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Biomedical subjects

H Scher

Publications and source records attributed to H Scher.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ursodeoxycholic acid improves cholestasis in infants with cystic fibrosis.

OBJECTIVE: To describe two infants with cholestatic jaundice treated with ursodeoxycholic acid (UDCA). CASE SUMMARY: Two infants with cystic fibrosis (CF)-associated hepatobiliary disease, manifesting as cholestatic jaundice and elevated liver enzymes within the first 6 weeks of life, had improved biochemical indices of liver function following treatment with UDCA 20-40 mg/kg/d. DISCUSSION: To our knowledge, this is the first report of UDCA treatment in infants with CF-associated cholestatic jaundice. Infants and children require treatment with increased doses of UDCA to compensate for reduced intestinal absorption of bile acid and immaturity of the enterohepatic circulation. CONCLUSIONS: UDCA appears to be a cost-effective treatment for CF-associated hepatobiliary disease in infants and children.

Cholagogues and Choleretics↗
PubMed1997

Cigarette smoking and chromosome 9 alterations in bladder cancer.

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

Chromosome Aberrations↗
PubMed1997

Expression of cyclin D1, but not cyclins E and A, is related to progression in bilharzial bladder cancer.

The present study was conducted to analyze the alterations affecting cyclins D1, E, and A in bilharzial bladder cancer and to assess their potential clinical significance. A total of 125 cases were examined. Histopathological subtypes included 68 squamous cell carcinomas, 55 transitional cell carcinomas, and 2 adenocarcinomas. Immunohistochemical analyses were performed using a panel of well-characterized antibodies. The results were correlated with proliferative index, as assessed by Ki67 antigen expression. The cyclin D1-positive phenotype, defined as the identification of positive immunoreactivity in the nuclei of >/=20% of tumor cells, was found in 33 of 107 (31%) evaluable cases. A significant association was observed between the cyclin D1-positive phenotype and deep muscle invasion (P = 0.02), high tumor grade (P = 0.02), and Ki67 high proliferative index (P = 0.03). The cyclin E-positive phenotype, defined as per cyclin D1, was found in 79 of 106 (75%) evaluable cases. The cyclin A-positive phenotype, defined using the above criteria, was identified in 60 of 108 (56%) evaluable cases. No statistically significant association was found between cyclins E or A and clinicopathological parameters or proliferative index. However, there was a strong association between the expression of cyclin D1 and the coexpression of cyclins A and/or E (P = 0.05). Ki67 proliferative index was considered high when >/=20% of tumor cells displayed positive nuclear staining, a phenotype that was observed in 99 of 115 (86%) cases. These data support the hypothesis that cyclin D1 activation determines the evolution of a particular subset of aggressive bladder tumors. In addition, cyclins E and A seem to follow an unscheduled pattern of expression, based on the high frequency of identifying a positive phenotype for these cyclins and the lack of correlation between their expression and Ki67 high proliferative index. It may be postulated that the expression of G1 cyclin genes is deregulated in bilharzial bladder cancer, and that cyclin D1 acts as an oncogenic event in these neoplasms. Moreover, the moderate number of tumors displaying the cyclin D1-positive phenotype (31%) versus the high frequency observed for both cyclins E (75%) and A (56%), suggests a short G1 disbalanced by a long S phase and a rapid transversal of the cell cycle, as evidenced by a high Ki67 index observed in 86% of these cases. This imbalance in the cell cycle, together with alterations reported on the p53 pathway, might underline the accumulation of DNA damage and the aggressive clinical course of bilharzial bladder cancer.

Adenocarcinoma↗
PubMed1996

Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145.

Autocrine production of transforming growth factor alpha and overexpression of the epidermal growth factor receptor (EGFR) may contribute to androgen-independent prostatic cancer growth at both primary and metastatic sites. Previously, we showed that human EGFR-blocking monoclonal antibody mAb225 inhibited the growth of DU145 human prostatic cancer cells. Here we explore the hypothesis that mAb225 may act by interfering with cell cycle traversal in these cells. Treatment with mAb225 induced G1 arrest, which was accompanied by a marked decrease in CDK2-, cyclin A-, and cyclin E-associated histone H1 kinase activities, and a sustained increase in cell cycle inhibitor p27KIP1. The increased p27KIP1 levels were attributable to elevation of both transcription and translation. CDK2 associated with p27KIP1 was increased in mAb225-treated DU145 cells. The retinoblastoma-related protein p130 remained hypophosphorylated in these retinoblastoma-negative cells. These studies demonstrate that the antiproliferative effect of EGFR blockade in DU145 cells may be mediated by up-regulation of p27KIP1 at both the mRNA and protein levels.

