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Biomedical subjects

S Olsen

Publications and source records attributed to S Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry.

BACKGROUND: The laboratory determination of the level of fetal cells in maternal circulation remains an important support in the obstetrical management of women with suspected uterine trauma and in the proper dose administration of anti-D for prevention of Rh hemolytic disease of the newborn. Limitations in the sensitivity and precision of the widely used manual Kleihauer-Betke test have prompted an increased utilization of flow cytometric methods for fetal cell detection in maternal blood samples. STUDY DESIGN AND METHODS: Murine monoclonal antibodies directed against fetal hemoglobin (HbF) were developed, conjugated to fluorescein isothiocyanate, and used in a multiparametric flow cytometric assay developed for the quantitation of fetal red cells. A rapid intracellular staining method using brief glutaraldehyde fixation and Triton X-100 permeabilization prior to monoclonal antibody incubation was developed, along with optimization of the flow cytometric analysis protocol for the analysis of 50,000 cells. The performance of the assay was assessed for linearity and precision and correlated with the Kleihauer-Betke acid elution method. RESULTS: The anti-HbF flow cytometric method showed good correlation with the Kleihauer-Betke method (r2 = 0.86) and superior precision with a CV < 15 percent for blood samples with > 0.1 percent fetal cells. Analysis of 150 blood samples from nonpregnant adults, including individuals with elevated HbF due to hemoglobinopathies and hereditary persistence of HbF, gave a mean value of 0.02 percent fetal cells, and all results were less than 0.1 percent. CONCLUSIONS: The anti-HbF flow cytometric method for detection of fetal cells offers a simple, reliable, and more precise alternative to the Kleihauer-Betke manual technique for the assessment of fetomaternal hemorrhage. The method has additional potential applications for the study of HbF levels or frequency of adult red cells with low levels of HbF (F cells) in individuals with hemoglobinopathies.

Adult↗
PubMed1998

The epidemiology of urban pediatric neurological trauma: evaluation of, and implications for, injury prevention programs.

OBJECTIVE: To describe the incidence and causes of pediatric head, spinal cord, and peripheral nerve injuries in an urban setting and to assess the implications of these data for injury prevention programs. METHODS: Pediatric deaths and hospital admissions secondary to neurological trauma included in the Northern Manhattan Injury Surveillance System from 1983 to 1992 were linked to census counts to compute incidence rates. Rates before the implementation of a nonspecific injury prevention program were compared with rates after the implementation, and rates for the target population were compared to rates for the control population. Rates were analyzed on the basis of the cause of injury as well as the age, gender, and neighborhood income level of the injured. RESULTS: The incidence of neurological injuries resulting in hospitalization or death was 155 incidents per 100,000 population per year; the mortality rate was 6 people per 100,000 population per year. Neurological injuries represented 18% of all pediatric injuries and accounted for 23% of all traumatic deaths. Spinal cord and peripheral nerve injuries were relatively rare (5%) compared to head injuries (95%). Minor head injuries, including isolated cranial fractures, minor concussions (<1 h loss of consciousness), and unspecified minor head injuries, accounted for the majority of neurological injuries (76%), whereas severe head injuries, including severe concussion (>1 h loss of consciousness), cerebral laceration/contusion, intracerebral hemorrhage, and unspecified major injuries, were less common (18% of all neurological injuries). Boys were more often affected than girls at every age, and this preference increased with age. Children younger than 1 year showed the highest incidence of both major and minor injuries. One- to 4-year olds showed the lowest rates, with steady increases thereafter. Traffic accidents and falls were the leading causes (38 and 34%, respectively), and assaults were the next leading causes (12%). Among children admitted to surveillance system hospitals, falls were most common in children younger than 4 years, pedestrian motor vehicle accidents were most common in late childhood, and assaults were most common in early adolescence. CASE: fatality rates were 5 to 7% for all age groups except 5- to 12-year-olds, for whom the case:fatality rate was 1.9%. Residence in a low-income neighborhood was associated with an increased risk of injury (rate ratio, 1.71; confidence interval, 95%, 1.54, 1.89). The average hospitalization cost per injury was $8502. Medicaid (54%) and other government sources (5%) covered the majority of expenses, including indirect reimbursement of usually uncollected self-pay billing (19%). Although injury incidence rates fell in both the control and intervention cohorts during implementation of a nonspecific injury prevention program, targeted age and population groups demonstrated greater relative reductions in injuries than nontargeted ones, suggesting a positive effect. CONCLUSIONS: Deaths and hospital admissions secondary to pediatric neurological trauma represent a significant public health problem, with the majority of the direct cost being born by government agencies. Future efforts to prevent neurological trauma in children who live in inner cities should focus on families with low incomes and provide novel education programs regarding infant abuse, infant neglect, and infant injury avoidance. Age-appropriate school-based programs should also be developed to address traffic safety and conflict resolution.

