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J Mora

Publications and source records attributed to J Mora.

At least 37 records · Page 2Linked to original sources
PubMed2001

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Antibodies, Monoclonal↗
PubMed2001

Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain.

Oligodendrocyte precursor development in the embryonic spinal cord is thought to be regulated by the secreted signal, Sonic hedgehog (Shh). Such precursors can be identified by the expression of Olig genes, encoding basic helix-loop-helix factors, in the spinal cord and brain. However, the signaling pathways that govern oligodendrocyte precursor (OLP) development in the rostral central nervous system are poorly understood. Here, we show that Shh is required for oligodendrocyte development in the mouse forebrain and spinal cord, and that Shh proteins are both necessary and sufficient for OLP production in cortical neuroepithelial cultures. Moreover, adenovirus-mediated Olig1 ectopic expression can promote OLP formation independent of Shh activity. Our results demonstrate essential functions for Shh during early phases of oligodendrocyte development in the mammalian central nervous system. They further suggest that a key role of Shh signaling is activation of Olig genes.

Animals↗
PubMed2001

Effects of alpha-tocopherol, beta-carotene and ascorbic acid on oxidative, hormonal and enzymatic exercise stress markers in habitual training activity of professional basketball players.

BACKGROUND: Intense physical exercise has been associated with an increase of free radical production. When the body's natural defense systems against free radicals are overwhelmed, oxidative stress increases. AIM OF THE STUDY: This study examined the effects of a vitamin antioxidant supplement, (composed of 600 mg alpha-tocopherol, 1000 mg ascorbic acid and 32 mg beta-carotene) on oxidative, hormonal, and enzymatic exercise stress markers during habitual training activity over 35 days. METHODS: The plasma concentrations of ascorbic acid, alpha-tocopherol, beta-carotene, testosterone, cortisol and lipid peroxides and the serum activities of lactate dehydrogenase and creatine kinase were measured at four time points: pre-supplementation (PS), pre-training (PT), after training (AT) and 24 h after training (24h-AT) in 13 professional basketball players of the first Spanish Basketball League (ACB). RESULTS: Antioxidant supplementation led to a significant increase of alpha-tocopherol and beta-carotene from PS to PT. Plasma lipid peroxides decreased about 27.7% after 35 days of antioxidant treatment. A significant decrease of lactate dehydrogenase serum activity was observed during the 24 h recuperation time. During this time the anabolic/catabolic balance increased about 29.8% in the antioxidant supplemented group, although this increase did not reach statistical significance. CONCLUSIONS: The results of the present study suggest that supplementation with alpha-tocopherol, beta-carotene and ascorbic acid might partially account for the hormonal and enzymatic stress marker profile observed during habitual training activity of professional basketball players.

Adult↗
PubMed2001

[Study of renal transplant by deconvoluted renogram with 99m Tc-mercaptoacetyltriglycine (Mag3)].

AIM: To evaluate the usefulness of the 99mTc-MAG3 renogram deconvolution and its derived parameters in kidney graft function monitoring. MATERIAL AND METHOD: 221 renograms were studied: 64 were diagnosed as functioning graft (FG), 37 as functioning graft with elevated serum creatinine (FG2), 59 as acute tubular necrosis (ATN), 30 as acute rejection (AR), 20 as urinary tract obstruction (OBS) and 11 as cyclosporine nephrotoxicity (TNX). The parameters evaluated were: maximal activity of conventional renogram and mean transit time (MTT), time to reach 20% (T20) and 80% (T80) of the height of the RRF and initial uptake (IU) from the deconvoluted renal retention function (RRF). RESULTS: MTT and T20 were significantly longer and IU significantly lower in non-functioning grafts. However, MTT and T20 became shorter than in FG when graft function is severely impaired. CONCLUSION: IU, MTT and T20 are more useful than maxim activity of renogram in monitoring kidney graft function and in evaluating renal dysfunction severity. IU is a very sensitive and early parameter.

