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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 19 recordsLinked to original sources
PubMed2000

Evidence that the serum inhibitor of hyaluronidase may be a member of the inter-alpha-inhibitor family.

A study of the uncharacterized serum inhibitors of hyaluronidase, first described half a century ago, was undertaken. Activity was measured against bovine testicular hyaluronidase using a microtiter-based assay and reverse hyaluronan substrate gel zymography. The predominant inhibitory activity was magnesium-dependent and could be eliminated by protease or chondroitinase digestion and by heat treatment. Kinetics of inhibition were similar against hyaluronidases from testis and snake and bee venoms. The inhibitor had no effect on Streptomyces hyaluronidase, indicating that inhibition was not through protection of the hyaluronan substrate. Inhibition levels in serum were increased in mice following carbon tetrachloride or interleukin-1 injection, inducers of the acute-phase response. Reverse zymography identified a predominant band of 120-kDa relative molecular size, with two bands of greater and one of smaller size. The predominant protein was tentatively identified as a member of the inter-alpha-inhibitor family. Inhibition was also observed using either purified inter-alpha-inhibitor or an inter-alpha-inhibitor-related 120-kDa complex. Inter-alpha-inhibitor, found in the hyaluronan-rich cumulus mass surrounding mammalian ova and the coat of fibroblasts and mesothelial cells, may function to stabilize such matrices by protecting against hyaluronidase degradation. Turnover of circulating hyaluronan is extraordinarily rapid, with a half-life of 2-5 min. Prompt increases in levels of serum hyaluronan occur in patients with shock, septicemia, or massive burns, increases that can be attributed, in part, to suppression of degradation by these acute-phase reactants, the inhibitors of hyaluronidase.

Alpha-Globulins↗
PubMed2000

HYAL1LUCA-1, a candidate tumor suppressor gene on chromosome 3p21.3, is inactivated in head and neck squamous cell carcinomas by aberrant splicing of pre-mRNA.

The hyaluronidase first isolated from human plasma, Hyal-1, is expressed in many somatic tissues. The Hyal-1 gene, HYAL1, also known as LUCA-1, maps to chromosome 3p21.3 within a candidate tumor suppressor gene locus defined by homozygous deletions and by functional tumor suppressor activity. Hemizygosity in this region occurs in many malignancies, including squamous cell carcinomas of the head and neck. We have investigated whether cell lines derived from such malignancies expressed Hyal-1 activity, using normal human keratinocytes as controls. Hyal-1 enzyme activity and protein were absent or markedly reduced in six of seven carcinoma cell lines examined. Comparative genomic and fluorescence in situ hybridization identified chromosomal deletions of one allele of HYAL1 in six of seven cell lines. Initial RT - PCR analyses demonstrated marked discrepancies between levels of HYAL1 mRNA and protein. Despite repeated sequence analyses, no mutations were found. However, two species of transcripts were identified when primers were used that included the 5' untranslated region. The predominant mRNA species did not correlate with protein translation and contained a retained intron. A second spliced form lacking this intron was found only in cell lines that produced Hyal-1 protein. Inactivation of HYAL1 in these tumor lines is a result of incomplete splicing of its pre-mRNA that appears to be epigenetic in nature. Oncogene (2000) 19, 870 - 877.

Alternative Splicing↗
PubMed2000

Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.

Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4-7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44-hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.

Animals↗
PubMed2000

Topical hyaluronidase decreases hyaluronic acid and CD44 in human skin and in reconstituted human epidermis: evidence that hyaluronidase can permeate the stratum corneum.

