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R Stern

Publications and source records attributed to R Stern.

At least 145 records · Page 8Linked to original sources
PubMed1992

[Is pre-hospital thrombolysis in acute myocardial infarct valuable as a routine measure?].

UNLABELLED: In 4920 consecutive missions of the mobile intensive care unit Klinikum Steglitz, 1226 patients (25%) had chest pain of presumed cardiac origin. In 272 patients (22%) an acute myocardial infarction (AMI) was diagnosed in the field. In four patients the diagnosis was wrong; 11 patients with proven coronary artery disease had significant ST-segment elevation, but did not develop AMI. In hospital, a total of 406 patients had evidence of AMI; 173 of these (41%) were seen by an emergency physician in the field already within the first hour after onset of symptoms. In 6%, diagnostic ST-elevation was not recognized by the emergency physician; 27% had non-diagnostic ECG changes (11% bundle-branch block). Prehospital thrombolysis within 4 h after symptom onset was performed in 126 of 205 patients (61%); 74 of these patients were seen by the emergency physician within the first hour. The main reason for exclusion was advanced age. Inclusion of older patients and also those with bundle-branch block could further increase the prehospital thrombolysis rate. CONCLUSION: With an effective emergency medical system a large proportion of all patients with AMI can correctly be identified and properly treated with a thrombolytic drug in the field. The time gain is considerable.

Aged↗
PubMed1991

Group cognitive and behavioural treatment for hypochondriasis.

OBJECTIVE: To assess the feasibility of carrying out group cognitive and behavioural treatment for hypochondriasis in a general hospital setting. DESIGN: Assessment of patients referred for therapy. SETTING: District general hospital. PATIENTS: Six patients aged 35 to 55 (mean 43) years with a mean duration of symptoms of 12 years who fulfilled the Diagnostic and Statistical Manual for Mental Disorders (DSM III-R) criteria for hypochondriasis. MAIN OUTCOME MEASURES: Number of visits to their doctors, time spent thinking about illness, and scores on the hospital anxiety and depression scales. RESULTS: The mean number of visits to a doctor fell significantly after treatment (3 before treatment v 0.8 after treatment; p = 0.03) as did the time spent thinking about illness (57.3 v 40.6; p = 0.14). The depression and anxiety scores also fell, although the differences were not significant (depression: 9.5 before v 8.5 after; anxiety: 13 before v 12 after). CONCLUSION: It is feasible to carry out group cognitive and behavioural treatment in patients with hypochondriasis, and controlled studies are now indicated.

Adult↗
PubMed1991

Hyaluronidase levels in urine from Wilms' tumor patients.

The pathophysiology of Wilms' tumor is associated with major alterations in hyaluronic acid metabolism. Elevated levels of both hyaluronic acid and a hyaluronic acid-stimulating activity occur in the urine and serum of patients with this tumor. In the current study, we describe elevated levels of urinary hyaluronidase in five patients with Wilms' tumor. Following surgical removal of the tumor, enzyme levels decreased toward normal. Characterization of enzyme activity indicates that hyaluronidase may be produced by the tumor itself. Alternatively, normal renal tissue may also be producing enzyme in a compensatory response to the elevated hyaluronic acid levels in these patients. We suggest that urinary hyaluronidase can be used as an additional marker for Wilms' tumor.

Biomarkers, Tumor↗
PubMed1991

A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins.

Epidemiologic and genetic data suggest an inverse relationship between plasma high density lipoprotein (HDL) cholesterol and the incidence of premature coronary artery disease. Some of the defects leading to low levels of HDL may be a consequence of mutations in the genes coding for HDL apolipoproteins A-I and A-II or for enzymes that modify these particles. A proband with plasma apoA-I and HDL cholesterol that are below 15% of normal levels and with marked bilateral arcus senilis was shown to be heterozygous for a 45-base pair deletion in exon four of the apoA-I gene. This most likely represents a de novo mutation since neither parent carries the mutant allele. The protein product of this allele is predicted to be missing 15 (Glu146-Arg160) of the 22 amino acids comprising the third amphipathic helical domain. The HDL of the proband and his family were studied. Using anti-A-I and anti-A-II immunosorbents we found three populations of HDL particles in the proband. One contained both apoA-I and A-II, Lp(A-I w A-II); one contained apoA-I but no A-II, Lp(A-I w/o A-II); and the third (an unusual one) contained apoA-II but no A-I. Only Lp(A-I w A-II) and (A-I w/o A-II) were present in the plasma of the proband's parents and brother. Analysis of the HDL particles of the proband by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two protein bands with a molecular mass differing by 6% in the vicinity of 28 kDa whereas the HDL particles of the family members exhibited only a single apoA-I band. The largely dominant effect of this mutant allele (designated apoA-ISeattle) on HDL levels suggests that HDL particles containing any number of mutant apoA-I polypeptides are catabolized rapidly.

