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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 73 records · Page 4Linked to original sources
PubMed1998

Prehospital thrombolysis in acute myocardial infarction.

Efficacy of reperfusion therapy in acute myocardial infarction is strictly time dependent. As is evidenced by several studies, most benefit in terms of myocardial salvage and short- and long-term mortality is achieved with initiation of therapy within the first 60-90 minutes after onset of symptoms. Nearly exclusively, prehospital initiation of thrombolysis makes it possible to take advantage of this early time window. Moreover a time gain of more than 30 minutes, up to 130 minutes, is possible by prehospital initiation of thrombolysis, depending on local circumstances. Randomized studies yielded a better outcome when a time gain of > or = 90 minutes was achieved. Since it has been shown that prehospital diagnosis of an acute myocardial infarction is reliable and out-of-hospital initiation of therapy has no additional specific risk, patients seen within the first 60-90 minutes after onset of symptoms or for whom a relevant time gain of > or = 90 minutes can be expected are ideal candidates for, and therefore should receive, prehospital thrombolysis.

Emergency Medical Services↗
PubMed1997

Purification and microsequencing of hyaluronidase isozymes from human urine.

We recently cloned the major hyaluronidase of human plasma, which we termed HYAL1. All hyaluronidase activity could be purified from human urine on an anti-HYAL1 monoclonal antibody column. However, urine contains two hyaluronidases of 57 kDa and 45 kDa, whereas plasma only contains the 57 kDa activity. Microsequencing confirmed that both urinary isozymes have N-termini identical to plasma hyaluronidase, but a second N-terminus was found in the smaller isozyme, apparently derived from the terminal 25 amino acids of HYAL1, at the C-terminus. The two polypeptides of the 45 kDa isozyme resulting from endoproteolytic cleavage of the 57 kDa isoform are presumably linked by disulfide bonds. Sperm contains two isozymes of the testicular hyaluronidase, PH-20, and the lower molecular weight isozyme is believed to be an endoproteolytically processed form of the larger protein. Analogously to PH-20, the smaller isozyme of HYAL1 is likely to be a proteolytically processed product of the larger isozyme.

Amino Acid Sequence↗
PubMed1997

A microtiter-based assay for hyaluronidase activity not requiring specialized reagents.

A sensitive, rapid microtiter-based assay for hyaluronidase activity is described that does not require highly specialized biological reagents, as required heretofore. The free carboxyl groups of hyaluronan are biotinylated in a one-step reaction using biotin-hydrazide. This substrate is then covalently coupled to a 96-well microtiter plate. At the completion of the enzyme reaction, residual substrate is detected with an avidin-peroxidase reaction that can be read in a standard ELISA plate reader. Because the substrate is covalently bound to the microtiter plate, artifacts such as pH-dependent displacement of the biotinylated substrate do not occur. The sensitivity permits rapid measurement of hyaluronidase activity from cultured cells and biological samples with an interassay variation of less than 5%. Using this new assay, we measured the distribution profile of plasma hyaluronidase levels in normal human sera. A 1-microl sample of plasma was sufficient for assays in triplicate. Hyaluronidase activity in human foreskin primary keratinocyte cultures was also quantitated. A 25-fold increase in hyaluronidase activity was observed in keratinocyte cultures induced to differentiate in high calcium (1.5 mM), compared to levels in low calcium (0.05 mM) media. The microtiter-based assay may be used as a routine clinical laboratory procedure.

Biotin↗
PubMed1997

Purification, cloning, and expression of human plasma hyaluronidase.

