Incipient ovarian failure and premature ovarian failure show the same immunological profile

PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failure. METHOD OF STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients, 50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did not differ between the groups. There was a statistically significant difference in lymphocyte subsets between the control group and the POF group, with the IOF group taking an intermediate position. We found a decrease in percentage of T-suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in natural killer cells, and an increase in B lymphocytes and HLA-DR positive T cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form of POF. The question remains whether these changes are the cause or the consequence of the ovarian failure.     

Effects of treatment of obstructive sleep apnea on circadian hemodynamics

INTRODUCTION: The role of obstructive sleep apnea syndrome (OSAS) in the etiology of daytime hypertension is still an issue of debate, which is fed by the high prevalence of the syndrome in hypertensive patients. In this study the anti-hypertensive effect of short-term treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nCPAP) was assessed. PATIENTS AND METHODS: In eight patients with documented OSAS (mean apnea index 62 apneas/h), two 24-h continuous finger blood pressure registrations (Portapres) were performed. At baseline and after 3 weeks of treatment with nCPAP. Ten hypertensive control subjects were studied. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were assessed by pulse contour analysis. RESULTS: Hemodynamics were highly reproducible in the controls. nCPAP therapy improved apnea-activity in all OSAS patients. This was associated with a reduction of nighttime systolic (SBP), mean arterial (MAP) and diastolic blood pressure (DBP). Treatment also reduced daytime MAP by -11 mm Hg (ranging from -27 to 1; P < 0.05), and DBP by -7 mm Hg (-24 to 3; P < 0.05). CO was significantly increased in daytime by 9% (-4 to 25; P < 0.05), whereas TPR was reduced by -15% (-34 to 3; P < 0.05). CONCLUSIONS: Treatment of OSAS caused a reduction in daytime MAP and DBP, associated with a reduction of vascular resistance. These findings are consistent with the hypothesis of a reduced sympathetic outflow at night after therapy of obstructive sleep apnea, carrying over to the day.     

CT Screening for Pulmonary Pathology in Common Variable Immunodeficiency Disorders and the Correlation with Clinical and Immunological Parameters

Background

Pulmonary disease is common in patients with common variable immunodeficiency disorders (CVID) and involves infections, chronic airway disease and interstitial lung disease. Chronic pulmonary disease is associated with excess morbidity and early mortality and therefore early detection and monitoring of progression is essential.

Methods and Purpose

Thin slice CT scan and pulmonary function were used to determine the prevalence and spectrum of chronic (pre-clinical) pulmonary disease in adult CVID patients regardless of symptoms. CT Scans were scored for airway abnormalities (AD) and interstitial lung disease (ILD). Other CVID related complications and B and T lymphocyte subsets were analyzed to identify patients at risk for pulmonary disease.

Results

Significant pulmonary abnormalities were detected in 24 of the 47 patients (51 %) consisting of AD in 30 % and ILD in 34 % of cases. In only 7 (29 %) of these 24 patients pulmonary function test proved abnormal. The presence of AD was correlated to (recurrent) lower respiratory tract infections despite IgG therapy. The presence of ILD was correlated to autoimmune disease and a reduction in the numbers of CD4?+?T cells, naïve CD4?+?T cells, naïve CD8?+?T cells and memory B cells and lower IgG through levels over time.

Conclusion

Preclinical signs of AD and ILD are common in CVID patients despite Ig therapy and do not correlate to pulmonary function testing. Patients at risk for ILD might be identified by the presence of autoimmunity or a deranged T cell pattern. Larger studies are needed to confirm these findings and to determine thresholds for the T lymphocyte subsets.     

Diagnostic value of simultaneous non-invasive continuous,ambulatory finger blood pressure and electrocardiogram monitoring in a patient with hypertrophic obstructive cardiomyopathy

BACKGROUND: The pathophysiology of hypertrophic obstructive cardiomyopathy (HOCM) is complex and heterogeneous, and it may be difficult to disentangle the various pathophysiologic properties leading to complaints. OBJECTIVES: To elucidate the sequence of acute pathophysiologic changes leading to complaints in a patient with HOCM. METHODS: Cardiopres measurements [the combination of non-invasive, continuous finger artery blood pressure monitoring, and three-lead electrocardiogram (ECG) recordings] were performed during physiologic, supine exercise--before and after replacement of metoprolol by verapamil. Within 24 h of the Cardiopres measurement standard Doppler echocardiography was performed. Finger artery pressure wave was analysed using Beatscope software (BMI-TNO, Amsterdam, The Netherlands), ST analysis was performed with H-Scribe (Mortara Instrument, Bilt, The Netherlands). RESULTS: Exercise under metoprolol: finger BP decreased from 130/65 mmHg to 90/60 mmHg, heart rate increased from 65 bpm to 100 bpm and ST analysis revealed significant ST depression in all leads. The occurrence of ST depression preceded the hypotension. Echocardiography showed a dynamic gradient of 70 mmHg. Exercise under verapamil: the patient had less complaints, BP increased from 125/60 mmHg to 165/65 mmHg, heart rate increased from 75 bpm to 107 bpm and ST analysis showed no ST depression > 1 mm. Echocardiography showed no change. CONCLUSIONS: The use of the Cardiopres during a physiological stimulus showed improvement in exercise capacity in a patient with HOCM, while the standard test, stress-echocardiography, showed no correlation with clinical status. The Cardiopres is a useful diagnostic and research tool, allowing non-invasive, ambulatory monitoring of blood pressure and ECG changes.     

