Application of a simplified method based on regular regime approach to determine the effective moisture diffusivity of mixture of low molecular weight sugars and maltodextrin during desorption

The binary diffusivities of water in low molecular weight sugars; fructose, sucrose and a high molecular weight carbohydrate; maltodextrin (DE 11) and the effective diffusivities of water in mixtures of these sugars (sucrose, glucose, fructose) and maltodextrin (DE 11) were determined using a simplified procedure based on the Regular Regime Approach. The effective diffusivity of these mixtures exhibited both the concentration and molecular weight dependence. Surface stickiness was observed in all samples during desorption, with fructose exhibiting the highest and maltodextrin the lowest. (C) 2002 Elsevier Science Ltd. All rights reserved.

Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231

Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARa activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis. (C) 2002 Wiley-Liss, Inc.

Zeolite/rock phosphate - a novel slow release phosphorus fertiliser for potted plant production

A glasshouse study was undertaken to determine if the zeolite mineral clinoptilolite from an Australian deposit in combination with rock phosphate (RP) could significantly enhance the uptake of P by sunflowers. The zeolite/RP combination was intended to act as an exchange-fertiliser, with Ca2+ exchanging onto the zeolite in response to plant uptake of nutrient cations (NH4+ or K) enhancing the dissolution of the RP. A reactive RP (Sechura) and a relatively non-reactive RP (Duchess) were examined. Zeolite was used in Ca2+-, K+- and NH4+-saturated forms at ratios of 3.5:1 and 7:1 with RP; Ca2+-zeolite was considered the control, with exchange-induced dissolution possible from K+-and NH4+-zeolite, The zeolite/RP mixture was applied as a vertical band adjacent to the sunflower seedling. In addition, N was supplied as urea in an effort to determine if RP dissolution resulted from H+ release by nitrification. Phosphorus supply from the zeolite/RP system was compared with an available P source (KH2PO4). The experiment clearly demonstrated greatly enhanced plant uptake of P from RP when applied in combination with NH4-zeolite, though the P uptake was lower than that from the soluble P source. The zeolite/RP interaction was much more effective with the reactive R-P than the non-reactive material, Within the NH4+-zeolite/RP band, root proliferation was greatly increased, as would be expected in an exchange-fertiliser system. The K+-zeolite system did not produce a significantly greater yield than the Ca2+-zeolite control, probably because adequate K+ supply from the basal application reduced uptake within the zeolite/RP band, thus reducing the extent of exchange-induced dissolution. Nevertheless, increased root proliferation within the band was observed, implying that exchange-induced dissolution may also be possible from this system. The zeolite/RP system offers the considerable advantage of P release in response to plant demand and is unique in this regard. (C) 2002 Elsevier Science B.V. All rights reserved.

Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis

Objective: To review the literature regarding the effectiveness of 5-hydroxytryptophan (5-HT) and L-tryptophan in the treatment of unipolar depression. Methods: A systematic review of the literature from 1966 to 2000 using the search terms 'tryptophan', 5-hydroxytryptophan', '5-HTP', '5-HT' and 'depression'. We extracted and grouped data for meta-analysis by pooling odds ratios (OR) and relative risks where possible. Results: One hundred and eight studies were located of which only two studies, one of 5-HT and one of L-tryptophan, with a total of 64 patients met sufficient quality criteria to be included. These studies suggest 5-HT and L-tryptophan are better than placebo at alleviating depression (Peto OR = 4.1, 95% CI = 1.3-13.2). However, the small size of the studies, and the large number of inadmissible, poorly executed studies, casts doubt on the result from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness. Conclusions: A large body of evidence was subjected to very basic criteria for assessing reliability and validity, and was found to largely be of insufficient quality to inform clinical practice. More well-designed studies are urgently required to enable an assessment of what may be an effective class of agents.

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. Patients and setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107730 (95% Cl, $68626-$209881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Achieving effective supervision

Super vision probably does have benefits both for the maintenance and improvement of clinical skills and for job satisfaction, but the data are very thin and almost non-existent in the area of alcohol and other drugs services. Because of the potential complexity of objectives and roles in super vision, a structured agreement appears to be an important part of the effective supervision relationship. Because sessions can degenerate easily into unstructured socialization, agendas and session objectives may also be important. While a working alliance based on mutual respect and trust is an essential base for the supervision relationship, procedures for direct observation of clinical skills, demonstration of new procedures and skills practice with detailed feedback appear critical to super vision's impact on practice. To ensure effective super vision, there needs not only to be a minimum of personnel and resources, but also a compatibility with the values and procedures of management and staff, access to supervision training and consultation and sufficient incentives to ensure it continues.

Carbamazepine augmentation for schizophrenia: How good is the evidence?

Background: Augmentation strategies in schizophrenia treatment remain an important issue because despite the introduction of several new antipsychotics, many patients remain treatment resistant. The aim of this study was to undertake a systematic review and meta-analysis of the safety and efficacy of one frequently used adjunctive compound: carbamazepine. Data sources and study selection: Randomized controlled trials comparing carbamazopine (as a sole or as an adjunctive compound) with placebo or no intervention in participants with schizophrenia or schizoaffective disorder were searched for by accessing 7 electronic databases, cross-referencing publications cited in pertinent studies, and contacting drug companies that manufacture carbamazepine. Method: The identified studies were independently inspected and their quality assessed by 2 reviewers, Because the study results were generally incompletely reported, original patient data were requested from the authors; data were received for 8 of the 10 randomized controlled trials included in the present analysis, allowing for a reanalysis of the primary data. Dichotomous variables were analyzed using the Mantel-Haenszel odds ratio and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. Results: Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. Conclusion: At present, this augmentation strategy cannot be recommended for routine use. The most promising targets for future trials are patients with excitement, aggression, and schizoaffective disorder bipolar type.

