Early acquisition and conversion of Pseudomonas aeruginosa in Hispanic youth with cystic fibrosis in the United States

BackgroundFor unknown reasons, Hispanic patients with cystic fibrosis (CF) have more severe pulmonary disease than non-Hispanic white patients. In CF, the pulmonary pathogen Pseudomonas aeruginosa is associated with worse outcomes. We sought to determine if Hispanic patients with CF are at an increased risk of acquiring P. aeruginosa or acquire it earlier than non-Hispanic white patients.MethodsThis is a longitudinal study comparing the timing and risk of acquisition of different forms of P. aeruginosa between Hispanic and non-Hispanic white patients aged 0-21 years old with CF in the CF Foundation Patient Registry (CFFPR) in 2008-2013. The age at the initial acquisition of P. aeruginosa (initial acquisition, mucoid, chronic, multidrug-resistant) was summarized using Kaplan-Meier survival curves and analyzed using Cox proportional hazards regression models.ResultsOf 10,464 patients, 788 (7.5%) were Hispanic and 9,676 (92.5%) were non-Hispanic white. Hispanic patients acquired all forms of P. aeruginosa at a younger age than non-Hispanic white patients. Hispanic patients had a higher risk of acquiring P. aeruginosa than non-Hispanic white patients: the hazard ratio (HR) was 1.26 (95% CI 1.16-1.38, p<0.001) for initial P. aeruginosa, 1.59 (95% CI 1.43-1.77, p<0.001) for mucoid P. aeruginosa, 1.91 (95% CI 1.64-2.23, p<0.001) for multidrug-resistant P. aeruginosa, and 1.39 (95% CI 1.25-1.55, p<0.001) for chronic P. aeruginosa.ConclusionsHispanic patients have an increased risk of acquiring P. aeruginosa and acquire it at an earlier age than non-Hispanic white patients in the United States. This may contribute to increased morbidity and mortality in Hispanic patients with CF.     

Does a mid-lumbar block level provide adequate anaesthesia for transurethral prostatectomy?

In this prospective, randomized study, 23 patients having spinal anaesthesia for transurethral prostatectomy (TURP) were evaluated for the adequacy of their block using a visual analog pain score (V4 PS). Each patient with a “standard”(≥T₁₀) block level (n = 5) or “intermediate” (L₁ or T₁₂) block level (n = 5) found the block adequate. Sixty-two percent (8/13) of patients with a “low”-L₃) block level found their block adequate. The VAPS was assessed every five minutes or whenever pain abruptly increased during TURP; an “inadequate block” was defined as a V4 PS ≥ 5 /10 during prostatic resection. Intravesical pressure was monitored and kept <15 mmHg to distinguish between pain from bladder distension and from prostatic resection. “Low” block patients (LBP) who found their block inadequate (n = 5) received supplemental intrathecal local anaesthetic given through a spinal catheter. The subsequent L₁ block level was adequate for TURP. In LBP, who found their block adequate (n = 8), a higher (P < 0.01) VAPS was observed than in patients with a “standard” block level. However, a smaller (P < 0.05) maximum percent decrease in diastolic blood pressure was found in LBPs, than in “intermediate” or “standard” block patients. It is concluded that a spinal block ≥L₁) is adequate during TURP when bladder pressure is monitored and kept low. Mid-lumbar block levels should be reserved for patients in whom the benefit of minimizing haemodynamic changes outweighs the risk of a “less complete” anaesthetic.     

Effects of different interval-training programs on cycling time-trial performance

