Effect of the scalar injection mechanism on passive scalar structure functions in a turbulent flow.

Higher-order passive scalar (temperature) structure functions are measured in the turbulent wake of a circular cylinder at a Taylor-microscale Reynolds number (Rlambda) of 370. The scalar is injected by two different means: (i) heating of the cylinder and (ii) use of a mandoline. Even though the second-order statistics (e.g., power spectra, second-order structure functions) of the scalar field are experimentally indistinguishable in the inertial and dissipative ranges, we observe notable differences in the inertial-range scaling exponents (xin) of the scalar structure functions at higher orders. The implication is therefore that the variations in previous estimates of xin may be attributable to differences in the scalar field initial conditions (and may not be deemed characteristic of a universal nature of the small-scale statistics of turbulent passive scalars).

Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension.

STUDY OBJECTIVES: We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health Care Finance Administration guidelines for long-term oxygen therapy. DESIGN, SETTING, AND PATIENTS: From 1996 to 1999, 23 adult patients (mean +/- SEM age, 51 +/- 4 years) with pulmonary arterial hypertension without left-heart failure underwent cardiac catheterization in a university teaching hospital while breathing air and then 100% oxygen. MEASUREMENTS AND RESULTS: Treatment with 100% oxygen increased arterial oxygen saturation (91 +/- 1% to 99 +/- 0.1%, p < 0.05) and PaO(2) (64 +/- 3 to 309 +/- 28 mm Hg, p < 0.05). Treatment with 100% oxygen also decreased mean pulmonary artery pressure (56 +/- 3 to 53 +/- 2 mm Hg, p < 0.05) and increased cardiac index (2.1 +/- 0.1 to 2.5 +/- 0.2 L/min/m(2), p < 0.05). Calculated mean pulmonary vascular resistance (PVR) decreased from 14.1 +/- 1.4 to 10.6 +/- 1.0 Wood units (p < 0.05). Vasodilatation with 100% oxygen occurred preferentially in the pulmonary circulation (PVR/systemic vascular resistance, 0.53 +/- 0.04 to 0.48 +/- 0.03; p < 0.05). The magnitude of the PVR response to oxygen therapy was correlated only with decreasing patient age (r = 0.45, p < 0.05). CONCLUSIONS: Treatment with 100% oxygen is a selective pulmonary vasodilator in patients with pulmonary hypertension, regardless of primary diagnosis, baseline oxygenation, or right ventricular function. Development of disease-specific oxygen prescription guidelines warrants consideration.

Comparison of time spent writing orders on paper with computerized physician order entry.

Computerized physician order entry (CPOE) has been shown to improve quality, and to reduce resource utilization, but most available data suggest that it takes longer to enter orders using CPOE. We had previously implemented a CPOE system, and elected to evaluate its impact on physician time in the new setting. To do this, we performed a prospective study using random reminder methodology. Key findings were that interns spent 9.0% of their time ordering with CPOE, compared to 2.1% before, although CPOE saved them an additional 2% of time, so that the net difference was 5% of their total time. However, this is counterbalanced by decreased time for other personnel such as nursing and pharmacy, and by the quality and efficiency changes. We conclude that while CPOE has many benefits, it represents a major process change, and organizations must factor this in when they implement it.

Biocompatibility of cardiovascular gene delivery catheters with adenovirus vectors: an important determinant of the efficiency of cardiovascular gene transfer.

Gene therapy approaches hold promise for the treatment of a wide variety of cardiovascular diseases. Many strategies for cardiovascular gene therapy involve catheter-mediated vector delivery via intramyocardial injection, intracoronary infusion, or direct gene transfer into the vessel wall. Several different gene delivery catheters have been developed and utilized in preclinical and clinical studies of cardiovascular gene therapy. However, rigorous studies of the biocompatibility of these catheters with gene therapy vectors have not yet been reported. In this report, we have examined the compatibility of cardiovascular gene therapy catheters and catheter constituents with first-generation E1/E3-deleted adenovirus vectors. We show that (i) currently available catheters rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this inactivation is mediated by a variety of commonly used catheter constituents including stainless steel, nitinol, and polycarbonate; (iii) catheter-mediated inactivation of adenovirus vectors can be prevented by preflushing catheters with solutions of serum albumin; and (iv) it is possible to identify a set of catheter materials that are compatible with current adenovirus vectors. These results underscore the importance of catheter/vector compatibility and suggest methods for increasing the efficiency of catheter-mediated cardiovascular gene therapy.

Quality of life and survival: the role of multidimensional symptom assessment.

