Antibodies interfering with the type 3 muscarinic receptor pathway inhibit gastrointestinal motility and cholinergic neurotransmission in Sjögren's syndrome

Objective

In primary Sjögren's syndrome (SS), impairment of the gastrointestinal (GI) tract is common, and includes reduced esophageal motor function, delayed gastric emptying, and abnormalities in colonic motility; the pathogenesis is as yet unknown. We undertook this study to investigate the role of functional antibodies to the type 3 muscarinic receptor (M3R) in GI dysfunction associated with primary SS.

Methods

Muscle strip and whole‐organ functional assays were used to determine whether IgG with anti‐M3R activity from patients with primary SS disrupted neurotransmission in tissue from throughout the mouse GI tract. Specificity of the autoantibody for the M3R was determined using knockout mice that were deficient in the expression of muscarinic receptor subtypes.

Results

Functional antibodies to the M3R inhibited neuronally mediated contraction of smooth muscle from throughout the GI tract and disrupted complex contractile motility patterns in the colon. The autoantibodies were not active on tissue from mice that lacked the M3R, providing compelling evidence of the direct interaction of patient autoantibodies with the M3R.

Conclusion

Our results indicate that anti‐M3R autoantibodies have the potential to mediate multiple dysfunctions of the GI tract in primary SS, ranging from reduced esophageal motor activity to altered colonic motility. We hypothesize that altered GI motility forms part of a broader autonomic dysfunction mediated by pathogenic anti‐M3R autoantibodies in primary SS.

     

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome

Background:

The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI.

Hypothesis:

Small heart is associated with OI in patients with CFS.

Methods:

Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(?) according to the presence or absence of OI. In addition, 11 OI patients and 27 age‐ and sex‐matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically.

Results:

The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end‐diastolic dimension, LV end‐systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(?) patients and healthy controls, and also in OI patients than in controls. A smaller LV end‐diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(?) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm²) was more prevalent in CFSOI(+) (65%) than in CFSOI(?) (5%, P<0.01), OI (27%), and controls (11%, P<0.01).

Conclusions:

A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well‐defined and predominant subgroup of CFS. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

The Effect of Pulmonary Hypertension on Left Ventricular Diastolic Function in Chronic Obstructive Lung Disease: A Tissue Doppler Imaging and Right Cardiac Catheterization Study

Background

Pulmonary hypertension (PH) caused by chronic obstructive lung disease (COLD) essentially involves the right heart. Also left ventricular (LV) systolic and diastolic functions may be affected.

Objectives

The aim of this study was to investigate the effect of on LV diastolic function in patients with COLD.

Methods

A total of 47 patients with COLD and 20 controls were included in this study. All patients underwent Doppler echocardiography, tissue Doppler imaging examinations and right cardiac catheterization. The patients were divided into 2 subgroups according to mean pulmonary arterial pressure (mPAP): patients without PH (group1, n = 25) and with PH (group 2, n = 22). The following measurements were taken: peak velocity of early diastolic filling (E), peak late filling with atrial contraction (A), E/A ratio, deceleration time (DT) of E, isovolumic relaxation time (IVRT), early (Em) and late (Am) diastolic mitral lateral annulus velocity.

Results

Mitral E/A < 1 and Em < 8 cm/sec were higher in group 2 than in group 1 and the control group. There were significant correlations between mPAP and both mitral E/A (r:? 0.60) and Em (r:? 0.45). In multivariate model, mPAP was not found to be significant on mitral E/A ratio < 1, but there was a significant effect on mitral Em < 8 cm/sec (odds ratio [OR]:1.14, P < 0.05).

Conclusion

This study shows that LV diastolic dysfunction in COLD is closely correlated to PH levels. Although increased mPAP may affect the mitral E/A ratio, it seems to have no effect on mitral E/A < 1, whereas it has an independent effect on Em < 8 cm/sec. Copyright © 2010 Wiley Periodicals, Inc.

     

Association of left atrial myocardial function with left ventricular diastolic dysfunction in subjects with preserved systolic function: a strain rate imaging study

Background:

The purpose of this study was to investigate the relationship between left atrial (LA) myocardial function and left ventricular (LV) diastolic dysfunction in subjects with preserved LV ejection fraction (LVEF).

Methods:

The study included a group of 118 hypertensive patients and normal subjects. LV diastolic dysfunction was classified into 4 groups: none, mild, moderate, and severe. Peak strain rates in systole (S‐Sr), early diastole (E‐Sr), and late diastole (A‐Sr) were obtained from Doppler‐derived strain rate imaging to evaluate LA myocardial deformation.