PURPOSE: We have investigated the effect of varying the intensity of interval training on 40-km time-trial performance in 20 male endurance cyclists (peak oxygen uptake 4.8+/-0.6 L x min(-1), mean +/- SD). METHODS: Cyclists performed a 25-kJ sprint test, an incremental test to determine peak aerobic power (PP) and a simulated 40-km time-trial on a Kingcycle ergometer. They were then randomly assigned to one of five types of interval-training session: 12x30 s at 175% PP, 12x60 s at 100% PP, 12x2 min at 90% PP, 8x4 min at 85% PP, or 4x8 min at 80% PP. Cyclists completed 6 sessions over 3 wk, in addition to their usual aerobic base training. All laboratory tests were then repeated. RESULTS: Performances in the time trial were highly reliable when controlled for training effects (coefficient of variation = 1.1%). The percent improvement in the time trial was modeled as a polynomial function of the rank order of the intensity of the training intervals, a procedure validated by simulation. The cubic trend was strong and statistically significant (overall correlation = 0.70, P = 0.005) and predicted greatest enhancement for the intervals performed at 85% PP (2.8%, 95% CI = 4.3-1.3%) and at 175% PP (2.4%, 95% CI = 4.0-0.7%). Intervals performed at 100% PP and 80% PP did not produce statistically significant enhancements of performance. Quadratic and linear trends were weak or insubstantial. CONCLUSIONS: Interval training with work bouts close to race-pace enhance 1-h endurance performance; work bouts at much higher intensity also appear to improve performance, possibly by a different mechanism.     

The Radiologic Features of Non-Neoplastic Tumors of Soft Tissue

Neoplasms of the soft tissues cause localized swelling and a variable degree of tissue response on the part of the host; these features they share with many non-neoplastic disorders. A spectrum of lesions that may simulate soft tissue neoplasms are described, with their radiologic appearances. The cellular nature of the matrix of a lesion cannot be identified absolutely as neoplastic by current imaging methods. Although sonography and magnetic resonance imaging can each produce valuable diagnostic information hitherto not provided by imaging the soft tissues, they do not per se show evidence of neoplasia. The differentiation of the two types of tumor, neoplastic and non-neoplastic, can only be achieved by a combination of clinical, radiologic and histologic information. Ultimately, biopsy with histologic examination may be required for the definitive diagnosis.     

Use of plasma cytotoxic activity to model cytotoxic pharmacodynamics of anticancer drugs

Summary We have developed a pharmacokinetic/pharmacodynamic approach that integrates the disposition, cytotoxic activity and interaction of anticancer drugs. Fundamental to this approach is the measurement of the cytotoxicity, against a target cell line, of patient plasma collected at different times after administration of the anticancer agent(s). To illustrate this approach, we have studied the plasma cytotoxic activity (PCA), against HL-60 cells, of plasma from 11 acute myeloblastic leukemic patients treated with daunorubicin (DNR). Plasma, obtained before and serially for 24 h after DNR treatment, was assayed by HPLC for DNR and daunorubicinol (DNRol), its active metabolite. The corresponding observed PCA values (PCA_obs) against HL-60 cells were also measured with a flow-cytometric cell-survival assay that we had developed previously. The pharmacodynamics, i.e. PCA, were co-modeled (dual Hill equation with an interaction term to allow synergism or antagonism) with the pharmacokinetics. The intergration of the PCA profile provided the area under the observed PCA versus time curve (AUC_obs). For each patient, we also generated an interaction panel, by adding known amounts of DNR and DNRol to his or her pretreatment plasma. The corresponding cytotoxicities were measured, and then applied to the pharmacodynamic model. This provided a standard surface from which the PCA of each sample obtained after therapy was predicted (PCA_prd), on the basis of assayed concentrations of DNR and DNRol in that sample. For plasma samples obtained after treatment, the model simultaneously fit all three outputs, i.e. PCA and DNR/DNRol concentration, very well. We observed substantial interpatient variability in HL-60 growth rate in medium containing patient pretreatment plasma, in DNR activity in pretreatment plasma, and in the in vitro activity (PCA) of plasma obtained after DNR treatment. We also compared the AUC_prd to the AUC_obs for each patient, and we identified a subset of 4/11 acute myeloblastic leukemic patients who had developed much more PCA after DNR administration than could be explained by the measured concentrations of DNR and DNRol. This may be due to unidentified active metabolites or to factors produced in the plasma in response to the treatment. This pharmacokinetic/pharmacodynamic model is promising to describe pharmacodynamics and interactions of anticancer drugs in cancer patients.This work was presented, in part, at the 31st annual meeting of the American Society of Hematology, Atlanta, Ga., December 1989, and at the 91st Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, San Francisco, Calif., March 1990. Supported in part by grant RO-1-CA40 188 from the National Institutes of Health, National Cancer Institute, a grant from the Scientific Committee of NATO, Brussels, Belgium, and a grant from the Oeuvre Belge du Cancer, Brussels, Belgium