BACKGROUND: Recent data from clinical trials suggest that quality-of-life (QOL) measurements may independently predict survival. The relation between survival and QOL measurements was tested among 122 inpatients and 96 outpatients with malignancies at one of four sites (colon, breast, ovary, or prostate) who participated in a cross-sectional validation study of the Memorial Symptom Assessment Scale (MSAS), a measure of the frequency of, severity of, and distress caused by physical symptoms. METHODS: The relation between MSAS summary scores and survival was evaluated in a multivariate analysis that adjusted concurrently for other important covariates, such as age, site and extent of disease, inpatient status, Karnofsky performance status (KPS), and other QOL measurements. RESULTS: In the multivariate analysis, extent of disease (P < 0.0001), inpatient status (P=0.014), higher MSAS physical symptom subscale score (P=0.004), and lower KPS score (P=0.009) independently predicted decreased survival. Other QOL measurements did not contribute significantly to the model. CONCLUSIONS: The MSAS physical symptom subscale score significantly predicts survival and adds to the prognostic information provided by KPS and extent of disease. Patients may be under-assessed regarding both the number and the severity of symptoms. Measurements of physical symptoms and related distress offer additional prognostic information concerning the survival of patients with cancer and may account for the predictive value of QOL scores.

An exploratory study of frequent pain measurement in a cancer clinical trial.

The ideal methodology for quality of life (QOL) measurement in cancer clinical trials matches the evaluation to the anticipated outcomes, thereby increasing the likelihood that clinically relevant changes are captured. The present study explored the importance of such methodological 'tailoring' in a phase II trial of paclitaxel and recombinant human granulocyte-colony stimulating factor (rhG-CSF) for metastatic breast cancer. Prior to the trial, clinical observation suggested that frequent short-lived episodes of pain might occur during this treatment regimen. Twenty-one patients provided longitudinal data for at least three cycles of chemotherapy. To assess transient pain, a routine QOL assessment at baseline and every third cycle was supplemented with pain measurements twice weekly. The interval assessment included a multidimensional QOL instrument (Functional Living Index-Cancer) and measures of psychological state (Rand Mental Health Inventory), symptom distress (Memorial Symptom Assessment Scale), and performance status (Karnofsky Performance Status Score). The frequent pain measurements were acquired using visual analogue and categorical scales for pain intensity (Memorial Pain Assessment Card). From baseline to the end of cycle three, global pain scores declined and the results on other QOL measures were variable. The data obtained using these measures did not reveal the existence of episodic pains. In contrast, the twice weekly pain measurements clearly demonstrated transient severe pains in approximately half the patients. These data highlight the importance of specific measurement of troubling symptoms or other relevant QOL concerns at clinically appropriate intervals during the routine QOL assessment of clinical trials. The additional burden involved in these assessments is warranted if the information derived is highly relevant, would not be adequately captured otherwise and could improve therapy.

Quality of life of women with ovarian cancer.

The primary objectives of this study were to determine the nature and extent of physical problems and psychological distress experienced by women with ovarian cancer and to identify medical and sociodemographic factors that were predictive of distress. Quality of life was assessed at 3-month intervals, for a maximum of 12 months in 151 ovarian cancer patients, most with advanced-stage disease (86%). Patients' pain, other physical symptoms, level of physical functioning, psychological state, and social functioning were evaluated using the following measures: a detailed pain questionnaire, Memorial Pain Assessment Card, Memorial Symptom Assessment Scale, Mental Health Inventory (MHI), Functional Living Index--Cancer (FLIC), and the Karnofsky Performance Status. Upon entry, 33% of patients reported significant psychological distress, as indicated by MHI Psychological Distress scores (MHI-PD) equal or greater to 1.5 standard deviations above the mean of a nationwide community sample. Impaired physical functioning (FLIC subscale) was the most important predictor of heightened psychological distress (MHI-PD) at baseline (1.5 SD or greater above the norm) (P = 0.0004) in a stepwise logistic regression involving medical/physical and sociodemographic variables as predictors. Further, significant differences were found in all quality of life scales between patients with Karnofsky Performance Status scores of < or = 80, and those with ratings of 90 or greater (P = 0.036 to P < 0.0001). These data suggest the need for an improved and more frequent assessment of ovarian cancer patients' psychological status, particularly as physical functioning declines, to improve early detection and referral to treatment of those suffering from psychiatric sequelae of cancer.

Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer.

