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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An inherited genetic disorder causes XY embryos of the horse to develop as mares. On the basis of our study of 38 such mares, we have identified four grades or classes of XY sex reversal according to this scheme: class I, nearly normal female, of which some are fertile; class II, female with gonadal dysgenesis, normal mullerian development; calss III, intersex mare with gonadal dysgenesis, abnormal mullerian development, enlarged clitoris; class IV, virilized intersex characterized by high levels of testosterone. In general, class I and calss II mares were typed H-Y antigen-negative whereas class III and class IV mares were typed H-Y antigen-positive.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We wished to determine the time of pregnancy at which optimal numbers of nucleated red blood cells (NRBC) are present in maternal blood. Because 30% of the NRBC in maternal blood are fetal, there are implications for prenatal screening and diagnosis. Samples of whole blood were collected from each of 225 women at various times during pregnancy. The samples were processed by charge flow separation (CFS), the NRBC enumerated, and the numbers compared on a week-to-week basis. To quantify the relationship between week of pregnancy and actual and log-transformed numbers of NRBC recovered, Pearson product moment and Spearman correlation coefficient were estimated for each of four CFS instruments and for the four instruments combined. When the data were analyzed, we found no relationship between stage of pregnancy and numbers of NRBC recovered. Even after logarithmic transformation, variability among the women, estimated by standard deviation, was large and relatively stable across the different stages of pregnancy. The number of NRBC recoverable by CFS appears to be constant between 7 and 25 weeks.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: aminolevulinic acid ; intravesical ; pharmacokinetics ; photodiagnosis ; bladder ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To examine the stability and systemic absorption of aminolevulinic acid (ALA) in dogs during intravesical administration. Methods. Nine dogs received an intravesical dose of ALA either with no prior treatment, after receiving ammonium chloride for urinary acidification, or after receiving sodium bicarbonate for urinary alkalinization. Urine and blood samples collected during and after administration were monitored for ALA using an HPLC assay developed in our laboratories. Concentrations of pyrazine 2,5-dipropionic acid, the major ALA degradation product, and radiolabeled inulin, a nonabsorbable marker for urine volume, were also determined. Results. Less than 0.6% of intravesical ALA doses was absorbed into plasma. Urine concentrations decreased to 37% of the initial concentration during the 2 hour instillation. Decreases in urinary ALA and radiolabeled inulin concentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversion to pyrazine 2,5-dipropionic acid was negligible. Conclusions. These studies demonstrate that ALA is stable and poorly absorbed into the systemic circulation during intravesical instillation. Future studies utilizing intravesical ALA for photodiagnosis of bladder cancer should include measures to restrict fluid intake as a means to limit dilution and maximize ALA concentrations during instillation.
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  • 4
    ISSN: 1573-7411
    Keywords: causal model ; pathophysiological model ; disease ; sepsis ; systematic inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Investigators establish connections among the underlying pathophysiological model of a particular disease, a clinician's perceptions of the clinical course of that disease, and the pharmacological properties and/or biologic effects related to individual components of an intervention protocol. To delineate various cause-and-effect relationships among events and a specific outcome, a causal model of the disease can be constructed by depicting longitudinally the connections between the pathophysiological model of the disease and events, occurring during the course of the disease. Connections between a causal model and a new treatment protocol can be formulated by superimposing each component of the protocol onto the specific pathway(s), affected by the treatment intervention. Flowcharting techniques are useful in producing a visual display of a causal model, with or without the superimposed protocol. It is especially important that, as emerging pathophysiological elements are identified through clinical or basic science investigations, a clinical investigator test and revise various elements and relationships of a previously accepted causal model. Moreover, if such new information is incompatible with a previously accepted causal model, a clinical investigator may need to abandon that model and formulate an alternative causal model. Finally, an example is presented that demonstrates the steps involved in formulating, testing, and revising a causal model of final outcome (i.e., survival or death) in patients with sepsis-induced acute respiratory distress syndrome and/or multiple organ dysfunction.
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  • 5
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Continuous-infusion etoposide was given to 15 patients with newly diagnosed small-cell lung cancer (extensive disease) and 10 patients with various refractory malignancies. The untreated patients with lung cancer received 200 mg/m2 etoposide over 24 h in combination with 100 mg/m2 cisplatin, and the pretreated patients received 400 mg/m2 etoposide over 36 h as monotherapy. Pharmacokinetic studies of etoposide were carried out in all patients. High-performance liquid chromatography (HPLC) was used to measure etoposide. All patients had normal hepatic and renal function tests and were followed weekly for hematologic toxicity after therapy. In all, 14 untreated and 9 pretreated patients were evaluable. Biostatistical analysis was done to correlate pharmacokinetic results to hematologic effects. Pearson correlation coefficients were calculated for continuous variables (i.e., blood counts), and Spearman correlation coefficients were calculated for ranked variables (i. e., toxicity grades). The values for the area under the plasma concentration vs time curve (AUC) and systemic clearance varied widely among patients. However, the AUC and clearance were significantly correlated (P〈0.05) with the WBC and platelet nadirs and the decrease in hemoglobin. The grade of leukopenia and total grade of hematologic toxicity were also correlated with AUC and clearance. Because the interpatient variability in etoposide pharmacokinetics correlates with the variable degree of hematologic toxicity, pharmacokinetic drug monitoring is suggested.
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  • 6
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objectives of this study were to define the pharmacodynamics of etoposide and to develop potentially useful models (1) to estimate the plasma clearance using a limited number of samples and (2) to describe the relationship between clearance and the dose-limiting toxicity. A total of 17 patients with extensive-stage small-cell lung cancer were treated with 150 mg/m2 etoposide daily for 3 consecutive days and with 100 mg/m2 cisplatin on day 3 only. Both drugs were given intravenously over 1 h. Treatment was repeated every 21 days for up to six courses. All patients were newly diagnosed (no previous chemotherapy or irradiation) and had a performance status of 0–2. Six patients achieved a complete response as confirmed by repeat bronchoscopy and five patients showed a partial response, for an overall objective response rate of 65% (95% confidence interval, 38%–87%). The median survival was 8 months (range, 1–24+ months). The dose-limiting toxicity was neutropenia. Etoposide pharmacokinetics were measured during the first course and determinations were repeated during courses 3 or 4 and 6. Complete blood counts were obtained weekly. Correlations for etoposide clearance and hematologic toxicities were evaluated for 17 initial courses and for an overall number of 33 courses. Pharmacodynamic correlations were significant for graded hematologic toxicities, as well as nadirs of leukocytes, neutrophils, and platelets for the initial courses and for all courses. To reduce the requirement for numerous blood samples, a limited sampling model was developed to estimate the area under the concentration versus time curve (AUC) with the following equation: $$AUC = 15.45 + 3.86 \times C_2 + 7.10 \times C_4 ,$$ where C2 and C4 represent the etoposide concentrations at 2 and 4 h, respectively. The total plasma clearance was calculated as the dose divided by the AUC; correlations with toxicity were better for clearance expressed in milliliters per minute than for that expressed in milliliters per minute per square meter of body surface area. The absolute neutrophil count at the nadir (ANCn) can be estimated by the following pharmacodynamic model, which is based on 33 courses: $$ANC_n = 0.399 + 0.024 \times E_{cl} ,$$ whereE cl represents the etoposide clearance expressed in milliliters per minute. Further studies are necessary to validate both models prospectively.
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