Hyaluronic acid (HA), a high molecular weight glycosaminoglycan of the extracellular matrix involved in growth, inflammation and wound healing, also contributes to the hydration and plastic properties of skin. Several drug and cosmetic formulations contain HA. We have initiated investigations that explore whether it is possible, by topical application, to modulate endogenous HA levels in skin. We developed a model epidermal culture system that exhibited a differentiated stratum corneum, and expressed HA and the HA receptor CD44, in a pattern similar to that observed in intact skin. Such in vitro skin equivalents are useful models for investigating the effect of topical drugs. HA and bacterial hyaluronidase were applied to the in vitro skin equivalent and to human skin. Their effects on endogenous HA and CD44 expression were examined using histochemical analysis. Topical HA treatment had no significant effect on HA or CD44 expression in either system. However, hyaluronidase decreased HA and CD44 expression in a dose-dependent manner in both the epidermal culture system and in skin. Apparently, HA is not able to permeate the epidermal culture system or human skin to a significant degree, but bacterial hyaluronidase does permeate both human skin and the culture system, depleting HA and decreasing CD44 expression. These effects were more prominent in the dermal than in the epidermal layers, suggesting that marked differences in HA metabolism exist in these two skin compartments. The ability of hyaluronidase to permeate the stratum corneum suggests that topical application may, additionally, be useful as a clinical modality.

Adult↗
PubMed2000

Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts.

Extracellular matrix hyaluronan is prominent during wound healing, appearing at elevated levels early in the repair process. It is prevalent throughout the course of fetal wound healing, which is scar-free, but decreases late in adult wound repair, that is often marked by scarring. To determine whether aberrant hyaluronan metabolism is associated with the excessive scarring that characterizes keloids, cultured fibroblasts derived from keloids and from the dermis of normal human skin and scar were compared. Levels of hyaluronan in 48 h conditioned media of keloid-derived cultures were significantly lower than in cultures of normal skin and scar fibroblasts. Profiles of hyaluronan polymer size were comparable in these two cell types, suggesting that excessive hyaluronan degradation was not involved. Hydrocortisone decreased hyaluronan levels approximately 70% in the conditioned media of both keloid and normal fibroblasts. Diminished hyaluronan accumulation in keloid-derived cells compared with normal fibroblasts was also observed in an in vitro wound healing model. Histolocalization of hyaluronan in keloids, normal skin, and scar samples confirmed the biochemical observations that the dermis of keloids, which comprises most of the scar tissue, contained markedly diminished levels of hyaluronan. Alterations in hyaluronan in the epidermis overlying keloids, however, were also observed. A modest increase in hyaluronan staining intensity was observed in the epidermis of keloids, as well as changes in the patterns of distribution within the epidermis, compared with that in normal skin and scar. Increased hyaluronan was present in the granular and spinous layers of the keloid epidermis Abnormalities are present apparently in both the overlying epidermis as well as in the dermis of keloids. Aberrations in signaling between keloid stroma and keloid epidermis may underlie abnormalities that contribute to the excessive fibrosis characteristic of these lesions.

Adolescent↗
PubMed2000

Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases.

AIMS: Several studies have reported circadian and seasonal variations in acute cardiovascular disease. In addition, a weekly variation has been observed in acute myocardial infarction. The aim of our study was to determine the circadian weekly, and seasonal variations of sudden death utilizing population-based data. METHODS AND RESULTS: We analysed the emergency medical system data of Berlin (West) from 1987-1991 with respect to all consecutive sudden deaths in subjects >18 years (n=24 061). There was a marked circadian variation of sudden death, with a minimum between 0 and 6 h and a maximum between 6 and 12 h (P<0.0001) for every day of the week. A minimum of events occurred on Sundays (n=3143), and a maximum on Mondays (n=3721), corresponding to a relative increase of 18.3% (P<0.0001). The increase was more pronounced (23.6%) in patients < or =65 than in patients >65 (15.7%). In addition, we found a significant seasonal variation (P<0.0001) in events, with a maximum during winter (December to February, n=6493), and a minimum during summer (June to August, n=5472), corresponding to a relative difference of 18.7%. The seasonal variation was more pronounced in patients >65 years. CONCLUSION: The present analyses demonstrate marked variations in the occurrence of sudden death with peaks during morning hours, on Mondays, and during winter months. The findings suggest that the onset of sudden death may be associated with endogenous rhythms and external factors including climatic conditions.