Hyaluronidase was purified from human plasma using Triton X-114 phase extractions and ion-exchange chromatography. Monoclonal antibodies generated against the purified protein by a novel screening assay were utilized to isolate homogeneous enzyme for microsequencing. The amino acid sequences obtained matched a cDNA in the Expressed Sequence Tag database which, with 5'-RACE-PCR, was used to clone the plasma hyaluronidase gene, termed Hyal-1. Hyal-1 codes for a protein of 435 amino acids that is over 40% identical to PH-20, a sperm-specific hyaluronidase. Unlike PH-20, which is only expressed in testis, transcripts of Hyal-1 were found in multiple tissues. Hyal-1 stably expressed in human embryonic kidney cells resulted in a 3,000 fold increase of secreted immunoreactive hyaluronidase activity that was biochemically indistinguishable from human plasma hyaluronidase. By immunological, molecular and biochemical criteria, we conclude that Hyal-1 is the predominant hyaluronidase found in human plasma.

Amino Acid Sequence↗
PubMed1997

Atorvastatin does not alter the anticoagulant activity of warfarin.

Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfarin dosing should not be necessary.

Adult↗
PubMed1997

Hereditary angioedema: case report and review of management.

The classification, pathophysiology, and treatment of angioedema is reviewed. An overview of acquired and hereditary angioedema is presented with an interesting case report that illustrates the importance of recognition and perioperative management of hereditary angioedema to prevent a potentially fatal outcome.

Anabolic Agents↗
PubMed1997

Aqueous hyaluronic acid concentration: comparison in pediatric and adult patients.

PURPOSE: To determine if there is an age-related increase in human aqueous hyaluronic acid (HA) concentration. METHODS: HA concentrations were measured in 102 specimens of human aqueous humour obtained during intraocular surgery. Patient age ranged from one month to 93 years. Measurement of the HA concentration in the specimens was performed by a modified ELISA-like assay using a biotinylated HA-binding peptide. RESULTS: An approximate five-fold increase in the mean aqueous HA concentration was observed between the pediatric (0.33 microgram/ml, n = 5) and the adult patients (1.72 micrograms/ml, n = 97, p < 0.0002). Among the adult patients, however, there was a poor correlation between age and aqueous HA concentration. CONCLUSIONS: Adult aqueous humor has a significantly higher HA concentration than aqueous obtained from pediatric patients. The source of this increase is unclear, but may be from anterior segment production of HA, or alternatively, from anterior diffusion of vitreous HA.

Adult↗
PubMed1997

Hyaluronan polymer size modulates intraocular pressure.

To investigate whether the occasional increase in intraocular pressure that may arise following injection of sodium hyaluronan into the anterior segment during intraocular surgery is related to the polymer size of hyaluronan, controlled fragmentation of hyaluronan chains in vitro was obtained using progressive incubation with testicular hyaluronidase. The profile of molecular sizes of the hyaluronan polymers in various preparations was determined using molecular sieve column chromatography. Individual preparations were injected into six rabbit eyes and intraocular pressures were measured every one-half hour for 12 hours. Longer incubations of hyaluronan with hyaluronidase resulted in more extensive degradation with accumulation of shorter chain lengths. In the rabbit, mean intraocular pressure for 12 hours following intracameral injection of hyaluronic acid (HA) is proportional to the polymer size of HA. The occasional elevation of intraocular pressure that occurs following injection of hyaluronan during ophthalmic surgery can be avoided in part by assuring the rapid fragmentation of the large molecular size hyaluronan polymer.

Animals↗
PubMed1997

Patterns of hyaluronan staining are modified by fixation techniques.

The apparent intensity of hyaluronan (HA) staining in tissue sections can vary as a function of fixation techniques. We examined the histochemical distribution of HA in normal human skin using an HA-specific binding peptide derived from bovine nasal cartilage. The HA, particularly in the dermis, was best preserved in sections fixed in 10% acid-formalin with 70% ethanol. In contrast, sections fixed in the routine 10% neutral-buffered formalin had a much weaker intensity of HA staining. Furthermore, acid-formalin/ethanol-fixed sections retained much of their apparent HA after incubation with saline, in contrast to the neutral formalin-fixed sections, in which most of the stainable HA was lost. Such marked differences in staining intensity were not observed in slides stained with Alcian blue, a procedure presumed to stain HA as well as other glycosaminoglycans. Staining using the HA binding peptide was entirely absent when sections were first preincubated in hyaluronidase, whereas similar Alcian blue-stained sections retained most of their staining intensity. Caution should be exercised in evaluating the distribution of HA in tissues using the HA binding peptide, particularly when different fixation techniques among several laboratories are being compared. In addition, the ability to evaluate the HA content of tissues using Alcian blue staining should be reconsidered. The sulfated glycosaminolglycans of the "ground substance" appear to be the predominant substrates for Alcian blue.

