On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of μ-whole blood samples

The aim of this work is to present a new concept, called on-line desorption of dried blood spots (on-line DBS), allowing the direct analysis of a dried blood spot coupled to liquid chromatography mass spectrometry device (LC/MS). The system is based on an inox cell which can receive a blood sample (10 μL) previously spotted on a filter paper. The cell is then integrated into LC/MS system where the analytes are desorbed out of the paper towards a column switching system ensuring the purification and separation of the compounds before their detection on a single quadrupole MS coupled to atmospheric pressure chemical ionisation (APCI) source. The described procedure implies that no pretreatment is necessary in spite the analysis is based on whole blood sample.     

A comparative controlled study of tiaprofenic acid (‘Surgam’) and naproxen in the treatment of rheumatoid arthritis

Summary

Tiaprofenic acid and naproxen were compared using a randomized double-blind, double-placebo crossover method in 32 hospital out-patients with rheumatoid arthritis. Patients received 200?mg tiaprofenic acid 3-times daily or 250?mg naproxen twice daily, each for a 2-week period with no initial or between-treatment washout periods. The results of objective and subjective assessments before and after treatments indicated that, overall, both anti-inflammatory drugs were equally effective and tolerated. Patient preference comparisons of the two treatment periods suggest that for some patients tiaprofenic acid will be a useful addition to this group of drugs.     

A double‐blind placebo‐controlled study of buspirone‐stimulated prolactin release in non‐ulcer dyspepsia—are central serotoninergic responses enhanced?

BACKGROUND: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. AIM: To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. METHODS: Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. RESULTS: Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. CONCLUSIONS: Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.     

Is the management of hepatitis C patients appropriate? A population‐based study

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.     

Cannabinoid findings in children hair – what do they really tell us? An assessment in the light of three different analytical methods with focus on interpretation of Δ9‐tetrahydrocannabinolic acid A concentrations

Hair analysis for drugs and drugs of abuse is increasingly applied in child protection cases. To determine the potential risk to a child living in a household where drugs are consumed, not only can the hair of the parents be analyzed but also the hair of the child. In the case of hair analysis for cannabinoids, the differentiation between external contamination and systemic uptake is particularly difficult, since the drug is quite often handled extensively prior to consumption (e.g. when preparing a joint) and smoke causes a further risk for an external contamination. Δ9‐tetrahydrocannabinolic acid A (THCA‐A), the non‐psychoactive biogenetic precursor of Δ9‐tetrahydrocannabinol (THC), is a suitable marker for external contamination since it is not incorporated into the hair matrix through the bloodstream in relevant amounts. In the presented study, hair samples from 41 children, 4 teenagers, and 34 drug‐consuming parents were analyzed for THCA‐A, THC and cannabinol (CBN) applying methanolic extraction and a fully validated liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method (Method 1). For comparison, a part of the samples was also analyzed applying alkaline hydrolysis followed by liquid/liquid extraction and gas chromatography‐mass spectrometry (GC‐M)S (Method 2), or by headspace‐solid phase microextraction‐gas chromatography‐mass spectrometry (HS‐SPME‐GC‐MS) (Method 3). Furthermore, 458 seized marihuana samples and 180 seized hashish samples were analyzed for the same cannabinoids by gas‐chromatography‐flame ionization detector (GC‐FID). In all but one of the hair samples, the concentration of THCA‐A was higher than the concentration of THC and in 14 cases no THC could be detected despite the presence of THCA‐A, suggesting that in almost all cases a significant external contamination had occurred. Within‐family comparison showed a higher THCA‐A/THC ratio in hair of children than of their consuming caregivers. Mean and median of this ratio of all hair samples (6.7 and 4.2) were between those of marihuana (11.0 and 8.3) and hashish (2.8 and 2.1) with a large variation in all samples. Comparison of the Methods 1 to 3 showed clearly that the choice of the analytical procedure has a strong influence on the quantitative results, mainly because of decarboxylation of THCA‐A during hair hydrolysis by NaOH and other analytical steps, which lead to artifactually elevated THC concentrations. In conclusion, these findings suggest that the major part of the cannabinoids detected in the hair samples from children arose from an external contamination through ‘passive’ transfer by e.g. contaminated hands or surfaces and not from inhalation or deposition of side stream smoke. Copyright © 2014 John Wiley & Sons, Ltd.     

