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Biomedical subjects

E Hernandez

Publications and source records attributed to E Hernandez.

At least 73 records · Page 4Linked to original sources

Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.

Chimeric TCR transfectants expressing human extracellular sequences and murine intracellular/transmembrane sequences were generated to analyze the trimolecular interaction between myelin basic protein (MBP) autoantigen, HLA, and a TCR isolated from a patient with multiple sclerosis. Chimeric transfectants responded to TCR activation by CD3- and TCRBV22S1-specific mAbs and by superantigen. Additionally, chimeric transfectants responded to autoantigen-specific activation with MBP 152-165 when presented by DR(alpha,beta1*1301) independent of the CD4 adhesion molecule. Transfectants did not respond to Ag presented by other HLA-DR molecules, including the closely related DR(alpha,beta1*1302). In peptide-binding studies with a panel of serial alanine-substituted MBP peptides, HLA contact residues necessary for anchoring MBP 152-165 to DR(alpha,beta1*1301) were also defined: 154 (F), 159 (R), and 162 (R). The chimeric TCR transfectant's differential response to a similar panel of MBP analogues defined residues that interact with the TCR: 153 (I), 155 (K), 156 (L), 160 (D), and 161 (S). Analysis of molecular interactions, such as those described in this work, may be central to developing new strategies for suppressing Ag-specific responses in human autoimmune disease.

Amino Acid Sequence↗

Day-night blood pressure variation in normotensive and hypertensive NIDDM patients with asymptomatic autonomic neuropathy.

In order to assess the characteristics of day-night blood pressure (BP) variation in normotensive and hypertensive non-insulin-dependent diabetic (NIDDM) patients with asymptomatic autonomic neuropathy, 54 NIDDM patients and 13 healthy control subjects were studied by casual BP measurements and 24-h ambulatory blood pressure monitoring. Signs but not symptoms of autonomic neuropathy were documented by results of standard cardiovascular function tests in each patient. Daytime (06:00-22:00) and nighttime (22:00-06:00) BP values were separately analyzed and delta day-night BP values and diurnal index were determined. Patients were classified as being normotensive or having hypertension according to the casual BP values and medical history. In normotensive NIDDM patients (n = 30), nighttime systolic BP was significantly higher, whereas delta day-night systolic and delta day night diastolic BP values as well as diurnal index were considerably lower than those in control subjects (n = 13). In hypertensive NIDDM patients (n = 24), similar alterations were found at higher BP levels. No significant difference was found in BP values if normoalbuminuric and microalbuminuric NIDDM patients were compared. 'Non-dipper' phenomenon could be found in normotensive and hypertensive NIDDM patients with asymptomatic autonomic neuropathy, suggesting that relative sympathetic overdrive due to incipient and predominantly parasympathetic impairment of cardiovascular innervation might play a role in early alterations of circadian BP variation.

Adult↗

Phase I/II study of concomitant irradiation and carboplatin for locally advanced carcinoma of the uterine cervix: an interim report.

The outcome of women treated with either definitive irradiation alone or in combination with cisplatin-based chemotherapy for locally advanced (>IIb) squamous cell carcinoma of the cervix has been disappointing. To improve upon our reported results with irradiation alone, a trial using irradiation plus carboplatin chemotherapy was designed for these patients. Twenty-seven women with unresectable squamous cell carcinoma of the uterine cervix were referred to our institution between July 1991 and September 1994. Seven of these patients were enrolled in a phase I/II protocol combining concurrent irradiation and carboplatin chemotherapy. Megavoltage irradiation was used to deliver 45-50.4 Gy to the pelvis (and paraaortic chain when nodes were involved) through a multiple-field technique followed by the application of Fletcher-Suit-Delclos tandem and ovoids to boost the point A dose to 85 Gy. Chemotherapy consisted of intravenous carboplatin (60 mg/m2) administered in conjunction with irradiation to a total dose of 300 mg/m2. The enrolled patients consisted of six women with stage IIIb disease and one with stage IIa with concomitant paraaortic adenopathy. All seven patients enrolled in the study completed the planned course of treatment and tolerated the treatment without severe acute morbidities. No dose modifications were required for the radiation therapy regimen. For one patient, a dose of carboplatin was withheld to allow recovery from thrombocytopenia. The overall response rate was 100% (four complete response, three partial response). The combination of concurrent irradiation (pelvic or pelvic + paraaortic fields) and carboplatin chemotherapy can be safely administered to patients with locally advanced squamous cell carcinoma of the cervix. The treatment is well tolerated and is associated with a high rate of response. Longer follow-up will be necessary to assess the durability of response. In the meantime, we have elected to escalate the dose of carboplatin (90 mg/m2) in the hope of increasing the rate of complete response without incurring unacceptable toxicity.

