A novel peroxy radical based oxidative stressing system for ranking the oxidizability of drug substances

A novel oxidative stressing system is described which generates high levels of peroxy radicals in solution at room temperature, without the use of azonitrile initiators. The oxidative stressing system is composed of a 10% solution of Tween 80 in water to which FeCl3 x 6H2O is added. The Tween 80 acts as a solubilizing agent for drug compounds, and also contains substantial amounts of organic hydroperoxides. It is shown that the Fe III/ Fe II couple operates on the hydroperoxide concentration to effectively generate new peroxy radicals, which then propagate in the Tween 80 solution. Key features of the Tween 80/Fe III system are investigated, and the oxidizability of seven known compounds and ten developmental compounds are examined. Relative reaction rates span a 300-fold range, from benzoic acid (nonreactive, defined as <0.5% reacted per day) to Vitamin D3 (7% reacted per hour). Oxidizability "rankings" thus generated are shown to agree well with azonitrile initiated oxidative stress. The potential for general correlations between this type of oxidizability data and actual oxidative performance in LFC and solid oral dosage forms is discussed.     

Polysorbate 80 UV/vis spectral and chromatographic characteristics--defining boundary conditions for use of the surfactant in dissolution analysis

Polysorbate 80 is used in the pharmaceutical industry as an additive to enhance the solubility of non-polar compounds in formulation design and during dissolution analysis. In this paper we present the spectroscopic and chromatographic characteristics for a series of commercially available sources of this non-ionic surfactant. The large UV/vis absorbance and broad chromatographic elution of Polysorbate 80 often makes it difficult to accurately quantitate pharmaceutically active compounds in solutions where the surfactant is present. Boundary conditions have been established where analytical interferences can be avoided in spectrophotometric analysis by choice of analysis wavelength and solution concentrations. Chromatographic method development is also presented enabling the removal of Polysorbate interference in instances where spectroscopic interference is too great.     

The Effect of Education and Self-monitoring of Blood Glucose on Glycosylated Hemoglobin in Type I Diabetes

ABSTRACT The influence on glycosylated hemoglobin (HbA₁) of formal education as compared with self-monitoring of blood glucose (SMBG) was studied in a randomized 18-month trial. All adult type I diabetics in a community were identified. Forty-one of these patients had had diabetes for 20 years or less. Thirty-seven patients were included in the study and finally randomized into four groups. Ten patients received individual formal education followed by SMBG, eight patients were instructed in SMBG without pre-education, nine patients were given only formal education and 10 patients made up a reference group. Education did not improve the mean HbA₁ values. SMBG resulted in a decrease by 2% in HbA₁ from 12 to 10% (p<0.05). The final HbA₁ level, however, did not differ significantly between any of the groups. SMBG was accepted by 80% of the patients. The liability to hypoglycemia was about equal in the four groups. It was concluded that SMBG, but not education, improved metabolic control to a certain degree.     

Trends in smokeless tobacco use among adults and adolescents in the United States

OBJECTIVES: Smokeless tobacco has many adverse health effects. We analyzed long-term national trends in smokeless tobacco use. METHODS: We used 1987 to 2000 National Health Interview Survey data for adults aged 18 years and older, 1986 to 2003 data from Monitoring the Future surveys of adolescents, and 1991 to 2003 data from the Youth Risk Behavior Survey for 9th- to 12th-grade students to examine overall and demographic-specific trends. RESULTS: Smokeless tobacco use among adult and adolescent females was low and showed little change. Smokeless tobacco use among men declined slowly (relative decline=26%), with the largest declines among those aged 18 to 24 years or 65 years and older, Blacks, residents of the South, and persons in more rural areas. Overall and demographic-specific data for adolescent boys indicate that smokeless tobacco use increased for 12th-grade students from 1986 until the early 1990s, but has subsequently declined rapidly in all grades since then (range of relative overall declines=43% to 48%). CONCLUSIONS: Smokeless tobacco use has declined sharply, especially among adolescent boys. Ongoing prevention and cessation efforts are needed to continue this trend.     

Building an automated SOAP classifier for emergency department reports

Information extraction applications that extract structured event and entity information from unstructured text can leverage knowledge of clinical report structure to improve performance. The Subjective, Objective, Assessment, Plan (SOAP) framework, used to structure progress notes to facilitate problem-specific, clinical decision making by physicians, is one example of a well-known, canonical structure in the medical domain. Although its applicability to structuring data is understood, its contribution to information extraction tasks has not yet been determined. The first step to evaluating the SOAP framework's usefulness for clinical information extraction is to apply the model to clinical narratives and develop an automated SOAP classifier that classifies sentences from clinical reports. In this quantitative study, we applied the SOAP framework to sentences from emergency department reports, and trained and evaluated SOAP classifiers built with various linguistic features. We found the SOAP framework can be applied manually to emergency department reports with high agreement (Cohen's kappa coefficients over 0.70). Using a variety of features, we found classifiers for each SOAP class can be created with moderate to outstanding performance with F(1) scores of 93.9 (subjective), 94.5 (objective), 75.7 (assessment), and 77.0 (plan). We look forward to expanding the framework and applying the SOAP classification to clinical information extraction tasks.     

Failure to achieve euglycemia despite aggressive insulin control signals abnormal physiologic response to trauma

Purpose

We hypothesize that a failure to normalize a patient's glucose on an automated euglycemia protocol signals an adverse response after trauma and that this response can identify patients with an increased mortality.

Materials and Methods

There were 1246 ventilated, critically ill trauma patients who were placed on an automated euglycemia. All glucose values collected both by laboratory serum measurements and by bedside arterial samples were included in the analysis.

