The effects of clonidine on cardiovascular responses to standing in healthy volunteers

This study assessed the effects of clonidine on blood pressure (BP) and heart rate responses to active standing, recorded continuously using a Finapres monitor. Ten subjects were given a placebo infusion over 1 h, followed by clonidine hydrochloride 1.5 µg/kg over 2 h. During placebo and at 1, 3 and 19 h following the clonidine infusion, heart rate and blood pressure were recorded during the second half of supine rest for 10 min, active standing and quiet standing for 7 min. Clonidine did not alter the size of immediate drop in BP on standing, although the nadir was lower. BP recovery was impaired, with a loss of the usual BP overshoot in most subjects and with delays in reaching supine levels of diastolic BP (6.1 versus 9.6 s; p < 0.01) and systolic BP (8.1 versus 12.3 s; p < 0.05). The compensatory initial heart rate rise was significantly increased from 47 to 53 beats/min (p < 0.05), athough the peak rate reached was reduced from 114 to 104 beats/min (p < 0.05). These results demonstrate that impairment of central sympathetic vasomotor drive leads to a delay in BP recovery and loss of initial BP overshoot immediately after standing, together with impaired maintenance of early steady-state BP.     

Practice and patient characteristics related to blood pressure in patients with type 2 diabetes in primary care: a cross-sectional study

BACKGROUND: Good blood pressure control reduces the risk of long-term complications of diabetes; however, most people with diabetes do not achieve recommended blood pressure targets. OBJECTIVE: To quantify the relationships between patient and practice factors and blood pressure in patients with type 2 diabetes. METHODS: A cross-sectional study was carried out in 42 general practices in Nottingham. Participants were 1534 people with type 2 diabetes. Patient characteristics were assessed by a clinical interview and case note review and practice characteristics by questionnaire. The outcome measures were systolic and diastolic blood pressure. RESULTS: In all, 46% of participants had well-controlled blood pressure (or= 25 kg/m(2), and increased with alcohol consumption. Systolic blood pressure increased whereas diastolic blood pressure decreased with increasing age and duration of diabetes. Current smokers and ex-smokers had a significantly lower diastolic blood pressure than those who had never smoked. Patients from practices where blood pressure targets were negotiated with most patients had significantly lower mean systolic and diastolic blood pressure than those where targets were negotiated with few patients. CONCLUSIONS: A number of patient characteristics are associated with blood pressure. Negotiating individual goals for blood pressure may be important in achieving blood pressure control in patients with type 2 diabetes. Further research is required to confirm this finding and to explore the process of negotiating targets.     

Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer

Purpose  CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment. Methods  Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA). CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative serum prostate-specific antigen (PSA) level by univariate and multivariate analyses. Results  Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44 (55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors (10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate. CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002). Conclusions  Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate target molecule for specific treatment interventions.