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Biomedical subjects

M E Cohen

Publications and source records attributed to M E Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Detection of periodontal probing change by analysis of distribution mean and skew.

A problem associated with probing measurement is that important site-specific change may be obscured by measurement variability. Furthermore, if many sites are monitored there is an increasing likelihood that any particular "detected change" might be the result of this measurement error. Since error and multiplicity effects would tend to increase mouth-wise false positive rate, demanding decision thresholds are often set. However, imposition of difficult criteria, increases site-wise false negative rate and therefore reduces utility in the clinical setting. Evaluation of mean change might sometimes be a useful alternative, but also problematic as a few dramatic site-level losses can be inconsequential among many stable or improving sites. A strategy is proposed for evaluating probing changes in a single patient, which is based on the statistical evaluation of two attributes of the change distribution. (1) Disease progression is concluded when mean probing loss increases over time, and (2) a clinically relevant asymmetry is concluded when the distribution tail corresponding to loss is skewed. Computerized simulation was used to determine alpha-error for tests of mean and skew, for three different distributions of probing change. Actual alpha-error was shown to be near nominal levels. Power was estimated as a function of the number and magnitude of sites with probing loss and as a function of whether there was change in both mean and skew or in skew alone. Under most conditions studied, simultaneous tests for skew and mean provided enhanced power relative to a test for loss alone and would appear to offer the clinician an additional statistical context for appraising disease status.

Bias↗
PubMed1995

Postoperative chemotherapy and delayed radiation in infants and very young children with choroid plexus carcinomas. The Pediatric Oncology Group.

Eight infants with choroid plexus carcinomas were treated with surgery, prolonged postoperative chemotherapy and delayed radiation. The results suggest that some infants with choroid plexus carcinomas can be successfully treated with multimodality therapy, even allowing children with less than a gross total resection to have prolonged disease-free intervals.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Alternative splicing and differential targeting of fibroblast growth factor receptor 1 in the pregnant rat uterus.

Recent studies suggest that steroid effects on uterine cell proliferation may be moderated by polypeptide growth factors. We now provide evidence that high affinity fibroblast growth factor (FGF) receptors are present temporally and spatially in the pregnant rat uterus (days 4-6) to support the idea that basic FGF action occurs via binding to its high affinity FGF receptor 1 (FGFR1). Reverse transcription-polymerase chain amplification indicates that both the full-length transcript and an alternatively spliced messenger RNA are present in the uterus. Western immunoblot analysis confirms that rat uterine membrane proteins contain two receptor isoforms, and these receptors bind basic FGF with high affinity and specificity. Immunolocalization of FGFR1 revealed receptor-positive cells in both the uterine stroma and epithelia on days 4-6 of pregnancy. However, the receptor was differentially localized in the disparate cell types. The nuclei of stromal cells were positive for FGFR1, whereas epithelial cell nuclei were negative. Together, these results suggest that FGF signal transduction in uterine stromal cells is mediated by activation of FGFR1.

Alternative Splicing↗
PubMed1995

A comparison of three statistics for detecting differences in digitized dental radiographs: a simulation study.

OBJECTIVES: Because of methodology-induced structural differences in dental radiographs, determination of change has always depended upon expert interpretation. However, new methods should be able to considerably reduce structured error in digitized subtracted images. Once true change in density is obscured only by random variation in pixel density, statistical methods may be brought to bear on the problem of detecting change. The most appropriate statistic is not obvious, however, since density change can be quantified with respect to both magnitude and dimensional extent. Whereas mean density loss is often intuitively defined as the average density of those pixels losing density (to preclude gaining pixels from offsetting losing pixels), the extent of change may be defined in a variety of ways. In this study, extent was defined as either (a) the total number of pixels losing density, or (b) the size of the largest cluster of losing pixels. The object was to evaluate the comparative statistical power of three possible statistics (based on mean density, number of losing pixels, and size of largest losing cluster) for detecting change. METHODS: In a series of simulations of comparative clinical trials, density was reduced in the centre of 1600-pixel square regions of interest by either one or 10 grey-scale units, and t-tests, based on the three statistics, were then compared for their ability to detect differences. RESULTS: Each of the three statistics was shown to exhibit superior relative power under particular conditions of loss magnitude, loss distribution, and pixel threshold for change. CONCLUSION: Selection of the appropriate statistic for identifying change between radiographs will require further information about the anticipated distribution of density changes for the different disease processes under investigation.

