Alpha1-adrenoceptor subtypes involved in vasoconstrictor responses to exogenous and neurally released noradrenaline in rat femoral resistance arteries

1. The alpha(1)-adrenoceptor subtypes involved in responses to exogenous and neurally released noradrenaline in rat femoral resistance arteries were characterised using a small vessel myograph, with antagonists prazosin (nonsubtype selective), 5-methyl-urapidil (alpha(1A)-selective), BMY 7378 (alpha(1D)-selective) and the alkylating agent chloroethylclonidine (preferential for alpha(1B)-). 2. Prazosin and 5-methyl-urapidil produced rightward shifts of the exogenous noradrenaline concentration - response curve (CRC) with pA(2) values of 9.2 and 9.1 respectively, in agreement with the presence of alpha(1A)-adrenoceptors. BMY 7378 (1 microm) shifted the noradrenaline CRC with an apparent pK(B) of 6.7, in agreement with the presence of alpha(1A)-, but not alpha(1D)-, adrenoceptors. Chloroethylclonidine at 1 microm had no effect and at 10 microm produced only a small reduction (c. 20%) in the maximum response to noradrenaline, indicating little, if any, contribution from alpha(1B)-adrenoceptors. 3. Responses of the rat femoral resistance arteries to electrical field stimulation (EFS) at 5-30 Hz for 10 s and 0.05 ms pulse width were principally due to alpha(1)-adrenoceptor stimulation. Prazosin and 5-methyl-urapidil inhibited EFS-mediated responses with pIC(50)s of 9.3 and 8.2, respectively, consistent with the alpha(1A)-adrenoceptor being the predominant subtype. Responses to EFS at 10-30 Hz were relatively insensitive to BMY 7378 (pIC(50), 6.5-6.7), while responses to 5 Hz were inhibited with a significantly higher pIC(50) of 8.02, suggesting the contribution of alpha(1D)-adrenoceptors. Chloroethylclonidine had no effect on responses to EFS, ruling out the contribution of an alpha(1B)-subtype. In the presence of cocaine, the predominant subtype involved in responses to EFS was the alpha(1A)-adrenoceptor, with a contribution from alpha(1D)-adrenoceptors at low frequency, as seen in the absence of cocaine. However, there was also a significant increase in the sensitivity to BMY 7378 at higher frequencies, suggesting that a further small alpha(1D)-adrenoceptor component may be uncovered in the presence of cocaine. 5. The present study has shown a predominant role of the alpha(1A)-adrenoceptor in contractions due to exogenous noradrenaline and to neurally released noradrenaline in rat femoral resistance arteries. alpha(1D)-Adrenoceptors are not involved in responses to exogenous noradrenaline but appear to be activated by neurally released noradrenaline at a low frequency of stimulation and at higher frequencies in the presence of neuronal-uptake blockade.     

Safety and efficacy evaluations for vaginal and rectal use of BufferGel in the macaque model

BACKGROUND: The nonhuman primate model allows for safety and efficacy testing of topical microbicide products. GOAL: The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of BufferGel (ReProtect, Inc.). STUDY DESIGN: The safety of repeated product applications was evaluated by microflora, pH, vaginal colposcopy, and rectal lavage. To test efficacy in preventing chlamydia, infection was documented by culture and nucleic acid amplification tests. RESULTS: Repeated vaginal or rectal applications of BufferGel were not associated with significant changes in microflora. BufferGel use had a transient acidifying effect on vaginal and rectal pH. Colposcopic observations remained relatively normal in all test animals. A slightly increased incidence of epithelial desquamation was noted after rectal product use compared with the control group. BufferGel did not prevent cervical or rectal chlamydial infection. CONCLUSION: BufferGel has an acceptable safety profile after repeated vaginal and rectal use, but does not prevent chlamydial infection in the macaque models.     

Imaging features of multicentric Castleman's disease in HIV infection

AIM: To describe the computed tomography (CT) features of human immunodeficiency virus (HIV)-associated Castleman's disease. MATERIALS AND METHODS: Nine HIV-positive patients with biopsy-proven Castleman's disease were studied. Clinical and demographic data, CD4 count, histological diagnosis and human herpes type 8 (HHV8) serology or immunostaining results were recorded. CT images were reviewed independently by two radiologists. RESULTS: CT findings included splenomegaly (n=7) and peripheral lymph node enlargement (axillary n=8, inguinal n=4). All nodes displayed mild to avid enhancement after intravenous administration of contrast material. Hepatomegaly was evident in seven patients. Other features included abdominal (n=6) and mediastinal (n=5) lymph node enlargement and pulmonary abnormalities (n=4). Patterns of parenchymal abnormality included bronchovascular nodularity (n=2) consolidation (n=1) and pleural effusion (n=2). On histological examination eight patients (spleen n=3, lymph node n=9, lung n=1, bone marrow n=1) had the plasma cell variant and one had mixed hyaline-vascular/plasma cell variant. The majority had either positive immunostaining for HHV8 or positive serology (n=8). CONCLUSION: Common imaging features of multicentric Castleman's disease in HIV infection are hepatosplenomegaly and peripheral lymph node enlargement. Although these imaging features may suggest the diagnosis in the appropriate clinical context, they lack specificity and so biopsy is needed for diagnosis. In distinction from multicentric Castleman's disease in other populations the plasma cell variant is most commonly encountered, splenomegaly is a universal feature and there is a strong association with Kaposi's sarcoma.     