Adult↗
PubMed2001

Ways of coping and the health of relatives facing drug and alcohol problems in Mexico and England.

AIMS: To compare two contrasting socio-cultural groups in terms of parameters relating to the stress - coping - health model of alcohol, drugs and the family, and to test hypotheses derived from the model in each of the two groups separately. DESIGN: Cross-sectional, comparative and correlational, using standard questionnaire data, supplemented by qualitative interview data to illuminate the findings. PARTICIPANTS: One hundred close relatives, mainly partners or parents, from separate families in Mexico City, and 100 from South West England. Data sources. Coping Questionnaire (CQ), Family Environment Scale (FES), Symptom Rating Test (SRT), Semi-structured interview. FINDINGS: Mean symptom scores were high in both groups, and not significantly different. The hypothesis that relatives in Mexico City, a more collectivist culture, would show more tolerant - inactive coping was not supported, but there was support for the prediction that relatives in South West England would show more withdrawal coping. This result may be as much due to differences in poverty and social conditions as to differences in individualism - collectivism. As predicted by the stress - coping - health model, tolerant - inactive coping was correlated with symptoms, in both groups, after controlling for family conflict, but there was only limited support for a moderating role of coping. Wives of men with alcohol problems in Mexico City, and wives of men with other drug problems in South West England, reported particularly high levels of both engaged and tolerant - inactive coping. CONCLUSIONS: Tolerant - inactive coping may be bad for relatives' health: causality may be inferred but is not yet proved. Certain groups are more at risk of coping in this way. Qualitative data help understand the nature of tolerant - inactive coping and why it occurs despite the view of relatives themselves that it is counter-productive.

Adaptation, Psychological↗
PubMed2001

The latanoprost monotherapy survey in New Zealand, 2000.

BACKGROUND: A State subsidy for latanoprost has been recently introduced. It is subject to several conditions including that it should only be used as monotherapy. METHOD: A prospective survey of all New Zealand ophthalmologists was undertaken to determine the outcome of the widespread trial of latanoprost monotherapy. The return rate was 82%. RESULTS: Of 2900 patients on latanoprost nation-wide, 14.7% were monotherapy failures. Of these, 93% were due to inadequate intraocular pressure control but this subgroup had adequate control on two or more medications in 88%. Ophthalmologists had 635 patients that were not trialed as monotherapy, of which 565 (89%) were due to a perceived risk. CONCLUSIONS: In those patients treated with latanoprost, 85% were adequately controlled as monotherapy.

Antihypertensive Agents↗
PubMed2001

p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis.

BACKGROUND: Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis. METHODS: Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing. RESULTS: Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease. CONCLUSION: p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.

Adolescent↗
PubMed2001

Gamma probe sentinel node localization and biopsy in breast cancer patients treated with a neoadjuvant chemotherapy scheme.

The aim of this study was to analyse the accuracy of scintigraphic and gamma probe sentinel node (SN) localization in breast cancer patients who have been submitted to neoadjuvant chemotherapy (NC). Seventy-six patients with single breast cancer were included in the study, and were classified into two groups. Group 1 consisted of 40 women who had received NC, and Group 2 consisted of 36 women who did not receive NC. All patients received 111 MBq (3 mCi) of 99Tcm-nanocolloid in 3 ml, by peritumoural injection. Anterior and lateral thoracic scans were obtained 2 h post-injection. The following day (18-24 h post-injection) the patients underwent surgery and sentinel nodes were localized by using a gamma probe. Complete axillary lymph node dissection was performed in all patients. Histological analysis included haematoxylin-eosin in all cases and immunohistochemistry in 10 cases. In Group 1, SNs were localized in 36/40 patients, histological analysis was performed in 34 and there were four false negatives (22%). In Group 2, SNs were localized in 32/36 patients, histological analysis was performed in 29 and there were two false negatives (9%). Predictive negative values were 78% and 90% in Groups 1 and 2, respectively. In summary, sentinel node localization in breast cancer patients submitted to previous neoadjuvant chemotherapy is less accurate than in patients who do not receive this therapy. The procedure is not sufficiently accurate to localize the sentinel node, thus it cannot be recommended in these patients.

