Evaluation of two shortened forms of the SAWAIS with three diagnostic groups

This study evaluated the shortened forms of the WAIS by Coolidge (1976) and Golden (1976), respectively. This was accomplished by administering the South African Wechsler Adult Intelligence Scale (SAWAIS) to subjects with depression (N = 42), mentally retarded subjects (N = 32), and subjects who presented with an organic brain syndrome (N = 79). Correlations between the full scale scores and the shortened form scores fluctuated between .80 and .91. With all three groups the shortened forms indicated significance (p less than .01 with all six correlations). It appears that these two shortened forms, depending on the reason for testing, can be used successfully with different psychiatric groups. However, the results must be used with caution, especially when used with mentally retarded patients.     

Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial

BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily). METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.     

Cellular drug resistance profiles in childhood acute myeloid leukemia: differences between FAB types and comparison with acute lymphoblastic leukemia

Determining in vitro drug resistance may reveal clinically relevant information in childhood leukemia. Using the methyl-thiazol-tetrazolium assay, the resistance of untreated leukemic cells to 21 drugs was compared in 128 children with acute myeloid leukemia (AML) and 536 children with acute lymphoblastic leukemia (ALL). The differences between 3 French-American-British (FAB) types (M1/M2, M4, and M5) were also compared. AML was significantly more resistant than ALL to the following drugs, as noted by the median resistance: glucocorticoids (greater than 85-fold), vincristine (4.4-fold), L-asparaginase (6.9-fold), anthracyclines (1.8- to 3.4-fold), mitoxantrone (2.6-fold), etoposide (4.9-fold), platinum analogues (2.4- to 3.4-fold), ifosfamide (3.5-fold), and thiotepa (3.9-fold). For cytarabine and thiopurines, the median LC50 values (the drug concentration that kills 5% of the cells) were equal. Also, busulfan, amsacrine, teniposide, and vindesine showed no significant differences, but the numbers were smaller, and the median LC50 values were 1.3- to 5.2-fold higher in AML. None of the drugs demonstrated greater cytotoxicity in AML. FAB M5 was significantly more sensitive than FAB M4 to most drugs frequently used in AML, as indicated by the following ratios of median sensitivities: the anthracyclines (2.6- to 3.2-fold), mitoxantrone (12.5-fold), etoposide (8.7-fold), and cytarabine (2.9-fold). For etoposide and cytarabine (5.4- and 3.4-fold, respectively) FAB M5 was also significantly more sensitive than FAB M1/M2. FAB M5 was equally sensitive to L-asparaginase and vincristine as ALL. Only 15% of the AML samples were "intermediately" sensitive to glucocorticoids, mainly in FAB M1/M2. The poorer prognosis of childhood AML is related to resistance to a large number of drugs. Within AML, FAB M5 had a distinct resistance pattern. These resistance profiles may be helpful in the rational design of further treatment protocols. (Blood. 2000;96:2879-2886)     

Antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the Democratic Republic of Congo: Croton mubango , Nauclea pobeguinii and Pyrenacantha staudtii

The antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as antimalarial remedies in the Democratic Republic of Congo were studied both in vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei berghei. The toxic effects of dried aqueous extracts of the plants were also investigated, in uninfected mice. The most active crude extracts in vitro, with median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the methanolic and dichloromethane extracts of C. mubango, and the dichloromethane extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml), followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py. staudii (IC(50) = 15.2 microg/ml).Results from the in-vivo tests of antimalarial activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water-soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n-butanolic fractions from Py. staudtii produced >80% chemosuppression of the parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii produced a slightly lower but still significant inhibition of parasitaemia (60%-80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%.The dried aqueous extract of the stem bark of C. mubango showed some signs of toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female mice and 900 mg/kg in the male. The extract significantly increased the serum concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood levels of creatinine or urea. No significant toxic effect was observed for the dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg). Neither of these extracts affected the serum concentrations of GPT or the blood concentrations of creatinine and urea, although the N. pobeguinii extract did increase the serum concentration of GOT.     

Assessing the additional impact of fitness training in depressed psychiatric patients receiving multifaceted treatment: a replicated single-subject design

Purpose: Exercise has been put forward as a therapeutic means for the treatment of clinical depression.

Methods: In this study, 29 patients, all with diagnosed with mood disorder, completed daily measurements of depression and physical well-being during periods ranging from 77 to 436 days (M = 146.5). Fitness training was added to the treatment after a period and changes before (A-phase) and after (B-phase) the implementation of this training were the subject of investigation. Data were analysed by means of randomization tests with an AB-design and time-series analysis. Replication of the findings was investigated using Fisher's multiplicative method.

