Mild mal de debarquement after sailing.
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Biomedical subjects
Publications and source records attributed to H Cohen.
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An important contributor to the malignancy of brain tumors is their ability to infiltrate the brain. Extracellular matrix molecules and cell adhesion molecules on cell surfaces play key roles in cell migration. In the present study, we used reaggregates of dissociated cells from freshly excised human brain tumors to analyze the migration of cells from human brain tumors of different types and grades on many different adhesion proteins adsorbed to glass substrates. Proteins were chosen based on their presence in normal or neoplastic nervous tissue, and included the extra-cellular matrix molecules fibronectin, collagens, fibrinogen, laminin, tenascin-C, thrombospondin, and the neuron-glia cell adhesion molecule, Ng-CAM. Cells from astrocytomas (n = 24) migrated on a variety of substrates, in contrast to cells from primitive neuroectodermal tumors cells (n=6), which only migrated well on laminin, fibronectin, or type IV collagen but not on the other substrates. Typically, migrating cells from astrocytomas of all grades had long, slender processes, were usually bipolar, and their cell bodies did not spread well on any substrate. Although there was variability in the migration of cells from astrocytomas of the same grade, cells from high-grade astrocytomas tended to migrate more extensively (42.3 +/- 4.7 micrometers/16 h: n = 16) than cells from lower grade astrocytomas (28.9 +/- 3.9 micrometers/16 h; P = 0.07; n = 8); the most striking differences were observed for collagen substrates, on which cells from lower grade astrocytomas migrated at very low levels (7.6 +/- 2 .6 micrometers/16 h) and cells from high-grade astrocytomas at higher levels (24.4 +/- 5.2 micrometers;P = 0.01). In contrast to primary cells from glioblastomas (n = 13), glioblastoma cell lines (n = 10) consistently spread on various substrates and migrated at high levels (69.5 +/- 7.6 versus 46.4 +/-5.7 micrometers/16 h; P = 0.03), in particular, on collagens (108.4 +/- 20.2 versus 28.0 +/- 6.1 micrometers/16 h; P= 0.001). Specific monoclonal antibodies to alphaV and beta1 integrin monomers completely inhibited the migration of astrocytoma cells on most substrates, suggesting that alphaV and beta1 integrins play a crucial role in brain tumor infiltration. These studies also suggest that although a large number of extracellular matrix molecules may promote tumor cell migration, disrupting the function of only a few tumor cell receptors may be critical for tumor infiltration in the brain.
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To gain some insight into the mechanisms involved in the opposing effects of arachidonic acid and docosahexaenoic acid on the growth of rat uterine stromal cells (UIII cells), the dynamics of the uptake, conversion, and incorporation of labeled 18:2(n-6), 18:3(n-3), 20:4(n-6), 20:5(n-3), and 22:6(n-3) into lipid pools and phospholipid subclasses were examined. A very active and time-dependent conversion of [14C]18:3(n-3) to higher homologs was observed; 64.7 +/- 0.7 and 11.5 +/- 0.4% of the [14C] radioactivity incorporated in cellular lipids was recovered as 22:5(n-3) and 22:6(n-3) after 72 h incubation, respectively. The distribution of labeled fatty acids obtained after 72 h incubation with [3H]20:5(n-3) was not significantly different from that observed with 18:3(n-3). Arachidonic acid was the major fatty acid formed from [14C]18:2(n-6) and only trace amounts of 22:5(n-6) were detected. When cells were incubated for 72 h with 20:4(n-6), more than 75% of the radioactivity was recovered as arachidonate and slightly higher amounts of 22:4(n-6) and 22:5(n-6) were formed compared to those obtained after incubation with 18:2(n-6). Using both [14C]- and [3H]22:6(n-3), no significant retroconversion of labeled 22:6(n-3) occurred in the cells. More than 90% of labeled 20:4(n-6) and 22:6(n-3) taken up by the cells were esterified into phospholipids, but significant differences in their distribution among phospholipid classes and subclasses were observed. Docosahexaenoic acid was more rapidly and efficiently incorporated into phosphatidylethanolamine than 20:4(n-6) and was principally recovered in plasmalogens. Arachidonic acid was mainly incorporated in the diacyl subclasses of phosphatidylcholine and phosphatidylethanolamine and in phosphatidylinositol. The divergent profiles of these two fatty acids within the phospholipid compartments provide some information for the mechanisms of their opposite effects on UIII cell growth.
