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Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial.

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.

Attention Deficit Disorder with Hyperactivity↗

Population structure and variation in red snapper (Lutjanus campechanus) from the Gulf of Mexico and Atlantic coast of Florida as determined from mitochondrial DNA control region sequence.

The mitochondrial DNA control regions of red snapper (Lutjanus campechanus) from the Gulf of Mexico (n = 140) and Atlantic coast of Florida (n = 35) were sequenced to generate a prestocking genetic baseline for planned stock enhancement. Intrasample haplotype and nucleotide diversities ranged from 0.94 to 1.00 and 1.8% to 2.5%, respectively. All population analyses were consistent with the hypothesis that red snapper constitute a single, panmictic population over the sampled range. A ubiquitous, predominant haplotype, shared by 23% of the specimens, appeared to be evolutionarily recent, in contrast to previous findings based on restriction fragment length polymorphism data. Tajima's D values were suggestive of a recent bottleneck. Mismatch distributions from Gulf samples were smooth and unimodal, characteristic of recent population expansion. However, the Atlantic sample exhibited a comparatively broader, possibly multimodal distribution, suggestive of a more stable population history. Additional control-region data may clarify potentially disparate demographic histories of Gulf and Atlantic snapper.

Animals↗

[Social and medical aspects of multimodality therapy for lymphogranulomatosis in children].

The high efficiency of treatment of lymphogranulomatosis in children by the currently available protocols determines the necessity of assessing them in terms of the quality of further life. The opportunity of creating a life and having the offspring, that of getting education and a profession are one of the main characteristics of the quality of life. The data on the reproductive function and social adaptation of 443 children receiving multimodality treatment for lymphogranulomatosis by 3 protocols (from 1976, 1978, and 1987). Two hundred and fifty eight individuals were 18 years old or more. Sixty four former patients have 88 children who are all healthy. The treatment performed in childhood intensively, which yielded a complete effect, exerts no substantial impact on the formation and performance of their reproductive function. The former patients have a high intellect, without limitations in getting professions, and they are easily adaptable to the changing social conditions.

Adolescent↗

[Nootropic agents in the complex treatment of patients with traumatic epilepsy].

A study was made of the therapeutic efficacy of nootropic agents in multimodality treatment of 62 patients with traumatic epilepsy. The treatment efficacy was appraised with regard to the time-course of changes in psychopathological symptomatology. The data obtained have been processed statistically according to criteria for the signs. When applied in multimodality treatment of patients with traumatic epilepsy the nootropic agents turned out most efficacious for the psycho-organic syndrome and for the status of deranged consciousness. The use of the nootropic agents as part of rehabilitation therapy allows improvement of the secondary prophylaxis of traumatic epilepsy.

Adult↗

Patient specific color texture mapping of CT-based anatomical surface models utilizing cryosection data.

In traditional medical imaging modalities, color and texture information can add considerable information for diagnostics. Presently, multimodal images of a patient are unregistered and referenced independent of each other, or registered and fused into a single hybrid volume. Doctors and other medical professionals need to be able to visualize and interrogate, on a per-patient basis, a wide variety of 2D and 3D data representations that can be created from non-invasive imaging modalities, such as MRI and CT. In addition, any colorization that may be applied to the image data is strictly based on tissue density, radiation emission, or magnetic signature, and not on any physiological foundation. In order for "true-to-life" color information to be incorporated with non-invasive imaging techniques, and for it to be of consistent quality across the entire body, a single whole-body cryosection specimen with associated medical image data is needed. The National Library of Medicine's Visible Human Project offers just such a specimen. Using the full-body medical image data along with the cryosection images of the Visible Human subject, a set of color lookup tables for all visually well defined structures and organs can be created. As a result, patient-specific colorization based on real tissue color and characteristics can be incorporated into traditional intensity-based imaging modalities. The primary goal of this work has been to create CT color lookup tables for all visually well-defined structures in the Visible Human male cryosection data set. The subsequent goal has been to develop a method for stripping textures from a volumetric data set for polygonal models and non-uniform rational B-spline (NURBS) models, also generated from the volumetric data.

Color↗

Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy.

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.

Aged↗

Clinical and microdissection genotyping analyses of the effect of intra-arterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.

PURPOSE: To determine the effect of intra-arterial cytoreductive chemotherapy (IACC) as an adjunct of a multimodality protocol for the treatment of lacrimal gland adenoid cystic carcinoma (ACC). METHODS: This was a retrospective, comparative, consecutive case series. Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, local-regional recurrence or distant metastases, and disease-free survival time. Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci using 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serve as markers for the presence of gene deletion. The effect of IACC was assessed by the radiographic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: The carcinoma cause-specific death rates between the two treatment groups was significant (P = .029, log-rank test). The cumulative 5-year carcinoma cause-specific death rate was 16.7% in the IACC-treated group compared with 57.1% in the conventional treatment group. 1p36 was the single most common site affected by allelic loss for microsatellite markers in this series. CONCLUSIONS: The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland ACC. Allelic loss for microsatellite markers at 1p36 may be a common and an early event in ACC formation and progression.

