Placental thrombosis and second trimester miscarriage in association with activated protein C resistance.
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Biomedical subjects
Publications and source records attributed to H Cohen.
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We analyzed the clinical and laboratory findings and outcome of 173 patients hospitalized at our institution from 1983 to 1994 with multidrug-resistant tuberculosis (MDR-TB) and evaluated outcome. The 173 patients (mean age 40 +/- 1 yr) were predominantly male (92%), African American or Hispanic (80%), and mostly undomiciled. Over half (52%) were known to be HIV-infected. HIV-positive MDR-TB patients had significantly more pulmonary and constitutional symptoms, more extrapulmonary disease, and fewer cavitary lesions on chest radiographs. Fifty-five percent of the patients in the cohort have died; mortality was significantly greater for HIV-positive than HIV-negative (72% versus 20%, p < 0.01). The median duration of survival of MDR-TB patients was 22 +/- 1 mo. Overall, extrapulmonary involvement was a risk factor for shorter survival, while a cavitary lesion on initial chest film and institution of appropriate treatment were positive predictors of survival. In HIV+ patients, only appropriate therapy was associated with prolonged survival (median of 14.1 mo). Interestingly, there was a trend toward better outcome in the first half of the decade reviewed. We conclude that although mortality from MDR-TB is high in both HIV-positive and HIV-negative patients, institution of appropriate therapy is the factor most strongly associated with a favorable outcome. Development of new diagnostic and therapeutic strategies for MDR-TB are urgently needed.
PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.
Ependymomas are rare central nervous system (CNS) neoplasms that occasionally disseminate along the neuraxis or to extraneural sites. Definitive criteria predictive of dissemination have yet to be determined. One hundred forty patients with CNS ependymoma (88 primary spinal and 52 primary intracranial tumors) were surgically treated by the senior author (F.J.E.) between 1986 and 1994. Sixteen patients (11.4%) demonstrated tumor dissemination. The disseminated group consisted of 11 (12.5%) of 88 primary spinal and five (9.6%) of 52 primary intracranial ependymomas. The authors retrospectively reviewed the patients with CNS ependymoma and have identified several characteristics associated with dissemination from the primary tumor site. The mean time from diagnosis to dissemination was 6.8 years. The patients with disseminated disease were younger (16.8 vs. 28.3 years old, p = 0.02), had fewer gross-total resections (29% vs. 68%, p = 0.015), and had tumors with higher proliferative indices (MIB-1 staining, 13.14% vs. 2.06%, p = 0.02). High-grade tumors had a mean proliferation index of 21%, versus 2.4% and 1.6% for myxopapillary and low-grade tumors, respectively (p = 0.0003). In contrast to previous studies, tumor histology was the most significant variable for time to dissemination as determined by multivariate analysis (p = 0.008). Myxopapillary and high-grade tumors were 3.6 and 5.6 times more likely to have a shorter time to dissemination than low-grade tumors. In addition, dissemination is associated with a worse prognosis. At follow-up review, 31% of patients with disseminated disease had died compared to 7% of patients without dissemination (p = 0.04). It is concluded that younger patients with subtotal resections, myxopapillary or high-grade histology, and tumors with high proliferative indices are at substantial risk for the development of disseminated disease during their clinical course.
Using color and pulsed Doppler ultrasonography, the interobserver reliability of measurements in the fetal circulation was evaluated in 41 pregnancies of 25 to 39 weeks' gestation. Two observers recorded flow velocity waveforms from the middle cerebral and renal arteries for measurement of peak systolic, minimum diastolic, and mean velocities, pulsatility index, and resistive index. Intraclass correlation coefficient of reliability was calculated by analysis of variance. Substantial interobserver agreement was found for pulsatility index and minimum diastolic velocity in both arteries. Therefore, these measurements have the greatest clinical applicability.