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OBJECTIVE: To evaluate intraocular pressure (IOP) control and surgical complications following trabeculectomy with 5-fluorouracil (5-FU) or mitomycin at the inferior limbus. METHODS: The charts of all patients undergoing trabeculectomy at the inferior limbus from July 1984 to March 1993 were reviewed. Surgical success was defined as IOP greater than 4 mm Hg and less than 22 mm Hg and at least a 20% reduction from preoperative IOP. PATIENTS: All 101 eyes of 101 patients had undergone prior intraocular surgery at the superior limbus. Mean patient age was 57.5 +/- 2.0 (+/-SE) years; mean follow-up was 23.4+/-2.3 months; mean preoperative IOP was 32.8+/-0.9 mm Hg; and mean number of preoperative antiglaucoma medications was 2.8+/-0.1. RESULTS: Ninety-four eyes (93.1%) received postoperative 5-FU (mean total dose, 36.3+/-1.7 mg) and seven eyes (6.9%) received intraoperative mitomycin (0.5 mg/mL). Cumulative success for all eyes at 2 and 5 years was 56% and 38%, respectively. Intraocular pressure control without medications was achieved in 39% and 15% of eyes at 2 and 5 years, respectively. Complications included 5-FU epitheliopathy (34.0% of eyes receiving 5-FU), early wound leak (26.7%), choroidal effusion (25.7%), late bleb leak (12.9%), and late bleb-related endophthalmitis (11.9%). CONCLUSION: Although trabeculectomy at the inferior limbus offers the opportunity for surgical success in eyes at high risk of failure, this procedure carries an increased risk for late complications and should be reserved for cases in which the therapeutic options are extremely limited.
OBJECTIVE: To compare trabecular meshwork height in a series of patients with juvenile primary open-angle glaucoma (JPOAG) with that in normal control patients. METHODS: Ultrasound biomicroscopy and A-scan biometry were performed on 16 eyes with JPOAG and 24 normal eyes. A radial, perpendicular image in the horizontal temporal meridian detailing the line of Schwalbe, scleral spur, and angle anatomy was obtained for each eye by a single examiner. Trabecular meshwork height was defined as the distance from the scleral spur to the Schwalbe line. RESULTS: Mean patient age (P = .85, t test), refractive error (P = .68), sex distribution (P = .26, Fisher exact test) and axial length (P = .39) were similar between the groups. Mean +/- SE trabecular meshwork heights were 0.36 +/- 0.03 mm (range, 0.19-0.53 mm) for JPOAG and 0.58 +/- 0.02 mm (range, 0.40-0.80 mm) for controls (P < .001). Eyes with greater axial length tended to have larger trabecular meshworks in both groups (P = .012, multivariate regression). A trabecular meshwork height-axial length ratio of 0.021 or less was associated with a significantly increased risk for JPOAG being present (odds ratio, 57; 95% confidence interval, 6.0-541). CONCLUSIONS: The trabecular meshwork is smaller in eyes with JPOAG compared with that in normal eyes. This finding suggests a structural abnormality that may underlie the reduced outflow.
An intraoperative cytological imprint of a well study case of collecting duct carcinoma of the kidney is reported. Papillary structures, fibrotic desmoplastic stroma, tubular formations, and tumoral cells with high grade cytological atypia were found. Cytological details described help to avoid misinterpretation of collecting duct carcinoma as a metastatic tumor. The peculiar morphology, the immunohistochemical and biological behavior of this rare tumor justifies its classification in a special group.