Is there a role for day‐to‐day home blood pressure variability in guiding management of hypertension?

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Is there penetration of titania nanoparticles in sunscreens through skin? A comparative electron and ion microscopy study

We report on a comparative study by Transmission Electron Microscopy (HRTEM) and Scanning Transmission Ion Microscopy (STIM) combined with Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-Ray Emission (PIXE) on ultra-thin and thin cross-sections, respectively, of various skin samples (porcine skin, healthy human skin, human skin grafted on a severe combined immuno-deficient mouse model) to which we applied topically various formulations containing titanium dioxide (TiO₂) nanoparticles with primary particle sizes in the range from 20–100 nm. Whereas the HRTEM and STIM/PIXE images reveal clear differences – mainly related to the different thickness of the cross-sections – they unambiguously show that penetration of TiO₂ nanoparticles is restricted to the topmost 3–5 corneocyte layers of the stratum corneum (SC).     

Is epinephrine administration by sublingual tablet feasible for the first‐aid treatment of anaphylaxis? A proof‐of‐concept study

PURPOSE: In order to explore the feasibility of sublingual administration of epinephrine tablets as a non-invasive first-aid treatment for anaphylaxis, we studied epinephrine absorption from this dosage form in an animal model. METHODS: In a prospective, randomized, four-way crossover study, six rabbits received epinephrine 2.5 or 10 mg as a sublingual tablet, epinephrine 0.03 mg (0.3 ml) by intramuscular (IM) injection (positive control), and 0.9% NaCl (0.3 ml) IM (negative control). Pre- and post-dose blood samples were obtained for measurement of plasma epinephrine concentrations by HPLC-EC. RESULTS: After administration of epinephrine 2.5 mg as a sublingual tablet, the mean (+/-SEM) C(max) was 2369+/-392 pg/ml, and the t(max) was 20.8+/-5.7 min. After administration of epinephrine 10 mg sublingually, the C(max) was 10836+/-2234 pg/ml, and the t(max) was 21.7+/-5.4 min. After IM epinephrine, the C(max) was 6445+/-4233 pg/ml, and the t(max) was 15.8+/-4.7 min. After IM 0.9% NaCl, the C(max) (endogenous epinephrine) was 518+/-142 pg/ml. The t(max) after both of the sublingual epinephrine tablet doses did not differ significantly from the t(max) after IM epinephrine, and the C(max) after the 10 mg sublingual epinephrine tablet dose did not differ significantly from the C(max) after IM epinephrine. CONCLUSIONS: In this proof-of-concept study, administration of epinephrine as a sublingual tablet formulation resulted in rapid achievement of peak plasma epinephrine concentrations. Absorption studies in humans are needed. DEFINITIONS: HPLC-high performance liquid chromatography; EC - electrochemical detection; C(max) - maximum plasma epinephrine concentration after dosing; t(max) - time of maximum plasma epinephrine concentration.     

How do pharmacists manage acute diarrhoea in an 8‐month‐old baby? A simulated client study

Objectives Community pharmacists claim a role in health care based on their added value as counsellors and providers of pharmaceutical care. The aim of this study was to assess to what extent they fulfil this role with respect to the management of acute diarrhoea in an 8‐month‐old baby. Methods In February 2008, two female simulated clients of 55 and 35 years old visited 101 Belgian pharmacies. Both entered the pharmacy and said: ‘I'm here for my grandchild/my sister's baby. She has diarrhoea.’ They only provided more information if the pharmacist asked for it. All the questions and the verbal advice provided by the pharmacist were audio‐recorded and the suggested medicines were registered. Key findings One pharmacist did not ask any questions. All the other pharmacists asked the age of the child, 19% asked how long the symptoms had been on‐going, 27% asked whether the baby had a fever and 24% inquired about vomiting. Seventy‐five per cent of the pharmacists emphasized the importance of sufficient fluid intake and/or the risk of dehydration, while 4% described how to recognize such dehydration symptoms. Oral rehydration solution was suggested by 30% of the pharmacists, while 86% suggested the yeast probiotic Saccharomyces boulardii. Of the 28% spontaneously giving dietary advice, no‐one said that normal feeding should restart ‘as soon as possible’. Thirty‐one per cent advised consulting a doctor, either immediately or in the case of the symptoms not improving after a while. Conclusions Apart from inquiring about the child's age, the majority of pharmacists asked too few questions to be able to analyse the situation properly. Ample information was provided on the risk of dehydration, but counselling on the suggested medicines was insufficient.     

