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Biomedical subjects

L Klein

Publications and source records attributed to L Klein.

At least 37 records · Page 2Linked to original sources

A phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood hematopoietic progenitor cells.

Fourteen patients with stage II-IV breast cancer were enrolled in a phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood progenitor cells (PBPC). All 14 women tolerated PIXY321 well, with the predominant toxicities being erythema at the injection site, fever, and arthralgias. A median of two aphereses yielded a mean of 1.3 x 10(8) mononuclear cells/kg, 8.9 x 10(4) colony-forming units-granulocyte/macrophage (CFU-GM)/kg, and 4.5 x 10(6) CD34+ cells/kg. All 14 patients underwent high-dose chemotherapy with PBPC support, the median day to ANC >500 cells/microliter was 10.6, and the median day to platelets >20,000 cells/microliter was 13. The day of 90th percentile platelet recovery was 15. When compared to PBPCs mobilized by cyclophosphamide followed by GM-CSF, the use of PIXY321 may confer an advantage of enhanced platelet recovery.

Adult

[Initial experience with the PCDiary: software for physicians for documenting and evaluating individual learning].

A computer diary was developed for physicians to create a portfolio of their self-directed learning. Each item of learning is recorded in the form of a question along with the stimulus, the learning resources used and the outcome planned for the learning. The records of 123 physicians which volunteered to use the diary were analyzed. Their response to the software, elicited by survey, is described. Items of learning were most often stimulated by scanning the literature and while seeking information to manage a patient. The physicians recorded their intent to change their practice as the outcome to learning most often when the learning was stimulated while managing a patient. One-half of the physicians reported that keeping the diary made them think about their patient care.

Attitude of Health Personnel

Her2/neu overexpression is associated with treatment failure in women with high-risk stage II and stage IIIA breast cancer (>10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy.

Twenty-five patients with high-risk stage II and IIIA breast cancer (>10 or more involved lymph nodes) were treated with six cycles of standard-dose chemotherapy (5-fluorouracil, doxorubicin, and cyclophosphamide) followed by high-dose chemotherapy (2.5 g/m2 cyclophosphamide for 3 days and 225 mg/m2 thiotepa for 3 days) with autologous hematopoietic progenitor cell support. The actuarial relapse free survival at 3 years is 80%; the actuarial survival at 3 years is 96%. Four patients relapsed systemically between 6 and 18 months; all four patients who relapsed had breast cancers that overexpressed Her2/neu. In contrast, none of the 21 patients who had no or borderline overexpression of Her2/neu relapsed (P = 0.00004, Fisher's exact test). Patients with high-risk stage II and IIIA breast cancer who have overexpression of Her2/neu appear to be at a high risk for relapse, even when treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support.

Adult

Predictors of restenosis after excimer laser coronary angioplasty.

One hundred twenty-five lesions successfully treated with excimer laser coronary angioplasty at 3 centers were analyzed in a central core laboratory using detailed quantitative angiographic analysis. Sixty-seven narrowings had restenosis (> or = 50% diameter stenosis at restudy). Correlates of restenosis were as follows: baseline diameter stenosis was 79% in the restenosis group versus 71% in the group without restenosis (p = 0.0002), baseline minimal diameter stenosis was 0.55 mm in the restenosis group versus 0.72 mm in the group without restenosis (p = 0.006), final diameter stenosis was 40% in the restenosis group versus 32% in the group without restenosis (p = 0.002), lesion length > or = 7 mm was present in 43% of the restenosis group versus 21% in the group without restenosis (p = 0.009), and Thrombolysis in Myocardial Infarction trial flow 0 to 2 was 33% in the restenosis group versus 15% in the group without restenosis (p = 0.025). The strongest multivariate correlate of restenosis was the baseline diameter stenosis (p = 0.003). Whereas most predictors were not controllable, achieving a low residual diameter stenosis that is operator-dependent can favorably influence the restenosis rate.

Aged

The impact of knowledge of human immunodeficiency virus serostatus on contraceptive choice and repeat pregnancy.