Adult↗

Poorer prognosis in older patients with endometrial adenocarcinoma.

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.

Adenocarcinoma↗

Bladder adenocarcinoma during pregnancy: a case report.

BACKGROUND: Renal tract neoplasms account for only 15% of all cases of hematuria and are rare before the age of 40. Few cases of bladder carcinoma diagnosed during pregnancy have been reported. CASE: Adenocarcinoma of the dome of the bladder caused hematuria beginning at 20 weeks' gestation but was not diagnosed until the postpartum period. CONCLUSION: Hematuria during pregnancy is usually associated with infection. However, neoplasms must be included in the differential diagnosis.

Adenocarcinoma, Mucinous↗

Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic.

OBJECTIVE: To evaluate and compare the safety, efficacy and cost of three cervical cytology sampling devices in pregnant women presenting for prenatal care to the obstetrics clinic, at Medical College of Pennsylvania Hospital. STUDY DESIGN: From September 7, 1993, to November 5, 1993, 61 cervical cytologic smears were obtained using the Cell-Sweep. From November 8, 1993, to January 7, 1994, 66 smears were obtained using the Ayre spatula/Cytobrush, and from January 10, 1994, to February 18, 1994, 55 smears were obtained using the Ayre spatula/cotton swab. The rate of smears with no endocervical component or with epithelial cell abnormality was determined for each group. The patients' medical records were reviewed retrospectively to determine complications occurring within two weeks of smear collection. RESULTS: Fifteen (25%) smears in the Cell-Sweep group, one (1.5%) in the Cytobrush group and nine (16%) in the cotton swab group were satisfactory but limited by absence of an endocervical component (P < .0006). None of the smears were unsatisfactory. Eleven (18%) smears in the Cell-Sweep group, eight (12%) in the Cytobrush group and nine (16%) in the cotton swab group revealed an epithelial cell abnormality (P = .643). For all three groups there was a low rate of spontaneous abortion, preterm spontaneous rupture of membranes or preterm labor occurring within two weeks of collection. There was no statistically significant difference in these complications between the three groups (P = .7). The Ayre spatula/cotton swab is the least expensive device. CONCLUSION: The Ayre spatula/cotton swab was the most satisfactory of the three methods tested for obtaining cervical cytology during pregnancy. It is safe and cost-effective and identifies the same proportion of epithelial cell abnormalities as the Ayre spatula/Cytobrush and the Cell-Sweep.

Abortion, Spontaneous↗

Laboratory findings in hypertensive disorders of pregnancy.

This study sought to determine whether a normal platelet count is a reliable predictor of the absence of other coagulation abnormalities in patients with a hypertensive disorder of pregnancy. A retrospective review of laboratory data obtained from 80 patients with hypertensive disorders of pregnancy was carried out. Results of complete blood cell count, prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, fibrin split products, and fibrinogen, bilirubin, and liver enzyme levels were reviewed. Minor abnormalities of PT, PTT, and fibrinogen level were frequent, even in the presence of a normal platelet count. These were found mostly in patients with severe pre-eclampsia. A baseline complete blood cell count including platelet count is probably sufficient in patients with a hypertensive disorder of pregnancy. Fibrinogen level and PT and PTT determinations are recommended in patients who have severe preeclampsia and for whom operative delivery or regional anesthesia is planned. This will detect minor abnormalities in a few patients despite a normal platelet count. This information may help prevent bleeding complications.

Adolescent↗

Clinical Significance of a cervical cytologic diagnosis of atypical squamous cells of undetermined significance. Favoring a reactive process or low grade squamous intraepithelial lesion.