Results

Forty six thousand two hundred eighteen data entries for glucose (mg/dL) were analyzed. Time to normalization, defined as the first value in the goal range of 80 to 110 mg/dL, was different between the 2 groups, survivors correcting significantly faster (396 vs 487 minutes; P = .003). Mortality in patients who normalized (80-110 mg/dL) in the first 6 hours of admission was 13.6% vs 18.3% in patients requiring greater than 6 hours (P = .02). Patients who never normalized also required significantly greater insulin doses despite there being no significant difference in demographic data between the 2 groups.

Conclusions

A posttraumatic patient's response to tight glycemic control revealed important prognostic information about the patients' physiologic status. Patients who failed to reach euglycemia in the first 6 hours of admission had an increased hospital mortality. The time to normalization is significantly longer in those patients who died. Patients who did not correct rapidly required significantly higher insulin doses, suggesting insulin resistance.     

Glucose metabolism, not obesity, predicts mortality in critically ill surgical patients

Our hypothesis was to determine if insulin resistance and hyperglycemia, rather than obesity, are predictive of mortality in the surgically critically ill. An observational study of an automated protocol in surgical and trauma intensive care units was performed. Two groups were created based on body mass index (BMI): Obese (OB) defined as BMI > or = 30 (n = 338) and nonobese defined as BMI < 30 (n = 885). Euglycemia was maintained using an automated protocol using an adapting multiplier, which we used as our marker of stress insulin resistance. The primary outcome was hospital mortality. One thousand, two hundred and twenty-three patients met criteria with 73,225 glucose values. The OB group required more insulin (4.5 U/hr vs 3.2 U/hr, P < or = 0.01) and had a higher mean multiplier (0.07 vs 0.06, P < 0.01) reflecting insulin resistance. There was no difference in mortality between OB and nonobese (11.6% vs 11.5%, P = 0.96). Logistic regression showed that insulin dose (odds ratio 0.864; 95% confidence interval 0.772-0.967, P = 0.01), and not BMI, was an independent predictor of survival in this population. Obesity is not an independent risk factor for mortality in the surgical critical care population. Insulin resistance and subsequent hyperglycemia are increased in obesity and are independent predictors of mortality.     

Effects and mechanisms of PCB ecotoxicity in food chains: Algae  fish  seal  polar bear 1

Wildlife populations are adversely affected in polluted environments. Nevertheless, a cause‐and‐effect relationship between excessive exposure to chlorinated hydrocarbons and induction of pathologic disorders in animals, is difficult to demonstrate without verification from experiments following the rationale of Koch's postulates. Deleterious effects of chlorinated chemicals such as DDT on songbird reproduction, as demonstrated by the clutch size of eggs in a nest, however, is an example, where exposure and causation are apparent. With amelioration of DDT pollution, clutch size increases, and the cause‐and‐effect relationship is established. Similar examples of exposure to DDT and PCBs inducing reproductive disorders and endocrine disruption among marine mammals have been documented in industrialized nations of northern Europe and in the upper latitudes of the Northern Hemisphere. Population declines in ringed, grey and harbor seals are apparently due to a rapid decrease in their rates of reproduction¹. These latter observations are best interpreted in light of experiments conducted by Reijnders². Reijnders exposed harbor seals to relatively high dietary levels of PCBs and induced PCB‐blood‐lipids among seals to an average of 25 mg/kg compared to 10 mg/kg among controls. The treated seals had a significantly reduced reproductive rate. A relationship between increased PCB‐blood‐levels in vivo and the decrease in reproductive rates in this experiment is highly instructive for interpreting the decline of fertility in seal populations in polluted Baltic Sea waters. These linked observations are dependent upon demonstration of pathologic mechanisms associated with occlusion and stenosis of the uterine lumen among affected females in seal populations.

PCB congeners apparently disrupt endocrine‐system‐functions leading to, or associated with, increases in endometriosis, fetal abortion, glomerulonephropathies and osteoporosis. This observation is further highlighted by Reijnders experiment, which closely replicated the range of PCB concentrations found in seal populations living in a variety of PCB polluted waters.

Various PCB congeners differentially accumulate in brain, liver and adipose tissues in young and old seals. Further research of PCB toxic effects on organ systems of these animals and other species is thus indicated.

This report, then, examines the process of PCB bioaccumulation within the marine food chain from fish to seals, whales, other marine mammals and to polar bears. Environmental toxic pollutants affect animals within the food chain in different ways but ultimately they affect humans as well.     

复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎的临床研究

目的　观察复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎患者的临床疗效和安全性。方法　采用开放、多中心临床研究设计。患者每次口服 1粒复方盐酸伪麻黄碱缓释胶囊、每日 2次、间隔 12h ,连服 7d ,然后观察患者症状和体征的改善情况。结果　本研究最终有 370例患者可供疗效分析 ,371例患者可供安全性分析。与服药前相比 ,患者服药第 1～ 7天各临床症状 (包括鼻塞、流涕、鼻痒、打喷嚏、流泪、眼痒、耳 /腭痒 )及体征 (包括鼻甲、鼻黏膜情况和眼部充血 )评分的改善均有统计学意义 (P <0 0 0 1)。复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎症状和体征的显效率分别为 70 %和 6 8% ,总有效率分别为 89%和 80 %。在用药过程中共有 5 4例患者报告了 6 1例次不良反应 ,主要为轻、中度困倦和口干。未出现严重不良反应。结论　复方盐酸伪麻黄碱缓释胶囊可持续有效控制季节性变应性鼻炎患者的症状和体征 ,疗效较高 ,耐受性较好