OBJECTIVE: To examine relationships among human immunodeficiency virus (HIV) serostatus, postpartum contraceptive choice, and the rate of repeat pregnancy within a short interval. METHODS: This retrospective cohort study was performed in 83 seropositive and 218 seronegative women identified from an inner-city prenatal population undergoing routine voluntary HIV antibody screening from July 1987 through June 1989. Postpartum contraceptive choices and rate of repeat pregnancies were compared based on HIV serostatus. RESULTS: Seropositive women were significantly more likely than seronegative women to undergo tubal sterilization (27 versus 15%; odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5-5.9). This relationship persisted after controlling for age, race, marital status, and parity by logistic regression modeling (adjusted OR 2.9, 95% CI 1.4-5.9). Seropositive women were significantly less likely than seronegative women to select oral contraceptives (34 versus 68%; OR 0.2, 95% CI 0.1-0.4), a relationship that persisted after controlling for age, race, marital status, parity, and foam and condom use (adjusted OR 0.2, 95% CI 0.1-0.5). Seropositive women were significantly more likely than seronegative women to select foam and condoms as their primary method of contraception (30 versus 15%; OR 2.4, 95% CI 1.2-4.5), a relationship that did not persist after controlling for age, race, marital status, and parity (adjusted OR 0.7, 95% CI 0.4-1.3). The risk of repeat pregnancy was slightly lower in seropositive versus seronegative women (34 versus 44%; OR 0.7, 95% CI 0.4-1.3). Most repeat pregnancies among seropositive and seronegative women were unplanned (90 and 82%, respectively). CONCLUSION: There was a relationship between the method of postpartum contraception and HIV serostatus, but no significant difference in repeat pregnancy rates associated with choice of method.

Adolescent

Cyclosporin A does not affect the absolute rate of cortical bone resorption at the organ level in the growing rat.

The weanling rat, an animal model of rapid bone turnover, was used to evaluate the effects of various doses of cyclosporin A (CsA) on various bones during different time periods. Sprague-Dawley male rats were extensively prelabeled with 3H-tetracycline during 1-3 weeks of age. At 4 weeks of age, four groups of rats were given daily subcutaneous injections: vehicle or CsA--low dose (10 mg/kg), intermediary dose (20 mg/kg), or high dose (30 mg/kg) for 7, 14, or 28 days. Three different whole bones--the femur (low turnover), scapula (moderate turnover), and lumbar-6 vertebra (high turnover) were harvested intact at 4, 5, 6, and 8 weeks of age. The whole bones were assayed weekly for total dry defatted weight, calcium mass (formation), and loss of 3H-tetracycline (bone resorption) following treatment with CsA. Serum CsA levels, calcium creatinine, and alkaline phosphatase were measured weekly. Significant decreases in serum calcium and alkaline phosphatase were observed at 1 and 2 weeks, and were normalized by 4 weeks of treatment. No significant changes in serum creatinine were noted. For all three doses of CsA, no effect was observed on the absolute rate of cortical bone resorption of three different, whole bones over three time periods. Body weight and bone formation in treated animals was significantly smaller in a dose- and time-related fashion compared with control animals at sacrifice. However, compared with the initial control animals, body weights and bone masses of the final treated animals were much larger, suggesting that the smaller bone masses were due to insufficient growth and slow gain in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase

Neurons and astroglia express distinct subsets of Na,K-ATPase alpha and beta subunits.

We have analyzed the expression pattern of Na,K-ATPase alpha and beta subunit isoforms within the rodent and primate central nervous system. Membrane fractions prepared from rat cerebral cortical type-1 astrocytes and rat cerebellar granule and hippocampal neurons were characterized by immunoblot analyses using a panel of alpha and beta subunit isoform-specific antisera. Each cell type was found to express the alpha 1 isoform but showed differences in the expression of other subunits. Cortical astrocytes displayed alpha 2 and beta 2 subunits, whereas cerebellar granule neurons showed expression of alpha 3 and beta 1 subunits. All three alpha subunit isotypes were detected in hippocampal neurons. A survey of the immunofluorescent staining pattern of the alpha 3 subunit in rat and monkey brain confirmed that expression of this Na,K-ATPase alpha subunit isoform was restricted exclusively to neurons. These results suggest that both neurons and astrocytes express multiple, yet distinct, Na,K-ATPase isoenzymes. The identification of cell types expressing limited combinations of alpha and beta subunits should provide a framework for understanding the physiological significance of Na,K-ATPase isoenzyme diversity and may provide useful tools for the analysis of cell lineage in the mammalian central nervous system.