Adolescent↗
PubMed1997

Glucocorticoid regulation of natural cytotoxicity: effects of cortisol on the phenotype and function of a cloned human natural killer cell line.

The ability of glucocorticoids to suppress cellular immune functions, including the cytotoxic activity of natural killer cells, is well known. However, the molecular mechanism(s) of glucocorticoid-mediated suppression of cellular cytotoxicity mediated by natural killer cells is not understood. We have investigated the effects of cortisol on protein expression and cytotoxic function of natural killer cells using NK3.3, a well-characterized, cloned human natural killer cell line. Cortisol, at concentrations up to 2 microM, does not significantly alter the viability or proliferative capacity of NK3.3 cells. However, micromolar concentrations of cortisol induce the expression of a small set of proteins which are not synthesized by NK3.3 cells in the absence of cortisol, and repress the synthesis of another set of proteins including several phenotypic determinants and cytokines. In the presence of added cortisol, the synthesis of perforin mRNA was partially repressed. However, the most striking effect of cortisol on this NK clone was its repression of granzyme A synthesis. In conjunction with the downregulation of adhesion proteins, NK3.3 cells cultured in the presence of cortisol exhibit a reduced capacity to form conjugates with K562 target cells. Whereas cortisol treatment of NK3.3 cells causes an approximately 50% decrease in their ability to form conjugates with K.562 target cells, the cytotoxic function of these cells is completely abolished under the same conditions. This first report of hormonal regulation of granzyme expression and the strong correlation between granzyme A repression and cytotoxic function suggests that cortisol may regulate NK function by repression of granzyme A synthesis. In addition to demonstrating the significant influence of cortisol on natural killer cell function, these studies provide a model system for elucidation of molecular mechanism(s) whereby glucocorticoids repress cellular immune function, especially with respect to natural killer cells.

Anti-Inflammatory Agents↗
PubMed1997

A quantitative immunohistochemical study of the expression of mesangial alpha-smooth muscle actin and the proliferation marker Ki-67 in glomerulonephritis in man.

Using a specific marker 1A4 (DAKO), a quantitative evaluation of alpha-smooth muscle actin (ASMA) in glomeruli has been performed on human renal biopsies from patients suffering from acute, postinfectious, endocapillary glomerulonephritis (GN; 9 biopsies), IgA nephropathy (11 biopsies) and membranoproliferative GN (11 biopsies) and appropriate controls expressing a very weak ASMA reactivity. A significantly increased expression was found in all categories of GN. The glomeruli from IgA nephropathy showed variation of ASMA expression (range 0.1-27.7%) and a pattern of ASMA staining that was mesangial, global and diffuse. This pattern was also seen in cases of IgA nephropathy with focal, segmental, proliferative GN. In all biopsies, the glomerular cell number and proliferation index was determined. All the categories of GN showed significantly increased glomerular cellularity and proliferation index. Among the three types of GN, the glomerular cellularity and proliferation was lowest in IgA nephropathy. The mean number of Ki-67-positive intraglomerular nuclei and the proliferation index were both significantly correlated with the mean number of glomerular cell nuclei. Morphometric estimates demonstrate increased ASMA expression in types of GN with different prognosis. This finding and the lack of correlation with proliferation markers together indicate that the role of ASMA in GN is complex. This method of ASMA estimation may be useful in further studies of its role in disease activity and prognosis.