Adult↗
PubMed1997

Hyaluronan is a prerequisite for ductal branching morphogenesis.

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44. Reverse transcriptase polymerase chain reaction analysis was used to map the temporal regulation of specific CD44 variant isoforms. In each age group, hyaluronan was localized exclusively in the stromal matrix. Hyaluronan was greatly reduced in the later ages and was entirely absent around the developmentally quiescent proximal regions of the ducts. Early in prostate development, CD44 was prominent in the mesenchyme. However, in the later phases, CD44 expression became associated with membranes of epithelial cells. The role of hyaluronan-CD44 interactions in ductal branching morphogenesis was studied by serum-free organ culture of mouse anterior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis. Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching morphogenesis. These results are suggestive of the significant role played by hyaluronan-CD44 interactions in mediating androgen-induced prostatic growth and morphogenesis.

Animals↗
PubMed1997

Using the international normalized ratio to standardize prothrombin time.

The international normalized ratio, or INR, was introduced in 1983 by the World Health Organization, or WHO, Committee on Biological Standards to more accurately assess patients receiving anticoagulation therapy. The INR mandates the universal standardization of prothrombin time. This article describes the method used to calculate INR, as well as its clinical relevance to the practice of dentistry.

Anticoagulants↗
PubMed1997

Corneal endothelial hyaluronidase: a role in anterior chamber hyaluronic acid catabolism.

The possible role of the human corneal endothelium in the turnover of anterior chamber hyaluronic acid (HA) was investigated. Hyaluronidase, an endoglycosidase that degrades HA and other glycosaminoglycans, is thought to play a role in HA homeostasis. The presence of hyaluronidase in the corneal endothelium was demonstrated immunohistochemically in sections from normal adult human cornea. Additionally, by using a modified enzyme-linked immunosorbent assay-like assay, active hyaluronidase was detected in the supernatant from primary culture human corneal endothelial cells. The optimal activity for the corneal endothelial hyaluronidase was in the acid range (pH 4.0), similar to previously isolated lysosomal hyaluronidase. Further immunohistochemistry showed that the corneal endothelial cells also express CD44, the receptor for HA, which would allow endocytosis of HA. Human corneal endothelial hyaluronidase may play a role in normal anterior segment HA metabolism and in the degradation of highly concentrated HA used as a visco-elastic.

Adult↗
PubMed1997

Hyaluronan in the human trabecular meshwork.

PURPOSE: Hyaluronan (HA) is a high-molecular weight glycosaminoglycan that can affect water and solute fluxes in the extracellular matrix. The distribution of HA in the human trabecular meshwork of nonglaucomatous eyes was examined to help understand the potential role of HA in the regulation of aqueous outflow resistance. METHODS: Histolocalization of HA was established in situ in the trabecular meshwork of human eyes with no known diseases of the anterior segment. A specific biotinylated HA-binding peptide was used as a probe for this study, with enhanced sensitivity of HA detection achieved by modifications of the fixation and staining procedures. RESULTS: Evaluation of HA staining in the aqueous outflow pathway in comparison to that in other ocular structures (e.g., the vitreous) showed pronounced staining in the trabecular meshwork. The staining intensity was similar between various layers of the meshwork. Both the filtering and the anterior nonfiltering portions of the trabecular meshwork showed pronounced HA staining. The staining was localized primarily to the trabecular meshwork endothelial cells. CONCLUSIONS: Pronounced HA staining observed in the various layers of the trabecular meshwork suggests that substantial amount of HA is present in the nonglaucomatous outflow pathway. The staining pattern suggests that HA is associated with the endothelial cells lining the trabecular beams. This finding supports potential roles for this glycosaminoglycan in the regulation of the physiological aqueous outflow resistance or in the maintenance of the outflow channels or both. Histochemical localization of HA in the various layers of the non-glaucomatous meshwork provides a useful basis for future comparative studies of HA distribution and relative amounts in the trabecular meshworks of eyes affected by various types of glaucoma.

