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Biomedical subjects

N Kohn

Publications and source records attributed to N Kohn.

15 recordsLinked to original sources

Immunophenotypic analysis of HIV-infected children: alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets.

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T-lymphocyte activation and maturation antigens in a cohort of 112 HIV-infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were evident in 22 HIV-infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally, a novel analysis of 56 HIV-infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease.

ADP-ribosyl Cyclase↗

A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.

BACKGROUND & AIMS: Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. METHODS: Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. RESULTS: Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. CONCLUSIONS: Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

Adolescent↗

The utility of quantitative body surface isoarea mapping for predicting ventricular tachyarrhythmias.

Noninvasive techniques, such as the signal averaged ECG, have been used to assess risk of ventricular tachyarrhythmias (VT). However, these methods produce false positive and negative results. The purpose of this study was to develop body surface map algorithms which would enhance prediction of susceptibility to VT. Fifty-three patients referred for programmed electrical stimulation were enrolled in this study. All patients underwent signal averaged ECG, body surface map, programmed electrical stimulation. Group I patients had no sustained inducible VT and group II patients had either inducible sustained VT at electrophysiology study or previously documented spontaneous, sustained VT. For body surface map analysis, the difference between extrema on isoarea maps was calculated and defined as the gradient range. An abnormal body surface map was defined as a QRST gradient range < or = 109 mv.ms. The mean QRST gradient range in group II was significantly < that in group I (P < 0.05). By logistic regression analysis, the presence of coronary artery disease, a QRST gradient range < or = 109 mv.ms, an EF < 40% and a signal averaged ECG QRS duration > 114 ms predicted VT. The sensitivity, specificity, positive and negative predictive values for predicting VT susceptibility of an algorithm which combines the signal averaged ECG QRS duration and the QRST gradients were 0.93, 0.76, 0.79, and 0.91, respectively, while those for the signal averaged ECG alone were 0.52, 0.69, 0.63, and 0.59 for VT susceptibility. A combined body surface map-signal averaged ECG algorithm was more sensitive in detecting susceptibility to VT than the signal averaged ECG alone.

Adolescent↗

CD95 expression and apoptosis during pediatric HIV infection: early upregulation of CD95 expression.

Pediatric HIV infection is characterized by a progressive decline in CD4 T lymphocytes and faster disease progression than is typically seen in adults. Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a mechanism for cell loss which eventually leads to immune dysfunction. In this study of peripheral blood lymphocytes from HIV-infected children, classified according to CDC immunologic categories, we found that the percentage of CD4 and CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing apoptosis were increased in children with HIV infection and were greater in children from immunologic Category III as compared to those in Category I. Most striking was our observation that an increased percentage of CD95-positive cells appeared as early as 3 months of age, at a time when these children did not have elevated levels of apoptosis. These data demonstrate early upregulation of CD95 expression in HIV-infected infants, an abberation which may have profound implications for the pathogenesis of perinatally acquired HIV disease.

Age Factors↗

Assessment of stereopsis in college baseball pitchers and batters.

BACKGROUND/PURPOSE: In baseball pitching is a much less visually demanding task than hitting is. We sought to find a stronger relationship between visual function (as measured by stereopsis) and hitting a baseball than between stereopsis and pitching skill. METHODS: Multiple parameters including near and distance stereopsis (as a measure of visual function) were measured in 23 returning college baseball players (with a prior year's record). Their level of stereopsis (measured at distance with use of the B-VAT II BVS Binocular Vision Testing System) was compared with their batting statistics (in the case of the 14 position players) or their pitching statistics (for the 9 pitchers). Batting average and slugging percentage were used as measures of hitting skill, and earned run average, "out percentage" (1.000--Opposing players' batting average) and "strike-out percentage" (frequency of batters struck out) were used as pitching parameters. RESULTS: As a group, visual parameters were excellent in these college athletes. Although the newer test of distance stereopsis correlated with the standard near stereo test (Spearman coefficients), there was no correlation between distance stereopsis and any of the pitching or hitting performance parameters. CONCLUSIONS: The nature of the visual demands required of successful baseball hitters may have yet to be determined or are difficult to identify among a population homogeneous for excellent visual function, true for most groups of competitive athletes. In addition, simpler parameters such as plain visual acuity may be the most important factor(s).