Antibodies, Monoclonal↗
PubMed1996

Granulocyte proteins in serum in childhood asthma: relation to spirometry and therapy.

BACKGROUND: Measurement of markers of eosinophil activation in asthmatics provides information indicative of ongoing inflammatory processes in the airways. OBJECTIVES: This study was conducted to determine the correlations between serum markers of allergic inflammation with spirometry parameters in asthmatic children in different treatment groups. METHODS: Blood eosinophils, serum levels of eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and tryptase were measured simultaneously with serial measurements of FEV1/FVC, FEF25-75 and FEF in 60 children with acute asthma on admission and after 2, 14, 30 and 60 days. Group A received bronchodilators only (n = 20), group B received sodium cromoglycate (SCG) (n = 20) and group C received oral and/or inhaled corticosteroids (n = 20). RESULTS: Oral steroid treatment (2 mg/kg/day), given at the onset of the asthma attack, resulted in significant reduction in the ECP and EPX levels in all the children. However, these reduced ECP and EPX levels were not sustained in the children, even in those who continued on maintenance steroid treatment. Significant, but inconsistent, correlations between ECP, EPX with total eosinophil count, Percentage eosinophils and spirometry parameters were observed at the different time-points. Tryptase levels were normal in all subjects. There were no significant correlations between myeloperoxidase levels and the spirometry parameters or eosinophil parameters. Serial monitoring of ECP and EPX levels was found to be of some use in predicting clinical outcome in certain steroid-dependent asthmatics (group C) but of no value in the mild asthmatics (group A). CONCLUSION: While elevation of ECP, EPX and MPO in the serum of childhood asthmatics suggests ongoing inflammation and may inversely correlate with spirometry parameters in some patients, the relationship between these markers and airway function is not a simple one.

Adolescent↗
PubMed1994

Cisplatin, fluorouracil, and leucovorin. Increased toxicity without improved response in squamous cell head and neck cancer.

OBJECTIVE: To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer. DESIGN: Nonrandomized, prospective trial. SETTING: Referral center (comprehensive cancer center). PATIENTS: Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy. INTERVENTIONS: Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days. MAIN OUTCOME MEASURES: Clinical response to chemotherapy and observed toxic effects during chemotherapy. RESULTS: Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10. CONCLUSIONS: While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.

Adult↗
PubMed1994

Tuberculous pericarditis in children: a review of 44 cases.

This retrospective study reports experience in 44 children with pericardial tuberculosis seen during a 6-year period, 1986 to 1991. Thirty-seven children presented with pericardial effusion (PE), 4 with constrictive pericarditis and 3 with effusive constrictive disease. Features of cardiac tamponade were present in 90%, and in 91% radiologic cardiomegaly was found. A two-dimensional echocardiogram is diagnostic for PE. Culture and biopsy yields for Mycobacterium tuberculosis were low (18%). The Mantoux test was positive (> 10 mm) in 75%. In 14 patients doubt about etiology necessitated treatment for possible pyogenic infection with anterior pericardiotomy as opposed to diagnostic pericardiocentesis with catheter drainage. Twelve cases with PE were treated with steroids and the other 25 received only anti-tuberculous medication. Five cases of PE developed constrictive pericarditis during treatment of whom none received steroids. No statistically significant differences were demonstrated between the two groups. Only 5 of the 12 cases with constrictive pericarditis required pericardiectomy. There were no deaths and recovery has been complete in 43 cases. This study shows that tuberculous pericardial disease is common in areas with a high prevalence of tuberculosis. Prognosis is excellent for a condition in which morbidity and mortality have previously been high.

