Newer Concepts of Managing Asthmatic Patients

A decline in deaths from asthma was generally noted in the 1950s, coincidental with the introduction of corticosteroids. However, since 1959, statistics in the United States and Great Britain have pointed to an apparent increase in mortality, the reason for which is not clear. Some observers blame this trend on excessive use of pressurized aerosol bronchodilators, which came to use in 1958; others, on the uncontrolled pollution of outdoor air.     

Use of Oxygen Scavengers to Stabilize Solid Pharmaceutical Dosage Forms: A Case Study

A case study is described where degradation of a solid pharmaceutical dosage form susceptible to oxidation is minimized by incorporation of an oxygen scavenger as part of the packaging. Extremely low oxygen levels are attainable within 24 hr of packaging, even with permeable high-density polyethylene bottles commonly used in the pharmaceutical industry. This packaging methodology allows for a practical formulation-independent pathway for reducing or eliminating oxidative instability. In addition, this technology provides a convenient mechanistic probe for the degradation mechanism of solid dosage forms.     

Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex

Objectives:To define the maximum tolerated dose (MTD), thetoxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods:Fourteen patients with advanced solid tumorsnot responsive to previous antitumor treatments received BBR 3464 on a daily× 5 schedule every twenty-eighth day. The drug was given as a one-hourinfusion with pre-and post-treatment hydration (500 ml in one hour) and noantiemetic prophylaxis. The starting dose was 0.03 mg/m²/day. Amodified accelerated titration escalation design was used. Total and freeplatinum (Pt) concentrations in plasma and urine were assessed by ICP-MS ondays 1 and 5 of the first cycle. Results:Dose was escalated four times up to 0.17mg/m²/day. Short-lasting neutropenia and diarrhea of late onsetwere dose-limiting and defined the MTD at 0.12 mg/m². Nausea andvomiting were rare, neither neuro- nor renal toxic effects were observed.BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-lifeof several days. At 0.17 mg/m² plasma Cmax and AUC on day 5 werehigher than on day 1, indicating drug accumulation. Approximately 10%of the equivalent dose of BBR3464 (2.2%–13.4%) wasrecovered in a 24-hour urine collection. Conclusions:The higher than expected incidence of neutropenia andGI toxicity might be related to the prolonged half-life and accumulation oftotal and free Pt after daily administrations. Lack of nephrotoxicity and thelow urinary excretion support the use of the drug without hydration. Thesingle intermittent schedule has been selected for clinical development.     

Pressure measurement artifact with analog-to-digital conversion

Pressure was transduced with the use of a fluidfilled catheter and standard medical monitoring equipment. When the signal was sampled at 200 Hz with an analog-todigital converter, an artifact was observed. The 3.5-Hz artifact had an amplitude of 0.3 to 0.9 mm Hg and was caused by aliasing of a noise contaminant from the 2,403.5-Hz electrical excitation signal of the transducer. The artifact was completely eliminated with a 100-Hz low-pass filter. Electrical filtering is necessary for accurate acquisition of pressure measurements with analog-to-digital conversion, even when the sampling rate satisfies the Nyquist criterion for the frequency response of the mechanical system. Although the impact of the artifact is small in the clinical area, it is important under some research circumstances.     

Multi-institutional phase 2 study of TLK286 (TELCYTA™, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer

The purpose of this study was to determine the safety and efficacy of TLK286 (TELCYTA(TM)), a glutathione analog prodrug, in patients with platinum and paclitaxel refractory or resistant ovarian carcinoma. Thirty-six patients with measurable disease were enrolled. TLK286 was administered at 1000 mg/m2 intravenously every 3 weeks. The endpoints were objective response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and survival. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria. Thirty-four platinum refractory or resistant patients (94%) were evaluable for objective tumor response. Five patients (15%) had objective tumor responses, including one durable complete response (CR) of greater than 3 years and continuing. The disease stabilization rate was 50%, including one CR (3%), four partial responses (12%), and 12 durable disease stabilizations (35%). Responses were accompanied by improvement in clinical symptoms and Eastern Cooperative Oncology Group Performance Status (ECOG PS) and decline in CA125 levels. Median survival was 423 days with survival of 60% at 1 year and 40% at 18 months. TLK286 was well tolerated in this population. TLK286 is an active agent in chemotherapy-resistant ovarian cancer. Further studies of TLK286 in platinum and paclitaxel refractory or resistant ovarian cancer are in progress.     

The ocular tolerability of a new ophthalmic drug delivery system (NODS)

In an open label, two period cross-over study we compared the ocular tolerability of NODS vs. Isopto-Naturale^R eye drops. Thirty healthy volunteers were asked to rate the application system they were using for ocular discomfort, utilizing a visual analog scale in which 100=no ocular discomfort and 0=severe ocular discomfort. In addition each subject had to answer a questionaire and underwent a full ophthalmic control before, at day 7, at day 14 and at day 21 of the study. Each application form had to be applied to one eye only once a day for 7 days, followed by a washout period of 1 week. The type of application form was then changed and again had to be applied to one eye only for 7 consecutive days, followed by a final ophthalmic examination. The mean irritation score was recorded at day 7 and at day 21 of the study. Volunteers had no history of eye disease, no acute pathology of the eye, no contact lenses, no conditional foreign body of the cornea within the last four weeks prior to the study or within the study, no local therapy, no systemic therapy, no diabetes, no pregnancy. Informed consent was obtained. At day 1 one of the two application forms was given to each volunteer in a randomized order. 29 volunteers finished the protocol (16 male, 13 female); mean age: 26 years (range 20–32 years). The mean irritation score of NODS: 35 (2-81); the mean irritation score of Isopto-Naturale^R: 80.4 (45.5–99). The difference of mean irritation score (NODS vs. Isopto-Naturale^R): 46.7 (3.3–82.1) (p<0.01). The results of the study indicate that in healthy volunteers NODS are not as well tolerated as conventional eye drops when compared for ocular discomfort. However, the chance of applying drugs without preservatives and the possibility of increasing the rate of bioavailability from the new route (NODS) as well as the proportionally reduced risk to the patient of systemic side effects after NODS application of any type of drugs should be taken into consideration.     