Absorptiometry, Photon↗
PubMed1995

Necrotizing ulcerative gingivitis, periodontitis, and stomatitis: clinical staging and predisposing factors.

Necrotizing ulcerative gingivitis (NUG), necrotizing ulcerative periodontitis (NUP), and necrotizing stomatitis (NS), collectively termed necrotizing gingivostomatitis (NG), represent a dramatic, but rare oral infection associated with diminished systemic resistance, including HIV infection. Over a 5-year period, 68 consecutive NG patients from a population with known HIV status were evaluated and treated. Lesions were staged (modified Pindborg), and clinical findings and predictor variables were compared to 68 random control subjects without NG. Most cases (52%) were stage 1, with necrosis of the tip of the interdental papilla only; 19% were stage 2, with the entire papilla affected; 22% had necrosis of marginal (stage 3) or attached gingiva (stage 4); and 7% were more advanced, with mucosal necrosis or bone exposure. Attachment loss was a feature of stage 2 or greater NG. Beside HIV infection, significant predisposing factors included poor oral hygiene, unusual life stress, inadequate sleep, Caucasian race, age 18 to 21 years, and recent illness. Ten of 68 NG patients were HIV-positive. These patients were older than seronegative patients, less likely to be Caucasian, and maintained better oral hygiene and sleep. HIV-positive NG cases were clinically indistinguishable from HIV-negative cases in this series.

Adult↗
PubMed1994

Etiologies of central diabetes insipidus in children.

The last major review of the etiologies of central diabetes insipidus in children was performed a quarter century ago, prior to the development of modern neuroimaging techniques. We retrospectively reviewed the records of children with central diabetes insipidus identified at Children's Hospital of Buffalo from 1979 to 1992. Of the 35 patients identified, 27 were males and 8 were females. Their ages ranged from 3 weeks to 20 years. Nineteen children had brain tumors, 7 had cerebral malformations, 3 had central nervous system infections, 1 had traumatic brain injury, and 5 were considered idiopathic. Patients with brain death were excluded from the review. Thirty-one of 35 patients developed diabetes insipidus in conjunction with other endocrinopathies. Brain tumor and its treatment account for the most common cause. Cranial magnetic resonance imaging has improved the identification of structural lesions and the understanding of the pathophysiology of central diabetes insipidus.

Adolescent↗
PubMed1994

Recommended revisions to American Dental Association guidelines for acceptance of chemotherapeutic products for gingivitis control. Report of the Task Force on Design and Analysis in Dental and Oral Research to the Council on Therapeutics of the American Dental Association.

This paper presents suggested revisions to the American Dental Association's 1985 guidelines for acceptance of anti-gingivitis chemotherapeutic agents. The areas of study design, choice and quality control of clinical gingivitis measurements, statistical analysis, and minimum strength of effect, are addressed. The revisions articulate certain aspects of study design which were implicit in the 1985 guidelines, clarify language on cross-over designs and independence of studies, and recommend use of a United States population in at least one trial supporting a product. Separate recording and analysis of a product's effect on gingival bleeding is proposed, and quality control of clinical measurements receives enhanced emphasis. Modestly elaborated statistical reporting guidelines and strengthened approval criteria, based on size of estimated effect as well as statistical significance, are advocated.

American Dental Association↗
PubMed1994

Proposed guidelines for American Dental Association acceptance of products for professional, non-surgical treatment of adult periodontitis. Task Force on Design and Analysis in Dental and Oral Research.