Results:

No significant difference in LA dimension was observed in subjects with different degrees of LV diastolic dysfunction, although LA myocardial strain rate parameters were all significantly different across the 4 groups (all with P < 0.001). Compared with patients of normal diastolic function, the mild diastolic dysfunction group had significantly lower E‐Sr (0.62 ± 0.18 s^?1 vs 1.20 ± 0.38 s^?1, P < 0.001) and S‐Sr (0.78 ± 0.16 s^?1 vs 0.94 ± 0.22 s^?1, P < 0.001) but increased A‐Sr (1.14 ± 0.29 s^?1 vs 1.00 ± 0.23 s^?1, P = 0.05).

Conclusions:

By using strain rate imaging, significant changes of LA deformation in response to different stages of LV diastolic dysfunction were detected in subjects with preserved LVEF. Quantification of LA myocardial function rather than LA size may have the potential to predict early LV diastolic dysfunction in subjects with preserved LVEF. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Echocardiographic Estimates of Left Ventricular Diastolic Dysfunction Do Not Predict the Clinical Course in Elderly Patients Undergoing Transcatheter Atrial Septal Defect Closure: Impact of Early Diastolic Mitral Annular Velocity

Objective

This study evaluated the effect of echocardiographic left ventricular (LV) diastolic dysfunction on acute congestive heart failure after transcatheter atrial septal defect (ASD) closure in elderly patients.

Background

Although there is concern that LV diastolic dysfunction develops acute congestive heart failure after ASD closure, limited information is available regarding the influence, especially in elderly patients with severe LV diastolic dysfunction.

Methods

Two hundred consecutive patients older than 60 years were divided into 3 groups according to echocardiographic LV diastolic dysfunction: severe (early diastolic mitral annular velocity [e’] <5.0 cm/s), mild (5.0≤ e’ <8.0 cm/s), and normal (e’ ≥ 8.0 cm/s). Changes in plasma B‐type natriuretic peptide (BNP) levels were evaluated.

Results

No patients with severe LV diastolic dysfunction developed acute congestive heart failure immediately after the procedure. BNP levels unchanged after the procedure in patients with severe LV diastolic dysfunction (126 ± 181 to 131 ± 148 pg/ml, P = 0.885), and this increase in BNP levels was not different from that between the diagnosis of ASD and the procedure. The change in BNP levels in patients with severe LV diastolic dysfunction, who were frequently treated with diuretics before the procedure, was equivalent to that in patients with mild LV diastolic dysfunction and normal LV diastolic function (5 ± 119 vs. 16 ± 101 vs. 9 ± 131 pg/ml, P = 0.724).

Conclusions

Our findings suggest that transcatheter ASD closure under volume management is safe and valuable in elderly patients with echocardiographic severe LV diastolic dysfunction.

     

Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. This study was undertaken to investigate whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV).

Methods

Eighty‐nine RA patients without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol level.

Results

LV diastolic diameter (4.92 cm versus 4.64 cm; P < 0.001), mass (136.9 gm versus 121.7 gm; P = 0.004 or 36.5 versus 32.9 gm/m^2.7; P = 0.01), ejection fraction (71% versus 67%; P < 0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P = 0.023) were all higher among RA patients versus controls. In multivariate analysis, presence of RA was an independent correlate of LV mass (P = 0.004). Furthermore, RA was independently associated with presence of LV hypertrophy (odds ratio 4.14 [95% confidence interval 1.24, 13.80], P = 0.021). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LV hypertrophy were older and had higher systolic pressure, damage index scores, C‐reactive protein levels, homocysteine levels, and arterial stiffness compared with those without LV hypertrophy.

Conclusion

The present results demonstrate that RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiologic link between chronic inflammation and LV hypertrophy. In contrast, LV systolic function is preserved in RA patients, indicating that systolic dysfunction is not an intrinsic feature of RA.

     

Increased risk of acute coronary syndrome in patients with bronchiectasis: A population‐based cohort study

Background and objective

There are few studies on the relationship between bronchiectasis and acute coronary syndrome (ACS). We conducted a population‐based cohort study to assess whether bronchiectasis was associated with an increased risk of ACS.