生长抑素类似物对肝癌细胞凋亡及c-myc蛋白表达的影响

目的　探讨生长抑素类似物 8肽 (SS 8)对人原发性肝癌细胞凋亡和c myc蛋白表达的影响。 方法　体外培养肝癌细胞SMMC 772 1 ,用 1 0 μg/mlSS 8处理后 ,流式细胞仪检测肝癌细胞凋亡率和c myc蛋白的表达。 结果　与对照组相比 ,SS 8使实验组S期和G2 /M期细胞数减少、G0 /G1 期细胞数增加 ,两组细胞的凋亡率分别为 6 .1 %和1 4 .2 % ,差异有显著性意义 (P<0 .0 5)。经SS 8作用 2 4h后 ,实验组c myc蛋白表达水平为 0 .833± 0 .0 35 ,与对照组相比差异无显著性意义 (P>0 .1 0 ) ,而在SS 8作用 48、72、96、1 2 0和 1 4 4h后 ,实验组c myc蛋白表达水平分别为 0 .81 8±0 .0 4、0 .72 1± 0 .0 2 9、0 .669± 0 .0 2 6、0 .648± 0 .0 4 5和 0 .642± 0 .0 2 8,较对照组显著降低 (P<0 .0 5)。结论　SS 8有诱导肝癌细胞SMMC 772 1凋亡和降低c myc蛋白表达的作用     

Effect of tamsulosin on the number and intensity of ureteral colic in patients with lower ureteral calculus

BACKGROUND: We aimed to objectively determine whether tamsulosin as an alpha(1)-blocker was effective in patients who had ureterolithiasis located in the lower part of the ureter. METHODS: Sixty patients with lower ureteral calculi (juxtavesical or intramural portion) were included in the present study. Conservative treatment, such as hydration and tenoxicam as a non-steroidal anti-inflammatory drug, was given to group 1 (30 patients). Group 2 (30 patients) was given tamsulosin (0.4 mg daily) in addition to the conservative treatment. All patients were followed up and questioned about the numbers and intensity of ureteral colic, and the rates of spontaneous passage after the procedure. RESULTS: Spontaneous passage was observed in 22 of the 30 patients in group 1 (73.3%) and 26 of the 30 patients in group 2 (86.6%). The difference within groups 1 and 2 was not significant (P=0.196). The difference between both groups was not statistically significant either, with the stone diameter being 6 mm (P=0.635) or >6 mm (P=0.407). As group 1 patients were passing their stones, they had more ureteral colic episodes than group 2 patients. This difference was statistically significant and correlated well with the administration of tamsulosin (P=0.038). Group 1 patients reported higher scores according to a visual analog scale than group 2 patients. Also, this difference was statistically significant (P=0.000). CONCLUSIONS: We think that the treatment of alpha(1)-blockers decreased the number of ureteral colic episodes and the intensity of pain during spontaneous passage at the lower ureteral calculi. Also, it will be beneficial to patients' quality of life.     

Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines

BACKGROUND: The allergic rhinitis and its impact on asthma (ARIA) guidelines provide a new classification of allergic rhinitis, but a quantitative analysis for severity assessment is lacking. OBJECTIVE: To study whether a visual analog scale (VAS) for global rhinitis symptoms could be used to assess the disease severity according to ARIA. METHODS: Three thousand fifty-two allergic rhinitis patients seen in primary care were tested. Fifty three per cent had an objective diagnosis of allergy and 58% of the patients were treated. Patients were categorized according to ARIA guidelines. The severity of nasal symptoms was assessed using a VAS. Quality of life was measured using the rhinoconjunctivitis quality of life questionnaire (RQLQ). RESULTS: Severity had more impact on VAS levels than duration: mild intermittent rhinitis (3.5, 2.4-5.0 cm), mild persistent rhinitis (4.5, 3.2-5.6 cm), moderate/severe intermittent rhinitis (6.7, 5.3-7.7 cm) and moderate/severe persistent rhinitis (7.2, 6.1-8.2 cm). The receiver operating characteristic curve results showed that patients with a VAS of under 5 cm could be classified as 'mild' rhinitis (negative predictive value: 93.5%) and those with a VAS of over 6 cm as 'moderate/severe' rhinitis (positive predictive value: 73.6%). Receiver operating characteristic curves and a logistic regression showed that current treatment and allergy diagnosis have no effect on the assessment of rhinitis severity using VAS. Visual analog scale and the RQLQ global score were significantly correlated (rho = 0.46; P < 0.0001). CONCLUSION: A simple and quantitative method (VAS) can be used for the quantitative evaluation of severity of allergic rhinitis.