Adult↗
PubMed2000

U-Pb Geochronologic, Nd Isotopic, and Geochemical Evidence for the Correlation of the Chopawamsic and Milton Terranes, Piedmont Zone, Southern Appalachian Orogen.

We report U-Pb crystallization ages from four metavolcanic rocks and two granitic gneiss samples as well as whole-rock chemical analyses and Sm-Nd isotopic ratios from 25 metaigneous and metasedimentary rocks from the Chopawamsic and Milton terranes, southern Appalachian Orogen. A metarhyolite sample from the Chopawamsic Formation and a metabasalt sample from the Ta River Formation in the Chopawamsic terrane have indistinguishable U-Pb crystallization ages of 471.4+/-1.3 Ma and 470.0+1.3/-1.5 Ma, respectively. A sample from the Prospect granite that intruded metavolcanic rocks of the Ta River Formation yields a younger U-Pb date of 458.0+/-1 Ma. Metarhyolite and granitic gneiss samples from the northern part of the Milton terrane yield U-Pb dates of 458.5+3.8/-1.0 Ma and 450+/-1.8 Ma, respectively. Metavolcanic and metaplutonic rocks from both terranes span a range in major element composition from basalt to rhyolite. Trace element concentrations in these samples show enrichment in large-ion lithophile elements K, Ba, and Rb and depletion in high field strength elements Ti and Nb, similar to those from island arc volcanic rocks. Initial epsilon(Nd) values and T(DM) ages of the metaigneous and metasedimentary samples range from 0.2 to -7.2 and from 1200 to 1700 Ma for the Chopawamsic terrane and from 3.7 to -7.2 and from 850 to 1650 Ma for the Milton terrane. The crystallization ages for the metavolcanic and metaplutonic samples from both terranes indicate that Ordovician magmatism occurred in both. Similar epsilon(Nd) values from representative samples from both terranes suggest that both were generated from an isotopically similar source. Xenocrystic zircons from metavolcanic rocks in the Chopawamsic terrane have predominately Mesoproterozoic (207)Pb/(206)Pb ages (600-1300 Ma), but a single Archean (2.56 Ga) core was also present. The xenocrystic zircons and the generally negative epsilon(Nd) values indicate that both terranes are composed of isotopically evolved continental crust.

Journal Article↗
PubMed2000

Vagal changes following cancer chemotherapy: implications for the development of nausea.

Many physiological changes that occur contemporaneously with nausea are mediated by the autonomic nervous system, but the specific autonomic changes associated with nausea have not been characterized. Cardiac parasympathetic (vagal) activity as indicated by heart rate variability, measured as the standard deviation of successive differences (SDSD) in beat-to-beat intervals, was assessed in 24 women with ovarian cancer immediately prior to and accompanying nausea that occurred following anticancer chemotherapy. A progressive increase in SDSD followed infusion of the chemotherapy agent, indicating a rise in cardiac parasympathetic (vagal) activity, with onset of nausea consistently occurring after the peak activity had been reached, at a time when SDSD was decreasing. An increase in parasympathetic activity seems to set the stage for the expression of nausea but an additional stimulus is apparently needed to finally trigger the event.

Aged↗
PubMed1999

Hyaluronidase expression in human skin fibroblasts.

