Frequency, nature and determinants of pharmaceutical consultations provided in private by Dutch community pharmacists

OBJECTIVE: According to a report published by the federation of Dutch patients' associations, patients would like to see a pharmacist, who acts more as a personal adviser. This raised the question, how often Dutch community pharmacists have personal consultations with their patients in daily practice, on which factors this depends, and what kind of topics are discussed during these meetings. SETTING: Community pharmacies in the Netherlands. METHOD: A questionnaire was distributed among 800 randomly selected pharmacies. Questions were restricted to consultations characterized by one-to-one contact, drug therapy related content, and adequate privacy. These consultations were labelled as pharmaceutical consultations in private to distinguish them from other contacts between pharmacists and patients. MAIN OUTCOME MEASURE: Number, content, and character of consultations. RESULTS: 198 (24.8%) community pharmacies responded. The pharmacists provide an average of roughly 1.2 consultations in private per working day. The vast majority of respondents provided face-to-face and telephone consultations (94.4 and 91.9%, respectively), only a minority gave consultations by e-mail (30.8%). These consultations primarily dealt with topics related to medication safety. The mean overall time spent was 290 min per month. A relatively high frequency of personal consultations was significantly associated with the absolute number of full-time equivalent pharmacists in the pharmacy. CONCLUSION: The frequency of pharmaceutical consultations in private is low, but may be improved by reorganisation of the pharmacist's activities. The possibility of personal consultations by e-mail is not yet well-developed. Further research is needed to assess the patient's view of pharmaceutical consultations in private.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

On the natural course of oral lichen lesions in a Swedish population-based sample

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.     

Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and simvastatin on inflammatory markers in hypercholesterolemic patients.

To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter the effects of micronized fenofibrate or simvastatin therapy on inflammatory markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P-selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients both before and after a 30-day treatment. Serum IL-6 levels were significantly higher in patients with the GC or CC genotypes (P=0.04). The presence of the C allele was associated with greater absolute reduction of IL-6 levels (P=0.04) following fenofibrate treatment. There was no significant association between the -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory action of fenofibrate reported might be useful in the optimization of the treatment regimen in patients receiving this class of drugs.     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Maximized combined modality treatment of an unselected population of oral and oropharyngeal cancer patients. Final results of a pilot study compared with a treatment-dependent prognosis index.

BACKGROUND: In an attempt to raise the survival of an unselected and representative population of oral and oropharyngeal squamous cell cancer patients, a pilot study of an integrated four-modality treatment was conceived. Final endpoints were compliance, loco-regional control, survival (after complete 5-year follow-up), and a concept of trial assessment using the treatment-dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with histologically proven untreated stages I-IV disease presented in the period between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit to be treated with the intention of achieving a cure. METHODS: All patients received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin (systemically neutralized with sodium thiosulphate), and, if possible, by consecutive treatment applying both surgery of the primary tumour and the neck lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety per cent of all cases and 96% of the patients treated with curative intention received more than one modality due to study design. Patient non-compliance in the group treated with curative intention has been 18/73 (=25%), and protocol compliance has been 32/73 (=44%). The locoregional control rate for all cases was 71% (62/87 patients) and for the patients treated with curative intention 83.5% (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period of 4 months. After a median observation time of 5 years, the final absolute survival of the unselected population was 53%, and of the patients treated with curative intention 62% (especially, 70% and 50% for patients with operable stages III and IV, respectively). CONCLUSION: The multimodality regimen as presented proved feasible and showed high objective and relative survival rates in comparison with known data from tumour registries of unselected populations. Intra-arterial chemotherapy should be considered a valuable addition to treatment. The potential of survival benefit from this multimodality regimen in comparison with the prognosis index TPI should be investigated in further studies.     

In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat.

The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. METHODS: We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. RESULTS: At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. CONCLUSION: Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.