The quality of drugs in private pharmacies in Lao PDR: a repeat study in 1997 and 1999

Objective: To present a repeated test of the quality of ampicillin, tetracycline, chloroquine and ASA from private pharmacies in Laos in 1997 and 1999, and to discuss the quality in relation to the National Drug Policy Programme.Method: A total of 115 of 214 licensed private pharmacies were selected in Savannakhet province, a pilot province in the Lao National Drug Policy Programme. The four drugs, if available, were collected at each pharmacy. Thirty tablets of each drug were taken from a selected container. In 1997, 366 samples were analysed and three hundred in 1999. Identity, assay (content of active component) and measurement of weight variation tests were performed. Drug quality was compared mainly according to the standards of the British and United States pharmacopoeias.Results: The percentage of substandard drugs decreased significantly from 46% to 22% between 1997 and 1999 (P < 0.001). Substandard ampicillin and tetracycline were reduced significantly from 67% to 9% and from 38% to 12%, respectively (P < 0.001). In total, 3% vs 1% contained no active ingredient, 12% vs 4% had too little or too much active ingredient, and 35% vs 14% had weight variation outside pharmacopoeial limits.Conclusion: Drug quality was improved. However, the prevalence of substandard drugs was still unacceptably high, which may result in adverse clinical effect or treatment failure for individual patients.     

Combined effect of recombinant CD19 x CD16 diabody and thalidomide in a preclinical model of human B cell lymphoma

Combining different treatment strategies offers the possibility of improving treatment results for cancer patients. The aim of our study was therefore to investigate the combination of treatment of established s.c. human B non-Hodgkin's lymphoma in severe immune deficient mice using a recombinant bispecific CD19 x CD16 diabody (targeting natural killer cells to CD19 cells) and the angiogenesis inhibitor thalidomide. Monotherapy with either thalidomide or diabody caused an approximate 50% reduction in tumor growth rate. The combined treatment showed evidence for a synergistic effect resulting in a 74% reduction in median tumor size. In the combined treatment group, two of five animals had complete remissions of their s.c. tumor. These results suggest that a combination treatment with recombinant diabodies and angiogenesis inhibition represents a useful approach in cancer therapy.     

Frequency of reoperations after amniotic membrane transplantation

BACKGROUND: Retrospective evaluation of the frequency of reoperations after amniotic membrane transplantation for different pathologic entities. MATERIAL AND METHODS: We included 81 cases of amniotic membrane transplantation (AMT), which were operated on at the university eye clinic Tübingen since 1997 and which had been followed up for at least 12 months. Patient diagnoses were subdivided as follows: conjunctival defects after tumour excision (N = 2), bullous keratopathy (N = 5), external fistula after glaucoma filtering surgery (N = 3), recurrent pterygium (N = 5), symblepharon (N = 6), corneal ulcer with descemetocele (N = 3), non-perforated corneal ulcer (N = 51), perforated corneal ulcer (N = 1), other (n = 5). RESULTS: The overall reoperation rate was determined to be 42 % after a follow-up period of one year. Most frequently, a second AMT (N = 16) and a perforating keratoplasty (N = 16) were performed after the initial AMT. The following reoperation rates were determined for the subgroups: Conjunctival defects after tumour excision (0 %), Bullous keratopathy (60 %), External fistula after glaucoma filtering surgery (67 %), Recurrent pterygium (60 %), Symblepharon (67 %), Corneal ulcer with descemetocele (67 %), Non-perforated corneal ulcer (49 %), Perforated corneal ulcer (100 %). CONCLUSIONS: Particularly in patients with conjunctival defects after tumour excision and with non-perforated corneal ulcers, stabilisation of the ocular surface homeostasis can be achieved with a single amniotic membrane transplantation for at least one year.     