Actins↗
PubMed1997

Identification of a cell surface protein with a role in stimulating human keratinocyte proliferation, expressed during development and carcinogenesis.

In an attempt to define cell surface molecules with an important role in the development of squamous cell carcinomas (SCCs), we generated monoclonal antibodies (MoAbs) to a human keratinocyte cell line (FEP18-11-T1) capable of giving rise to SCCs in nude mice. MoAb 10G7 was selected for further study because it bound to a cell surface component preferentially expressed by this cell line as compared with normal human foreskin keratinocytes. This MoAb recognizes a cell surface protein (10G7 antigen) that is not detectable on normal keratinocytes in the foreskin in vivo, but whose expression is induced when the keratinocytes are dissociated from this tissue and placed in culture. Interestingly, the 10G7 antigen is downregulated upon keratinocyte differentiation in vitro. Consistent with its expression in hyper-proliferative epithelia in vitro, 10G7 antigen exhibited a classic oncofetal pattern of expression in vivo. Thus, although no reactivity was obtained with MoAb 10G7 in the epithelia of normal foreskin or cervical tissue, strong reactivity was detected in epithelia from genital lesions ranging from benign warts to invasive SCCs. Epidermis from developing fetal tissue also exhibited strong reactivity with MoAb 10G7. We have been able to demonstrate that this MoAb is capable of stimulating FEP18-11-T1 keratinocyte proliferation in vitro in a concentration-dependent manner in the absence of growth factors, suggesting that the 10G7 antigen may play an important role in regulating cellular proliferation during development and in carcinogenesis in epithelial tissues.

Animals↗
PubMed1997

Renal biopsy findings in long-term cyclosporin treatment of psoriasis.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Adult↗
PubMed1996

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart.

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.

Adrenergic beta-Antagonists↗
PubMed1996

Acute tubulointerstitial nephritis: phenotype of infiltrating cells and prognostic impact of tubulitis.

The prognostic impact of tubulitis and the phenotype of the infiltrating cells in the tubules were studied in ten percutaneous renal biopsies from six patients with acute tubulointerstitial nephritis (ATIN). The inflammatory cell subsets in the tubules and interstitium (CD3+, CD4+, CD8+, CD20+, CD45RO+, CD56+, CD57+, CD68+ and TIA-1+ cells), the expression of vimentin and the proliferation-associated antigen Ki-67 by cortical tubular cells, and the grade of tubulitis, interstitial infiltration and fibrosis were analysed. Cytotoxic injury to tubular cells in the vicinity of tubular-wall-localized lymphocytes was studied ultrastructurally. ATIN was drug-induced in three patients, related to Legionella infection in two and idiopathic in one patient. Four patients recovered, one with reduced renal function. Two patients developed end-stage renal disease. CD8+ and CD4+ lymphocytes, and a smaller number of macrophages, infiltrated the tubules. The predominant lymphocyte subset in the tubules was the same as in the interstitium. Cytotoxic injury to tubular cells was not seen electron microscopically. The tubular cells exhibited increased proliferative activity and expressed vimentin, indicating non-specific tubular damage. The cell subset, the severity of tubulitis, and the tubular expression of vimentin were not related to outcome. The main prognostic factor was the severity of the interstitial fibrosis. Tubulitis in ATIN may be a harmless non-immune reaction, mediated by tubular expression of cytokines, together with adhesion and other molecules.

Adult↗
PubMed1996

How often is NIDDM complicated with non-diabetic renal disease? An analysis of renal biopsies and the literature.