Characterisation of chronic lateral epicondylalgia using the McGill pain questionnaire, visual analog scales, and quantitative sensory tests

Aims: To characterise chronic lateral epicondylalgia using the McGill Pain Questionnaire, Visual Analog Scales for pain and function, and Quantitative Sensory Tests; and to examine the relationship between these tests in a population with chronic lateral epicondylalgia. Method: Fifty-six patients (29 female, 27 male) diagnosed with unilateral lateral epicondylalgia of 18.7 months (mean) duration (range 1-300), with a mean age of 50.7 years (range 27-73) participated in this study. Each participant underwent assessment with the McGill Pain Questionnaire (MPQ), Visual Analog Scales (VAS) for pain and function. and Quantitative Sensory Tests (QST) including thermal and pressure pain thresholds, pain free grip strength, and neuromeningeal tissue testing via the upper limb tension test 2b (ULTT 2b). Results: Moderate correlation (r = .338-.514, p = .000-.013) was found between all indices of the MPQ and VAS for pain experienced in the previous 24 hours and week. Thermal pain threshold was found to be significantly higher in males. A significant poor to moderate correlation was found between the Pain Rating Index (PRI) in the sensory category of the MPQ and ULTT2b scores (r = .353, p = .038). There was no other significant correlation between MPQ and QST data. Pain free grip strength was poorly yet significantly correlated with duration of pathology (r = 318, p = .038). Conclusion: The findings of this study are in agreement with others (Melzack and Katz, 1994) regarding the multidimensional nature of pain, in a condition conventionally conceived as a musculoskeletal pain state. The findings also suggest that utilisation of only one pain measurement tool is unlikely to provide a thorough clinical picture of pain experienced with chronic lateral epicondylalgia.

Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect

Diabetes mellitus is now occurring in epidemic proportions in many countries. Owing to the limited effectiveness of drug prophylaxis of diabetic complications after diabetes has developed, it may be more appropriate to investigate ways to prevent the onset of diabetes. A recent trial published by the Diabetes Prevention Programme Research Group investigated whether lifestyle changes or metformin were effective in delaying the onset of diabetes in subjects with impaired glucose tolerance. The goals of the intensive lifestyle intervention were to achieve and maintain a weight reduction of 7% through a low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 min/week. The effectiveness of the intensive lifestyle intervention on body weight was initially quite good but decreased over time. Metformin caused some weight loss but to a lesser extent than the intensive lifestyle intervention. Both therapies decreased the fasting plasma glucose levels to a similar extent initially. The intensive lifestyle intervention decreased plasma glycosylated haemoglobin levels to a greater extent than metformin. Both intensive lifestyle intervention and metformin reduced the incidence of diabetes, with the lifestyle intervention having the greater effect.

Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate

1 Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-{N-methyl-N-[6-(N-methylammoniohexyl)amino]}diazen-l-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-ajquinoxalin-1-one), and to investigate the possible role of activation of sarco-encloplasmic reticulum calcium-ATPase (SERCA), independent of soluble guanylate cyclase, using thapsigargin. 2 MAHMA NONOate concentration-dependently inhibited sub-maximal aggregation responses to collagen (2 - 10 mug ml(-1)) and adenosine diphosphate (ADP; 2 mum) in platelet rich plasma. It was (i) more effective at inhibiting aggregation induced by collagen than by ADP, and (ii) less potent at inhibiting platelet aggregation than relaxing rat pulmonary artery. 3 ODQ (10 mum) caused only a small shift (approximately half a log unit) in the concentration-response curve to MAHMA NONOate irrespective of the aggregating agent. 4 The NO-independent activator of soluble guanylate cyclase, YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzy] indazole; 1 - 100 mum), did not inhibit aggregation. The cGMP analogue, 8-pCPT-cGMP (8-(4-chlorophenylthio)guanosine 3'5' cyclic monophosphate; 0.1 - 1 mm), caused minimal inhibition. 5 On collagen-aggregated platelets responses to MAHMA NONOate (ODQ 10 PM present) were abolished by thapsigargin (200 nm). On ADP-aggregated platelets thapsigargin caused partial inhibition. 6 Results with S-nitrosoglutathione (GSNO) resembled those with MAHMA NONOate. Glyceryl trinitrate and sodium nitroprusside were poor inhibitors of aggregation. 7 Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ-resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA.

A Pilot Randomized Trial Comparing CD-34Selected Versus Unmanipulated Hemopoietic Stem Cell Transplantation for Severe, Refractory Rheumatoid Arthritis

Objective. Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.

Lateral epicondylalgia: a musculoskeletal physiotherapy perspective

Tennis elbow or lateral epicondylalgia (LE) is a challenging musculoskeletal condition to treat. This is largely due to the lack of research-based evidence of the clinical efficacy of the myriad of treatment approaches espoused in the literature. In view of this, successful rehabilitation of LE is based on choosing treatments that address the physical impairments found during clinical examination. The primary physical impairment in LE is a deficit in grip strength predominately due to pain and its consequences on motor function. Hence the mainstay of successful management of this condition is therapeutic exercise, providing it is not pain provocative. Adjunctive procedures such as manipulative therapy and sports taping techniques have recently been shown to provide substantial initial pain relief. Early relief of pain in the rehabilitation program helps accelerate recovery and most importantly motivates the client to persist with the therapeutic exercise program. The manipulative therapy and taping treatments presented in this masterclass warrant consideration in the clinical best practice management of LE, and serve as a model for other similar musculoskeletal conditions. (C) 2003 Elsevier Science Ltd. All rights reserved.