OBJECTIVES: To compare the efficacy and safety of mesalamine (5-ASA) suspension enema versus oral sulfasalazine (SAS) in patients with active mild to moderate distal ulcerative colitis. METHODS: Thirty-seven patients were randomly assigned to treatment with either rectal mesalamine, 4 g at night, (n = 19) or oral sulfasalazine, 1 g four times a day, (n = 18) in a 6-wk, double-blind, double-dummy, parallel-group, multicenter study. Patients known to be refractory to SAS or 5-ASA preparations were excluded. Efficacy was assessed by a physician-rated Disease Activity Index (DAI), which included symptom evaluations and sigmoidoscopic findings, by physician-rated Clinical Global Improvement (CGI) scores, and by Patient Global Improvement (PGI) scores. Safety was assessed by adverse event reports, clinical laboratory tests, and physical examination. Results. Mean DAI scores indicated significant improvement from baseline in both treatment groups. CGI scores indicated that 94% of the 5-ASA patients were either "Very Much Improved" or "Much Improved" at wk 6 versus 77% of the SAS patients. PGI ratings showed more improvement in the 5-ASA treatment group than in the SAS group at wk 2 (p = 0.02) and at wk 4 (p = 0.04). Adverse events, primarily headache and nausea, occurred significantly more frequently (p = 0.02) in the SAS than in the 5-ASA group (83 vs 42%). Three patients were withdrawn from SAS treatment because of adverse events. CONCLUSIONS: Rectally administered 5-ASA is as effective as oral SAS in treatment of active distal ulcerative colitis but is associated with fewer and milder adverse events. Patients treated with 5-ASA reported improvement earlier than those treated with SAS.
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Single-stranded deoxyribonucleic acid (ssDNA) thymidylic acid icosanucleotides (dT20) were synthesized on the surfaces of derivatized quartz optical fibers to create an optical DNA biosensor. The synthesis made use of an automated solid-phase synthesizer and phosphoramidite synthons. The covalently immobilized oligomers were found to hybridize with complementary ssDNA (cDNA) or ssRNA (cRNA) from solution, and the device was regenerable for multiple cycles of application. Hybridization on optical fibers was detected by the use of the fluorescent DNA stain ethidium bromide (EB). The procedure used hybridization assay techniques and provided a detection limit of 86 ng x mL(-1) cDNA and a sensitivity of 200% fluorescence intensity increase per 100 ng x mL(-1) of cDNA, with one cycle of hybridization analysis requiring 45 min. The sensor has been observed to be regenerable (minimum of five cycles) and to sustain full activity after prolonged storage times (1 year), harsh washing conditions (sonication), and sterilization (autoclaving). The extent of hybridization between the immobilized and complementary nucleic acid strands was determined by UV absorbance thermal denaturation studies wherein all 20 bases on each strand of the nucleic acid were found to be involved in duplex formation.
To determine the association of renal function and the course of blood pressure in antihypertensive therapy, we studied the changes in serum creatinine as a measure of renal function and in-treatment blood pressure in black and white hypertensive patients. We measured serum creatinine in 2125 mild and moderately hypertensive men during treatment over an average of 5 years. Both unadjusted mean initial and final serum creatinine of 758 blacks (113 and 117 mumol/L respectively) were significantly higher than those of 1367 whites (108 and 107 mumol/L), with a small increase of 4 mumol/L (p < 0.01) for blacks and a fall of 0.9 mumol/L (p > 0.05) for whites. Less than 2% of all patients attained or remained at a final serum creatinine of 177 mumol/L or more. Of this small group (3% blacks, 1.4% whites), 31% had proteinuria at entry. After stratification by in-treatment diastolic blood pressure (< 95 and > or = 95 mm Hg) in each race, mean slopes of reciprocal serum creatinine were estimated, adjusting for age at entry, initial serum creatinine, diastolic pressure, and body-mass index by analysis of covariance. The two adjusted mean slopes did not differ significantly within each race. Multiple regression analysis confirmed that in-treatment diastolic pressure was not independently associated with final serum creatinine. The change in renal function was most likely a reflection of regression towards the mean, and does not support the view that antihypertensive treatment is an important determinant of renal function in mild-to-moderate hypertensive patients. Patients with substantial renal insufficiency may have pre-existing intrinsic renal disease.