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This study was designed to evaluate the impact of the protocol-driven antihypertensive therapy on outcomes guided by the Joint National Committee (JNC) on Detection, Evaluation, and Treatment of high blood pressure. In a systematic hypertension control program for union employees conducted in New York City, untreated patients who began treatment on monotherapy guided by JNC recommendations during three representative periods: I-pre-JNC IV (1986-1987); II-post-JNC IV (1990-1991); and III (JNC V)-period of application of what were later published as JNC-V guidelines (1992) were observed during 1 year of treatment. A total of 550 presumably untreated patients were prescribed either diuretics, beta-blockers, calcium channel blockers, or angiotensin converting enzyme inhibitors. There were 231 in period I, 213 in II, and 106 in III. The patient composition over time became more predominantly female and Hispanic (I to III: 28% to 34%, and 35% to 45%, respectively). The main outcome measures were type of drug first prescribed and the outcomes at the end of 1 year-changes in blood pressure, clinical chemistry measures and therapy, and clinic attendance are dropout rate. The pattern of first drug prescription changed from 85% to 90% of patients given diuretics or beta-blockers in I to 90% begun on calcium channel blockers or angiotensin converting enzyme inhibitors in II and finally, to an even distribution of drugs in III. Blood pressure response was similar across the three periods, 135/89 mm Hg (I), 138/89 (II), and 140/89 (III). Proportion of patients remaining on their initial drug in each period was fairly similar (60%, 67%, and 69%). Scheduled clinic visits fell significantly from 7.4 visits in I, 6.9 in II, and 6.4 in III (I upsilon III P = .004). Dropouts diminished significantly from 17% in I, to 10% in II, and 9% in III (I upsilon II or III P = .045). Modest positive changes in cholesterol and fasting blood sugar level occurred over time. In this general community setting, dramatic shifts in the choice of initial drug based upon application of JNC guidelines had little discernable impact on short term patient outcomes.
BACKGROUND: Rapid urease testing is the initial endoscopic test of choice for the diagnosis of Helicobacter pylori. Determination of the relative diagnostic yields and times to a positive test for the different rapid urease tests is important for endoscopists. We compared three commercially available tests using histologic examination and culture as a gold standard. METHODS: Patients undergoing upper endoscopy had six biopsy specimens taken from the antrum and six from the body with a large-channel biopsy forceps. Each set of six specimens was divided as follows: one each for CLOtest, Hpfast, and Pyloritek rapid urease tests; one for culture; and two for histologic examination (H&E, Genta). All tests were read every 15 minutes for 1 hour; the final reading for Pyloritek was at 1 hour. CLOtest and Hpfast were also read at 4 hours and 24 hours. RESULTS: One hundred seventy-three sets of biopsy specimens from 87 patients were evaluated; 98 (57%) of the 173 sets were positive for H. pylori by histologic examination and/or culture. The mean and median times to a positive test were significantly less for Pyloritek (0.5 +/- 0.02 hour and 0.5 hour) than for CLOtest (2.0 +/- 0.6 hour and 0.75 hour) or Hpfast (2.2 +/- 0.6 hour and 0.5 hour). The sensitivities at the final readings were similar among the three tests (CLOtest: 93%; Hpfast: 88%; Pyloritek: 89%), but sensitivities at 1 hour were significantly better for Pyloritek (89%) than for CLOtest (71%) or Hpfast (66%). At 4 hours, sensitivities for CLOtest and Hpfast improved significantly and were not significantly different from those of Pyloritek. Specificities were 99% to 100% at all times for all three tests. CONCLUSION: The three rapid urease tests, CLOtest, Hpfast, and Pyloritek, provide comparable results, with sensitivities around 90% and specificities around 100%. The Pyloritek becomes positive more rapidly than the CLOtest or Hpfast. If a reading is desired within 1 hour, the Pyloritek provides a greater sensitivity than the CLOtest or Hpfast without any sacrifice in specificity.