Amino Acid Sequence↗
PubMed1991

Delayed access to health care: risk factors, reasons, and consequences.

OBJECTIVE: To determine characteristics of patients reporting delays in care before hospitalization and the reasons for those delays. DESIGN: Survey; personal interviews. SETTING: Five hospitals in Massachusetts. PATIENTS: Subjects were drawn from a consecutive sample of all adult patients (excluding obstetrics or psychiatry patients) hospitalized during the first 6 months of 1987 as part of a larger study of hospital costs. For the current study, if patients were re-admitted, we included in our analysis only data on the first admission during the study period. We obtained usable survey data from 12,068 of 17,231 eligible patients. RESULTS: Delays in care were reported by 16% of patients. The odds of reporting delays in care among patients who were black, poor, uninsured, or without a regular physician were 40% to 80% greater than those for other patients (P less than 0.01). Most patients who reported delays thought that their problem was not serious (64%). Cost was an important factor in delaying care for patients in lower socioeconomic positions; the odds of delaying care because of cost for patients who were both poor and uninsured were 12 times greater than the odds for other patients (P less than 0.001). After controlling for diagnosis-related groups (DRGs) and severity, patients who reported delays had 9% longer hospital stays compared with others (P less than 0.001). CONCLUSIONS: Patients generally thought to be disadvantaged are at especially high risk for delaying care for conditions that eventually lead to hospitalization. Because these delays are associated with longer hospital stays and potentially poorer health outcomes, interventions that reduce delays seem especially important.

Adolescent↗
PubMed1991

Early and late events in the development of human breast cancer.

We hypothesize that early events in the development of at least some human breast cancers involve faulty epithelial-mesenchymal interactions and that the stromal cells themselves play an active role in this abnormal process. In contrast, later events accelerating breast tumor progression may occur in association with genetic changes involving only the malignant epithelial cells. These conclusions arise from a review of the literature, our comparative studies of HA metabolism in fibroblasts cultured from either normal or malignant breast tissues, and from molecular-genetic studies performed on sequential specimens from a single patient and on a wide variety of human breast tumor samples. HA is a proteoglycan component of the ECM which is known to stimulate epithelial cell detachment and motility and is most abundant in fetal and rapidly growing tissues. We find that many breast cancer-derived fibroblasts are stimulated to produce HA in response to TGF-beta under conditions where HA accumulation by normal tissue fibroblasts is almost uniformly inhibited. In a single patient, we had the opportunity to examine three malignant effusions that occurred sequentially to identify genetic changes associated with the later stages of breast cancer progression. Although, common cytogenetic abnormalities were found in all the effusion samples, only the last effusion exhibited a loss of heterozygosity at the c-Ha-ras locus. In this case, the allelic loss correlated with improved growth in vitro of the primary cells and with ability to become a permanently established cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1991

Hyaluronic acid in a cardiac myxoma: a biochemical and histological analysis.

Cardiac myxoma is the most common primary tumor of the heart. This tumor has a gelatinous stroma that is thought to be composed of glycosaminoglycans, the classical acid mucopolysaccharide ground substance. We examined both biochemically and histologically the hyaluronic acid in a case of cardiac myxoma using a newly developed hyaluronic acid-binding protein probe. We observed that hyaluronic acid was localized in the amorphous stroma and occurred at levels 30 times that found in normal atrial septum.

Heart Neoplasms↗
PubMed1991

Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid.