According to extensive autopsy studies, non-diabetic renal disease seems to be rare in diabetes mellitus, but recent publications suggest a significant prevalence of non-diabetic renal disease in non-insulin-dependent diabetic (NIDDM) patients, especially in the absence of retinopathy. The purpose of this study was to evaluate the prevalence of non-diabetic renal disease in NIDDM patients in renal biopsies from clinical practice, in patients suspected of having non-diabetic renal disease. In addition we systematically reviewed the literature. Biopsies were evaluated at the University Department of Pathology, Aarhus, Denmark, but had been collected at several departments of nephrology. In total 33 consecutive biopsies were available from 1988-1995 (mean age of patients: 62 years (range 39-75) (mean known diabetes duration 8 years (range 1-25); the main clinical reason for a biopsy was proteinuria. Renal function changes ranged from slight elevation of serum creatinine to uraemia. In addition 9 original papers, including our own material 580 patients were examined. On the basis of careful morphological evaluation according to international criteria, no patient exhibited an unequivocal sign of non-diabetic glomerular disease. Two patients had strongly but not completely convincing evidence of glomerulonephritis. One patient had some evidence of glomerulonephritis. These 3 patients also exhibited diabetic lesions. One patient with end-stage renal disease showed evidence of interstitial nephropathy without glomerular lesions. Thus, in 4 patients evidence of non-diabetic lesions was found. In the remaining 29 patients typical diffuse (n = 9) or nodular (n = 20) diabetic lesions were found. Twenty patients showed evidence of diabetic retinopathy. One of the patients with evidence of non-diabetic renal disease had simplex retinopathy. In the literature a considerable bias exists towards including patients with non-diabetic renal disease. In non-biased materials with proteinuria the prevalence of non-diabetic renal disease is very similar to our series. In microalbuminuric patients non-diabetic renal disease seems to be very rare. It can be concluded that in our material non-diabetic renal disease is uncommon in NIDDM patients, even if a clinician has suggested renal disease of other origin. A considerable bias towards including non-diabetic renal disease in NIDDM patients exists in the literature. The indication for biopsy should be evaluated carefully, and biopsy should by no means be routinely performed in NIDDM patients with proteinuria.

Adult↗
PubMed1996

Atrioventricular block occurring late after heart transplantation: presentation of three cases and literature review.

Sinus node dysfunction is a well-known occurrence following orthotopic heart transplantation, but atrioventricular block is rarely described. We compare the incidence and clinical presentation of atrioventricular block and sinus node dysfunction among the first 200 consecutive patients receiving heart transplantation at the University of Utah. Two of 200 patients (1%) required pacemaker implantation for symptomatic atrioventricular block compared to 13 of 200 (6.5%) who required pacemaker for symptomatic sinus node dysfunction. Of the patients with atrioventricular block, one had intermittent Mobitz II second-degree atrioventricular block and one had high grade atrioventricular block without ventricular escape. The most striking difference between the patients with atrioventricular block and those with sinus node dysfunction was the interval between transplantation and pacemaker implantation; time to pacemaker implantation in the atrioventricular block patients was 955 and 810 days compared to a median time of 26 days for sinus node dysfunction patients (P = 0.037). The patients requiring permanent pacemaker implantation were similar to those not requiring pacemaker implantation with respect to age, sex, ischemic time, and donor age. None of the patients requiring permanent pacemaker implantation was on amiodarone therapy within 2 months of transplant.

Adult↗
PubMed1996

The influence of spontaneous otoacoustic emissions on the amplitude of transient-evoked emissions.

The aim of the study was to analyse whether the presence of spontaneous otoacoustic emissions (SOAEs) in a group of normal-hearing adults is related to larger transient evoked otoacoustic emission (TEOAE) amplitudes when compared to a similar adult population without SOAEs. Twenty-four normal-hearing subjects participated in the investigation. They were selected to form two groups of 12, one containing only subjects with measurable spontaneous emissions, the other of members who had no measurable spontaneous emissions. Each group comprised 7 males and 5 females. TEOAEs were recorded in both linear and non-linear mode, and equivalent sound pressure levels in different octave frequency bands were calculated. For each frequency band, the comparison of the equivalent sound pressure levels in the two selected groups showed statistically significant differences. Therefore, when normative TEOAE data were collected with the purpose of establishing a normative reference for the assessment of cochlear hearing loss, it is mandatory to search for and, when pertinent, to compensate for the presence of SOAEs.

Adolescent↗