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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of single versus multiple dosing on perfluorochemical distribution and elimination during partial liquid ventilation.

The objective of this study was to quantitate perfluorochemical (PFC) elimination kinetics during partial liquid ventilation (PLV) following an initial fill with or without hourly dosing. Young New Zealand rabbits were studied in two groups: Gr I (n = 6), PLV with a single dose of PFC liquid (perflubron: LiquiVent, Alliance Pharmaceutical Corp.); and Gr II (n = 5), PLV with PFC liquid and multiple hourly dosing . All rabbits were studied for 4 h, following initial instillation of a volume of PFC liquid equal to the measured gas functional residual capacity. Animals were ventilated at a constant breathing frequency (30 br/min), tidal volume (9.3+/-0.3 SE mL/kg), positive end expiratory pressure (4 cm H2O), and inspiratory time (0.30 s). PFC saturation of mixed expired gas (PFC-Sat) was assessed with a thermal conductivity analyzer, and PFC elimination was calculated from PFC-Sat, minute ventilation, and temperature of the expired gas. In GR II, PFC was supplemented hourly at a volume determined by PFC elimination calculations. The results demonstrated a decrease in PFC-sat and PFC loss with time, independent of group (P< 0.05). In addition, with hourly supplementation (GR II), PFC-Sat and PFC elimination over time was significantly (P < 0.05) greater than in animals (GR I) which did not receive additional doses. These data demonstrate that the PFC elimination rate is not constant and is related to the amount of PFC in the respiratory system. This may have occurred due to distributional differences of ventilation and PFC liquid between the single and multiple dosing groups. These findings also suggest that evaluation of PFC concentrations in expired gas may be a clinically useful index of intrapulmonary PFC distribution during PLV, and that maintained elevation of expired gas PFC saturation may guide optimal PFC dosing intervals and distribution to maximize protection against barotrauma.

Animals↗
PubMed1999

[Short- and long-term effects of intensified versus conventional antilipidemic therapy in patients with coronary heart disease. Results from the Lipid-Coronary Artery Disease (L-CAD) Study].

In a prospective, randomized study of patients with acute manifestation of coronary heart disease and hypercholesterolemia (LDL cholesterol >/= 130 </= 250 mg/dl), we compared the effect of an early-initiated, intensified therapy to usual care antilipidemic therapy with respect to coronary lesions and clinical events. Patients were included immediately following acute myocardial infarction and/or PTCA because of severe/instable angina pectoris. The intensified therapy consisted of pravastatin 20-40 mg with addition of colestyramine and/or nicotinic acid, if necessary, to achieve an LDL cholesterol </= 130 mg/dl. In the control group, antilipidemic therapy was left up to the private physician. The group with intensified therapy consisted of 70 patients (LDL cholesterol 179 +/- 27 mg/dl, age 55 +/- 10 years, 81% males), the control group of 56 patients (LDL cholesterol 177 +/- 28 mg/dl, age 58 +/- 11 years, 79% males). Cholesterol was reduced longterm by 28% under intensified therapy, but it remained constant in the control group. Quantitative coronary angiography revealed a mean of increase minimal lumen diameter of 0.05 mm after 6 months with intensified therapy and of 0.13 mm after 24 months. Under conventional therapy, however, it decreased by 0.08 mm after 6 months, and by 0.18 mm after 24 months (p < 0.01). In addition, within 12 months of therapy, significantly (p < 0.01) less cardiovascular clinical events were observed in patients under intensified therapy. After 2 years 43% (n = 22) of the controls, but only 17% (n = 14) of the patients with intensified therapy experienced a major clinical event (p < 0.03), i. e. death, myocardial infarction, necessary coronary intervention, cerebral infarction or new peripheral vascular disease. This study is the first to show that aggressive early - initiated cholesterol-lowering therapy can induce regression and reduce progression of coronary lesions already after 6 months. These changes are accompanied by a significant reduction in clinical events. The results of our study underline the necessity of immediate cholesterol screening and early intensive antilipemic therapy at the latest when of coronary heart disease becomes manifest.

Adult↗
PubMed1999

Human trabecular meshwork cells as a thyroid hormone target tissue: presence of functional thyroid hormone receptors.