Adult↗

Neuromonitoring in the cardiopulmonary bypass surgical patient: clinical applications.

Intraoperative multimodality neurodiagnostic monitoring utilizing a transcranial Doppler, electroencephalography (EEG), and cerebral oximetry has been shown to reduce the incidence of neurological complications greatly. Potential problems affecting the brain can be detected and resolved or managed before disastrous consequences result. The use of multimodality neuromonitoring combined with traditional hemodynamic monitoring provides the clinician with additional data to manage the cardiac/vascular surgical patient better. Because the brain has the highest blood flow and metabolic demand of any organ, it seems the ideal and most logical place to monitor the adequacy of body perfusion. This review discusses our experiences and research over the last decade with the use of multimodality EEG monitoring on cardiopulmonary bypass surgical patients.

Brain↗

Acute myelogenous leukemia as a late complication of the multimodality therapy for Hodgkin's disease.

Progressive thrombocytopenia developed in a patient following the completion of total lymphoid irradiation and combination chemotherapy for Hodgkin's disease. Thorough evaluation eventually yielded a diagnosis of acute myelogenous leukemia (AML). Previous workers have suggested that the development of thrombocytopenia with a hypoplastic marrow following total lymphoid irradiation indicated recurrent Hodgkin's disease. When the combination cytopenias and hypoplastic marrow is recognized these workers have recommended early combination chemotherapy. Recent data suggest a 1300-fold increase in the risk of AML following multimodality therapy for Hodgkin's disease. We feel that a careful search for AML should be conducted in patients with deteriorating hematologic parameters following therapy for Hodgkin's disease and that this search should include sampling bone marrow outside irradiated areas.

Adult↗

Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma.

Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 micromol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes.

Atrophy↗

Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation.

Initial trials of irradiation and chemotherapy followed by operation for squamous carcinoma of the esophagus have produced encouraging results. Over the past three years, with palliative and curative intent, we have treated 27 unselected patients initially with two courses of chemotherapy (fluorouracil and either cisplatin, mitomycin, or cisplatin and vincristine sulfate) given 29 days apart and 3000 rad (30 Gy) of radiation. Ten patients have then undergone esophageal resection and two patients have undergone esophageal bypass. Results are compared with those of 70 unselected historical control patients treated since 1979. Survival at 30 months was significantly improved for multimodality-treated patients (21.4% +/- 10.1%, mean +/- SEM) when compared with historical control patients (4.8% +/- 2.7%). Twenty-four percent of multimodality-treated patients had complete remission of all tumor. These data indicate that overall therapy for carcinoma of the esophagus has been improved in our institutions.

Carcinoma, Squamous Cell↗

The early time course of smoking withdrawal effects.

RATIONALE: There has been little study of the very early time course of the smoking withdrawal syndrome, despite its relevance to the maintenance of both smoking and postcessation abstinence. The literature contains a range of estimates about the early appearance of withdrawal symptoms, but without reference to empirical data. OBJECTIVES: The study aim was to conduct a comprehensive, multimodal assessment of the early time course of the symptoms associated with smoking withdrawal among cigarette smokers. METHODS: Participants were 50 smokers randomly assigned to either abstain or smoke at their own pace during 4 h in the laboratory. Dependent measures included resting heart rate, sustained attention (Rapid Visual Information Processing task; RVIP), selective attention to smoking stimuli (an emotional Stroop task), and self-report (Wisconsin Smoking Withdrawal Scale; WSWS). After baseline assessment, participants were assigned to the two conditions and the dependent measures were collected every 30 min. RESULTS: Generalized estimating equations revealed that abstaining participants displayed greater withdrawal than smoking participants on all measures with the exception of the Stroop task. Statistically significant differences in withdrawal were found within 60 min on heart rate, within 30 min on the RVIP, and between 30 and 180 min postcessation on the various subscales of the WSWS. CONCLUSIONS: These findings provide the first evidence of the early time course of smoking withdrawal symptoms, although further research is needed to distinguish withdrawal from drug offset effects. Implications for understanding the maintenance of daily smoking and for the treatment of tobacco dependence are discussed.

Adult↗

Clinical analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.