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial

Background. Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in clinical hypertension trials. A second objective of this article was to describe the baseline characteristics of the HOMERUS-trial. Methods. The HOMERUS population consisted of 459 mild-to-moderate hypertensive subjects (54% males) with a mean age of 55 years. These patients were prospectively randomized with the minimization method to either the office pressure (OP) group, where antihypertensive treatment was based on office blood pressure (BP) values, or to the self-pressure (SP) group, where treatment was based on self-measured BP values. Minimization was compared with two other randomization methods, which were performed post-hoc: (i) non-stratified randomization with four permuted blocks, and (ii) stratified randomization with four permuted blocks and 16 strata. In addition, several factors that could influence outcome were investigated for their effect on BP by 24-h ambulatory blood pressure monitoring (ABPM). Results. Minimization and stratified randomization did not lead to significant differences in 24-h ABPM values between the two treatment groups. Non-stratified randomization resulted in a significant difference in 24-h diastolic ABPM between the groups. Factors that caused significant differences in 24-h ABPM values were: region, centre of patient recruitment, age, gender, microalbuminuria, left ventricular hypertrophy and obesity. Conclusion. Minimization and stratified randomization are appropriate methods for use in clinical trials. Many outcome factors should be taken into account for their potential influence on BP levels. Recommendation. Due to the large number of potential outcome factors that can influence BP levels, minimization should be the preferred method for use in clinical hypertension trials, as it has the potential to randomize more outcome factors than stratified randomization.     

Hypertension in young adults: indication for possible aortic coarctation

Three adult patients, a woman aged 37 and two men aged 22 and 23 years respectively, were admitted due to an unexplained hypertension. After a significant delay, the diagnosis of aortic coarctation was established for these patients. In two of them the abnormality was operatively corrected and the blood pressure subsequently normalised; the third patient is on the waiting list for the operation. In all three patients an earlier diagnosis could have been established, had accurate blood-pressure measurements of both arms and at least one leg been performed. Late detection and treatment of aortic coarctation have a profound detrimental effect on survival. Therefore it is extremely important to accurately measure the blood pressure in the limbs of young patients with hypertension.     

Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer

BACKGROUND & AIMS: Systemic treatment of Crohn's disease patients using recombinant interleukin (rIL)-10 has not resulted in significant therapeutic benefit presumably because of limited bioavailability and unexpected proinflammatory effects of high-dose rIL-10. Ex vivo gene transfer of the interleukin (IL)-10 gene to gut-homing CD4(+) cells may lead to improved long-term management. METHODS: Peripheral blood mononuclear cells (PBMCs) were transduced with a retroviral vector containing the IL-10 and green fluorescent protein (GFP) gene or a control vector containing GFP only. Transduced CD4(+) cells were sorted and maintained in culture for phenotypic and functional analysis. RESULTS: Stimulated IL-10-GFP CD4(+) cells produced significantly higher levels of IL-10 than control cells for at least 4 months. The IL-10 transgene was biologically active and decreased proliferation of IL-10-GFP CD4(+) cells as well as expression of major histocompatibility class (MHC) class II, proliferation of autologous responder cells, and IL-12 production by dendritic cells (DCs). The majority of transduced CD4(+) cells had a gut-homing potential because they expressed the mucosal integrin alpha4beta7, and displayed efficient binding to MAdCAM-1-expressing cells in vitro. CONCLUSIONS: Transduction of peripheral blood CD4(+) lymphocytes with IL-10 results in a regulatory phenotype. The use of regulatory gut-homing human CD4(+) cells may provide a novel approach to local delivery of immunomodulatory signals to the intestine in Crohn's disease.     

Task Force I: methodological aspects of blood pressure measurement

OBJECTIVE: To reach a consensus on important methodological aspects of blood pressure measurement. METHODS: A Task Force on the methodological aspects of blood pressure measurement wrote this review after the Eighth International Consensus Conference on Blood Pressure Monitoring, in Sendai, Japan (28-31 October 2001). This consensus paper is based on the papers presented by Task Force I and on the discussion sessions, and is therefore representative of a broad spectrum of expert opinion. POINTS OF CONSENSUS: Consensus was reached on the following five issues: (1) there is an urgent need for a simplified protocol for the validation of blood pressure measuring devices; (2) there is a need for a means of updating the "state of the market" for validated devices so that users can have easy access to this information; (3) new devices must be validated independently, and existing devices that have not been validated must be reappraised; (4) manufacturers should confirm when new models use algorithms which have been validated previously; (5) the Food and Drug Administration now accepts that when ambulatory blood pressure measurement is used in clinical short-term trials in which side-effects are not being assessed, a placebo arm is not required.