Release stability of 5-fluorouracil liposomal concentrates, gels and lyophilized powder

Possible leakage of 5-fluorouracil from stable plurilamellar vesicles was monitored during storage of the liposomal concentrates, gels and lyophilized powders. Changes in release profile of dibucaine were taken as indicator of instability. Release profiles were obtained using the dialysis technique for a freshly prepared liposomal concentrate, gel or reconstituted lyophilized powder (zero time) and storage for one, two and four weeks in well closed tubes at 4 degrees C for the liposomal concentrate or gel and at 25 degrees C for liposomal lyophilized powder. Aiming at increasing stability of 5-fluorouracil liposomal dispersion, freshly prepared liposomal concentrates were directly incorporated in hydroxypropyl methylcellulose gel. Stability release profiles of liposomal gels and concentrates indicated a significant increase in stability of liposomal formulations. Also, lyophilization increases the shelf life of liposomes by preserving it in a dry form as a lyophilized cake to be reconstituted immediately prior to administration or direct incorporation into a final dosage form. Release and physico-chemical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison to concentrate and gel forms. It could be concluded that lyophilization of liposomes loaded with a water-soluble drug such as 5-fluorouracil could significantly increase the stability of the liposomal vesicles and decrease leakage from it.     

A comparison of quality of care indicators in urban acute care hospitals and rural critical access hospitals in the United States.

OBJECTIVE: Two recent Institute of Medicine reports highlight that the quality of healthcare in the US is less than what should be expected from the world's most extensive and expensive healthcare system. This may be especially true for critical access hospitals since these smaller rural-based hospitals often have fewer resources and less funding than larger urban hospitals. The purpose of this paper was to compare quality of hospital care provided in urban acute care hospitals to that provided in rural critical access hospitals. DESIGN: Cross-sectional study analyzing secondary Hospital Compare data. T-test statistics were computed on weighted data to ascertain if differences were statistically significant (P=0.01). SETTING: Centers for Medicare and Medicaid Services hospitals. PARTICIPANTS: US Acute Care and Critical Access hospitals. MAIN OUTCOME MEASURES: Differences between urban acute care hospitals and rural critical access hospitals on quality care indicators related to acute myocardial infarction, heart failure and pneumonia. RESULTS: For 8 of the 12 hospital quality indicators the differences between urban acute care and rural critical access hospitals were statistically significant (P=0.01). In seven instances these differences favored urban hospitals. One indicator related to pneumonia favored rural hospitals CONCLUSIONS: Although this study focused on only three disease states, these are among the most common clinical conditions encountered in inpatient settings. The findings suggested that there may be differences in quality in rural critical access hospitals and urban acute care hospitals and support the need for future studies addressing disparities between urban acute care and rural critical access hospitals.     

Influence of seasonal variation on pregnancy-induced hypertension and/or preeclampsia

Seasonal variation of temperature and humidity are said to influence the incidence of hypertensive disorders of pregnancy. The aim of this study was to determine if temperature and humidity exert any influence on the incidence of pregnancy-induced hypertension and preeclampsia in Kuwait. This is a retrospective study performed in the Maternity Hospital, Kuwait (MHK) in the years 1992-1994. Monthly distribution of all deliveries and those in which the patients had pregnancy-induced hypertension and preeclampsia were recorded. There are some studies including ours which do not show any significant correlation between meteorological factors and hypertensive disorders of pregnancy. We found that the incidence of pregnancy-induced hypertension per 1,000 deliveries was high in June when the temperature was very high and the humidity at its lowest. The reverse was true for the incidence of preeclampsia per 1,000 deliveries, which was high in November when the temperature was low and the humidity high.     

Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion

It has been proposed that successful pregnancy is a T helper 2-type phenomenon, and that T helper (Th)1-type reactivity is deleterious to pregnancy. The objective of this study was to compare the concentrations of Th1 and Th2 cytokines produced by peripheral blood mononuclear cells from women undergoing unexplained recurrent spontaneous abortion (RSA) with those produced during normal pregnancy at a similar gestational stage. The control group consisted of 24 women with a history of successful pregnancies and the abortion group comprised of 23 women with a history of unexplained RSA. Blood from the control group was obtained at the end of the first trimester as gestational age controls for the abortion group from whom blood was collected at the time of abortion. Phytohaemagglutinin-stimulated peripheral blood cell culture supernatants were analysed for concentrations of cytokines. Significantly higher concentrations of Th2 cytokines were produced by the first trimester normal group than by the RSA group, while significantly higher concentrations of Th1 cytokines were produced by the abortion group as compared to first trimester normal pregnancy, indicating a distinct Th2-bias in normal pregnancy and a Th1-bias in unexplained RSA.     

Alpha-synuclein locus duplication as a cause of familial Parkinson's disease

Genomic triplication of the alpha-synuclein gene (SNCA) has been reported to cause hereditary early-onset parkinsonism with dementia. These findings prompted us to screen for multiplication of the SNCA locus in nine families in whom parkinsonism segregates as an autosomal dominant trait. One kindred was identified with SNCA duplication by semiquantitative PCR and confirmed by fluorescent in-situ hybridisation analysis in peripheral leucocytes. By contrast with SNCA triplication families, the clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent. These findings suggest a direct relation between SNCA gene dosage and disease progression.     