Midgestation fetal wound healing is characterized by healing without fibrosis or scar formation. The mechanisms that underlie this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid. In this study a newly developed assay was used to determine the hyaluronic acid levels in fetal and adult wound fluid. Adult wound fluid had a rapid increase in hyaluronic acid, which peaked at 3 days and decreased to 0 by 7 days. In contrast levels of hyaluronic acid in fetal wound fluid increased rapidly and remained significantly elevated for 3 weeks. This prolonged presence of hyaluronic acid in the matrix of fetal wounds creates a 'permissive' wound environment that promotes fetal fibroblast movement and proliferation and inhibits cytodifferentiation. Such a matrix environment promotes healing by regeneration rather than by scarring. This observation has therapeutic implications. The prolonged application of hyaluronic acid or hyaluronate protein complexes to wounds in children or adults may modulate healing in a manner that makes the wounds more fetal-like.

Animals↗
PubMed1991

Effects of rheumatoid factor, antinuclear antibodies and plasma reagin on the serologic assay for Lyme disease.

Rheumatoid factor (RF), antinuclear antibodies (ANA) and the presence of other spirochetal infections have been reported to be the source of false positive serologic tests of Lyme disease. To evaluate this, we studied their effect upon the Lyme assay in use in our clinical laboratory. Of 64 rapid plasma reagin (RPR) test positive sera, 2 had positive Lyme antibody tests, not statistically different than controls. Of 43 RF positive sera, 2 had positive lyme tests, no different than controls, and 1 of 53 ANA containing sera had positive Lyme tests, again, not different from controls. There was no relationship of titer of RPR or ANA with Lyme results, nor of ANA pattern. Sera containing high titer RF, however, had slight interference, producing an increase in equivocal Lyme assay results. From the other point of view, sera that were Lyme test positive had no increased frequency of RPR or RF, but had an increased frequency of ANA. Therefore, neither RPR, RF or ANA were found to markedly interfere with the Lyme assay. However, Lyme antibodies may interfere with the ANA test.

Antibodies↗
PubMed1990

Collagen, proteoglycan and hyaluronidase activity in cultures from normal and scoliotic chicken fibroblasts.

Connective tissue matrix components were investigated using skin fibroblasts from normal or inbred scoliotic lines of chickens. Specifically, the fibroblasts were obtained from either an isogenic line or a backcross, derived by crossing the isogenic line with a pure line of scoliotic birds. From the backcross, both affected (35-45%) and non-affected (55-65%) progeny were produced. The affected birds had spinal curves greater than 20 degrees. Several abnormalities of connective tissue were observed when cells from scoliotic chicks were grown in culture: increased collagen extractability, decreased aggregatability of proteoglycans under associative conditions and lower than normal levels of hyaluronic acid. There was also less collagen deposited in the cell layer with proportionately increased amounts of collagen secreted into the culture media by cells from scoliotic versus normal chick fibroblasts. Values for collagen matrix stability, as estimated by extractability and net deposition, were intermediate for cells from the backcrossed, but non-affected, birds. Moreover, hyaluronidase, an enzyme that degrades hyaluronic acid, was abnormally elevated in the fibroblast cultures from scoliotic chicks. It is proposed that the increase in hyaluronidase contributes to the abnormalities observed in extracellular matrix components and may be a factor in the expression of scoliosis in susceptible birds.

Animals↗
PubMed1990

Hyaluronic acid-stimulating activity in the pathophysiology of Wilms' tumors.

Markedly elevated levels of hyaluronic acid occur in the serum and urine of some patients with Wilms' tumor. We have recently described a glycoprotein factor in fetal serum that stimulates deposition of hyaluronic acid. In a survey of bovine fetal tissue extracts, we have identified the fetal kidney as the source of this circulating activity. Wilms' tumors arise from transformed "rests" of fetal kidney. We demonstrate here that such tumors continue to produce this fetal factor and that the hyaluronic acid-stimulating activity is found in the urine of children with Wilms' tumors. In the three patients with Wilms' tumor who were followed, elevated levels of hyaluronic acid-stimulating activity were found in their urine before treatment. By 2 months after surgical removal of their tumors, these levels had returned to baseline. We propose that hyaluronic acid-stimulating activity is the mechanism for the elevated levels of hyaluronic acid in the sera and urine of these patients. The activity is an oncofetal protein and the first for which a function has been identified. It also is a marker for this common childhood solid tumor and has the potential for identifying children at increased risk.

Animals↗
PubMed1990

Instability of the myofibroblast phenotype in culture.