Methods

We identified 3521 patients diagnosed with bronchiectasis between 2000 and 2010 (bronchiectasis cohort) and frequency matched them with 14 084 randomly selected people without bronchiectasis from the general population (comparison cohort) according to sex, age and index year using the Longitudinal Health Insurance Database. Both cohorts were followed until the end of 2010 to determine the ACS incidence. Hazard ratios of ACS were measured.

Results

Based on 17 340 person‐years for bronchiectasis patients and 73 639 person‐years for individuals without bronchiectasis, the overall ACS risk was 40% higher in the bronchiectasis cohort (adjusted hazard ratio (HR) = 1.40; 95% CI: 1.20–1.62). Compared with those in the comparison cohort with one respiratory infection‐related emergency room (ER) visit per year, the ACS risk was 5.46‐fold greater in bronchiectasis patients with three or more ER visits per year (adjusted HR = 5.46, 95% CI: 4.29–6.96). Patients with bronchiectasis and three or more respiratory infection‐related hospitalizations per year had an 8.15‐fold higher ACS risk (adjusted HR = 8.15, 95% CI: 6.27–10.61).

Conclusion

Bronchiectasis patients, particularly those experiencing frequent exacerbations with three or more ER visits and consequent hospitalization per year, are at an increased ACS risk.

     

Later onset of herpes zoster-associated immune reconstitution inflammatory syndrome

Objectives

The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS.

Methods

Statistical analysis of onset times of herpes zoster‐associated IRIS and other cases of IRIS was carried out in a retrospective cohort starting antiretroviral therapy at advanced stages of HIV infection.

Results

Herpes zoster‐associated IRIS was significantly more frequent after the first 3 months of successful highly active antiretroviral therapy (HAART), than other instances of IRIS (IRIS associated with tuberculosis, Mycobacterium avium complex, Kaposi's sarcoma, etc.) which mainly occurred during the first 3 months of treatment.

Conclusions

The characteristic onset time pattern of herpes zoster‐associated IRIS, coincident with the second phase of immune recovery under HAART, suggests that the immune recovery events underlying herpes zoster‐associated IRIS are different from those underlying other types of IRIS. Our findings may be useful in improving the follow‐up of individuals who start HAART at an advanced stage of HIV infection.

     

Favorable Effects of Vasodilators on Left Ventricular Remodeling in Asymptomatic Patients With Chronic Moderate‐Severe Aortic Regurgitation and Normal Ejection Fraction: A Meta‐Analysis of Clinical Trials

Background:

The role of vasodilator therapy in asymptomatic patients with chronic moderate to severe aortic regurgitation (AR) and normal left ventricular (LV) function is uncertain. We assessed the effects of vasodilator therapy (hydralazine, calcium channel blockers, and angiotensin‐converting enzyme inhibitors) in this subgroup of patient population.

Hypothesis:

Vasodilators have favorable effects on LV remodelling in asymptomatic patients with chronic moderate to severe aortic regurgitation and normal LV function.

Methods:

We performed a systematic literature search for randomized clinical trials using long‐term vasodilator therapy in asymptomatic patients with chronic severe AR and normal LV function. The magnitude of difference between the vasodilator and nonvasodilator groups was assessed by computing the mean difference (MD). Heterogeneity of the studies was analyzed by Cochran Q statistics. The MD for LV ejection fraction, LV end systolic volume index, and LV end diastolic volume index were computed by random effects model. The MD for LV end‐systolic diameter and LV end‐diastolic diameter were computed by fixed effects model. A 2‐sided alpha error <0.05 was considered to be statistically significant.

Results:

Seven studies with 460 patients were included. Meta‐analysis of the studies revealed a significant increase in LVEF (MD: 5.32, 95% confidence interval [CI]: 0.37 to 10.26, P = 0.035), a significant decrease in LV end diastolic volume index (MD: ?16.282, 95% CI: ?23.684 to ?8.881, P < 0.001), and a significant decrease in LV end diastolic diameter (MD: ?2.343, 95% CI: ?3.397 to ?1.288, P < 0.001) in the vasodilator group compared with the nonvasodilator group. However, there was no significant decrease in LV end systolic volume index (MD: ?6.105, 95% CI: ?12.478 to 0.267, P = 0.060) or in LV end systolic diameter (MD: 0.00, 95% CI: ?0.986 to 0.986, P = 1.0) in the vasodilator group compared with the nonvasodilator group.