The effect of different families of fatty acids on the proliferation of rat uterine stromal cells (UIII) was studied. Docosahexaenoic acid (DHA) exerted a strong and dose-dependent inhibitory effect (IC50 approximately 2 microM), whereas arachidonic acid (AA) stimulated UIII cell proliferation at the optimal concentration of 10 microM. Oleic, linoleic and linolenic acids were ineffective from 0.1 to 10 microM. The inhibitory effect of DHA was independent of the eicosanoid biosynthesis and lipid peroxidation, since it was not reversed by the addition of the antioxidant BHT and no significant production of oxidized species from DHA occurred in our culture conditions.
We investigated the expression and distribution of the extracellular matrix protein tenascin (TN) in 59 astrocytomas and 11 samples of normal brain by Western blot analysis and immunohistochemistry using antibodies against human TN. The tumors included 14 juvenile pilocytic astrocytomas (grade 1), 13 low grade fibrillary astrocytomas (grade II), 8 anaplastic astrocytomas (grade III), and 24 glioblastomas multiforme (grade IV). Proliferation indices were calculated by computer-based image analysis after immunostaining with the MIB-1 antibody against the Ki-67 proliferation-associated antigen. Western blot analysis for TN on fresh frozen tumor tissue from 23 of the 59 astrocytomas indicated up to 4-fold higher TN expression in glioblastomas multiforme than in nontumorous control tissues. Enhanced intercellular expression of TN was observed by immunohistochemistry in glioblastomas multiforme. More-over, TN immunostaining was consistently greater within and around the walls of hyperplastic blood vessels than nonhyperplastic vessels of both high grade tumors and juvenile pilocytic astrocytomas. Juvenile pilocytic astrocytomas with increased TN expression by Western blot analysis had vascular hyperplasia by light microscopy. Proliferation indices moderately correlated with tumor grade. Enhanced immunohistochemical expression of TN was associated with higher tumor grade with higher proliferation indices. The strong association of TN and vascular hyperplasia, regardless of tumor grade, suggests that TN may play a crucial role in angiogenesis.
OBJECTIVE: The purpose of this study was to determine the level of disability among patients with Menière's disease, information needed by clinicians when evaluating patients for coverage under the Americans With Disabilities Act. We hypothesized that the unpredictability of vertiginous episodes or "Menière's attacks" would be the most disabling problem, combined with the lack of a safe place to sit down during Menière's attacks. DESIGN: All patients seen in the otolaryngology faculty practice at Baylor College of Medicine, Houston, Tex, and diagnosed as having Menière's disease over a 3-year period were sent a self-administered questionnaire. SETTING: This practice is located at a tertiary care center. SUBJECTS: One hundred forty-nine potential subjects constituted the pool, from which data from 50 subjects provided complete data sets. RESULTS: The data from 50 adults suggested that the most problematic symptom was vertigo, followed by hearing loss. The unpredictability of Meniere's attacks and the lack of a safe place to rest during attacks was a significant problem for few subjects.
BACKGROUND: Pure tones stimulated oscillopsia in a 30-year-old man with bilateral hearing loss and Tullio's phenomenon. DESIGN: The subject's eye movements were recorded with electro-oculography while he was seated with his head stabilized facing a visual array. Pure tones were given in each ear, individually, from 500 to 2000 Hz, 90 to 110 dB. The subject reported the intensity of oscillopsia, if any, during each trial. He was also tested while standing on a force platform and receiving pure tones. RESULTS: No increased postural sway was found, but oscillopsia and vertical eye movements followed stimulation to the more impaired ear. CONCLUSIONS: These results support the hypothesis that Tullio's phenomenon is caused by inner ear pathology and suggest that oscillopsia is caused by the occurrence of unplanned vertical eye movements, the perceptual consequences of which were unexpected.
Pulmonary vasculitis is an uncommon complication of systemic lupus erythematosus (SLE), and has not been previously documented in pregnancy. This case report describes the rapidly fatal course of a pregnant SLE patient, whose terminal illness was manifested by severe pulmonary hypertension and unexpected autopsy findings of medium and large vessel vasculitis. The relationship of these unusual manifestations to other clinical and serologic features of SLE, as well as novel therapeutic options, are discussed.