Adult↗
PubMed2001

Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer.

BACKGROUND: The significance of K-ras codon 12 mutation in pancreatic juice is still unclear. Although considerable controversy surrounds this question, the diagnostic utility of K-ras in patients with clinical suspicion of pancreatic cancer (PC) and in PC-risk patients remains unknown. OBJECTIVE: To study prospectively the utility of the K-ras gene mutation and cytology in the diagnosis and screening of PC, and to assess its contribution to clinical decision making. METHODS: Pancreatic juice samples obtained from 90 patients were evaluated prospectively. Group I (n = 40) comprised patients with clinical suspicion of PC; group II (n = 50) comprised 49 patients with chronic pancreatitis and one patient proceeding from a PC family screening. The K-ras mutation was detected by means of artificial restriction fragment length polymorphisms (RFLP) in DNA after polymerase chain reaction (PCR) amplification. RESULTS: In group I, of those patients with a definitive diagnosis of PC, malignant cells were found in 27% and K-ras mutation in 44%. In five cases, molecular analysis contributed to diagnosis (4/11 with negative cytology and 1/2 with insufficient cytological material). K-ras mutation revealed an early tumour in one patient, and was the only sample available for diagnosis in another. In group II, the K-ras gene mutation was detected in 8/49 patients (16%) with chronic pancreatitis, one of whom developed PC (2%). CONCLUSIONS: K-ras mutation analysis of pancreatic juice may complement cytological evaluation in the diagnosis of PC, in spite of its limited contribution to clinical decision making. The presence of K-ras mutation in chronic pancreatitis classifies a subgroup of PC-risk patients who should be evaluated carefully by long-term follow-up.

Adult↗
PubMed2001

Innovative treatments for non-small cell lung cancer.

Lung cancer remains the most frequent and most lethal cancer worldwide. Non-small cell lung cancer (NSCLC) comprises the vast majority of the histological types. Surgery remains the standard therapy for early stage disease but for advanced stage disease, modern treatment is unsatisfactory. However, during the past ten years, improvements in response and survival have been seen with the use of newer chemotherapy regimens. Early studies of neo-adjuvant (pre-operative) chemotherapy for resectable stage III patients have shown promising results. For patients with non-resectable NSCLC platinum-based doublets are now established as first-line treatment, either alone or in combination with radiotherapy. Innovative non-platinum based combinations are actively being evaluated. The most promising non-platinum agents at this time include gemcitabine, paclitaxel, docetaxel, irinotecan and vinorelbine. These agents appear to be effective as single agents and in combinations and also have improved toxicity profiles. Several other systemic approaches are under active evaluation; the most promising areas include anti-angiogenesis agents, immunotoxins, interleukins, vaccines and molecular therapy.

Angiogenesis Inhibitors↗
PubMed2001

Molecular genetics of neuroblastoma and the implications for clinical management: a review of the MSKCC experience.

Neuroblastoma (NB) is a biological, genetic, and morphological heterogeneous neoplasm and demonstrates diverse clinical behavior. There exist at least three clinical patterns of NB: A) spontaneously regressing widespread disease; B) not metastatic local-regional disease, and C) metastatic disease (stage 4), frequently with lethal consequences. Patients with non-stage 4 NB are expected to survive even without medical treatment whereas stage 4 patients have an overall survival rate of 20% despite multimodality therapy protocols. The clinical management of patients with NB is therefore challenged by the objective identification of cases in which noncytotoxic approaches can be safely taken. Experience in the last decade at Memorial Sloan-Kettering Cancer Center supports the hypothesis that the natural history of disease defines relevant clinical groups of NB and has distinct molecular genetic profiles allowing therapeutic approaches tailored for each group. Here we review the natural history and clinicobiological features of 113 NB cases managed uniformly in our institution in an attempt to characterize useful genetic markers to support the decision making of noncytotoxic versus cytotoxic approaches for each category of NB.

