melanotic tumor formation in Drosophila melanogaster.

We are using Drosophila as a model system for analysis of immunity and tumor formation and have conducted two types of screens using enhancer detector strains to find genes related to these processes; genes expressed in the immune system (type A; hemocytes, lymph glands and fat body) and genes increased in expression by bacterial infection (type B). For type A, tissue-specific reporter gene activity was determined. For type B, a variation of enhancer detection was devised in which beta-galactosidase is assayed spectrophotometrically with and without bacterial infection. Because of immune system involvement in melanotic tumor formation, a third type was hypothesized to be found among types A and B; genes that, when mutated, have a melanotic tumor phenotype. Enhancer detector strains (2800) were screened for type A, 900 for B, and 11 retained for further analysis. Complementation tests, cytological mapping, P-element mobilization, and determination of lethal phase and mutant phenotype have identified six novel genes, Dorothy, wizard, toto, viking, Thor and dappled, and one previously identified gene, Collagen IV. All are associated with reporter gene expression in at least one immune system tissue. Thor has increased expression upon infection. Mutations of wizard and dappled have a melanotic tumor phenotype.

Animals↗

Histopathological changes in the reproductive organs of Manchego ewes grazing on lucerne.

The effects of prolonged exposure to phyto-oestrogens (coumestrol) on the morphology of the reproductive organs of ewes were studied in 28 lucerne-grazing animals, and compared with 28 control ewes given a standard coumestrol-free diet. The anatomical studies showed that 43% of the ewes fed lucerne displayed macroscopic changes within the genital tract, of which the uterine alterations were especially prominent. The microscopic examination of the test group ewes identified specific histopathological features of the uterus and cervix. A greater than normal development of the cervical folds was observed, as well as cystic formations of different sizes whose content was eosinophilic. In the rest of the uterus, more glandular activity was detected in the lucerne-grazing group than in the control ewes, although cystic formations were not seen.

Animals↗

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↗

Herpes zoster peripheral ulcerative keratitis in patients with the acquired immunodeficiency syndrome.

The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes zoster infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy. Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications.

Acquired Immunodeficiency Syndrome↗

Vitamin A status of children in five Ecuadorian provinces.

In mid-1993 Ecuador's Health Research Institute conducted a survey to evaluate the general nutrition and vitamin A status of children in five provinces (three in the mountains and two on the coast) containing pockets of extreme poverty. The survey enrolled 1555 children 12-59 months old who constituted a multi-phased stratified cluster sample obtained by random selection methods. Among its other aims, the survey sought to assess all or part of the study subjects' serum retinol levels, dietary vitamin A intake and ocular signs of vitamin A deficiency, and to weigh the influence on vitamin A status of age, sex, parental (maternal) education, residence in a rural or urban area, and the ethnic background of the residence area. Questionnaire interviews were conducted to gather information about each survey child's identify, diet, pathologic history, and breast-feeding history; a blood sample was obtained; and the child was weighed, measured, and given a complete physical examination (including an eye examination). Of the 1232 survey children whose serum retinol levels were measured, 18% and 2% were found to have levels below 0.7 and 0.35 mumol/L, respectively. Low serum retinol levels were more common among children of mothers who had relatively little education and resided in rural areas. The presence of Bitot's spots was confirmed in two of the study children. Interviews conducted with 39% of the study children's families to assess the children's diets showed the risk of insufficient vitamin A intake to be greater in the mountain provinces and among Indian populations, children born to mothers with no formal education, children living in rural areas, and underweight and stunted children. Forty-eight percent of the study population had serum retinol levels between 0.70 and 1.05 mumol/L, indicating marginal vitamin A deficiency. It would therefore appear that dietary supplementation would cause a substantial part of the Ecuadorian population to improve its vitamin A status. Overall, the results of the survey were consistent with a previous national survey and confirmed the existence of a pronounced subclinical vitamin A deficiency that clearly constitutes a public health problem, especially in Ecuador's rural Andean areas.

Child, Preschool↗

[Radiological study of the migration of prosthetic implants following hip arthroplasty].

Migration of the acetabular and femoral implants after THR is a better index of the stability of the bone-implant interfaces than are clinical or radiological results. Roentgenstereophotogrammetry (RSA) studies 3-D migration of the implants with high accuracy (0.15 to 0.28 mm for linear migrations). RSA presents several drawbacks which restrict its use to prospective studies on small numbers of patients. Simpler methods have therefore been developed to assess 2-D migration on standard films in retrospective studies. The precision of these "simple" methods is limited, due to several factors: the difficulty to define reliable landmarks on femur or pelvis, sometimes even on implants, measurement errors, related to variations in radiographic technique (focal distance, beam centering, patient positioning). Sutherland, Wetherell and Nunn have proposed methods with an accuracy around 2-3 mm. It appears impossible to correct migration measurements for distorsions due to patient positioning; the EBRA method was therefore developed to reject non-comparable films using a comparability algorithm. A precision of 0.20 to 0.32 mm can thus be reached for the study of cup migration. The same pitfalls are encountered in assessment of migration of the femoral implant; a preliminary theoretical study is mandatory for every implant studied. The data presently available show that migration at 2 years is predictive of the long-term evolution of an implant; for the cup, migration of 1 mm or more at 2 years is predictive of late failure, and similar conclusions can be drawn regarding the femoral implant. The 2-D assessment of implant migration using a correct "simple" method provides a mean to evaluate a new implant or an innovative technical modification in a reasonable amount of time, on a limited number of patients.