PURPOSE: To evaluate the efficacy and safety of paclitaxel administered by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Forty-nine patients with metastatic breast cancer received paclitaxel via 3-hour intravenous infusion after standard premedication. Prophylactic granulocyte colony-stimulating factor (G-CSF) was not used, and chemotherapy was cycled every 3 weeks. For 25 patients who received paclitaxel as initial therapy (group I), the starting dose was 250 mg/m2. Twenty-four patients who had received two or more prior regimens, including an anthracycline (group II), started at 175 mg/m2. Paclitaxel pharmacokinetics were evaluated in 23 patients in group I. RESULTS: Grade 3 and 4 toxicities included (groups I/II) neutropenia (36%/33%), thrombocytopenia (0%/8%), anemia (0%/13%), neuropathy (8%/0%), arthralgia/myalgia (16%/4%), and mucositis (4%/4%). No significant hypersensitivity-type reactions or cardiac arrhythmias were seen. Six patients who received paclitaxel at > or = 250 mg/m2 experienced transient photopsia, without apparent chronic neuro-ophthalmologic sequelae. The mean peak plasma paclitaxel concentration was 5.87 mumol/L (range, 1.99 to 7.89) for these patients, and 6.08 mumol/L (range, 0.81 to 13.81) for 17 of 19 patients who did not experience visual symptoms. In 25 assessable patients in group I at a median follow-up time of 12 months, one complete response (CR) and seven partial responses (PRs) have been observed, for a total response rate of 32% (95% confidence interval [CI], 15% to 53%). In group II, five PRs were noted in 24 assessable patients (20.8%; 95% CI, 7% to 42%). Median response durations were 7 months for group I and 4 months for group II. CONCLUSION: Paclitaxel via 3-hour infusion, without prophylactic G-CSF, is active and safe as initial and subsequent therapy for metastatic breast cancer. The transient visual symptoms noted at higher doses seem unrelated to peak plasma paclitaxel concentration. Further studies that compare 3- and 24 hour (or other) infusion schedules are necessary to determine the optimal administration of paclitaxel in metastatic breast cancer.

Quality of life in phase II trials: a study of methodology and predictive value in patients with advanced breast cancer treated with paclitaxel plus granulocyte colony-stimulating factor.

BACKGROUND: Despite the clinical benefit that may be associated with reduction of tumor volume, chemotherapy may produce physical or psychological distress that could compromise a patient's quality of life. Although palliation may be as relevant as tumor response in patients with metastatic breast cancer, quality of life is not commonly evaluated in phase II clinical trials of new therapeutic agents. PURPOSE: We evaluated the utility of quality-of-life assessment in two phase II clinical trials of patients receiving paclitaxel (Taxol) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage therapy for metastatic breast cancer. METHODS: A battery of instruments (i.e., Memorial Symptom Assessment Scale [MSAS], Functional Living Index-Cancer [FLIC], Rand Mental Health Inventory [MHI], Brief Pain Inventory [BPI], and Memorial Pain Assessment Card [MPAC]) designed to capture information about social, psychological, and functional aspects of quality of life, as well as symptom prevalence and distress, was completed prior to treatment; serial assessments were obtained at regular intervals during the treatment period. Univariate and multivariate analyses were performed evaluating base-line quality-of-life parameters and standard prognostic factors in relation to outcome measures of survival, tumor response, and toxicity. For 30 consecutive patients with extensive prior chemotherapy for metastatic disease, longitudinal data were analyzed associating tumor response to changes in quality-of-life scores throughout the course of treatment with paclitaxel. RESULTS: Base-line scores of two validated quality-of-life instruments, the MSAS and the FLIC, independently predicted the overall survival (P < .01 for each). In this model, however, neither standard prognostic factors nor quality of life instruments predicted the likelihood of tumor response or the probability of encountering grade 3 or grade 4 nonhematologic toxicity. With serial assessments of quality of life, the majority of patients who achieved partial tumor response or stable disease reported improved or unchanged quality-of-life scores, while those patients with progressive disease experienced rapid deterioration in quality of life. CONCLUSIONS: Base-line quality-of-life assessment may provide prognostic information distinct from that obtained through standard prognostic indicators alone. The combination of two factors--extent of disease and a base-line quality-of-life assessment--predicted survival more accurately than either used separately. Evaluation of quality-of-life outcomes in relation to tumor response may illuminate previously unmeasured palliative effects of chemotherapy, such as pain relief, as well as the burdens it imposes. IMPLICATIONS: Information obtained from quality-of-life assessment in conjunction with phase II testing of new chemotherapeutic agents for metastatic breast cancer can guide quality-of-life evaluation planned in large, randomized future studies.

Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17.

Nitric oxide synthases (NOSs) are a family of enzymes responsible for the synthesis of nitric oxide from L-arginine and molecular oxygen. Three human NOS enzymes (I, II, and III) with differing cellular distribution and regulatory mechanisms have been identified. To determine whether additional NOSs are encoded in the human genome, a bovine NOS II-related cDNA was used to screen two human genomic libraries. Clones containing three independent genes were isolated. One clone encoded the previously identified NOS II gene (NOS2A). The two other genes specified amino acids homologous, but not identical, to human NOS II (NOS2B and NOS2C). Southern blot hybridization demonstrated that all three genes are present in the human genome. DNA from human-mouse somatic cell hybrids were used to determine the chromosomal location of the NOS II-related genes. All three NOS II-related genes colocalized to human chromosome 17 between bands p13.1 and q25. These observations suggest that there is more than one NOS II-related gene in the human genome. This finding may have important implications for the design of NOS isoform-specific inhibitors.