Humans↗
PubMed2001

[Bone metastasis from gastrinoma without hepatic involvement. Utility of the scintigraphy with 111 In-pentetreotide].

The case of a 54 year old patient suffering from gastrinoma (within a type I multiple endocrine neoplasm) is presented. In 1990, she underwent a surgical resection. Eight years later, she suffered from a pain in the left thigh. The 99mTc-MDP bone scintigraphy showed bone metastasis. The CT scan did not show any hepatic involvement and the scintigraphy with 111In-Pentetreotide verified bone metastasis of a neuroendocrine tumor as a single expression of the recidive. In this case, the utility of the scintigraphy with octreotide to facilitate the localization and extent of the neuroendocrine tumors is demonstrated.

Adrenalectomy↗
PubMed2001

Loss of heterozygosity at 19q13.3 is associated with locally aggressive neuroblastoma.

A genome-wide allelic analysis of neuroblastoma (NB) revealed a previously undescribed increased incidence of loss of heterozygosity (LOH) on chromosome arm 19q13 primarily affecting stages 3 and 4N disease. Further allelic analysis of chromosome 19q13 in a cohort of 116 NB patients using 17 polymorphic microsatellite markers identified the shortest common region of loss between D19S606 and D19S112 at 19q13.3. In some cases, clonal LOH at 19q13 was acquired during the course of disease, and deleted clones remained after cytotoxic therapy. In multivariant analysis, 19q13 LOH was associated with overall survival in local-regional International Neuroblastoma Staging System stages 1, 2, and 3 patients and was specifically present in tumors at the site of recurrence.

Chromosomes, Human, Pair 19↗
PubMed2000

Early diagnosis of brain death in patients treated with central nervous system depressant drugs.

BACKGROUND: Among the main causes for the relatively small number of organ donors, the delay in the diagnosis of brain death plays a major role. Administration of drugs causing central nervous system (CNS) depression prevents diagnosis of brain death by clinical and electroencephalographic criteria until serum clearance of the drug has occurred. Confirming brain death by demonstrating persistent intracranial circulatory arrest might decrease the length of the diagnostic process. We have carried out a prospective study to investigate whether 99 mTc-hexamethyl propylenamino oxime (99mTc-HMPAO) brain scintigraphy and/or transcranial Doppler ultrasound can speed up the diagnosis of brain death in patients treated with CNS depressant drugs. METHODS: All 138 consecutive patients with severe brain lesion that progressed to brain death in our center between January 1994 and December 1996 were controlled. Of them, 36 patients aged 1 to 65 years old (mean=25.6+/-18.3 years) who met clinical and EEG criteria for the diagnosis of brain death, except for the presence of significant serum levels of barbiturates (n=34), opiates (n=8), and benzodiazepines (n=3) were distributed in three groups according to the confirmatory test used; group 1: waiting for the metabolic clearance of CNS depressant drugs, or by demonstrating intracranial circulatory arrest with 99mTc-HMPAO (group 2) or transcranial Doppler (group 3). The delay in diagnosing brain death by the three methods was analyzed. RESULTS: The mean interval between the presumptive and the definitive diagnosis of brain death was 34.4+/-32.2 hr in group 1, 17.7+/-18.3 hr in group 2, and 5.0+/-4.6 hr in group 3 (P=0.004). The between-groups analysis showed that 99mTc-HMPAO and transcranial Doppler decreased the delay in diagnosing brain death with respect to waiting for drug clearance by 49% (P=0.16) and 85% (P<0.001), respectively. Moreover, transcranial Doppler decreased this time by 72% with respect to 99mTc-HMPAO (P<0.01). CONCLUSIONS: Transcranial Doppler ultrasound and 99mTc-HMPAO brain scintigraphy can significantly reduce the time taken to confirm brain death in patients with significant serum levels of CNS depressant drugs. In this setting, transcranial Doppler is superior to 99mTc-HMPAO in reducing the waiting time for a firm diagnosis of brain death.