Acetabulum↗

Meta-analysis of randomised trials comparing coronary angioplasty with bypass surgery.

A patient with severe angina will often be eligible for either angioplasty (PTCA) or bypass surgery (CABG). Results from eight published randomised trials have been combined in a collaborative meta-analysis of 3371 patients (1661 CABG, 1710 PTCA) with a mean follow-up of 2.7 years. The total deaths in the CABG and PTCA groups were 73 and 79, respectively, with a relative risk (RR) of 1.08 (95% CI 0.79-1.50). The combined endpoint of cardiac death and non-fatal myocardial infarction occurred in 169 PTCA patients and 154 CABG patients (RR 1.10 [0.89-1.37]). Amongst patients randomised to PTCA 17.8% required additional CABG within a year, while in subsequent years the need for additional CABG was around 2% per annum. The rate of additional non-randomised interventions (PTCA and/or CABG) in the first year of follow-up was 33.7% and 3.3% in patients randomised to PTCA and CABG, respectively. The prevalence of angina after one year was considerably higher in the PTCA group (RR 1.56 [1.30-1.88]) but at 3 years this difference had attenuated (RR 1.22 [0.99-1.54]). Overall there was substantial similarity in outcome across the trials. Separate analyses for the 732 single-vessel and 2639 multivessel disease patients were largely compatible, though the rates of mortality, additional intervention, and prevalent angina were slightly lower in single vessel disease. The combined evidence comparing PTCA with CABG shows no difference in prognosis between these two initial revascularisation strategies. However, the treatments differ markedly in the subsequent requirement for additional revascularisation procedures and in the relief of angina. These results will influence the choice of revascularisation procedure in future patients with angina.

Angina Pectoris↗

Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide.

Not all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens, we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells, and is a leading cause of human blindness. Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes, possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.

Animals↗

Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir.

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.

Acquired Immunodeficiency Syndrome↗

Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation. A prospective randomized study.

The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autologous bone marrow transplantation (ABMT) has recently been established. Considerable knowledge about adequate doses and route of administration has been accumulated in the past few years. Nonetheless, the optimal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) prophylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 micrograms/kg/day) and route of administration were employed in both groups. We found no significant differences in the time to reach an absolute neutrophil count (ANC) of 0.1, 0.5, and 1 x 10(9)/l and 50 x 10(9) platelets/l (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1 x 10(9)/l ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of G-CSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p < 0.0001). This is equivalent to a saving of 1120 $US per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Antithrombotic effects of peroxynitrite: inhibition and reversal of aggregation in human platelets.

The inhibition of platelet aggregation by peroxynitrite, a reactive oxygen species derived from the interaction of nitric oxide (NO) and superoxide, was examined in platelet-rich plasma. In this report, we have used a preparation of peroxynitrite that was free of H2O2 and MnO2. As such, peroxynitrite dose-dependently (50-200 microM) inhibited aggregation of human platelets stimulated by ADP (5 microM), collagen (0.5 microgram), thrombin (0.5U/microL) and U46619 (1 microM). In addition, peroxynitrite reversed platelet aggregation induced by collagen, ADP, and thrombin. Peroxynitrite, preincubated with platelet-poor plasma or albumin (7%) for 30 min, did not alter the inhibition of platelet aggregation. This suggested that the inhibitory action of peroxynitrite may be due to nitrosylation of proteins, which by themselves possess activity, rather than conversion to NO or NO donors. Furthermore, we show that peroxynitrite increased the cGMP level only at 200 microM concentrations, further suggesting that the action of peroxynitrite was not completely due to its conversion to NO or NO donors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

The value of combined serum angiotensin-converting enzyme and gallium scan in diagnosing ocular sarcoidosis.

PURPOSE: To evaluate the role of combined serum angiotensin-converting enzyme (ACE) activity and whole-body gallium (67GA) scanning in diagnosing sarcoidosis in patients with features consistent with ocular sarcoidosis but with normal or equivocal chest radiographs. METHODS: Serum ACE levels and whole-body 67GA scans were obtained as part of the initial workup in 22 patients with active ocular inflammation and ultimately biopsy-proven sarcoidosis (sarcoid uveitis group). A second group consisting of 70 patients with active uveitis in whom sarcoidosis also was considered a diagnostic possibility also was studied. All 70 patients ultimately had a definitive diagnosis other than sarcoidosis (nonsarcoid uveitis). All patients in this group also had a serum ACE and whole-body 67GA scan performed as part of their initial investigations. RESULTS: All patients in the sarcoid uveitis group had either an elevated ACE level or an abnormal scan. In 16 of the 22 patients, results of both tests were abnormal. In no patient in the nonsarcoid uveitis group were results of both tests abnormal. The sensitivity of an elevated ACE in diagnosing sarcoidosis was 73% and the specificity was 83%. Using the combination of a positive 67GA scan and an elevated ACE, the specificity for diagnosis was 100% and the sensitivity was 73%. CONCLUSIONS: The combination of serum ACE level and whole-body 67GA scan increases the diagnostic specificity without affecting sensitivity in patients with clinically suspicious ocular sarcoidosis who have normal or equivocal chest radiographs.

Adolescent↗