Plasma versus serum for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies with a glycoprotein G2-based enzyme immunoassay

To evaluate the consonance between plasma and serum for the detection of herpes simplex virus type 2-specific immunoglobulin G antibodies, we compared results from concurrently obtained plasma and sera in 710 sexually active women by using a glycoprotein G2-based enzyme-linked immunosorbent assay (Focus Technologies, Cypress, Calif.) and found 98.9% agreement between the two specimen types. Plasma appears to be an acceptable matrix for use with this assay.     

Endothelial function is preserved in pregnant women with well-controlled type 1 diabetes

Objective Pregnant women with diabetes mellitus have a higher incidence of adverse pregnancy outcomes. Vascular, and in particular, endothelial function may be significantly modified in diabetes resulting in impaired endothelium-dependent relaxation. This study aims to investigate endothelium-dependent relaxation in pregnant women with pre-existing type 1 diabetes mellitus.
Methods Small arteries (mean luminal diameter ∼295 μm) were isolated from biopsies of subcutaneous fat from pregnant women with pre-existing type 1 diabetes mellitus, non-diabetic pregnant women, and non-diabetic non-pregnant women. Endothelial and smooth muscle function were determined using wire myography, and the contributions of nitric oxide, vasodilator prostanoid and endothelial hyperpolarisation were studied using specific inhibitors.
Results Arteries obtained from the diabetic pregnant women did not demonstrate any difference in either endothelial or smooth muscle function when compared with non-diabetic pregnant women. The contribution of nitric oxide to endothelium-dependent relaxation was ∼20% in the pregnant women regardless of whether they were diabetic, and ∼11% in the non-pregnant women. Endothelial hyperpolarisation appeared to contribute largely to vasorelaxation in human subcutaneous arteries, and was at least twice that of nitric oxide in pregnant women and fivefold greater in non-pregnant women.
Conclusions This study provides evidence that pregnant women with well-controlled pre-existing type 1 diabetes mellitus have both normal endothelial and smooth muscle function. Endothelium-dependent hyperpolarisation appears to play a large role in vascular relaxation in human subcutaneous resistance arteries. This study suggests that the problems associated with diabetic pregnancies are unlikely to be due to vascular dysfunction.     

Anaesthesia for lung volume reduction surgery

Lung volume reduction surgery is a surgical treatment for severe emphysema that is increasing in popularity. The aim is to reverse the hyperexpansion of the lungs that leads to expiratory airflow limitation, compromises the diaphragm and chest wall mechanics, and tamponades the right ventricle. Optimal patient selection has not yet been established, but it has become clear that those patients with the most severe disease have an unacceptably high surgical mortality. The anaesthetic management of patients undergoing lung volume reduction surgery requires a good understanding of both the pathophysiology of the disease and the surgical procedure. It is important for the anaesthetist and the surgeon to work closely, supported by a large multidisciplinary team. Excellent analgesia is essential to a successful outcome; whether this is best provided by thoracic epidural is as yet unclear.     

Characteristics of an adult population with newly diagnosed type 2 diabetes: the relation of obesity and age of onset

OBJECTIVE: To determine whether adults diagnosed with type 2 diabetes at 18-44 years of age (early type 2 diabetes) have different metabolic profiles at diagnosis than adults diagnosed at > or =45 years of age (usual type 2 diabetes). RESEARCH DESIGN AND METHODS: Within a health maintenance organization, we studied characteristics among 2,437 adults newly diagnosed with type 2 diabetes between 1996 and 1998 who had measured weight, HbA(1c), blood pressure, and cholesterol within 3 months of diagnosis. We abstracted clinical data from electronic medical records. We compared mean and proportional differences with parametric t tests and chi(2) analyses, respectively. We used multiple logistic regression to identify the factors independently associated with the onset group (early vs. usual type 2 diabetes). RESULTS: There was an inverse linear relationship between BMI and age at diagnosis of type 2 diabetes (P < 0.001). On univariate analysis, adults with early type 2 diabetes were more obese (BMI 39 vs. 33 kg/m(2), P < 0.001), were more likely to be female (P = 0.04), had slightly worse glycemic control (HbA(1c) 7.7 vs. 7.5%, P = 0.03), had a higher prevalence of diastolic hypertension (37 vs. 26%, P < 0.001), despite a lower prevalence of systolic hypertension (34 vs. 55%, P < 0.001), and had an equally high rate of abnormal lipids (82 vs. 78%, P = 0.13) than adults with usual type 2 diabetes. BMI, female gender, cholesterol, and diastolic and systolic blood pressure remained independently associated with onset group at multivariate analysis. CONCLUSIONS: Although both onset groups were on average obese, the inverse linear relationship of obesity and age of diabetes onset that we observed suggests that obesity is a continuous risk rather than a threshold risk for diabetes onset. Both onset groups had a high prevalence of cardiovascular disease risk factors.     

Assessing the impact of a nurse-led health education intervention for people with peripheral vascular disease who smoke: the use of physiological markers, nicotine dependence and withdrawal

This study evaluated the impact of a nurse-led health education programme on the behaviour, nicotine dependence and nicotine withdrawal in patients who smoke and suffer from peripheral vascular disease, based in a large teaching hospital in the north of England. Smoking behaviour was measured by self report, end-expired carbon monoxide and urinary cotinine. Nicotine dependence and withdrawal were measured using a nicotine dependence scale and a nicotine withdrawal scale. The findings demonstrated that the programme did have some impact on behaviour. The study raised issues concerning the measurement of physiological markers for smoking as nursing outcomes. Issues about the measurement of nicotine dependence and withdrawal are highlighted.