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Biomedical subjects

J Meza

Publications and source records attributed to J Meza.

9 recordsLinked to original sources
PubMed2001

Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma--a report from the IRSG.

PURPOSE: To evaluate the outcome and toxicity of hyperfractionated radiotherapy (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group III rhabdomyosarcoma (RMS). METHODS AND MATERIALS: Five hundred fifty-nine children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group III RMS. Sixty-nine were ineligible for the analysis because of incorrect group or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4 Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy daily fractions). The age range was <1-21 years. All patients received chemotherapy. RT began at Week 9 after induction chemotherapy for all but those with high-risk parameningeal tumors who received RT during induction chemotherapy. The patient groups were equally balanced. The median follow-up was 3.9 years. RESULTS: Analysis by randomized treatment assignment (intent to treat) revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall survival (OS) of 75%. In the univariate analysis, the factors associated with the best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5 cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or head and neck; and embryonal histologic features (p = 0.001 for all factors). No differences in the FFS or OS between the two RT treatment methods and no differences in the FFS or OS between HFRT and CFRT were found when analyzed by age, gender, tumor size, tumor invasiveness, nodal status, histologic features, stage, or primary site. Treatment compliance differed by age. Of the children <5 years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT. Of the children >or=5 years, 88% assigned to both HFRT and CFRT received their assigned treatment. The reasons for not receiving the appropriate randomized treatment were progressive disease, early death, parent or physician refusal, young age, or surgery. The toxicity assessment revealed more mucositis with HFRT (66%) than with CFRT (46%) (p = 0.03) for the parameningeal patients, and more skin reactions (16%) and nausea/vomiting (13%) with HFRT than with CFRT (7% and 5%, respectively) for patients with nonparameningeal primary tumors (p = 0.03 and p = 0.02, respectively). The analysis by treatment actually received revealed a 5-year FFS rate of 73% and OS rate of 77%, with no difference between CFRT and HFRT. As well, there was no difference in FFS or OS between CFRT and HFRT when analyzed by age, gender, tumor size, tumor invasiveness, modal status, histology, stage or site of primary. The 5-year estimated cumulative incidence of failure for the irradiated patients was local, 13%; regional, 3%; and distant, 13%; with no differences between HFRT and CFRT. The 5-year local failure rate by site was orbit, 5%; head and neck, 12%; parameningeal, 16%; bladder/prostate, 19%; extremity, 7%; and all others, 14%. The 5-year regional failure rate was parameningeal,1%; extremity, 20%; and all others, 5%. The 5-year distant failure rate was orbit, 2%; head and neck, 6%; parameningeal, 11%; bladder/prostate, 15%; extremity, 28%; and all others, 17%. CONCLUSIONS: HFRT, as given in this study, did not improve local/regional control, FFS, or OS compared with CFRT. The risk of local/regional failure was comparable to that of distant failure in children with Group III RMS. The standard of care for Group III RMS continues to be CFRT with chemotherapy.

Adolescent↗
PubMed2001

Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study.

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m(2) of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m(2), dactinomycin 1.5 mg/m(2), and cyclophosphamide 2.2 g/m(2) (VAC) and vincristine 1.5 mg/m(2), topotecan 0.75 mg/m(2) daily x 5, and cyclophosphamide 250 mg/m(2) daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone. RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P: = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival. CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

Adolescent↗
PubMed1998

The cancer-predisposing mutation C61G disrupts homodimer formation in the NH2-terminal BRCA1 RING finger domain.

The breast and ovarian cancer tumor suppressor gene, BRCA1, encodes for a Zn2+-binding RING finger motif located near the protein NH2 terminus. The RING finger motif is characterized by eight conserved Cys and His residues which form two Zn2+-binding sites termed Site I and Site II. We used limited proteolysis in conjunction with matrix-assisted laser desorption ionization time-of-flight mass spectroscopy to investigate the metal binding properties and to probe the solution structures of wild-type and mutant BRCA1 constructs that include the RING finger. Our results show that the RING finger motif is part of a larger proteolysis-resistant structural domain which encompasses the first 110 residues of BRCA1. Analytical gel-filtration chromatography and chemical cross-linking experiments demonstrate that the BRCA1 NH2-terminal domain readily homodimerizes in solution. The cancer-predisposing C61G mutation, which alters a conserved Zn2+-binding residue, abolishes metal binding to Site II of the RING finger motif, while Site I remains intact and functional. The C61G mutation also results in increased proteolytic susceptibility of the COOH-terminal portion of the NH2-terminal domain and perturbs the oligomerization properties of BRCA1.