The peculiar nature of simultaneous colour contrast in uniform surrounds

We present evidence from asymmetric colour matching experiments which strongly suggests that uniform surrounds evoke induction effects of a very peculiar nature, not representative of colour induction effects in variegated surrounds. Given the widespread use of uniform surrounds in studies of colour vision, this finding is of interest in relation to a number of current research issues, such as contrast coding of colour, functionally equivalent surrounds and colour constancy. A framework that systematises the seemingly complex colour appearance changes induced by uniform surrounds is presented and its implications are discussed.     

Metabolic changes in rat lens after in vivo exposure to ultraviolet irradiation: measurements by high resolution MAS 1H NMR spectroscopy

PURPOSE: In the present study, high-resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS (1)H NMR) spectroscopy was used to investigate changes in the metabolic profile of intact rat lenses after UVB irradiation of the eyes. METHODS: Three groups of Sprague-Dawley rats were exposed to UVB radiation at 2.5, 5.0, and 7.5 kJ/m(2). One eye was exposed, and the contralateral eye served as the control. One week after exposure, the lenses were removed and forward light-scattering was quantified. Thereafter, proton NMR spectra from the intact lenses were obtained. Relative changes in metabolite concentrations were determined. RESULTS: The lenses in all three groups showed significant increases in light-scattering after UVB irradiation. The high-quality HR-MAS (1)H NMR spectra permitted more than 30 different metabolites to be identified. UVB irradiation caused a significant decrease (P < 0.05) in concentrations of taurine, hypotaurine, tyrosine, phenylalanine, valine, myo-inositol, phosphocholine, betaine, succinate, and glutathione at all three UV doses. For glycine, glutamate, and lactate, significant decreases in concentration were observed at the two lowest UVR-B doses. The total amount of adenosine tri- and diphosphate and (ATP, ADP) decreased significantly and that of adenosine monophosphate AMP increased significantly at the two highest doses. Alanine was the only amino acid that increased after UVB irradiation. None of these metabolites exhibited a significant UVB dose-dependent relationship. CONCLUSIONS: This study demonstrates for the first time the potential of HR-MAS (1)H NMR spectroscopy as an analytical tool for use on intact lenses. Near-threshold UVR-B doses led to a generally significant decrease in water-soluble metabolites 1 week after exposure. The lack of dose-dependent changes in the metabolites indicates that repair processes during the first week after UVB irradiation overcome the immediate metabolic disturbances.     

The adenosine A1 receptor contributes to the stimulatory, but not the inhibitory effect of caffeine on locomotion: a study in mice lacking adenosine A1 and/or A2A receptors

Caffeine has biphasic effects on locomotion, and blockade of the adenosine A(2A) receptor (A2AR) is necessary for the stimulatory effect of low doses of caffeine, but not for the locomotor depressant effect observed at high doses. We wanted to elucidate the role of the adenosine A(1) receptor (A1R) in mediating the locomotor effects of increasing doses of caffeine using wild-type mice (A1R(WT)), mice heterozygous for (A1R(HET)), and mice lacking the adenosine A(1) receptor (A1R(KO)). Caffeine had the typical biphasic dose-effect relationship in all three genotypes, but the stimulatory action of caffeine was facilitated in the A1R(KO) mice. In order to investigate the interaction between blockade of A1Rs and A2ARs, mice lacking both receptors (A1R(KO)/A2AR(KO)) were tested. Regardless of A1R genotype, animals lacking A2AR were not stimulated by caffeine, whereas animals heterozygous for A2AR were. As expected, the A1R is not crucial for the stimulatory effect of caffeine, but seems to modulate the effect of caffeine exerted via A2AR blockade. Furthermore, these results suggest that the inhibitory effect of high doses of caffeine is due neither to blockade of the A1R, nor of the A2AR, and an effect independent of these adenosine receptors is likely.     

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo

Rationale The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered.Objective This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo.Methods Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers (n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo.Results Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response.Conclusions Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.     