We investigated the contribution of different screening criteria to the prenatal detection of Down syndrome (DS) as well as other chromosomal anomalies in the Jewish population in Israel during 1990 and 1992. There was a significant decrease (P < 0.03) in the incidence of DS live-births during 1992 (40:78 442) compared with 1990 (69:73 751) which paralleled a marked increase in total prenatal testing and in DS cases detected prenatally. Private laboratories, which perform amniocenteses mostly for women with a low risk of DS and without genetic counselling, had a significantly lower detection rate (1:917) compared with that of the genetic institutes, which following genetic counselling test both women > or = 37 years of age (1:91) and women younger than 37 years (1:113). The detection of chromosomal anomalies other than DS was less affected by the reason for amniocentesis. Amniocentesis indicated by maternal serum marker screening of women younger than 37 years identified a greater number of chromosomal anomalies other than DS than amniocentesis based on age (> or = 37 years) alone (111:9604 versus 94:9810; P < 0.06). Prenatal detection of DS is most effective when the indication for amniocentesis follows genetic counselling. The increasing use of maternal serum marker screening leads to a significant improvement in the positive detection rate of chromosomal anomalies other than DS in young women.
The relationship between the level of gamma delta T cells and cellular immunity of T lymphocytes was assessed in the peripheral blood of active sarcoidosis patients and healthy controls. We divided the active sarcoidosis patients into two groups: a group of patients with a normal distribution of circulating gamma delta T cells (group A; n = 11, less than 8.2% lymphocytes) and another group with increased gamma delta T cell levels (group B; n = 11, greater than 8.2% lymphocytes). The proportion and absolute count of CD4+ lymphocytes in group B (28.6 +/- 11.2%, 374.1 +/- 193.8/microliters) were remarkably smaller than control subjects (45.7 +/- 6.8%, 818.3 +/- 290.2/microliters, P < 0.001, P < 0.002, respectively). Group A, however, showed a moderate reduction in CD4+ lymphocytes when compared with controls. Serial measurements of T cell subtypes were performed on five patients in group B. gamma delta T cells and CD4+ lymphocytes were inversely correlated over the observation period which ranged from 2 to 18 months. When peripheral blood T cells were stimulated with PHA or PPD in vitro, the responses were weaker in group B compared with both group A and control subjects. These results suggest that the increase in circulating gamma delta T cells in sarcoidosis closely relates to a defect in cellular immunity which progresses during the disease process.
The technique used in performing selective posterior rhizotomies to treat spastic cerebral palsy remains controversial. One hundred nine children who had undergone selective posterior rhizotomies were studied 6 months after their surgery. Their residual spasticity was correlated to the number of roots and whether or not abnormally responding roots were left, in order to validate the surgical technique used to treat spastic cerebral palsy at most neurosurgical centers in North America. The children were divided into three groups (group A: children who had their L2-S1 roots tested and selectively lesioned, n = 15; group B: children who had their L2-S2 roots tested and selectively lesioned, n = 62; group C: children who had their L2-S2 roots tested and whose lesioning was directed both by the response to the stimulation and mapping of the S1-S3 dorsal roots for afferent pudendal nerve activity, n = 32). Clinically significant residual spasticity was present in the gastrocnemius in 33% of the group A children, 11% of the group B children, and 6% of the group C children. We found that there was no significant increase in residual spasticity in the group C children when abnormally responding roots were not cut in order to preserve pudendal nerve activity. This study shows that the inclusion of the S2 roots decreases the amount of residual spasticity (P < 0.01). It also shows that leaving abnormally responding S2 roots to preserve pudendal nerve activity does not affect the incidence of postoperative spasticity (P > 0.1).
A 13-month-old boy, who had been diagnosed in utero as having bilateral hydroceles, was found to have bilateral abdominoscrotal hydroceles. To date, there has been only one previous case of bilateral abdominoscrotal hydroceles in an infant. Magnetic resonance imaging was used to make the diagnosis: bilateral dumbell shaped fluid filled masses were seen in a coronal image. The patient had the abdominoscrotal hydroceles excised through bilateral groin incisions. The postoperative course was uneventful, without complication. The etiology and diagnosis of abdominoscrotal hydroceles are discussed.