Guidelines are suggested for determining efficacy of products to supplement scaling and root planing in professional, non-surgical treatment of adult periodontitis. They result from an extended process including a conference on clinical trials in gingivitis and periodontitis, a subsequent workshop, and commentary from industrial, academic, professional and governmental members of the periodontal research community on two drafts. Recommendations are made in the broad areas of basic study design, subject and periodontal site selection, clinical management, choice of outcome variables, statistical summarization and analysis, and criteria for acceptance. Prominent dissenting views, with justifications for positions taken here, are also provided. Groundwork is laid for possible future guidelines addressing products for primary prevention or over-the-counter uses, or for determining superiority or equivalence of competing products. However, issues are identified which require further exploration before responsible and widely acceptable recommendations can be made in these areas. The guidelines suggested here are meant to form the basis of an evolving document rather than a static standard. It is suggested that they be reviewed frequently in the light of improvement in the technology available for periodontal research, and the emergence of products representing new approaches to periodontal therapy.

Adult↗
PubMed1994

Brush-border tyrosine phosphorylation stimulates ileal neutral NaCl absorption and brush-border Na(+)-H+ exchange.

The drug genistein, a tyrosine (Tyr) kinase inhibitor, was used to define a role for Tyr phosphorylation in regulation of basal and stimulated neutral NaCl absorption in rabbit ileum. Brush-border vesicles contain Tyr-phosphorylated peptides. Genistein freeze-thawed into the vesicles caused a concentration-dependent inhibition of at least three peptides with M(r) 111,000, 83,000, and 80,000. Studied with the Ussing chamber-voltage clamp technique, genistein added to the ileal mucosal surface inhibited neutral NaCl absorption. Direct addition of genistein to brush-border vesicles made from ileal villus cells inhibited brush-border Na(+)-H+ exchange but not D-glucose-stimulated Na+ uptake. These effects were not duplicated by genistin, a drug with similar structure to genistein but lacking Tyr kinase inhibiting properties. Serosal but not mucosal epidermal growth factor (EGF) stimulated NaCl absorption. Mucosal genistein but not genistin also altered second-messenger regulation of neutral NaCl absorption, inhibiting the effect of Ca2+ ionophore A-23187 and of serosal EGF but not affecting the transport changes caused by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). In contrast, the Cl secretory effects indicated by the increase in short-circuit current for all three agents, A-23187, EGF, and 8-BrcAMP, were inhibited by mucosal genistein. These results suggest that 1) a Tyr kinase is involved in basally stimulating ileal neutral NaCl absorption and brush-border Na(+)-H+ exchange; 2) EGF stimulates NaCl absorption by an effect exerted from the serosal surface, but the effect also involves a brush-border Tyr kinase; 3) brush-border Tyr kinase is involved in the ability of Ca2+ ionophore A-23187 to inhibit neutral NaCl absorption but is not involved in the transport effects of cAMP. This study suggests that Tyr kinase(s) acting over short time periods is involved in stimulation of neutral NaCl absorption and brush-border Na(+)-H+ exchange and also in Ca(2+)-induced inhibition of NaCl absorption. These studies represent the first example of a brush-border Tyr kinase being involved in short-term signal transduction in intestinal epithelial cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Lung volume specificity of inspiratory muscle training.

We examined the extent to which training-related increases of inspiratory muscle (IM) strength are limited to the lung volume (VL) at which the training occurs. IM strength training consisted of performing repeated static maximum inspiratory maneuvers. Three groups of normal volunteers performed these maneuvers at one of three lung volumes: residual volume (RV), relaxation volume (Vrel), or Vrel plus one-half of inspiratory capacity (Vrel + 1/2IC). A control group did not train. We constructed maximal inspiratory pressure-VL curves before and after a 6-wk training period. For each group, we found that the greatest improvements in strength occurred at the volume at which the subjects trained and were significantly greater for those who trained at low (36% for RV and 26% for Vrel) than at high volumes (13% for Vrel + 1/2IC). Smaller increments in strength were noted at volumes adjacent to the training volume. The range of vital capacity (VC) over which strength was increased was greater for those who trained at low (70% of VC) than at high VL (20% of VC). We conclude that the greatest improvements in IM strength are specific to the VL at which training occurs. However, the increase in strength, as well as the range of volume over which strength is increased, is greater for those who trained at the lower VL.