Baseball↗

Commitment to X inactivation precedes the twinning event in monochorionic MZ twins.

To gain insight into the timing of twinning, we have examined a closely related event, X-chromosome inactivation, in female MZ twin pairs. X-inactivation patterns in peripheral blood and buccal mucosa were compared between monochorionic MZ (MC-MZ) and dichorionic MZ (DC-MZ) twins. Overall, the MC-MZ twins displayed highly similar X-inactivation patterns, whereas DC-MZ twins frequently differed in their X-inactivation patterns, when both tissues were tested. Previous experimental data suggest that commitment to X inactivation occurs when there are 10-20 cells in the embryo. Simulation of embryo splitting after commitment to X inactivation suggests that MC-MZ twinning occurs three or four rounds of replication after X inactivation, whereas a DC-MZ twinning event occurs earlier, before or around the time of X inactivation. Finally, the overall degree of skewing in the MZ twins was not significantly different from that observed in singletons. This indicates that X inactivation does not play a direct role in the twinning process, and it further suggests that extreme unequal splitting is not a common mechanism of twin formation.

Adolescent↗

Immunophenotyping of T lymphocytes by three-color flow cytometry in healthy newborns, children, and adults.

Reagents are now available which allow simultaneous assessment of three different fluorescence wave-lengths on most commercially available flow cytometers. Such three-color analyses provide more information than single- or dual-color analyses. The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in newborns, children, and adults. A whole blood method was used to label cells with antibodies conjugated to FITC, PE, and perCP. We found that the percentage of lymphocytes expressing HLA-DR/CD28/CD8, HLA-DR/ CD38/CD8, CD95/CD45RO/CD8, CD95/CD45RO/CD4, CD95/CD4, and CD95/CD8 showed relative increases with age. The percentage of lymphocytes expressing CD28/CD8, CD38/CD8, and CD38/CD4 showed relative decreases with age, while the subset HLA-DR/CD38/ CD4 did not change. Three-color flow cytometry is a powerful tool to more precisely define lymphocyte subsets than the current two-color methods. We present values using a three-color panel in healthy newborns, children, and adults.

Adolescent↗

Thoracic kyphosis and the prevalence of advanced uterine prolapse.

OBJECTIVE: To determine if there is an association between the degree of thoracic kyphosis and the prevalence of advanced uterine prolapse in women. METHODS: A retrospective case-control study compared the degree of thoracic kyphosis among white women with advanced uterine prolapse with that of matched controls. Medical records were reviewed for 412 consecutive women who underwent either abdominal or vaginal hysterectomy. The cases were those with uterine prolapse to or beyond the level of the introitus, and women with no evidence of prolapse served as controls. Spinal curvature was measured preoperatively for each patient using a lateral chest x-ray and the Ferguson method. Forty-eight cases were matched to 48 controls for age, weight, menopausal status, and hormonal status. Results were stratified to analyze the effect of parity on the relationship between uterine prolapse and thoracic kyphosis. RESULTS: The degree of thoracic kyphosis was higher in patients with uterine prolapse than in controls (mean paired difference = 4.9 degrees, 95% confidence interval [CI] 3.1-6.7; P < .001). Patients with uterine prolapse had a mean spinal curvature of 13.0 degrees (95% CI 11.5-14.5), whereas controls had one of 8.1 degrees (95% CI 6.9-9.4). A higher degree of thoracic kyphosis was associated with an incremental higher occurrence of uterine prolapse (odds ratio 1.35, 95% CI 1.11-1.65; P < .01). CONCLUSION: Thoracic kyphosis appears to be associated with uterine prolapse.

Case-Control Studies↗

Immunological characteristics of HIV-infected children: relationship to age, CD4 counts, disease progression, and survival.