OBJECTIVE: To define the clinical significance of qualifying the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) as favoring either a reactive process or a low grade squamous intraepithelial lesion (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of 118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring either a reactive process or LSIL were evaluated in our colposcopy clinic by repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic diagnosis of ASCUS favoring a reactive process had a repeat smear that was normal. None was found to have CIN. Of the 60 patients who had a cervical diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity of a repeat smear, in this limited series, after an initial smear of ASCUS favoring a reactive process is 100%, while it was 66% after an initial smear of ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is associated with a very low risk that the patient is haboring CIN. In the patient whose initial smear shows ASCUS favoring a reactive process, a repeat smear that is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL probably requires further evaluation even in the presence of a normal repeat smear.

Adolescent↗

Lack of effectiveness of magnesium in chronic stable asthma. A prospective, randomized, double-blind, placebo-controlled, crossover trial in normal subjects and in patients with chronic stable asthma.

BACKGROUND: Magnesium sulfate has been helpful in the treatment of acute exacerbations of asthma. We hypothesized that magnesium would also be an effective bronchodilator in patients with chronic stable asthma. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled, crossover trial in 15 patients with chronic, stable asthma and 10 nonasthmatics. On study day 1, spirometry and albuterol challenge were used to confirm the presence of asthma according to American Thoracic Society criteria. On study day 2, subjects received intravenous magnesium sulfate (2 g) or placebo (saline). On study day 3, subjects were crossed over to receive the other drug. Spirometry was performed before, during, and after drug or placebo administration. Circulating ionized magnesium concentrations were determined before and after intravenous magnesium or placebo administration. RESULTS: Magnesium infusion caused no statistically significant changes in forced expiratory volume in 1 second (mean +/- SEM, 1.92 +/- 0.13 L before, 1.98 +/- 0.12 L during, and 2.01 +/- 0.14 L after magnesium administration), forced vital capacity (mean +/- SEM, 3.44 +/- 0.25 L before, 3.60 +/- 0.26 L during, and 3.59 +/- 0.25 L after magnesium administration), or maximum forced expiratory flow rate (mean +/- SEM, 5.42 +/- 0.44 L/second before, 5.46 +/- 0.46 L/second during, and 5.57 +/- 0.49 L/second after magnesium administration). Placebo caused no changes in these three physiologic variables. CONCLUSION: Magnesium is not effective as a bronchodilator in chronic, stable asthmatics or in normal non-asthmatic adults.

Adult↗

The effectiveness of the Masterson curette in sampling the endometrial cavity.

The Masterson curette was used to sample the endometrial cavity of 25 women prior to scheduled hysterectomy for benign or malignant pathology. Adequate amount of tissue was obtained in 20 (87%) of 23 patients who did not have endometrial atrophy. The Masterson curettage detected all seven cases of endometrial hyperplasia or adenocarcinoma for a sensitivity of 100%. However, the Masterson curette does not sample the entire endometrial cavity. If abnormal uterine bleeding persists despite normal histology on curettings obtained with the Masterson or other endometrial sampling device, hysteroscopy is recommended.

Adenocarcinoma↗

Plasma thrombospondin levels in patients with gynecologic malignancies.

BACKGROUND: Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell-cell and cell-substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. METHODS: Blood samples were collected by venipuncture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme-linked immunosorbent assay. Wilcoxon's two-sample rank-sum test was used to evaluate differences between the patient and control groups. RESULTS: The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. CONCLUSIONS: Tumor-synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion.

Adult↗

Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal implant for the sustained release of fluorouracil.