Effect of α-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats

The aim of this study was to determine the effects of α-tocopherol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar-Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of α-tocopherol (α₁, 17 mg/kg diet; α₂, 34 mg/kg diet; and α₃, 170 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressures were recorded every 10 days for 3 months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity, and lipid peroxide levels in plasma and blood vessels was carried out following well-established methods.From our study it was found that lipid peroxides in thoracic aorta (N, 0.47 ± 0.17; H, 0.96 ± 0.37; P < .0001) and plasma (N, 0.06 ± 0.01; H, 0.13 ± 0.01) were significantly higher in hypertensives than in normal rats. SOD activity was significantly lower in hypertensive than normal rats (N, 172.93 ± 46.91; H, 110.08 ± 14.38; P < .005). Total antioxidant status was significantly higher in normal than hypertensive rats (N, 0.88 ± 0.05; H, 0.83 ± 0.02; P < .05). After the antioxidant trial, it was found that in the treated groups rise of blood pressure was prevented significantly (P < .001) and lipid peroxides in blood vessels were significantly reduced more than in the controls (P < .001). For plasma lipid peroxide it was only significant for groups α₂ (P < .001) and α₃ (P < .05). Although all three treated groups showed improved total antioxidant status, only groups α₂ (0.87 ± 0.04, P < .005) and α₃ (1.20 ± 0.18, P < .001) were statistically significant. All the three groups showed significant increases in their SOD activity (P < .001).Correlation studies showed that total antioxidant status and SOD were significantly negatively correlated with blood pressure in normal rats (P = .007; P = .008). Lipid peroxides in both blood vessel and plasma showed a positive correlation. In the treated groups, lipid peroxides in blood vessels maintained a significant positive correlation with blood pressure in all groups (α₁, P = .021; α₂, P = .019; α₃, P = .002), whereas for plasma lipid peroxides the correlation was in groups α₁ (P = .005) and α₂ (P = .009). For SOD activity, significant negative correlations were found with blood pressure in the α₂ (P = .017) and α₃ (P = .025) groups. Total antioxidant status maintained a significant negative correlation with blood pressure in all three groups (α₁, P = .012; α₂, P = .044; α₃, P = .014).In conclusion it was found that supplement of α-tocopherol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels, and enhance the total antioxidant status, including SOD activity.     

Knowledge of heart attack and stroke symptomology: a cross-sectional comparison of rural and non-rural US adults

Background

Understanding the signs and symptoms of heart attacks and strokes are important not only in saving lives, but also in preserving quality of life. Findings from recent research have yielded that the prevalence of cardiovascular disease risk factors are higher in rural populations, suggesting that adults living in rural locales may be at higher risk for heart attack and/or stroke. Knowledge of heart attack and stroke symptomology as well as calling 911 for a suspected heart attack or stroke are essential first steps in seeking care. This study sought to examine the knowledge of heart attack and stroke symptoms among rural adults in comparison to non-rural adults living in the U.S.

Methods

Using multivariate techniques, a cross-sectional analysis of an amalgamated multi-year Behavioral Risk Factor Surveillance Survey (BRFSS) database was performed. The dependent variable for this analysis was low heart attack and stroke knowledge score. The covariates for the analysis were: age, sex, race/ethnicity, annual household income, attained education, health insurance status, having a health care provider (HCP), timing of last routine medical check-up, medical care deferment because of cost, self-defined health status and geographic locale.

Results

The weighted n for this study overall was 103,262,115 U.S. adults?>?=18 years of age. Approximately 22.0% of these respondents were U.S. adults living in rural locales. Logistic regression analysis revealed that those U.S. adults who had low composite heart attack and stroke knowledge scores were more likely to be rural (OR?=?1.218 95%CI 1.216-1.219) rather than non-rural residents. Furthermore, those with low scores were more likely to be: male (OR?=?1.353 95%CI 1.352-1.354), >65 years of age (OR?=?1.369 95%CI 1.368-1.371), African American (OR?=?1.892 95%CI 1.889-1.894), not educated beyond high school (OR?=?1.400 955CI 1.399-1.402), uninsured (OR?=?1.308 95%CI 1.3-6-1.310), without a HCP (OR?=?1.216 95%CI 1.215-1.218), and living in a household with an annual income of?<?$50,000 (OR?=?1.429 95%CI 1.428-1.431).

Conclusions

Analysis identified clear disparities between the knowledge levels U.S. adults have regarding heart attack and stroke symptoms. These disparities should guide educational endeavors focusing on improving knowledge of heart attack and stroke symptoms.

     

The use of blood in obstetrics and gynecology in the developing world

Access to safe blood is critical in comprehensive emergency obstetric care and for reducing maternal mortality. Many countries have inadequate blood supplies, and this disproportionately affects women and children in need of life-saving blood transfusions. Although preventative measures aimed at reducing postpartum hemorrhage by treating underlying anemia and infectious diseases are critical, they are insufficient for obstetric hemorrhage. In the developing world, efforts should focus on alternative means of providing safe blood in cases of hemorrhage, with particular focus on rapid testing, donation of warm whole blood, and autologous blood transfusion.     

Maternal health considerations during disaster relief

When disasters strike resource-poor nations, women are often the most affected. They represent the majority of the poor, the most malnourished, and the least educated, and they account for more than 75% of displaced persons. The predisaster familial duties of women are magnified and expanded, and they have significantly less support and fewer resources than they had before the incident. Moreover, after the disaster, they bear the responsibility of caring for their children, the elderly, the injured, and the sick. Besides the effects of the disaster, women become more vulnerable to reproductive and sexual health problems and are at increased risk for physical and sexual violence. Women become both victims and the primary caretakers. Health practitioners are often not aware of these issues when providing emergency care. Developing a disaster relief team with experts in maternal health is necessary to improve women's health outcome.