PURPOSE: To determine whether human trabecular meshwork cells (HTM) are a potential target tissue for thyroid hormone (3,3',5-triiodothyronine, T3). METHODS: Cultured HTM were assayed for the presence of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polymerase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohistochemistry to detect nuclear TR and RXR proteins. Functionality of the TR was determined by analysis of 125I-T3 binding affinity and capacity in HTM nuclear extracts. Effects of T3 on modulation of hyaluronic acid (HA) levels in HTM were measured as a function of dose and duration of T3 administration. RESULTS: Analysis of RT-PCR and immunohistochemistry demonstrated that cultured HTM expressed TRalpha1, TRalpha2, and TRbeta1 but not TRbeta2; and RXRalpha but not RXRbeta and RXRgamma isoforms. Saturation binding and analysis of 125I-T3 to HTM nuclear extracts revealed Kd of 57 pM. The number of T3 binding sites extrapolated from a Scatchard plot was 7.3 x 10(10)/microg of HTM nuclear protein extract. T3 supplementation reduced the concentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T3. CONCLUSIONS: Cultured HTM express three TR isoforms and one RXR isoform, bind T3 with an affinity similar to that of TR in responsive cells, and modulate their HA production in response to T3. These findings indicate that the human trabecular meshwork tissue has the capacity to respond to thyroid hormones.

Adult↗
PubMed1999

Prevalence of skin disease in a cohort of shelter-based homeless men.

BACKGROUND: Cutaneous disease is a frequent cause of morbidity in homeless people. A variety of infectious and noninfectious conditions have been described in this population that are exacerbated by malnutrition, exposure to hazardous environment, psychiatric disease, physical injuries, and limited access to health care. OBJECTIVE: Our purpose was to study the prevalence of skin disease in a selected group of the homeless population. METHODS: We evaluated skin diseases in a cohort of 142 homeless men who were staying overnight in a major Boston homeless shelter for men over a period of 3 months (March-June 1992). The subjects participated in the study by volunteering for a free skin examination. Completion of a detailed questionnaire on age, race, duration of homelessness, and general medical status was followed by a thorough skin examination performed by dermatologists. RESULTS: The most prevalent skin diseases in the examined population were tinea pedis (38%), pitted keratolysis of the feet (20.4%), traumatic injuries (19.7%), toenail onychomycosis (15.4%), acne vulgaris (18.3%), and seborrheic dermatitis (13.3%). CONCLUSION: To our surprise the majority of patients had relatively normal findings from skin examinations with only a few pathologic findings, most often related to poor foot hygiene and long-term exposure to moisture. We attribute the relatively good condition of our cohort to the excellent care provided by the shelter with regard to clothing, cleaning facilities, and medical care. Our findings may represent the prevalence of skin diseases in shelter-based homeless but not in street homeless persons who are likely to have much poorer hygiene and perhaps more skin disease.

Adult↗
PubMed1999

Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent.

Fifteen healthy women participated in a study to determine the effect of multiple doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (35 micrograms ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants received three cycles (21 days each of active drug followed by 7 days without medication) of Ortho-Novum. During the third cycle, participants also received troglitazone 600 mg qd for 22 days. Pharmacokinetic profiles of EE and NE were determined on day 21 of the second and third cycles. Progesterone and sex hormone binding globulin (SHBG) levels were also measured. Troglitazone decreased EE Cmax and AUC(0-24) by 32% and 29%, respectively. Likewise, troglitazone decreased NE Cmax and AUC(0-24) by 31% and 30%, respectively. Plasma SHBG concentrations increased from 113 nmol/L during cycle 2 to 220 nmol/L during cycle 3. Troglitazone reduced plasma unbound AUC for NE by 49%. Serum progesterone levels were lower than 1.5 ng/mL on all occasions. Thus, coadministration of troglitazone and Ortho-Novum decreases the systemic exposure to EE and NE. A higher dose of oral contraceptive or an alternate method of contraception should be considered for patients treated with troglitazone.

Adult↗
PubMed1999

Localization of hyaluronan in pseudocapsule from total hip arthroplasty.