Dietary habits and growth and recurrence of colorectal adenomas: results from a three-year endoscopic follow-up study

Diet has been associated with sporadic colorectal cancer (CRC) risk. The relationship to the growth rate of adenomas is largely unknown. Previous analyses of our cohort of polyp cases have shown 1) indicators of a healthy diet were inversely associated with adenoma occurrence, 2) diet was related to the fecal profile, 3) obesity was positively associated with adenoma growth, 4) familial predisposition of CRC was positively associated with adenoma growth, and 5) intervention with calcium and antioxidants was not associated with adenoma growth. The present aim was to study the effects of diet on growth and recurrence of adenomas. Data were collected from a 3-yr polyp growth and intervention study. Polyps larger than 9 mm were removed, whereas the remainder and newly discovered polyps smaller than 10 mm were left in situ for 3 yr. Diet was assessed by a 5-day dietary record by weighing (DR) and food-frequency questionnaire (FFQ). Weak inverse associations were found only between adenoma growth and fruits and berries (adjusted odds ratio, aOR = 0.3; 95% CI = 0.1-0.9) and carbohydrates (aOR = 0.1; 95% CI = 0.1-0.6; both only DR data) and between adenoma recurrence and vegetables (crude odds ratio, cOR = 0.4; 95% CI = 0.1-0.9; only FFQ data). Taken together, the present and previous findings from this cohort may indicate an early role for dietary factors in CRC development.     

Clinical outcome and atherothrombogenic risk profile after prolonged wash-out following long-term treatment with high doses of n-3 PUFAs in patients with an acute myocardial infarction

BACKGROUND: Sustained effects following withdrawal of n-3 PUFAs are unknown. METHODS: Clinical outcome [cardiac death, resuscitation, recurrent myocardial infarction (MI) or unstable angina pectoris] was assessed after prolonged wash-out following randomised treatment with high-dosed n-3 PUFAs or corn oil for 12-24 months in 300 acute MI patients. Atherothrombogenic risk markers, serum glucose and markers of lipid peroxidation and inflammation were evaluated in 89 out of the 100 last included patients. RESULTS: After a total median observation period of 45 (range 0-53) months no intergroup difference in prognosis was observed for any of the cardiac events. Favourable effects on serum triglycerides and HDL-cholesterol by n-3 PUFAs were lost after washout, but triglycerides decreased in the corn oil as compared to the n-3 group, P < 0.001. The decline in total cholesterol after withdrawal was similar in both groups. No intergroup difference in the change in thiobarbituric acid-malondialdehyde, a marker of lipid peroxidation, ultrasensitive C-reactive protein, homocysteine, glucose or blood platelets was noted at sustained follow-up. CONCLUSION: Clinical outcome was similar in both patient groups, and the atherothrombogenic risk improvement by n-3 PUFAs was lost after prolonged wash-out. Withdrawal did not affect homocysteine, glucose or markers of lipid peroxidation or inflammation.     

Community-based health insurance in low-income countries: a systematic review of the evidence

Health policy makers are faced with competing alternatives, and for systems of health care financing. The choice of financing method should mobilize resources for health care and provide financial protection. This review systematically assesses the evidence of the extent to which community-based health insurance is a viable option for low-income countries in mobilizing resources and providing financial protection. The review contributes to the literature on health financing by extending and qualifying existing knowledge. Overall, the evidence base is limited in scope and questionable in quality. There is strong evidence that community-based health insurance provides some financial protection by reducing out-of-pocket spending. There is evidence of moderate strength that such schemes improve cost-recovery. There is weak or no evidence that schemes have an effect on the quality of care or the efficiency with which care is produced. In absolute terms, the effects are small and schemes serve only a limited section of the population. The main policy implication of the review is that these types of community financing arrangements are, at best, complementary to other more effective systems of health financing. To improve reliability and validity of the evidence base, analysts should agree on a more coherent set of outcome indicators and a more consistent assessment of these indicators. Policy makers need to be better informed as to both the costs and the benefits of implementing various financing options. The current evidence base on community-based health insurance is mute on this point.