PURPOSE: To determine the effect of intraarterial cytoreductive chemotherapy (IACC) as an adjunct to conventional surgery and radiation therapy for lacrimal gland adenoid cystic carcinoma (ACC). DESIGN: A retrospective, comparative, interventional case series. METHODS: setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies in the same institution. intervention procedure: Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, incidence of locoregional recurrence or distant metastases, and disease-free survival and overall survival time. main outcome measure: The effect of IACC was assessed by the radiographic and histologic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. RESULTS: The difference between the carcinoma cause-specific death rate of the study group versus conventional treatment was significant (P = .029, log rank test). The cumulative 5-year carcinoma cause-specific death rate in the IACC treated group was 16.7% compared with 57.1% in the conventional treatment group. The cumulative 5-year recurrence rate in the IACC treated group was 23.8% compared with 71.4% in the conventional treatment group. CONCLUSIONS: The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland adenoid cystic carcinoma.

Adult↗

Rituximab maintenance therapy in indolent NHL: a clinical review.

Rituximab maintenance therapy following successful induction has emerged as a highly effective treatment for follicular lymphoma. Several randomized trials have been conducted analyzing the impact of rituximab maintenance compared to observation alone on treatment outcome. These studies have been conducted in patients receiving single-agent rituximab, standard chemotherapy or rituximab plus chemotherapy as initial cytoreduction, in both previously treated and untreated patients. In all the trials, rituximab maintenance resulted in a clinically and statistically significant benefit in clinical endpoints such as progression-free survival. Moreover, first data indicate that rituximab maintenance can prolong overall survival in patients with follicular lymphoma. These data have established rituximab maintanance as an important part of multimodal therapeutic strategies. Ongoing studies will help to determine the best schedule for the maintenance therapy in the treatment of follicular lymphoma.

Antibodies, Monoclonal↗

Small cell carcinoma of the oesophagus.

Small cell carcinoma of the oesophagus is an uncommon malignancy. Only 272 cases have been reported to date. Inconsistency in therapeutic approaches reflects the paucity of individual experience and the unsatisfactory response to current management strategies. We report 11 cases drawn from a series of 1012 cases of oesophageal malignancy and perform a statistical analysis on treatment and survival data of 189 cases drawn from the world literature. Small cell carcinoma of the oesophagus was seen to have an incidence of 1%. Seven of 11 patients were female. A variety of therapeutic modalities were employed, and the median survival was 6.6 months. Statistical analysis of these and worldwide data showed a significant survival advantage for patients who received multimodality therapy.

Adult↗

Advanced oropharyngeal carcinoma treated with surgery and radiotherapy: oncologic outcome and functional assessment.

INTRODUCTION/PURPOSE: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease. METHODS: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS). RESULTS: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance. CONCLUSIONS: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.

Adult↗

Long-term follow-up after curative surgery for early gastric lymphoma.

OBJECTIVE: This study was designed to examine the long-term survival of a homogenous group of patients with stage IE or IIE-1 gastric lymphoma after complete surgical resection. SUMMARY BACKGROUND DATA: The management of gastric lymphoma remains controversial. Enthusiasm for multimodality approaches for gastric lymphoma has lead to the current trend of using chemotherapy as primary treatment, thus avoiding gastric resection. Surgery, however, may result in improved long-term survival rates. METHODS: The records of all patients with the diagnosis of gastric lymphoma from 1980 to 1991 were reviewed retrospectively. Of 106 patients examined, 34 underwent curative resection and regional lymphadenectomy for pathologically staged IE or IIE-1 (pN1) gastric lymphoma. Fifteen patients underwent surgery alone, whereas 19 also received postoperative adjuvant therapy. RESULTS: The median follow-up time was 74 months. The 10-year actuarial disease-free survival was 91% for stage IE disease (n = 23) and 82% for stage IIE-1 disease (n = 11). There were no operative deaths and a 26% morbidity rate. No difference in survival was found for those treated with adjuvant therapy. CONCLUSIONS: The results compare favorably to those reported with the use of primary chemotherapy and radiation therapy and suggest that surgery remains the best frontline therapy for early gastric lymphoma.

Female↗

Pediatric high-grade gliomas.

High-grade gliomas, including glioblastoma multiforme, anaplastic astrocytoma, and intrinsic pontine, are very difficult to treat in children. Despite aggressive treatment with multimodal therapy, most children with these diseases do not survive. Data from published series support aggressive surgical resection when clinically feasible. Patients who have had aggressive resections tend to have a longer survival than those who have undergone only biopsies or partial resections. Almost all patients with high-grade gliomas respond to radiation therapy, and it is the current mainstay of adjuvant therapy. Radiation therapy also tends to prolong survival, but it is rarely curative. Although responses to chemotherapy have been demonstrated, there are no compelling data indicating that it prolongs survival for this group of patients. Current and proposed studies are combining radiation therapy and/or chemotherapy with agents that have shown preclinical promise as radiosensitizers, anti-angiogenesis factors, growth factor receptor inhibitors, and free radical inducers. Other biologic therapies, including gene therapy, are also being investigated. Improved survival for these patients will likely require combined therapy that includes novel treatment.

Brain Neoplasms↗