Myofibroblasts are cells that have features of both smooth muscle cells and fibroblasts. Myofibroblasts from rat granulation tissue were studied using a coordinated biochemical and morphological approach. These myofibroblasts were maintained in culture for more than 17 passages. After establishing that these cells were indeed myofibroblasts by immunohistochemical and ultrastructural criteria, their biochemical parameters and phenotypic stability were studied. Rat dermal fibroblasts grown under similar conditions served as controls. Biochemically, it was found that both cells produced similar types of procollagens, namely collagens I and III, in similar proportions at or near a 1:1 ratio. However, myofibroblasts at early passage produced threefold more procollagens than did fibroblasts at the same stage of passage, while similar quantities were produced in each at late passage. These observations for procollagens were confirmed by separate studies for collagens, as measured by hydroxyproline determinations. Such differences were also reflected ultrastructurally. Secretory vesicles were identified in myofibroblasts at early stage, but not at late stage of passaging. No such vesicles were seen in fibroblasts at any stage of passage. In conclusion, myofibroblasts are active secretory variants of fibroblasts which have an unstable phenotype in culture and become indistinguishable from fibroblasts at late passage.

Animals↗
PubMed1990

Ascorbic acid stimulates production of glycosaminoglycans in cultured fibroblasts.

The effect of ascorbic acid on collagen synthesis is well characterized. Proteoglycans and their attached glycosaminoglycans are components of the extracellular matrix closely associated with collagen fibers. We examined whether ascorbic acid also plays a role in glycosaminoglycan production. Synthesis and deposition of glycosaminoglycans into the extracellular matrix and secretion into the media were followed in human skin fibroblasts cultured in the presence and absence of ascorbic acid. Specific glycosaminoglycans were identified and quantitated by differential enzyme digestion, ion-exchange column chromatography, and cellulose-acetate electrophoresis. No major qualitative changes in glycosaminoglycans were observed. However, quantitatively, synthesis of glycosaminoglycans increased 30 to 90%, and deposition into the extracellular matrix increased 80% in the presence of ascorbic acid. This effect was only in part secondary to decreased levels of collagen, and the diminished capacity of underhydroxylated collagen to bind proteoglycans. The effect of ascorbic acid on extracellular macromolecules is thus more pervasive than previously assumed.

Ascorbic Acid↗
PubMed1990

Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid.

Fetal wound healing occurs rapidly and without inflammation, fibrosis, or scar formation. It is a process fundamentally different from adult wound healing. The mechanisms that underlie such unique healing properties are unknown. However, hyaluronic acid, a glycosaminoglycan component of the extracellular matrix, is prominent throughout the course of fetal wound healing, and is thought to play a major role in the healing process. Amniotic fluid contains high levels of hyaluronic acid. Amniotic fluid also contains a number of potent growth factors that are critical for fetal development. In this report, a new factor in amniotic fluid that stimulates deposition of hyaluronic acid is described. This activity is measured in an in vitro assay system in which cultured fibrosarcoma cells are used as indicator cells. Amniotic fluid thus provides two separate mechanisms for the deposition of hyaluronic acid. One is by exogenous application directly onto fetal skin wounds; the second is by providing a factor to increase the production of hyaluronic acid endogenously, by stimulating cells around the wound site. The resulting hyaluronic acid-rich area may support the ability of the fetal wound to heal with its unique properties.

Amniotic Fluid↗
PubMed1990

Studies in fetal wound healing, VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation.

The mechanisms that underlie the lack of scarring in fetal wounds are unknown, but probably relate to the control of collagen fibrillogenesis. The role of collagen in the fetal wound matrix is controversial, and several wound implant models have been used to evaluate collagen deposition in fetal wounds. Unfortunately, these models create an artificial wound environment and may thereby affect the results. In order to study fetal wound collagen deposition in linear wounds without artificially altering the wound environment, we applied a highly sensitive immunohistochemical technique that uses antibodies to collagen types I, III, IV, and VI. We found that collagen was deposited in fetal wounds much more rapidly than in adult wounds. Wound collagen deposition occurred in a normal dermal and mesenchymal pattern in second and early third trimester fetal lambs. These findings are consistent with the observation that the fetus heals rapidly and without scar formation. In contrast, wounds in late gestation fetal lambs showed some evidence of scar formation. Further studies may suggest ways to alter the adult wound so that it heals in a fetal manner.

Animals↗