Hyaluronan is a large glycosaminoglycan present in normal synovial fluid imparting important viscoelastic properties for joint lubrication. In normal and noninflammatory conditions, hyaluronan has been localized to the lining layer of the synovial membrane, specifically synovial fibroblasts. Prosthetic joint fluid contains large amounts of hyaluronan, the source of which has not been determined. Pseudocapsules from patients who had total hip arthroplasty and were having revision surgery for nonloosened and nonseptic conditions were fixed in 10% acid formalin with 70% alcohol and stained for hyaluronic acid with biotinylated hyaluronic acid binding protein as a probe. Hyaluronan was localized strongly to the lining layer of the pseudocapsule, as in normal and osteoarthritic synovial membranes. The fibroblasts in the pseudocapsule of total hip arthroplasty may be responsible for the persistent production of hyaluronan in prosthetic joint fluid.

Adjuvants, Immunologic↗
PubMed1998

The hyaluronidase gene HYAL1 maps to chromosome 3p21.2-p21.3 in human and 9F1-F2 in mouse, a conserved candidate tumor suppressor locus.

We recently cloned and expressed the major hyaluronidase activity from human plasma, HYAL1, and found that the protein is 40% identical to the testicular hyaluronidase, PH-20. The HYAL1 mRNA sequence was used in a homology search of the mouse database of expressed sequence tags (dbEST). Two ESTs were obtained and, in combination with 5'RACE-PCR, were used to clone the mouse HYAL1 ortholog (Hyal1). Hyal1 codes for a protein of 462 amino acids that is 73% identical to the human sequence. Hyal1 stably expressed in human embryonic kidney cells resulted in a 20,000-fold increase of hyaluronidase activity. Sequence-tagged sites derived from the HYAL1 gene from both species were used to isolate P1 genomic clones that were used as probes for fluorescence in situ hybridization. The human gene was localized to chromosome 3p21 and the mouse gene to a syntenic region on chromosome 9F1-F2. In mouse, serum hyaluronidase polymorphism has previously been mapped by an interspecific backcross to 60 cM from the centromere of chromosome 9, which corresponds to a cytogenetic location of 9F1-F2. The mouse Hyal1 gene is therefore very likely to be responsible for the hyaluronidase polymorphism linked to this locus. We also present evidence that human HYAL1 is identical to an uncharacterized gene positionally cloned by others from chromosome 3p21.3 that is homozygously deleted in several small-cell lung carcinoma cell lines.

Amino Acid Sequence↗
PubMed1998

Effect of troglitazone on steady-state pharmacokinetics of digoxin.

Twelve healthy subjects participated in a study to determine the effect of multiple doses of troglitazone on the steady-state pharmacokinetics of digoxin. Subjects received digoxin 0.25 mg orally once daily on days 1 through 20 and 400 mg of troglitazone orally once daily on days 11 through 20. Serial plasma samples and 24-hour urine samples collected before and after the doses on days 10 and 20 were analyzed for digoxin using a radioimmunoassay method. Eleven subjects completed the study. Administration of multiple oral doses of digoxin and troglitazone was well tolerated. Mean values for maximum concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from 0 to 24 hours (AUC0-24) of digoxin on day 10 were similar to those on day 20. Mean day 10 digoxin values for minimum concentration (Cmin), apparent oral clearance (Cl/F), total urinary excretion from 0 to 24 hours (Ae0-24), and renal clearance (Clr) were also similar to corresponding values on day 20. Thus, concomitant administration of multiple-dose troglitazone does not alter the steady-state pharmacokinetics of digoxin.

Administration, Oral↗
PubMed1998

The Palomo procedure in the treatment of boys with varicocele: a retrospective study of testicular growth and fertility.

The Palomo procedure has often been criticized with regard to possible atrophy of the testis. Measuring the testicular volume is mainly used in pre- and postoperative assessment. Evidence concerning fertility remains unclear. The aim of this study was to learn whether now-adult former patients had any disturbance of their testicular growth and/or fertility. Out of 79 patients operated upon with Palomo's procedure between 1979 and 1990, 33 could be evaluated. They all had grade II or III left-sided varicoceles. Investigations consisted of: the patient's history, testicular-volume measurement by means of an orchidometer (OM) (Prader) and ultrasonography (US), and semen analysis (27/33) 6-17 years after surgery. No recurrence of grade II varicoceles was observed. Only 1 of the 33 patients might have had testicular atrophy, yet he had already fathered 3 children! Twenty-three had a normal sperm count and 24/27 showed normal sperm motility. Eight hydroceles were either present at the time of investigation or had been operated upon in the past. Estimations of testicular volume by OM and US showed significant differences between the two methods concerning volume and relation of right to left side. In general, the volume was overestimated by the OM. The study shows that in boys the simple surgical technique proposed by Palomo has - in the long run - no disadvantages for testicular development and sperm production. Fertility should therefore not be compromised.