Pain in ovarian cancer patients. Prevalence, characteristics, and associated symptoms.

BACKGROUND: The prevalence, characteristics, and impact of pain and other symptoms have not been studied systematically in women with ovarian cancer. Anecdotally, pain has been associated with the onset of the disease and is a common problem among those with advanced cancer; symptoms other than pain appear to be highly prevalent. Given the profound influence of pain and other symptoms on quality of life, the evaluation of these phenomena could provide data relevant to the clinical management of these patients and advance quality of life research in the area of symptom assessment. METHODS: Questionnaires were completed by 111 inpatients and 40 outpatients with ovarian cancer who were undergoing treatment at a cancer center. Measures included a comprehensive pain questionnaire; the Rand Mental Health Inventory, Functional Living Index--Cancer; and the Memorial Symptom Assessment Scale. RESULTS: The sample (N = 151) represented 74% of the eligible patients. The median age was 55 years (range, 23-86), 82% had Stage III or IV disease at presentation, and 69% had active disease at the time of the survey. Pain, fatigue, and psychologic distress were the most prevalent symptoms. Sixty-two percent (N = 94) described a pain syndrome that preceded the onset or recurrence of the disease, and 42% (N = 63) reported "persistent or frequent pain" during the preceding 2 weeks. The latter pain had a median duration of 2 weeks (range, less than 1 to 756 weeks) and usually was in the abdominopelvic region (80%), frequent or almost constant (66%), and moderate to severe. Most patients reported moderate or greater pain-related interference with various aspects of function, particularly activity (68%), mood (62%), work (62%), and overall enjoyment of life (61%). Performance status, inpatient status, and unmarried status were significant predictors of pain presence or intensity, and both performance status and extent of tumor were significant predictors of pain interference with function. CONCLUSIONS: Among those with ovarian cancer, greater than 40% experienced pain that substantially undetermined function in one half to two thirds of these patients. Impaired performance status is associated most strongly with pain. The onset or recurrence of disease often is heralded by a stereotypic pain syndrome.

Symptom prevalence, characteristics and distress in a cancer population.

Despite the importance of symptom control in the cancer population, few studies have systematically assessed the prevalence and characteristics of symptoms or the interactions between various symptom characteristics and other factors related to quality of life (QOL). As part of a validation study of a new symptom assessment instrument, inpatients and outpatients with prostate, colon, breast or ovarian cancer were evaluated using the Memorial Symptom Assessment Scale and other measures of psychological condition, performance status, symptom distress and overall quality of life. The mean age of the 243 evaluable patients was 55.5 years (range 23-86 years); over 60% were women and almost two-thirds had metastatic disease. The Karnofsky Performance Status (KPS) score was < or = 80 in 49.8% and 123 were inpatients at the time of assessment. Across tumour types, 40-80% experienced lack of energy, pain, feeling drowsy, dry mouth, insomnia, or symptoms indicative of psychological distress. Although symptom characteristics were variable, the proportion of patients who described a symptom as relatively intense or frequent always exceeded the proportion who reported it as highly distressing. The mean (+/- SD range) number of symptoms per patient was 11.5 +/- 6.0 (0-25); inpatients had more symptoms than outpatients (13.5 +/- 5.4 vs. 9.7 +/- 6.0, p < 0.002) and those with KPS < or = 80 had more symptoms than those with KPS > 80 (14.8 +/- 5.5 vs. 9.2 +/- 4.9, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress.

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.

Nursing management of the patient receiving Taxol therapy.

Taxol is an important new antitumor agent with demonstrated efficacy in ovarian and breast cancer. Toxicities identified, including cardiac, hypersensitivity reactions, and neurologic, require careful nursing assessment for management, Additional toxicities may be identified as Taxol is combined with other chemotherapeutic agents. Studies to determine the most effective dose and schedule are ongoing. The current evaluation of this new drug presents an important opportunity for nurses to contribute to its development through both clinical and research endeavors. Such contributions will facilitate the optimal nursing care of patients treated with Taxol.

Factors affecting the ion-pair chromatography of water-soluble vitamins.

Factors controlling the separation of seven water-soluble vitamins on reversed-phase columns were systematically evaluated. Factors studied include both mobile phase constituents and column parameters. Data showed that a mobile phase containing hexanesulfonate (5 mM), methanol (15%), acetic acid (1%), and triethylamine (0.10-0.13%) yielded excellent separations with several C8 and C18 columns. Lowering the methanol concentration in the mobile phase enhanced the resolution of early eluting peaks, while the triethylamine level controlled the peak shape and retention of thiamine. The analytical precision, robustness, and sensitivity of the developed liquid chromatographic (LC) separation were evaluated. The stability of the LC separation was found to be satisfactory for over a 4-month period.