BRCA1 Protein↗
PubMed1994

Photorefractive keratectomy after radial keratotomy.

We report the results of a prospective study that evaluated the efficacy, predictability, and safety of excimer laser photorefractive keratectomy (PRK) to correct residual myopia after radial keratotomy (RK). Using a 193 nm excimer laser, we performed PRK on ten undercorrected myopic eyes that had previous RK surgery. The mean interval between the RK and PRK was 1.5 years. Mean follow-up was seven months. Mean preoperative refraction was -4.08 +/- 1.35 diopters (D) and after PRK was +1.61 +/- 1.18 D at three months, +1.05 +/- 0.75 D at six months, and +0.79 +/- 0.83 D at 12 months. An uncorrected visual acuity of 20/40 or better was achieved in eight eyes at three months, seven eyes at six months, and three eyes at 12 months. One eye had a transient loss of two Snellen lines of best spectacle corrected visual acuity because of increased haze. No other significant complication was noted. Our study shows that PRK is a predictable, effective, stable, and safe technique to correct residual myopia after RK. The results were similar to those of PRK without prior surgery, although we noted a slightly greater hyperopic deviation. We believe that eyes undercorrected by RK may benefit from subsequent PRK.

Adult↗
PubMed1993

Ischemic optic neuropathy after intraocular lens implantation to correct high myopia in a phakic patient.

A 33-year-old patient had uncomplicated anterior chamber intraocular lens implantation (Worst-Fechner biconcave myopia lens) to correct high myopia. Immediately after surgery, she developed anterior ischemic optic neuropathy likely associated with increased intraocular pressure and systemic hypotension. To our knowledge, this is the first documented case of anterior ischemic optic neuropathy after anterior chamber intraocular lens implantation to correct high myopia in a phakic eye.

Adult↗
PubMedDate not supplied

[Double outlet right ventricle with discordant atrioventricular connection. Clinical study].

The clinical and anatomic findings were reviewed in 17 patients with double-outlet right ventricle and atrioventricular discordance. Ten cases had atrial situs solitus, seven with right-sided heart three with left-sided heart. Seven cases had atrial situs inversus, five with left-sided heart and two with right-sided heart. All cases presented ventricular septal defect, 13 subvalvar pulmonary stenosis, two tricuspid regurgitation and two complete atrioventricular block. The spatial relationship between the arterial valves are variable. Most cases in atrial situs solitus had a left-sided and anterior aorta and all patients in atrial situs inversus had a right-sided and anterior aorta. In this study we compared the anomalies found in our cases with double outlet right ventricle with those in 58 patients with corrected transposition. Absolute, relative and attributable risks were calculated for the presence of subvalvular pulmonary stenosis, ventricular septal defect, tricuspid regurgitation and atrioventricular block for each the two groups. We concluded that patients with double-outlet right ventricle are more prone to present ventricular septal defect and subvalvar pulmonary stenosis, while those with corrected transposition have a greater likelihood of presenting with tricuspid regurgitation and atrioventricular block. There is no typical clinical picture for the malformations. Symptoms depend upon the associated anomalies. The final diagnosis is best achieved by the echocardiographic and angiocardiographic studies, but electrocardiogram and chest radiograph may suggest the presence of a discordant atrioventricular connection.

Adolescent↗
PubMedDate not supplied

Short-term corneal endothelial changes after photorefractive keratectomy.

Clinical results show that photorefractive keratectomy (PRK) offers good predictability, efficacy, and safety. However, its potential risks on the human corneal endothelium are poorly known. We report the results of a prospective study conducted to evaluate the corneal endothelium changes after photorefractive keratectomy. Preoperative and serial postoperative specular microscopy was performed in 14 eyes undergoing excimer laser photorefractive keratectomy. The endothelium was analyzed for a variety of parameters, including cell density, coefficient of variation in cell size, and hexagonality. The follow-up was 6 months. The mean cell density was unchanged from 2463 cells/mm2 to 2498 cells/mm2 at 6 months after photorefractive keratectomy. The coefficient of variation of cell size (polymegathism) changed from 0.303 to 0.280 at 1 month, to 0.293 at 3 months, and to 0.290 at 6 months after surgery. The changes in this parameter were statistically significant when comparing pre- versus 1 month postoperative values. The hexagonality was unchanged from 72.08% at baseline to 73.35% at 6 months. No endothelial abnormalities were found after photorefractive keratectomy. Our results suggest a cell migration from the peripheral to central cornea after photorefractive keratectomy in contact lens wearing patients prior to photorefractive keratectomy.

Adult↗