Results: Adding fitness training to the treatment of clinical depression does not systematically lead to changes in self-reported feelings of depression on top of benefits that may be due to other treatments.

Conclusion: Since the present findings are not in agreement with previous studies, the absence of statistically significant changes in self-reported feelings of depression is discussed within the complexity of the 'exercise - depression' relationship in inpatient populations. These included the severity of their depression, the potential ceiling effect of a multifaceted treatment programme and the initial increase in depression due to the confrontational nature of the intervention.     

Rational use of stacking principles for signal enhancement in capillary electrophoretic separations of poliovirus samples

The use of an earlier developed capillary electrophoresis (CE) method, either to investigate poliovirus (PV) samples with a low viral-purity level or to study the less abundant sub-viral particles, revealed the necessity for an intra-column signal enhancement strategy. Although intra-column signal enhancement is a very popular approach to assay small molecules, it is less straightforward for the analysis of biological macromolecules or particles. A reason could be that, for a proper signal enhancement approach, these samples have to be thoroughly studied to understand the factors affecting the separation process. For the investigated PV samples, a screening design revealed that injecting larger sample plugs significantly enhanced the analytical signal, but also significantly decreased the separation efficiency. A subsequently executed central composite design determined the largest sample plug that can be injected without compromising the separation. Finally, the sample dilution and the length of the injected plug were used for tuning the intensity of the analytical response. Two combinations of sample dilution and injected plug size, at extreme values, were investigated in detail to define the best procedure for PV analysis using CE. In both situations, PV was effectively separated and quantified in rather complex samples, showing a good repeatability, an acceptable linearity for the PV particles and a decreased limit of detection in comparison with the existing method. In conclusion, intra-column signal enhancement can be successfully applied for viral suspensions, extending the applicability of CE methods to samples with lower virus concentrations, and/or allowing a significant reduction in the minimum required volume of sample. For PV samples, 5μl of sample is necessary instead of the previous 20μl, while the analytical signal was enhanced up to 14 times. The results of this study can provide a basis for the development of routine CE methods for viral particle analysis, especially when rational and reproducible signal enhancement is required.     

Alterations in Epithelial and Mesenchymal Intestinal Gene Expression During Doxorubicin-Induced Mucositis in Mice

In the current study we aimed to gain insight into epithelial-mesenchymal cross-talk and progenitor compartment modulation during doxorubicin (DOX)-induced mucositis in mice. Intestinal segments were collected on various days after DOX treatment. DOX-induced damage at day 1–2 was characterized by increased epithelial proliferation and apoptosis and a decrease in the expression of epithelial differentiation markers. Concurrently, T-cell factor-4 (TCF4) levels increased and the epithelial differentiation enhancing factor, bone morphogenic protein-4 (BMP4), decreased. During severe damage (day 3), BMP4 levels were significantly increased, which inversely correlated with epithelial proliferation. At the same time, the expression of the epithelial differentiation markers was increasing again. At day 7, BMP4 levels were down-regulated, while the levels of the epithelial differentiation markers and TCF4 were normalized again. These data suggest that in response to DOX-induced damage, BMP4 and TCF4 are modulated in such a way that homeostasis of the progenitor compartment is partly preserved.     

Differences in the association of PAI-1 activity with the metabolic syndrome between African and Caucasian women

Background and aimsThe association between PAI-1_act and markers of the metabolic syndrome is well established in Caucasian populations, but data on African subjects is lacking. The aim of this study was to investigate possible differences between the association of PAI-1_act and markers of the metabolic syndrome in Caucasian and African women.Methods and resultsCross-sectional data were collected from 95 African and 114 Caucasian women in the Potchefstroom district of the North West Province, South Africa. Plasma PAI-1_act was almost twice as high in Caucasians compared to Africans (10.2 versus 5.2 U/mL, p < 0.001). Correlations between markers of the metabolic syndrome and PAI-1_act were remarkably stronger in Caucasians than in Africans. In multivariate regression analyses 56% of the variance of PAI-1_act could be explained by metabolic syndrome variables in the Caucasian group compared to 12% in the African women. Waist circumference was the strongest independent predictor of PAI-1_act in both groups.ConclusionThis study showed lower PAI-1_act in African than in Caucasian women, along with less associations of PAI-1_act with markers of the metabolic syndrome in the African than in the Caucasian women. The role of PAI-1_act in the metabolic syndrome may be less prominent in Africans than in Caucasians.