Adult↗
PubMed1994

Pressure-flow specificity of inspiratory muscle training.

The inspiratory muscles (IM) can be trained by having a subject breathe through inspiratory resistive loads or by use of unloaded hyperpnea. These disparate training protocols are characterized by high inspiratory pressure (force) or high inspiratory flow (velocity), respectively. We tested the hypothesis that the posttraining improvements in IM pressure or flow performance are specific to training protocols in a way that is similar to force-velocity specificity of skeletal muscle training. IM training was accomplished in 15 normal subjects by use of three protocols: high inspiratory pressure-no flow (group A, n = 5), low inspiratory pressure-high flow (group B, n = 5), and intermediate inspiratory pressure and flow (group C, n = 5). A control group (n = 4) did no training. Before and after training, we measured esophageal pressure (Pes) and inspiratory flow (VI) during single maximal inspiratory efforts against a range of external resistances including an occluded airway. Efforts originated below relaxation volume (Vrel), and peak Pes and VI were measured at Vrel. Isovolume maximal Pes-VI plots were constructed to assess maximal inspiratory pressure-flow performance. Group A (pressure training) performed 30 maximal static inspiratory maneuvers at Vrel daily, group B (flow training) performed 30 sets of three maximal inspiratory maneuvers with no added external resistance daily, and group C (intermediate training) performed 30 maximal inspiratory efforts on a midrange external resistance (7 mm ID) daily. Subjects trained 5 days/wk for 6 wk. Data analysis included comparison of posttraining Pes-VI slopes among training groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Neurology training.

Explore the source record for details and available documents.

Internship and Residency↗
PubMed1994

Desmoplastic infantile gangliogliomas: an approach to therapy.

Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Information integration in a decision support system.

Electronic medical records pose a challenge because of the complex types of data which are included. Decision support systems must be able to deal effectively with these data types. In the expert system demonstrated here, a diversity of data types are included. These data are processed by three different methods. However, the different methods of processing are transparent to the user. An overall rule-based interface integrates the different methods into one comprehensive system.

Artificial Intelligence↗
PubMed1993

Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study.

PURPOSE: In September 1984, the Pediatric Oncology Group began accrual to a Phase I/II study designed to assess the efficacy and toxicity of sequentially escalated doses of hyperfractionated (twice daily) radiotherapy in children with poor-prognosis brain stem tumors. Pediatric Oncology Group Study #8495 closed in June 1990 with a total of 136 patients on study. We report here the outcome of patients treated at the third and final dose level (75.6 Gy), and compare the results to those obtained at the 66 and 70.2 Gy dose levels. METHODS AND MATERIALS: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the midbrain, pons or medulla. Histological confirmation of diagnosis was not mandatory provided that the clinical and radiological findings were typical for brain stem glioma. Treatment consisted of radiotherapy delivered to local fields. At the third dose level, fraction sizes of 1.26 Gy were given twice daily, with a minimum interfraction interval of 6 hr to a dose of 75.6 Gy in 60 fractions over 6 weeks. Between 5/89 and 6/90, 41 patients were accrued to the study. Two were excluded from analysis leaving 39 evaluable patients, 21 male and 19 female, whose ages ranged from 3 to 15 years (median 7.5 years). RESULTS: Following treatment, neurological improvement was reported in 30/39 (77%) of the patients. On central review of imaging studies in 29 patients, one patient was found to have had a complete response to radiotherapy, five a partial (> 50% response), and only three had non-responding or progressive disease. The median time to disease progression was 7 months; median survival time was 10 months; survival at 1 year was 39.9% (SE 8.3%) and at 2 years, 7% (SE 4.8%). The pattern of failure was local in all patients; in addition six had evidence of leptomeningeal seeding. Morbidity of treatment included an enhanced skin reaction (21%), otitis media and/or externa (26%), and steroid use > 3 months (62%). Intralesional necrosis was a frequent finding (45%) on imaging studies performed at a median time of 6 weeks post treatment. CONCLUSION: The results of treatment in terms of progression-free survival and overall survival are not significantly different (at p = .55 and p = .46, respectively) from those obtained at the two previous dose levels. There is no evidence that higher doses of hyperfractionated radiotherapy given as in this study improve the outlook of patients with poor-risk brain stem gliomas.