Adult↗
PubMed1998

Beta-human chorionic gonadotropin in cervicovaginal secretions as a predictor of preterm delivery.

OBJECTIVE: This study's objective was to determine whether the concentrations of beta-human chorionic gonadotropin in the secretions of the cervix and vagina could be used to predict preterm delivery in a group of women at high risk for this complication. STUDY DESIGN: Women attending a prematurity prevention clinic at an inner-city hospital July 1, 1996-October 1, 1997, were invited to participate. From those who consented, secretions from the cervix and posterior vaginal fornix were sampled every 2 weeks until delivery, beginning at 24 weeks' gestation. Concentrations of beta-human chorionic gonadotropin were measured with a commercially available enzyme-linked immunosorbent assay. Providers of obstetric care were blinded to the results. Levels of beta-human chorionic gonadotropin in those who were delivered before 34 weeks' gestation and those who were delivered at term were compared. A value >50 mIU/mL was considered elevated. This cutoff value was determined according to beta-human chorionic gonadotropin values obtained during pregnancies that were delivered at term. RESULTS: Of the 146 women asked to participate, 77 consented. There was no difference between participants and nonparticipants with respect to age, race, indication for enrollment in the clinic, gestational age at delivery, or parity. Of the 77 participants, 24 (31%) were delivered before 37 weeks' gestation and 12 (16%) were delivered before 34 weeks' gestation. A single beta-human chorionic gonadotropin value >50 mIU/mL obtained between 24 and 28 weeks' gestation was associated with a significant increase in the incidence of delivery before 34 weeks' gestation (P = .03). This cutoff value had sensitivity, specificity, and positive and negative predictive values for predicting delivery before 34 weeks' gestation of 50%, 87%, 33%, and 93%, respectively. CONCLUSION: These data suggest that the concentration of beta-human chorionic gonadotropin in cervicovaginal secretions may be a useful predictor of preterm delivery.

Adult↗
PubMed1998

Phosphorylation stabilizes alternatively spliced CD44 mRNA transcripts in breast cancer cells: inhibition by antisense complementary to casein kinase II mRNA.

CD44, the predominant vertebrate cell surface receptor for hyaluronan, exists in a variety of isoforms resulting from alternative splicing of a single gene. Particular spliced variants of CD44 correlate with increased cell motility, and with poor clinical prognosis in several kinds of carcinomas. Combinations of 9 variant exons that confer this enhanced motility on tumor cells are inserted into a single site in the middle of the extracellular domain of CD44. Evidence suggests that phosphorylation of 2 serine residues in the intracellular domain of CD44 are involved in controlling these events. However, evidence is lacking as to the nature of such kinases. Acidic amino acids in close proximity to these 2 serine residues suggests casein kinase II (CKII) is involved. We now show an antisense phosphorothioate oligonucleotide designed to hybridize to the AUG translation initiation codon of subunit CKII alpha' mRNA blocks in vivo phosphorylation of CD44 in MDA231 breast tumor cells, and at the protein level decreases ectopic expression of total CD44 as well as the metastatic v-7 CD44 isoform. Furthermore subplateau RT-PCR analysis demonstrated antisense transfected MDA231 tumor cells had significant down-regulated or eliminated mRNA transcripts of metastatic CD44 isoforms. CKII as a CD44-associated serine kinase therefore may serve as an important molecule in a signaling cascade that produces a variety of cellular responses in MDA231 breast cancer cells. Since the 3'-untranslated region of CD44 mRNA contain 4 dispersed AUUUA sequences which serve as signals targeting mRNA for rapid turnover, a mechanism is proposed by which CD44 phosphorylation mediates labile message stabilization, hence providing insights into the processes involved in cancer cell growth, invasion and metastasis.

Alternative Splicing↗
PubMed1998

Hyaluronan and CD44 expression in minor salivary gland tumors.