Do dried blood spots (DBS) have the potential to support result management processes in routine sports drug testing?

Dried blood spots (DBS) have been considered as complementary matrix in sports drug testing for many years. Especially concerning substances prohibited in‐competition only, the added value of DBS collected concomitantly with routine doping control urine samples has been debated, and an increasing potential of DBS has been discussed in the scientific literature. To which extent and under which prerequisites DBS can contribute to enhanced anti‐doping efforts is currently evaluated. As a proof‐of‐principle, two analytical applications, one targeting cocaine/benzoyl ecgonine and the other prednisone/prednisolone, are presented in this perspective to indicate potential added value but also presently existing limitations of the DBS approach.     

Is a 9‐month treatment sufficient in tuberculous enterocolitis? A prospective,randomized, single‐centre study

BACKGROUND: Tuberculosis has increased in parallel with the acquired immunodeficiency syndrome epidemic and the use of immunosuppressive therapy, and the growing incidence of extra-pulmonary tuberculosis, especially with intestinal involvement, reflects this trend. However, the duration of anti-tuberculous therapy has not been clarified in intestinal tuberculosis. AIM: To compare the efficacy of different treatment durations in tuberculous enterocolitis in terms of response and recurrence rates. METHODS: Forty patients with tuberculous enterocolitis were randomized prospectively: 22 patients into a 9-month and 18 into a 15-month group. Diagnosis was made either by colonoscopic findings of discrete ulcers and histopathological findings of caseating granuloma and/or acid-fast bacilli, or by clinical improvement after therapeutic trial. Patients were followed up with colonoscopy every other month until complete response or treatment completion, and then every 6 months for 1 year and annually. Complete response was defined as a resolution of symptoms and active tuberculosis by colonoscopy. RESULTS: Complete response was obtained in all patients in both groups. Two patients in the 9-month group and one in the 15-month group underwent operation due to intestinal obstruction and perianal fistula, respectively. No recurrence of active intestinal tuberculosis occurred during the follow-up period in either group. CONCLUSIONS: Tuberculous enterocolitis can be managed by 9-month chemotherapy without disease recurrence. Further investigations are needed in immunocompromised patients.     

Do benzodiazepines extend the duration of follow‐up treatment in patients with bipolar disorder?

INTRODUCTION: In patients with bipolar disorder, relapse and recurrence from the premature discontinuation of pharmacotherapy are serious clinical problems. Thus, clinicians must make every effort to ensure the sufficient duration of continual treatment even after the remission of acute episodes. Here, we examine whether there is any association between benzodiazepine (BZD) use and the duration of follow-up treatment in patients with bipolar disorder. METHODS: The medical records of 70 bipolar patients hospitalized in a university hospital psychiatry ward were reviewed. Selected demographic and clinical variables, such as extent of BZD use and the total duration of outpatient follow-up treatment, were compared. RESULTS: The duration of maintenance treatment at the outpatient department differed significantly between patients who were or were not given BZDs during admission (571 vs. 179 days) and after discharge (836 vs. 154 days). The variables that differed significantly between patients who received follow-up treatment for 6 or more months and those who did not was the number of days of BZD administration during admission (11 vs. 5 days) and after discharge (280 vs. 7 days), and years of education (11 vs. 13 years). CONCLUSION: In the present study, BZDs are suggested as a possible adjunctive therapy for extending follow-up and thus preventing recurrence in patients with bipolar disorder.