Animals

Separation of high-density lipoproteins into apolipoprotein E-poor and apolipoprotein E-rich subfractions by fast protein liquid chromatography using a heparin affinity column.

The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E-rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions.

Apolipoproteins

The risk of sexually transmitted diseases in human immunodeficiency virus-infected parturients.

OBJECTIVE: We assessed the prevalence of and defined the relationship between other sexually transmitted diseases and human immunodeficiency virus infection. STUDY DESIGN: We performed a case-control study among 121 human immunodeficiency virus-infected and 222 randomly selected seronegative parturient women. These women were identified from a prenatal population undergoing routine voluntary antibody screening in a large urban hospital in the southeastern United States. RESULTS: During the 24-month study period, 16,868 women consented to human immunodeficiency virus antibody screening; 121 (7.2/1000) were infected with human immunodeficiency virus. Cases were significantly more likely than controls to be infected with at least one sexually transmitted disease during pregnancy (48% vs 21%; odds ratio 3.4, 95% confidence interval 2.1 to 5.7). The prevalence of Chlamydia trachomatis and hepatitis B infection did not differ significantly among the groups. Cases were significantly more likely than controls to be infected with Treponema pallidum (29% vs 4%; odds ratio 9.6, 95% confidence interval 4.2 to 22.4). This relationship persisted after we controlled for confounding risk factors (odds ratio 9.2, 95% confidence interval 2.1 to 13.3). In addition, cases were significantly more likely than controls to be infected with Neisseria gonorrhoeae (17.2% vs 4%; odds ratio 5.2, 95% confidence interval 2.1 to 13.3). This relationship also persisted after we controlled for confounders (odds ratio 3.7, 95% confidence interval 1.4 to 10.0). CONCLUSION: Human immunodeficiency virus-infected parturient women in our center are at substantial risk of having other sexually transmitted diseases.

Adult

BPF-1, a pathogen-induced DNA-binding protein involved in the plant defense response.

The mechanisms by which plants restrict the growth of pathogens include transient activation of numerous defense-related genes. Box P is a putative cis-acting element of a distinct group of such genes, including those encoding the enzyme phenylalanine ammonialyase (PAL). A DNA-binding activity to Box P was identified in nuclear extracts from cultured parsley cells and a cDNA encoding the protein BPF-1 (Box P-binding Factor) partially characterized. BPF-1 binds to this element with specificity similar to that of the binding activity in nuclear extracts. BPF-1 mRNA accumulates rapidly in elicitor-treated parsley cells and around fungal infection sites on parsley leaves. This accumulation is, at least partly, due to a rapid and transient increase in the transcription rate of BPF-1. Moreover, tight correlation between the relative amounts of BPF-1 and PAL mRNAs was observed in different organs of a parsley plant. These results are consistent with the hypothesis that BPF-1 is involved in disease resistance by modulating plant defense gene expression.

Amino Acid Sequence

Human immunodeficiency virus infection among patients in a gynecology emergency department.

OBJECTIVE: To determine the extent of human immunodeficiency virus (HIV) infection risk factors and the relationship to the clinical diagnosis in women seen in a busy inner-city gynecology emergency department. METHODS: We performed a cross-sectional survey by offering routine voluntary HIV-1 antibody screening and obtaining HIV risk behavior profiles in 1033 (35%) of 2952 women seeking care in our gynecology emergency department during a 5-week period. RESULTS: The HIV seroprevalence was 2%. Six (35%) of the infected women reported a history of intravenous drug use, five (29%) reported a history of crack cocaine use, and five (29%) reported no risk factors for infection. Seropositive women were more likely than were seronegative women to have clinical symptoms consistent with pelvic inflammatory disease (18 versus 3%; P < .01). CONCLUSION: These data suggest that women attending the gynecology emergency room in our hospital are at substantial risk for HIV infection.