Aged↗
PubMed1997

Hyaluronidases in tissue invasion.

Hyaluronidases are broadly distributed enzymes with varying substrate specificities, a wide range of pH optima, and different catalytic mechanisms. They may be used by organisms to invade one another. Hyaluronidases have also been invoked as mechanisms for tumor invasion and metastatic spread. In this review, we will concentrate more on the different kinds of hyaluronidases involved in tissue invasion other than cancer metastasis, present some of the rapidly accumulating new data, and address the paradox that both hyaluronidase as well as its hyaluronan substrate are associated with invasion.

Animals↗
PubMed1996

Cardiac myxomas.

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Heart Neoplasms↗
PubMed1996

Hyaluronan-binding properties of human serum hemopexin.

Hemopexin, the heme-binding serum glycoprotein, exhibits a complex electrophoretic pattern on two-dimensional immunoelectrophoresis on agarose gels into which hyaluronic acid is incorporated in the first and monospecific anti-hemopexin in the second dimension. This heterogeneity reflects a range of interactions of hemopexin isoforms with hyaluronic acid. Electrophoretic patterns of individual human sera greatly differ in their contents of hyaluronan-interacting hemopexin species. Hemopexin itself has no hyaluronidase activity.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1996

[Are emergency physicians' diagnoses accurate?].

METHODS AND AIM OF THE STUDY: The on-scene performance during all missions of the emergency physician-operated rescue helicopter and mobile intensive care unit based at a large-city hospital over a period of 1 year was retrospectively analysed; 2,254 hospital discharge reports were available (92% of the patients treated by the emergency physicians [n = 2,493]). The following parameters were investigated: reliability of the primary diagnosis established by the emergency physician (by comparison with the discharge diagnoses); initial on-scene therapeutic measures; means of transportation (with or without accompanying emergency physician); and level of care of the target hospital. RESULTS: The most common reasons for a mission were cardiopulmonary diseases (55%), neurological disorders (18%), and traumatic events (7%). The diagnoses, therapeutic measures, and mode of transportation were correct in 2,033 (90%) patients with a discharge report. Severe errors of assessment by the emergency physician were identified in 73 patients (3%): life-threatening conditions were not recognised and/or grossly incorrect therapeutic measures were taken and/or the chosen means of transportation was unsuitable. Relative errors in assessment occurred in 4% (n = 83): the most crucial diagnosis was not made, but the patient was escorted by the emergency physician (without therapeutic errors) to a suitable hospital. In 3% (n = 65) of the cases, the patient's condition was overestimated by the emergency physician as suggested by the obviously exaggerated on-scene therapy. Underestimations of the severity were most common in patients with cardiopulmonary diseases and increased in frequency and severity with increasing age and the presence of a concomitant neurologic deficit. Underestimations of a severe condition in younger patients were extremely rare; overestimations of the severity and consequent overtreatment were particularly common in traumatised patients independent of age. CONCLUSIONS: In the context of quality management measures, a careful evaluation of on-scene diagnoses, therapeutic measures, and decisions made by the emergency physician is a suitable procedure for identifying systematic errors. A high percentage of correct diagnoses and therapy at the emergency site can only be ensured by clinically experienced physicians who constantly deal with patients with acutely life-threatening conditions.

Adolescent↗