Adolescent↗
PubMed1993

Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.

BACKGROUND: Among patients with malignant brain tumors, infants and very young children have the worst prognosis and the most severe treatment-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncology Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the developing brain. METHODS: Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. This sequence was repeated until the disease progressed or for two years in 132 children 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of age at diagnosis. After this, the patients received radiation therapy. The response to the first two cycles of chemotherapy was measured in 102 patients with residual postoperative disease. RESULTS: The first two cycles of cyclophosphamide and vincristine produced complete or partial responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas or embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one year for children who were 24 to 36 months old at diagnosis and 39 percent at two years for those under 24 months of age at diagnosis. Multivariate analysis identified embryonal tumors as a significant adverse prognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative risk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete responses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparison of cognitive evaluations obtained at base line and after one year of chemotherapy revealed no evidence of deterioration in cognitive function. CONCLUSIONS: Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Glucocorticoid stimulation of ileal Na+ absorptive cell brush border Na+/H+ exchange and association with an increase in message for NHE-3, an epithelial Na+/H+ exchanger isoform.

Methylprednisolone stimulates rabbit ileal neutral NaCl absorption; and aminoglutethimide, which decreases glucocorticoid levels, decreases NaCl absorption. Studies were carried out to determine the mechanism of these effects and to determine which members of the gene family of mammalian Na+/H+ exchangers were involved. Rabbits were treated subcutaneously with methylprednisolone (40 mg daily for 24 or 72 h), aminoglutethimide (100 mg twice daily for 72 h), or saline as a control. Ileal brush border membranes were prepared by magnesium precipitation, and brush border Na+/H+ exchange was determined by 22Na+ uptake over 3-8 s. The 22Na+ uptake experiments were performed in the presence of a voltage clamp using either valinomycin/potassium or tetramethylammonium/nitrate to eliminate potential contributions by other electrogenic transport processes. Methylprednisolone treatment approximately doubled ileal brush border Na+/H+ exchange, whereas aminoglutethimide led to a 50% decrease in Na+/H+ exchange. These effects were specifically on Na+ uptake with an acid inside pH gradient, whereas diffusive Na+ uptake (no pH gradient), glucose-dependent Na+ uptake, and glucose and Na+ equilibrium volumes were not affected. To determine if the increase in Na+/H+ exchange was associated with an increase in message expression, mRNA levels were measured by ribonuclease protection assay. Methylprednisolone stimulated the NHE-3 mRNA level by 4-6-fold at 24 h, which remained increased at 72 h. In contrast, messages for NHE-1 and NHE-2 were not affected by methylprednisolone. In summary, 1) methylprednisolone stimulation of rabbit ileal Na+ absorption is due to stimulation of ileal villus cell brush border Na+/H+ exchange; 2) basal ileal brush border Na+/H+ exchange is dependent on glucocorticoid levels; and 3) an increase in NHE-3 message, but not in NHE-1 or NHE-2 message, correlates with the stimulation of ileal brush border Na+/H+ exchange. It is likely that NHE-3 is an Na+/H+ exchanger that is involved in ileal Na+ absorption.

Aminoglutethimide↗