Age Distribution↗
PubMed1993

A phase II trial of deoxyspergualin in recurrent squamous cell head and neck cancer.

Fifteen patients with recurrent squamous cell head and neck cancer were treated with deoxyspergualin. There were no objective responses in 14 evaluable patients. The most common toxicity was reversible hypotension, which prompted dose reduction in nine patients. Deoxyspergualin is not recommended for the treatment of squamous cell head and neck cancer.

Adult↗
PubMed1993

Unawareness of illness and neuropsychological performance in chronic schizophrenia.

This research attempts to explore empirically the relationship between lack of awareness of illness and neuropsychological performance in a group of chronic schizophrenic subjects. Thirty one chronic schizophrenics were administered the recently developed Scale to Assess Unawareness of Mental Disorder (SUMD) and 3 neuropsychological tests that have demonstrated ability to assess frontal lobe performance: the Wisconsin Card Sorting Test (WCST, Verbal Fluency Test and Trials A and B. The number of categories completed and the percent perseverative responses on the WCST were found to significantly correlate with lack of illness awareness as measured by the SUMD. These two WCST variables were also able to significantly discriminate between subjects of high versus low awareness. A discriminant function analysis found that a linear combination of WCST percent perseverative responses and symptom severity could successfully categorize 84% of the aware versus unaware subjects. These results are taken to support the hypothesis that at least in some of its manifestations lack of awareness among chronic schizophrenics has an organic etiology probably mediated by the frontal lobes.

Adult↗
PubMed1993

Treatment of brain metastases from bladder cancer.

The records of 28 patients with transitional cell cancer who had brain metastases were retrospectively reviewed. Data from 19 patients were considered suitable for analysis and were included in this study. One patient was treated with surgery alone, 10 with radiation alone and 7 with radiation and surgery, while 1 received no treatment. Mean and median survival times, respectively, were 57 and 42 months from the initial diagnosis, and 11 and 4 months from diagnosis of central nervous system metastases. Patients treated with surgery and radiation demonstrated a mean survival time of 19 months compared to 6 months for patients treated with radiation alone (p = 0.03). There were 2 long-term survivors in the combined modality group at 50 and at 12 months. Enthusiasm for combined modality treatment should be tempered by the fact that selection bias favored the combined modality group; 13 patients with single lesions demonstrated a mean survival of 14 months compared to 3 months for 6 patients with multiple lesions (p = 0.009) and only patients with solitary lesions underwent surgical resection. Brain metastases have an ominous prognosis in patients with bladder cancer primaries. Considering the sum of the retrospective and prospective reports, we recommend that patients with solitary brain lesions and good performance status be aggressively managed with surgical resection and postoperative radiation therapy.

Adult↗
PubMed1992

T-wave amplitude utility revisited: some physiological and psychophysiological considerations.

The last decade has seen some quite polemicized discussions concerning the utility of T-wave amplitude as a psychophysiological measure, but more recent reports indicate that we are now moving into a more empirically oriented and analytic examination of this topic. Such a report is one by Contrada et al. (1989), who manipulated sympathetic (beta-adrenergic) influences both pharmacologically and behaviorally, and whose main conclusion was that their results "support the hypothesis that T-wave is significantly affected by beta-sympathetic influence on the heart". However, we question their other conclusion that "a nonspecific effect of heart rate change on T-wave amplitude would also account for these results", and also suggest that their discussion of the "implications for the utility of T-wave amplitude in psychophysiological research" bears further consideration. In particular, for psychophysiologists, of fundamental importance is the distinction between T-wave amplitude's utility as a physiological index and its utility as a psychophysiological index. Concerning the former issue, we consider: (a) the alpha/beta adrenergic distinction, (b) inappropriate T-wave amplitude augmentation effects to sympathomimetic stimulation, (c) the nonspecific-response-to-tachycardia argument, and (d) the view of pulse transit time as a criterial standard, rather than as a candidate index. Regarding the issue of psychophysiological index utility, we consider: (a) dependent-variable sensitivity, drawing a further distinction between reactive and specific sensitivity, and (b) independent-variable-manipulation effectiveness.

Autonomic Nervous System↗
PubMed1992

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.

Brain↗