We have evaluated immunologic markers of disease progression in 79 children perinatally infected with HIV. Laboratory testing included T lymphocyte subsets and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM), antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into grades I, II, and III based on results of CD4 counts, and into grades A, B, and C based on results of LPR, with grades I and grades A being normal, III and C being the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and lymphoproliferative responses were markedly decreased in a majority of children. Grade III CD4 counts were almost always associated with decreased LPR. A majority of the children with grade I CD4 numbers, however, also had abnormal lymphoproliferative responses. Results of laboratory testing were analyzed in relation to clinical disease progression and survival. The first AIDS defining illnesses (ADI), especially opportunistic infections (OI), was usually associated with Grade III/C results in immunologic assays. Survival was significantly decreased in children with grade III CD4 cell counts, and grade C LPR, and was poorest if these abnormalities developed within the first year of life. In this latter age group, if the CD4 counts fell to grade III, the risk for dying was at least five times greater than those children with higher CD4 counts (grades II and I); if the proliferative responses to PHA and MLC were in Grade C, the survival was 22 months. Severe immune defects in the first year of life in children with HIV infection, as assessed by CD4 counts and a battery of functional tests, predicted rapid disease progression.

Age Factors↗

Comparative study of laparoscopy vs. laparotomy for adnexal surgery: efficacy, safety, and cyst rupture.

Operative laparoscopy is becoming routine in gynecologic surgery. This study was designed to compare the safety and efficacy of laparoscopy and laparotomy for ovarian cystectomy and adnexectomy. The medical records of 32 patients who underwent operative laparoscopy for adnexal masses (group L) were reviewed and compared with those of 32 patients who underwent surgical laparotomy (group S) for similar indications. All patients sustained either an ovarian cystectomy or adnexectomy. The group were matched for age, weight, and history of previous laparotomy. Median operating time for group L was 90 min and for group S was 85 min. Blood loss was significantly less in group L (33.4 +/- 22 mL) than in group S (84.6 +/- 22.2 mL), p < 0.0001. There were two intraoperative complications in group L and one in group S. Significantly less patients in group L had postoperative fevers (16%) as compared with those in group S (69%), p < 0.0001. There was a higher incidence of cyst rupture when cystectomy was performed in patients from group L (7 of 21) as compared with patients from group S (2 of 17). No such difference in cyst rupture was noted when an adnexectomy was affected in group L (1 of 11) and group S (1 of 15). Patients in group L remained in the hospital a shorter time period, 1.5 +/- 0.8 days, than patients in group S, 4.7 +/- 0.9 days, p < 0.0001. Patients in group L required a shorter postoperative recovery time before resuming normal activities, 9.1 +/- 6.6 days, than patients in group L, 27.5 +/- 9.2 days, p < 0.0001. Similarly, patients in group L required less time to become pain free, 10.1 +/- 7.4 days, than patients in group L, 17.7 +/- 6.1 days, p < 0.0005. This study demonstrates a statistically significant decrease in postoperative morbidity and faster recovery in patients undergoing laparoscopy for adnexal surgery as compared with patients undergoing laparotomy for the same procedure. When cystectomy is performed via the laparoscope, there is a higher incidence of cyst rupture than with laparotomy.

Adnexa Uteri↗

Altered restriction endonuclease cleavage pattern of simian virus 40 DNA.

Three different groups of temperature-sensitive mutants of simian virus 40, isolated and characterized by Chou and Martin (J. Virol. 13:1101--1109, 1974), have been analyzed by using restriction endonucleases. Differences between the restriction endonuclease cleavage pattern of these mutants and that of the standard simian virus 40 strain have been mapped. These include the following observations: (i) tsD202 carries a defective HaeIII cleavage site at position 0.9 map units; (ii) tsB204 exhibits a defective HaIII site at position 0.21 and a defective HinIII site at 0.655 map units, and (iii) tsC219 carries a new HinIII site at position 0.15. We have isolated a few wild-type revertants from each of the temperature-sensitive mutant strains; each displays the endonuclease cleavage pattern of its parental temperature-sensitive strain.

DNA Restriction Enzymes↗

Statistical and methodological issues in the evaluation of case management studies.

For the past 3 years, the nursing case management team at North Shore University Hospital in Manhasset, NY, has been involved in a project to implement more than 50 clinical pathways, which provide a written "time line" for clinical events that should occur during a patient's hospital stay. A major objective of this project was to evaluate the efficacy of these pathways with respect to a number of important outcomes, such as length of stay, hospital costs, quality of patient care, and nursing and patient satisfaction. This article discusses several statistics-related issues in the design and evaluation of such case management studies. In particular, the role of a research approach in implementing and evaluating hospital programs, the choice of a comparison (control) group, the exclusion of selected patients from analysis, and the problems of equating pathways with diagnosis-related groups are addressed.

Case Management↗