Hyaluronidase activity has been detected for the first time in normal human dermal fibroblasts (HS27), as well as in fetal fibroblasts (FF24) and fibrosarcoma cells (HT1080). Enzymatic activity was secreted predominantly into the culture media, with minor amounts of activity associated with the cell layer. In both classes of fibroblasts, hyaluronidase expression was confluence-dependent, with highest levels of activity occurring in quiescent, post-confluent cells. However, in the fibrosarcoma cell cultures, expression was independent of cell density. The enzyme had a pH optimum of 3.7 and on hyaluronan substrate gel zymography, activity occurred as a single band corresponding to an approximate molecular size of 57 kDa. The enzyme could be immunoprecipitated in its entirety using monoclonal antibodies raised against Hyal-1, human plasma hyaluronidase. PCR confirmed that fibroblast hyaluronidase was identical to Hyal-1. The conclusion by previous investigators using earlier technologies that fibroblasts do not contain hyaluronidase activity should be reevaluated.

Cell Count↗
PubMed1999

Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31.

Two new members of a family of putative hyaluronidase genes involved in glycosaminoglycan catabolism have been identified and mapped by FISH and YAC library screening to chromosome 7q31.3. One of these (HYALP1) is an expressed pseudogene with mutations in the genomic DNA and cDNA. The six members of the hyaluronidase family are grouped into two tightly linked triplets on human chromosomes 3p21.3 (HYAL1, HYAL2, and HYAL3) and 7q31.3 (HYAL4, SPAM1 (PH-20), and HYALP1). This arrangement could arise by an ancient cluster formation, followed by a more recent cluster block-duplication. All of the hyaluronidase genes have unique tissue-specific expression patterns as determined by Northern blot analysis of 23 human tissues. HYAL1, HYAL2, and HYALP1 are widely expressed, but HYAL3 is differentially expressed in bone marrow and testis, while HYAL4 is differentially expressed in placenta and skeletal muscle. SPAM1 (PH-20) was detectable only in testis by Northern blot as previously reported, but was detectable in fetal and placental cDNA libraries by PCR, suggesting a possible role for this gene during embryonic development.

Amino Acid Sequence↗
PubMed1999

Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy: a case-control study. Study Group of the International Case Control Study on Severe Cutaneous Adverse Reactions.

BACKGROUND: There is still controversy about whether all antiepileptic drugs are associated with the severe cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We have studied the role of antiepileptic drugs in SJS and TEN, taking into account potential cofactors that might confound or modify the risk. METHODS: The case-control study in France, Italy, Germany, and Portugal identified cases of SJS/TEN that developed when the patient was not in hospital and were validated by an expert committee. Controls were patients admitted to the same hospital as the case for an acute illness or an elective procedure. FINDINGS: 73 (21%) of the 352 SJS/TEN cases and 28 (2%) of the 1579 controls reported intake of antiepileptic drugs. Among the 73 exposed SJS and TEN patients, 36 reported intake of phenobarbital, 14 of phenytoin, 21 of carbamazepine, 13 of valproic acid, and three of lamotrigine. Risk was highest in the first 8 weeks after onset of treatment. For individual antiepileptic drugs the univariate relative risk of SJS/TEN for 8 weeks or less of use was 57 (95% CI 16-360; multivariate risk 59 [12-302]) for phenobarbital; 91 (26-infinity) for phenytoin; 120 (34-infinity) for carbamazepine; 25 (5.6-infinity) for lamotrigine, and 24 (5.9-infinity) for valproic acid. The result for valproic acid was based on four case users, all of whom reported concurrent use of other associate drugs. The univariate relative risk for more than 8 weeks of use was 6.2 (2.4-17.0; multivariate risk 2.1 [0.5-9.3]) for phenobarbital, 1.2 (0-5.4) for phenytoin, 0.4 (0.02-2.1) for carbamazepine, and 7.0 (2.4-21.0; multivariate risk 2.0 [0.3-15.0]) for valproic acid. INTERPRETATION: SJS and TEN are associated with short-term therapy with phenytoin, phenobarbital, and carbamazepine. The association with valproic acid seems to be confounded by concomitant short-term therapy with other causal drugs. Lamotrigine also has the potential for severe skin reactions. The period of increased risk is largely confined to the first 8 weeks of treatment.

Adolescent↗
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↗