Adolescent↗
PubMed2000

Tumor markers at the time of recurrence in patients with germ cell tumors.

BACKGROUND: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation.

Adolescent↗
PubMed2000

Large cell non-Hodgkin lymphoma of childhood: Analysis of 78 consecutive patients enrolled in 2 consecutive protocols at the Memorial Sloan-Kettering Cancer Center.

BACKGROUND: The authors report a study of pediatric patients with advanced diffuse large cell lymphoma (DLCL) who were treated with 2 consecutive regimens, LSA2-L2 and LSA4, over a 25-year-period at the Memorial Sloan-Kettering Cancer Center. They also describe a comparative analysis of two subgroups retrospectively identified as having CD30 positive (+) anaplastic large cell lymphoma (ALCL) and CD30 negative (-) DLCL. To the authors' knowledge, this study represents the longest follow-up on the largest series of uniformly treated pediatric DLCL patients reported to date. METHODS: A total of 78 consecutive patients were treated for Stage III/IV DLCL. Immunophenotypic data were obtained retrospectively for 52 patients using a panel of monoclonal antibodies against CD30, CD15, CD45, CD45Ro, CD43, epithelial membrane antigen, CD5, BCL-2, cyclin-D, and p53. RESULTS: A disease free survival rate of 72% in patients with advanced stage DLCL using the LSA2-L2 and LSA4 regimens. Of the 78 treated patients, 56 are alive and without evidence of disease with a median follow-up of 120 months (range, 24-312 months). The recurrence rate was significantly higher in the CD30+ ALCL subgroup (33%) than in the CD30- DLCL group (0.04%). Of 52 patients for whom immunophenotypic data were available, 28 had disease of B-cell lineage, 24 had disease of T-cell/null phenotype, 19 were CD30+ (36. 5%), 18 had disease of T-cell phenotype, and 1 had disease of B-cell lineage. CONCLUSIONS: The CD30- DLCL cases mostly were of B-cell lineage, had a small risk of treatment failure, and did not develop a recurrence off therapy. A distinct clinical pattern was identified for the CD30+ ALCL group; although these tumors were of T-cell lineage and had a significantly higher rate of late recurrences (median follow-up of 24 months) they all were salvageable. Based on the findings of the current study, the authors propose that T-cell CD30+ ALCL be addressed in the future according to equal dose intensity regimens in induction therapy, as is done for B-cell lymphomas; prolonged periods of maintenance chemotherapy, as is done for T-cell lymphoblastic lymphomas; and no central nervous system prophylaxis beyond the induction period unless other recognized risk factors are present.

Adolescent↗
PubMed2000

A highly sensitive method for K-ras mutation detection is useful in diagnosis of gastrointestinal cancer.

Detection of molecular features such as K-ras mutations has been used to evaluate potential tumour markers in a wide variety of clinical samples. Here we have applied a recently developed highly sensitive method for detection of K-ras codon 12 mutations to colorectal and pancreatic cancer diagnosis. We analysed 67 faecal samples from patients undergoing diagnostic colonoscopy under suspicion of colorectal cancer. PCR products were obtained in 62 of 67 (93%) faecal samples. Mutations were detected in exfoliated cells in 6 of 22 (27%) of the adenomas and in 6 of 11 (55%) of adenocarcinomas. No false positives were observed. Agreement between faecal samples and corresponding tissues was 100% for adenocarcinomas and 65% for adenomas. Mutations were also analysed in 61 pancreatic fine-needle aspirates. Mutations were detected in 36 of 45 (80%) of the pancreatic aspirates diagnosed as pancreatic cancer without false positives. Our findings suggest that, when colorectal cancer is suspected, detection of K-ras codon 12 mutations in faecal samples using this new method is specific for colorectal tumours. Additionally, this technique is a good alternative for evaluation of pancreatic masses.

Adenocarcinoma↗