Conclusions:

In asymptomatic patients with chronic severe AR and normal LV function, vasodilators have favorable effects on LV remodeling. Clin. Cardiol. 2012 doi: 10.1002/clc.22019 The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease

Regnström J, Jovinge S, Båvenholm P, Ericssond C-G, de Faire U, Hamsten A, Hellenius M-L, Nilsson J, Tornvall P (Karolinska Hospital and Danderyd Hospital, Stockholm, Sweden). Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and coronary artery disease. J Intern Med 1998; 243 : 109–13.

Objectives

To determine the prevalence of chronic infection with Helicobacter pylori (HP) in patients with established coronary artery disease (CAD) and in healthy controls. Furthermore, to investigate whether HP infection is associated with inflammatory parameters, lipid concentrations and degree and progression of CAD.

Design

A case–control study combined with a prospective angiographic study.

Setting

Stockholm Metropolitan Area, Sweden.

Patients and methods

A material consisting of 92 young men aged 40.9 ± 3.2 (mean ± SD) years, with previous myocardial infarction and documented coronary atherosclerosis, and 95 healthy sex-matched controls, aged 43.2 ± 3.0 (mean ± SD) years, with similar socio-economic status and ethnic background was analysed for the prevalence of HP seropositivity, plasma concentrations of the inflammatory parameters fibrinogen, tumour necrosis factor alpha and orosomucoid, and serum concentrations of lipids. The impact of HP seropositivity on degree and progression of CAD, as assessed by quantitative coronary angiography, was also determined.

Results

The study population of mainly Scandinavian origin had a low prevalence of HP seropositivity in comparison with previously published European populations. No significant increase in HP seropositivity was found in patients compared with controls (42.2 vs. 32.6%). Furthermore, HP infection was not associated with increased levels of inflammatory parameters, lipid concentrations or with degree of angiographically determined CAD at baseline, or progression of CAD and clinical events over 5 years.

Conclusions

HP infection is not associated with inflammatory parameters and lipid concentrations and could not be confirmed as a risk factor for CAD.

     

Acute low back pain self‐management intervention for urban primary care patients: Rationale,design, and predictors of participation

Objectives

To describe the rationale and design of a self‐management program for low‐income, urban, primary care patients with acute low back pain. Issues related to recruitment and protocol delivery, and attendance patterns and predictors of program attendance are described.

Methods

Two hundred eleven adult patients (73% female; 60% African American) were recruited from primary care neighborhood health centers. Focus groups were conducted for program development, and participants then completed a baseline interview and were randomized into groups receiving either usual care or a self‐management intervention.

Results

Twenty‐nine percent of the intervention group attended the self‐management class. Significant predictors of attendance included being older, reporting less income, and not working for pay. Attendees did not differ from nonattendees on back pain severity, symptoms, health‐related quality of life, self‐management processes, or satisfaction with care.

Conclusion

Effective minimal‐contact behavioral interventions are needed to reach larger portions of the patient population.

     

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine

Florén C-H, Ahrén B, Bengtsson M, Bartosik J, Obrant K (Lund University, Malmö, Sweden). Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine. J Intern Med 1998; 243 : 123–26.

Objectives

To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone.

Design

Retrospective study.

Setting

University Hospital of Malmö, Sweden.

Subjects

A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease.

Methods

Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2 – L4.

Results

Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P= 0.011) lower Z-score of L₂–L₄ (?0.87 ± 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 ± 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density.

Conclusions

Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.

     

Selective therapeutic control of C5a and the terminal complement complex by anti‐C5 single‐chain Fv in an experimental model of antigen‐induced arthritis in rats

Objective

To determine the role of the terminal complement complex (TCC) in the development of experimental antigen‐induced arthritis (AIA) and the therapeutic effects of human anti‐C5 single‐chain Fv (scFv).

Methods

Two different anti‐C5 scFv, one that inhibits both release of C5a and assembly of the TCC (TS‐A 12/22) and another that selectively blocks formation of the TCC (TS‐A 8), were injected at the onset of AIA. The effects of these scFv on disease severity were evaluated for up to 21 days and compared with the effects of injection of an unrelated scFv. AIA was also established in C6‐deficient and C6‐sufficient PVG rats to obtain further information on the role of the TCC in this model.

Results

TS‐A 12/22 and TS‐A 8 proved to be equally effective in reducing joint swelling, cell counts and tumor necrosis factor α levels in synovial lavage fluids, and the degree of histomorphologic changes compared with the effects of the unrelated scFv. TS‐A 12/22 and TS‐A 8 prevented the deposition of C9 but not that of C3, confirming the ability of the 2 scFv to neutralize C5. Administration of the 2 anti‐C5 scFv after AIA onset also reduced disease severity. In C6‐deficient rats with AIA, disease activity was reduced markedly compared with that in C6‐sufficient rats.

