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Biomedical subjects

L Klein

Publications and source records attributed to L Klein.

At least 55 records · Page 3Linked to original sources

Polycystic kidney disease in a raccoon (Procyon lotor).

During March 1988, a case of bilateral polycystic kidney disease (PKD) occurred in an aged raccoon (Procyon lotor) at a zoo in Wilmington, Delaware (USA). Prior to its death, the raccoon had no clinical signs. On necropsy there was bilateral enlargement of kidneys which, on cut sections, had many variable sized fluid-filled cystic cavities. Endometrial hyperplasia with presence of multiple variable-sized cysts were also seen in the uterus of this raccoon. Microscopical examinations were characteristic of an end-stage renal failure due to PKD. Neither PKD nor cystic endometerial hyperplasia appears to have been previously described in this species.

Animals↗

Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.

The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.

Adult↗

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↗