Acquired Immunodeficiency Syndrome

Urinary excretion of indolylacryloylglycine, indolylacetic acid and 5-hydroxyindolylacetic acid in burn patients.

Indolylacryloylglycine (IAcrGly) is a regular constituent of human urine. Changes in its excretion have been observed, among other conditions, in some skin diseases. Skin lesions in burns are dealt with in the present paper. IAcrGly excretion has been followed during several weeks of hospital treatment and compared with that of two other tryptophan metabolites, namely indolylacetic acid (IAA) and 5-hydroxyindolylacetic acid (5-HIAA). The average excretion of IAcrGly was significantly lower especially between day 3 and 15 post injury. Some alternative explanations of these results are put forward.

Adolescent

Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E-rich very low density lipoprotein fraction.

To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.

Adult

The effects of vascularity and cyclosporin A on the mechanical properties of canine fibular autografts.

We studied the biomechanical behavior of orthotopic canine autografts as influenced by vascularized supply and the administration of cyclosporin A at three months and six months post-surgery. The model was the proximal 8 cm of the fibula in young adult dogs. In vascularized grafts, blood supply was re-established by microvascular re-anastomosis. Experimental controls were sham-operated and unoperated bones. Mid-graft test sections were subjected to loading-to-failure in torsion to determine the strength and stiffness. In both three- and six-month groups, vascularized grafts were significantly stronger and stiffer than contralateral nonvascularized grafts. Vascularized grafts were not significantly different from sham-operated bones. A 30-day regimen of cyclosporin A was found to have no measurable effect on mechanical properties for any individual treatment group. The results indicate that re-established blood supply can be a major factor in maintaining the mechanical integrity in large-segment cortical autografts.

Animals

Blood and amniotic fluid contact sustained by obstetric personnel during deliveries.

OBJECTIVE: The objective of this study was to characterize blood and amniotic fluid contact sustained by obstetric personnel during deliveries. STUDY DESIGN: Trained observers collected data on 1376 person procedures during 230 deliveries at Grady Memorial Hospital from May to October 1989. Rates of contact were compared by means of the chi 2 test. RESULTS: At least one blood or amniotic fluid contact occurred during 79 (39.1%) of 202 vaginal and 14 (50.0%) of 28 cesarean deliveries; a needle stick occurred in 4 (2.0%) of the vaginal deliveries. Obstetricians and midwives had the highest rates of blood and amniotic fluid contact (18.7% and 28.8% of person procedures, respectively). Half of the contacts sustained by midwives might have been prevented by the use of gowns. Most contacts sustained by obstetricians might have been prevented by face shields, impervious gowns, and impervious shoe covers. CONCLUSIONS: Obstetricians and midwives had substantial risk of blood and amniotic fluid contact during delivery; many of their contacts were potentially preventable.

Amniotic Fluid

Human immunodeficiency virus infection among inner-city adolescent parturients undergoing routine voluntary screening, July 1987 to March 1991.

OBJECTIVE: The objective of our study was to describe the human immunodeficiency virus epidemic among pregnant adolescents undergoing follow-up in a large inner-city hospital. STUDY DESIGN: We conducted a case-control study comparing demographic and risk behaviors of seropositive and seronegative adolescents (aged 13 to 20) identified from a population undergoing routine voluntary antibody screening at Grady Memorial Hospital in Atlanta, Georgia, between July 1987 and March 1991. RESULTS: Of 10,794 pregnant adolescents screened, 51 (4.7/1000) were infected with human immunodeficiency virus. More than one fourth of case patients were < or = 17 years old. Significantly more case patients than controls reported a history of crack cocaine use (10 [19.6%] vs 23 [8.2%] p < 0.05). A majority (58.8%) of case patients reported no risk factors for infection, and the remainder (41.2%) were presumably infected by heterosexual contact. Thirty-nine controls (13.8%) had self-identified risk factors for infection. CONCLUSIONS: Pregnant adolescents in our center are at risk for human immunodeficiency virus infection and should be targeted for human immunodeficiency virus education and risk reduction counseling.

Adolescent

Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia.

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.

Adult