Conclusion

These 2 human anti‐C5 scFv could represent potential therapeutic reagents to be used in patients with rheumatoid arthritis. In addition, the finding that TS‐A 8 was as effective as TS‐A 12/22 in reducing disease severity suggests that the TCC is mainly responsible for the joint inflammation and damage observed in AIA.

     

Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Objective

Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques.

Methods

A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women.

Results

In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean ± SD 11.9 ± 1.6 arbitrary units [AU] versus 13.4 ± 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean ± SD 2.1 ± 0.4 versus 2.4 ± 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher.

Conclusion

The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

     

Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia

Hoogerbrugge N, Kerkhofs LGN, Jansen H (University Hospital Dijkzigt, Rotterdam, The Netherlands). Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia. J Intern Med 1998; 243 : 355–59.

Objectives

Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low-density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis.

Design

Open treatment with 2 × 600 mg gemfibrozil daily for 12 weeks.

Setting

Outpatient lipid clinic of a tertiary referral centre.

Subjects

Twenty-three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia.

Main outcome measures

Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification.

Results

During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 ± 0.85 to 2.02 ± 0.89 mmol L^?1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in-vitro oxidation slightly decreased from 105 ± 22 to 99 ± 18 min (P= 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 ± 9.9 to 13.1 ± 9.2 mg L^?1 (P < 0.01).

Conclusions

The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.

     

Renal dysfunction in heart failure is due to congestion but not low output

Background

Renal dysfunction in heart failure is thought to be due to poor perfusion of the kidney.

Hypothesis

We tested the hypothesis that passive congestion is more important than poor perfusion.

Methods

We retrospectively studied the data on 178 patients who underwent right heart catheterization for evaluation of heart failure and had serum creatinine (Cr) measured on the same day.

Results

Serum Cr and glomerular filtration rate (GFR) correlated with central venous pressure (r = 0.22, P = 0.001 and r = ?0.55, P < 0.0001, respectively) and renal perfusion pressure (r = 0.21, P = 0.001 and r = 0.27, P = 0.015, respectively). Neither correlated with cardiac index or left ventricular ejection fraction. Serum Cr was significantly higher and GFR was significantly lower in the upper tertile of central venous pressure, pulmonary capillary wedge pressure as well as in the lower tertile of renal perfusion pressure.

Conclusions

Renal dysfunction in heart failure is determined more by passive congestion than by low perfusion. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery

Lindgren A, Lindstedt G, Kilander AF (Borås Central Hospital and Sahlgrenska University Hospital, Göteborg, Sweden). Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery. J Intern Med 1998; 244 : 341–349.

Objectives

Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency.

Design

Clinical study of consecutive patients.

Setting

The catchment area of Sahlgrenska University Hospital, Göteborg.

Subjects

A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery.

Interventions

Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin.

Main outcome measures

Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin.

Results

About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests.

Conclusions

Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.

     

Clinical investigation of left ventricular pacing using coronary sinus in patients with mechanical prosthetic tricuspid valve replacement

Background

Although transvenous right ventricular (RV) endocardial lead placement is routine practice in clinical pacing, RV inaccessibility in certain clinical situations mandates the search for other sites.

Hypothesis

This study is aimed to verify whether left ventricular lead through coronary sinus is safe and efficient.

Methods

Based on a retrospective analysis of a single‐center series of 4 patients with inaccessibility for RV pacing, we report on the feasibility and reliability of coronary sinus (CS) pacing via left ventricular (LV) lead, which usually is used in cardiac resynchronization therapy. Four patients with valvular heart disease and bradycardias post–mechanical prosthetic tricuspid valve replacement were studied. The LV leads were implanted into the lateral vein or great cardiac vein of the CS, and all parameters were programmed postprocedure.

Results

In all cases procedures yielded favorable parameters, with 1 CS dissection. At long‐term follow‐up, there was no threshold increase or lead dislocation.

Conclusions

LV lead implantation through the CS appears safe and efficacious in patients with inaccessibility for RV pacing.

     

Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg‐Strauss syndrome

Objective

Churg‐Strauss syndrome (CSS) is classified among the so‐called antineutrophil cytoplasmic antibody–associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75–95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features.

Methods

Immunofluorescence and enzyme‐linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status.

Results

ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti‐MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042).

Conclusion

ANCAs are present in ∼40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA‐positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.