Use of markers in defining urothelial premalignant and malignant conditions

Markers have revealed the presence of phenotypically abnormal areas in histologically benign urothelium in bladders containing transitional cell carcinomas. This finding strongly suggests that at least some bladder cancers are associated with changes in the field and that markers can detect these lesions before they reach a grossly malignant stage. Markers have been used clinically for the detection of cancer in patients who are under regular surveillance for recurrence of bladder cancer. Much less information is available regarding the use of markers to detect bladder cancer without a prior history of the disease and for the prediction of which tumors are biologically more aggressive. However, ongoing clinical trials are addressing the latter issue. The type of specimen and its preparation will determine what type of markers can be analyzed. Although marker performance is based upon sensitivity and specificity, the prevalence of bladder cancer in the population being tested will dramatically affect the positive predictive value of an assay. Markers with high positive predictive value are indicators for interventions, such as biopsy, while markers with high negative specific values are useful for avoiding interventions. Cytology is used to detect occult high-grade neoplasms such as carcinoma in situ. While not yet clinically validated, tests with high negative predictive value could be used to decrease the frequency of cystoscopic evaluation. Markers must be validated by testing them prospectively using previously defined cut-off values. Furthermore, markers that will be used to alter treatment should be tested prospectively to determine the safety and cost-effectiveness of this strategy. Recommendations for future work include: (1) evaluation of markers in patients with dysplasia defined by the current pathologic classification; (2) evaluation of markers as indicators of tumor recurrence; (3) evaluation of markers as indicators of tumor progression; and (4) evaluation of markers in chemoprevention studies.     

Terguride--a new dopamine agonist drug: a comparison of its neuroendocrine and side effect profile with bromocriptine

Terguride, the C9-10 dihydrogenated derivative of lisuride, is a new drug which inhibits pituitary prolactin (PRL) secretion. It has mixed dopaminergic-antidopaminergic and alpha 2-antiadrenergic activity, and has proved useful in the clinical management of hyperprolactinemia. However, no trial comparing its use with the standard dopamine agonist bromocriptine has been reported. We have therefore compared three doses of terguride with bromocriptine 2.5 mg and placebo in a randomized double-blind crossover trial in eight normal volunteers. Terguride showed a potent dose-dependent PRL-inhibiting and growth hormone (GH)-releasing effect, while no significant changes were observed in thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), or luteinizing hormone (LH) in comparison to placebo. The neuroendocrine profile of terguride 1 mg was identical to that of bromocriptine, with a significant reduction in PRL still evident at 24 hours. However, in this small group of normal subjects, the side effects experienced at any dose of terguride were significantly less than with bromocriptine. Terguride 1 mg was always preferred to bromocriptine, while the lower doses were indistinguishable from placebo. Terguride is therefore likely to play an important role in the treatment of hyperprolactinemia.     

Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report

A randomized, prospective trial utilizing cisplatin and fluorouracil as neoadjuvant chemotherapy in the treatment of advanced squamous cell carcinomas of the upper aerodigestive tract was initiated in January 1983. Sixty patients were stratified by site (oral cavity, 19; larynx, 14; hypopharynx, 14; oropharynx, 11; nasopharynx, one; and paranasal sinuses, one) and by stage (III, 19; IV, 41), and then randomized to receive either standard treatment (defined as preoperative irradiation followed by radical excision or irradiation alone) or adjuvant chemotherapy followed by standard treatment. An additional three patients were entered into the study, but withdrew. Chemotherapy consisted of three cycles for those patients in whom an objective tumor response was observed; nonresponders received standard treatment. Response to chemotherapy was complete in five and partial (greater than 50%) in 18 patients, for an overall response rate of 85%. The follow-up for surviving patients was a minimum of 24 months and a maximum of 44 months. Survival was compared for patients in both treatment groups according to the method of Lee and Desu. Despite excellent tumor response, actuarial survival was 70% in the standard treatment group as opposed to 56% in the experimental group. It was therefore evident that the high response rates reported in previous pilot studies do not necessarily result in improved survival in these cancers.     

Use of computed tomography in pediatric oncology

Computed tomography (CT) has dramatically changed the imaging of pediatric oncologic disease. CT precisely displays and characterizes cross-sectional anatomic pathology. This provides important information for diagnosing and staging tumors in infants and children. The principles, techniques, and indications for computed tomography in the evaluation of pediatric extracranial tumors are reviewed in this article. Selected applications of computed tomography for pediatric tumors of the mediastinum, chest wall, lung parenchyma, abdomen, pelvis, and extremities are discussed and illustrated.     

High dose systemic methotrexate-associated acute neurologic dysfunction

Two patients treated with high dose methotrexate otrexate with citrovorum rescue (HDMTX-CF) for osteogenic sarcoma developed the acute onset of neurologic deficits. Prior to the onset of symptoms, one child suffered brief episodes of altered consciousness. Both patients developed hemiparesis and then steadily improved over 72 hours. Laboratory evaluations disclosed normal coagulation parameters and nontoxic serum methotrexate levels at onset of symptoms. Computed tomography in one child disclosed a large low absorption abnormality. This patient represents the first reported case of positive radiologic findings associated with this syndrome. The two patients recovered completely and received further HDMTX-CF without sequelae. This condition may result from transient demyelination or embolic cerebrovascular disease.     

The staffing crisis

It's not just a matter of hiring more nurses: hospital leaders need to make human resources a priority--and fast. The situation cries out for strategic decisions that will benefit workers as well as patients.     

A randomized placebo-controlled trial of risperidone for the treatment of aggression,agitation, and psychosis of dementia

BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. METHOD: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. RESULTS: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. CONCLUSION: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.     

Progressive aphasic syndromes: clinical and theoretical advances

PURPOSE OF REVIEW: Knowledge of the neural basis for language and related aspects of cognition has been advanced through detailed studies of patients with primary progressive aphasia. This brief review highlights some recent work. RECENT FINDINGS: The impairment of semantic knowledge in patients with semantic dementia appears to influence performance in a wide variety of linguistic and cognitive domains, including morphological agreements such as the irregular past tense. Computational studies modeling the deficits of these patients have advanced interpretations of the impairments in semantic dementia. Imaging analyses have confirmed the presence of temporal atrophy cross-sectionally and longitudinally in these patients. In patients with semantic dementia, it appears that both the left temporal and right temporal regions contribute in different proportions to naming and comprehension, although the nature of the process underlying the consolidation of knowledge in semantic memory continues to be actively debated. In patients with progressive non-fluent aphasia, recent work has emphasized an impairment with verbs. Functional neuroimaging work with progressive non-fluent aphasics, compared directly to non-aphasic patients with frontotemporal dementia, has demonstrated a dissociation for grammatical and working memory aspects of sentence processing within the left frontal cortex. SUMMARY: These findings will improve diagnostic accuracy, prognostic ability, and therapeutic potential in patients with progressive aphasia.