OBJECTIVE: To test the efficacy of a biodegradable device for the intravitreal sustained release of fluorouracil in the treatment of tractional retinal detachment due to proliferative vitreoretinopathy. METHODS: A 6 x 0.9-mm (20-gauge) cylindrical solid implant molded from copolymers of lactide and glycolide admixed with 1 mg of fluorouracil was placed in the vitreous cavity of rabbits in which retinal detachment with proliferative vitreoretinopathy had been initiated. Comparisons of the control (drug-free polymer) and experimental (fluorouracil polymer) groups were made with weekly indirect ophthalmoscopic examinations. In another experiment, the intravitreal concentration of fluorouracil was tested at each time point. RESULTS: Retinas of eight (89%) of nine rabbits that received the polymer with fluorouracil remained attached compared with only one animal (11%) that received the control polymer without the drug. The therapeutic effect of the drug-containing implant was associated with sustained intravitreal concentrations of fluorouracil between 1 and 13 mg/L for at least 14 days, and fluorouracil concentrations remained above 0.3 microgram/mL for almost 21 days. No evidence of the toxic effects of the drug or polymer implant was observed with electroretinographic and histopathologic study. CONCLUSION: Intravitreal implantation of biodegradable polymers containing fluorouracil can prevent proliferation of epiretinal membranes resulting in complicated retinal detachment in an animal model of proliferative vitreoretinopathy and indicate their possible usefulness for intravitreal delivery of therapeutic agents.

Animals↗

Thrombocytosis in surgically treated stage IB squamous cell cervical carcinoma (A Gynecologic Oncology Group study).

Thrombocytosis has previously been shown to be an unfavorable prognostic factor in cervical cancer patients treated with irradiation. We evaluated the significance of thrombocytosis (platelet count > 400 x 10(9)/liter in 623 surgically treated patients with stage IB squamous cell carcinoma of the cervix. These patients had no gross evidence of extrauterine disease at the time of exploration, and none had metastasis to the para-aortic nodes. Fifty-nine (9.5%) of these 623 patients had thrombocytosis. The 5-year survival for patients with thrombocytosis was 82% compared to 83.5% for patients with normal platelet count (P = 0.4). Pelvic node metastasis was present in 13 (22%) of 59 patients with thrombocytosis, and 77 (13.7%) of 564 patients with normal platelet count (P = 0.1). There was a significant correlation between tumor size and platelet count. Patients with thrombocytosis had a mean tumor size of 27.9 mm, while it was 20.4 mm in patients without thrombocytosis (P = 0.002). Other factors found to be associated with thrombocytosis in this population were elevated white blood cell (WBC) count (P = 0.009) and history of chronic obstructive pulmonary disease (COPD) (P = 0.02). In a multivariate analysis for thrombocytosis adjusted for COPD, WBC count, and tumor size, tumor size continued to be statistically significant (P = 0.01). These data suggest that thrombocytosis is a marker of tumor burden and not an independent prognostic factor for progression-free interval or survival.

Adult↗

The Cell-Sweep. A new cervical cytology sampling device.

The Cell-Sweep, a new cervical cytology sampling device, was prospectively evaluated. From September 1, 1992, to October 31, 1992, 548 cervical cytology smears were prepared using the Cell-Sweep. They were compared to 524 cervical smears performed between January 1, 1993, and February 28, 1993, using the Cytobrush and Ayre spatula. One smear in the Cell-Sweep group and nine in the Cytobrush/Ayre spatula group were unsatisfactory for evaluation secondary to drying artifact (P < .01). Seven (1.2%) of the Cell-Sweep smears and 13 (2.4%) of the Cytobrush/Ayre spatula smears were inadequate due to obscuring of the epithelial cells by blood (P = .11). Of the smears obtained with the Cell-Sweep, 66 (12%) contained no endocervical component versus 42 (8%) of the smears obtained with the Cytobrush/Ayre spatula (P = .03). In the Cell-Sweep group there were 130 (23.7%) abnormal smears versus 110 (20.9%) in the Cytobrush/Ayre spatula group (P = .3). However, high grade squamous intraepithelial lesions (SILs) were identified in 10 (1.8%) smears obtained with the Cell-Sweep and in 2 (0.4%) obtained with the Cytobrush/Ayre spatula (P = .02). The Cell-Sweep produced a small proportion of unsatisfactory smears due to drying artifact or blood. Even though the proportion of smears lacking endocervical cells was statistically greater with the Cell-Sweep than with the Cytobrush/Ayre spatula, there was no difference in the rate of detection of atypical squamous cells and low grade SIL. The Cell-Sweep appears to detect an increased number of high grade SILs. This device deserves further study with histopathologic correlation.

Adolescent↗