OBJECTIVES: Hyaluronan (HA) and CD44 are most likely associated with tumor invasion and metastasis. Malignancies with different degrees of aggressiveness may express different levels and patterns of HA and CD44. The aim of this project was to examine the distribution of HA and CD44 in minor salivary gland tumors to determine if staining could be correlated with biologic behavior or tumor type. MATERIALS AND METHODS: Biotinylated hyaluronan binding protein as a probe for HA and monoclonal antibodies specific for CD44 were used to stain classic examples of the five most commonly encountered minor salivary gland tumors: monomorphic adenomas, pleomorphic adenomas, polymorphous low grade adenocarcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas. RESULTS: Tumor cells of monomorphic adenomas were negative for both HA and CD44, and tumor capsules were intensely HA-positive. Pleomorphic adenomas exhibited HA and CD44 positivity in both mesenchymal and epithelial components, and HA in capsular tissues. All malignant salivary gland tumors expressed similar intense HA in tumor stroma. HA staining was more intense in stroma than in parenchymal cells. Tumor cells of most adenoid cystic carcinomas were HA-positive, while most polymorphous low grade adenocarcinomas were HA-negative. HA was uniformly distributed throughout supporting stroma of high and low grade malignancies, except for two polymorphous low grade adenocarcinomas (PLGAs) in which HA was more intense at the invading edge of the tumors. CD44 expression was seen only in tumor cells (not stroma) of malignancies, and was of similar intensity in both low and high grade tumors. CONCLUSIONS: Differences in the expression of HA and CD44 among different types of salivary gland tumors were noted. These findings, however, could not be correlated with known biologic behaviors of the tumor groups studied. Immunohistochemical staining of salivary gland tumors for HA and CD44 may be useful in separating monomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma, lesions that may be difficult to distinguish with routine light microscopy.

Adenocarcinoma↗
PubMed1998

American Association of Physicists in Medicine Radiation Therapy Committee Task Group 53: quality assurance for clinical radiotherapy treatment planning.

In recent years, the sophistication and complexity of clinical treatment planning and treatment planning systems has increased significantly, particularly including three-dimensional (3D) treatment planning systems, and the use of conformal treatment planning and delivery techniques. This has led to the need for a comprehensive set of quality assurance (QA) guidelines that can be applied to clinical treatment planning. This document is the report of Task Group 53 of the Radiation Therapy Committee of the American Association of Physicists in Medicine. The purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a comprehensive but viable program of quality assurance for modern radiotherapy treatment planning. The scope of the QA needs for treatment planning is quite broad, encompassing image-based definition of patient anatomy, 3D beam descriptions for complex beams including multileaf collimator apertures, 3D dose calculation algorithms, and complex plan evaluation tools including dose volume histograms. The Task Group recommends an organizational framework for the task of creating a QA program which is individualized to the needs of each institution and addresses the issues of acceptance testing, commissioning the planning system and planning process, routine quality assurance, and ongoing QA of the planning process. This report, while not prescribing specific QA tests, provides the framework and guidance to allow radiation oncology physicists to design comprehensive and practical treatment planning QA programs for their clinics.

Algorithms↗
PubMed1998

Expression of CD44 isoforms in cultured human trabecular meshwork cells.

PURPOSE: To determine the expression of CD44 isoforms in cultured human trabecular meshwork (HTM) and to discuss their possible relationship with outflow facility. METHODS: CD44 isoform expression in cultured HTM was qualitatively examined using immunohistochemistry and RT-PCR analysis. RESULTS: Immunohistochemistry of cultured HTM showed intense staining with a CD44s antibody, and with antibodies against CD44 exon 7, exon 11-12 and exon 14. By RT-PCR, at least three isoforms of CD44 were expressed in HTM: CD44s, CD44v-III and CD44v-I. CONCLUSIONS: At least three isoforms of CD44 are expressed in the HTM. CD44 may play a role in binding and turnover of hyaluronic acid in the trabecular meshwork, thereby regulating outflow facility.

Cells, Cultured↗
PubMed1998

The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression.

RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated protein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility. To assess whether RHAMM and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patients using reverse transcription-PCR and immunocytochemistry. We show that overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression. Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the primary tumor, and this staining pattern was associated with lymph node metastases. The metastases exhibited a significantly higher level of staining for RHAMM than did the primary tumor. RHAMM expression strongly correlated with overexpression of both ras and ERK, although overexpression of either of these two signaling molecules was not by itself a prognostic indicator. These results identify a new parameter that is involved in lymph node metastasis of primary breast cancers and suggest that quantification of RHAMM overexpression may be a useful prognostic indicator for breast carcinoma progression.

Breast Neoplasms↗