BACKGROUND: A rapid urease test is the initial test of choice for the diagnosis of Helicobacter pylori at endoscopy. Incubating the CLOtest at 30 degrees to 40 degrees C is recommended, but this decreases simplicity and requires the purchase of additional equipment. We compared results of testing at room temperature versus incubation at 37 degrees C. METHODS: Four biopsy specimens were taken from the same portion of the antrum in 200 patients undergoing upper endoscopy. One was placed in each of two CLOtests and two were sent for histologic examination. One CLOtest was incubated at 37 degrees C while the other remained at room temperature (22 degrees to 24 degrees C). Tests were checked every 15 minutes for the first 3 hours, every 1 hour from 3 to 6 hours, and at 24 hours. RESULTS: One hundred twenty one (61%) of 200 patients had H. pylori on histologic examination. Median time to a positive test was 3/4 hour at 37 degrees C and 1 hour at room temperature (p < 0.0001). Sensitivities were greater at 37 degrees C at 1 hour (70% vs 49%; p = 0.001) and 2 hours (86% vs 76%, p = 0.07), but were nearly identical thereafter. Specificities, identical at the two temperatures, were 99% to 100% at 1 to 6 hours and 95% at 24 hours. The CLOtest became positive more rapidly at 37 degrees C in 72% of patients: more than 1/2 hour faster in 42%; and more than 1 hour faster in 16% of patients. CONCLUSIONS: Incubation of the CLOtest at 37 degrees C hastens the time to a positive test in most patients, although the time saved is usually less than 1 hour. Sensitivity is improved when the test is read at 1 to 2 hours, but no improvement is seen beyond this time. Specificity is not influenced by warming. CLOtest incubation at 37 degrees C should be done if a final reading of the CLOtest is desired within 1 to 2 hours of biopsy.
We have investigated whether activated protein C resistance (APCR) is associated with second-trimester miscarriage. The prevalence of APCR was significantly higher amongst women with a history of second-trimester miscarriage (10/50; 20%) compared with either women with a history of first-trimester miscarriages only (4/70; 5.7%) or a control group of parous women with no previous history of pregnancy losses (3/70; 4.3%) (P < 0.02). These results suggest that APCR may be an important mechanism of second-trimester pregnancy loss, possibly related to the increase in intravascular coagulation that occurs during pregnancy.
The goals of this study were to collect normative data on asymptomatic, ambulatory, community-dwelling adults on a standard diagnostic test of vestibular function in balance and to determine if their responses differ significantly from younger adults. Subjects were divided into four age groups, 18-44 years (young), 45-69 years (middle-aged), 70-79 (old), and 80-89 (elderly). Subjects were seen in the neurotologic diagnostic laboratory at a tertiary care facility. Their dynamic balance was tested under a variety of sensory conditions using the EquiTest (NeuroCom), a standard diagnostic test. The data from one subtest, the Sensory Organization Test (SOT) were evaluated. These data showed significant age-associated declines in overall score and changes in movement strategy. These results suggest that those parts of the vestibular system involved with balance have age-related declines through the end of the life span, even in asymptomatic people, and that these changes do not level off but continue into the ninth decade. Therefore, when elderly people are evaluated for balance disorders age-appropriate norms should be used. These results also suggest that declines in motor performance on laboratory tests are not directly related to reduced independence in essential activities of daily living in elderly people.
High-resolution computed tomography (HRCT) scans have been advocated as providing greater sensitivity in detecting parenchymal opacities in asbestos-exposed individuals, especially in the presence of pleural fibrosis, and having excellent inter- and intraobserver reader interpretation. We compared the 1980 International Labor Organization (ILO) International Classification of the Radiographs of the Pneumoconioses for asbestosis with the high-resolution CT scan using a grid scoring system to better differentiate normal versus abnormal in the ILO boundary 0/1 to 1/0 chest roentgenograph. We studied 37 asbestos-exposed individuals using the ILO classification, HRCT grid scores, respiratory symptom questionnaires, pulmonary function tests, and bronchoalveolar lavage. We used Pearson correlation coefficients to evaluate the linear relationship between outcome variables and each roentgenographic method. The normal HRCT scan proved to be an excellent predictor of "normality," with pulmonary function values close to 100% for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO) and no increase in BAL inflammatory cells. Concordant HRCT/ILO abnormalities were associated with reduced FEV1/FVC ratio, reduced diffusing capacity, and alveolitis consistent with a definition of asbestosis. In our study, the ILO classification and HRCT grid scores were both excellent modalities for the assessment of asbestosis and its association with impaired physiology and alveolitis, with their combined use providing statistical associations with alveolitis and reduced diffusing capacity.
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