How useful is the ultrastructural study of the cilia of the respiratory tract in the diagnosis of an immotile cilia syndrome?

The immotile cilia syndrome (ICS) comprises a range of congenital defects of the ciliary apparatus most probably transmitted by autosomal recessive inheritance. Because cilia occur mainly in the respiratory and genital tract, the clinical symptoms of ICS are most commonly chronic sinusitis, bronchitis, bronchiectasis and male sterility. The syndrome can be associated with a situs inversus and is then called Kartagener's syndrome. We studied the ciliary ultrastructure in airway biopsies of 5 patients suffering from chronic upper and lower respiratory tract infections. With the single exception of one female patient with confirmed ICS diagnosis (Kartagener's syndrome) the etiology of the recurrent infections was unknown. The following ciliary defects were observed: missing dynein arms, radial spoke defects, missing nexin links, microtubular transpositions, compound cilia, supernumerary, absent, or incomplete microtubules, lack of ciliary orientation and various abnormal patterns of microtubular arrangement. In no instance did a patient show only a single anomaly; defects were always combined. Missing dynein arms, radial spoke defects and microtubular transpositions have frequently been described as lesions specific for ICS. Whenever these lesions were found simultaneously in both the respiratory and genital tracts, their genetic origin cannot be doubted. In our confirmed ICS patient the outer dynein arms were not missing but were reduced in number and length in a large number of cilia. The biopsy was, however, obtained from the heavily infected maxillary sinus and it is known that inflammation can lead to a loss of dynein arms. In the light of our investigations and of a review of the published cases of ciliary anomalies, it is concluded that none of the above defects in itself is specific for ICS. They may all occur as secondary lesions or sporadically as varieties in otherwise healthy subjects. It therefore appears questionable whether ICS can be diagnosed from the ciliary ultrastructure of a single airway biopsy. Assessment of ICS cannot be based simply on the ultrastructural demonstration of a particular ciliary defect, but necessitates additional considerations particularly regarding the origin of the biopsy, the sampling procedures and quantitation of defects. It appears necessary to investigate samples from different parts of the airways and quantitatively analyze the prominent lesions.

Glacier advances in northeastern Turkey before and during the global Last Glacial Maximum

Abstract Our study in the Başyayla Valley in northeastern Anatolia showed evidence of four glacier advances that built terminal and lateral moraines. Surface exposure dating of boulders on these moraines showed that the Maximum Ice Extent (MIE) was asynchronous with the global Last Glacial Maximum (LGM; 22.1 ± 4.3 thousand years; ka). The local {MIE} took place at least 57.0 ± 3.5 ka ago. The extent of the Başyayla Glacier during this advance is not known exactly because the boulders are only preserved on a lateral moraine. The next advance was prior to 41.5 ± 2.5 ka, and it descended down the valley to approximately 2320 m above sea level (m a.s.l.), with a glacier length of 5.3 km. During the early global LGM, the Başyayla Glacier extended for a distance of 4.9 km down to approx. 2430 m a.s.l. The last recorded advance occurred during the global LGM. This extension was 0.7 km smaller than the local {MIE} and its terminus reached 2490 m a.s.l. only. The exposure ages of boulders in a retreat position at an altitude of approx. 3045 m a.s.l. indicate that the valley has remained ice-free since the Lateglacial period. Therefore, the Lateglacial extent was limited to the cirque system in the uppermost part of the catchment. Furthermore, Holocene glacier oscillations seem to be either absent or restricted to solifluction in the whole catchment and to rock glacier movements in the southern tributary of the Başyayla Valley system.

Methodologies for the Analysis of HCV-Specific CD4(+) T Cells

Virus-specific CD4(+) T cells play a major role in viral infections, such as hepatitis C virus (HCV). Viral clearance is associated with vigorous and multi-specific CD4(+) T-cell responses, while chronic infection has been shown to be associated with weak or absent T-cell responses. Most of these studies have used functional assays to analyze virus-specific CD4(+) T-cell responses; however, these and other detection methods have various limitations. Therefore, the important question of whether virus-specific CD4(+) T cells are completely absent or primarily impaired in specific effector functions during chronic infection, has yet to be analyzed in detail. A novel assay, in which virus-specific CD4(+) T-cell frequencies can be determined by de novo CD154 (CD40 ligand) expression in response to viral antigens, can help to overcome some of the limitations of functional assays and restrictions of multimer-based methods. This and other current established methods for the detection of HCV-specific CD4(+) T cells will be discussed in this review.

Übergangslösungen beim Eintritt in die Schweizer Berufsbildung: Brückenschlag oder Sackgasse?

In der Schweiz finden viele Jugendliche keinen direkten Zugang zu einer beruflichen Grundbildung; vielmehr durchlaufen sie zunächst eine so genannte Übergangslösung oder ein Brückenangebot wie z.B. ein zehntes Schuljahr. Wir beleuchten in diesem Beitrag zum einen, wie schulische, individuelle, familiäre und kontextuell-systemische Faktoren den Übertritt in solche Brückenangebote beeinflussen. Zum anderen gehen wir der Frage nach, wie sich ein verzögerter Einstieg via ein Brückenangebot auf die Chance auswirkt, einen Abschluss der Sekundarstufe II zu erwerben. Die empirische Analyse stützt sich auf die TREE-Studie, welche eine Kohorte von Schulentlassenen des Jahres 2000 längsschnittlich beobachtet. Wir modellieren dabei zunächst die interessierenden Übertrittsprozesse mittels einer multinomialen logistischen Regression, um dann mittels Propensity Score Matching deren Wirkung auf die nachobligatorischen Bildungschancen abzuschätzen.

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Arterial stiffness depends on serum ionized calcium levels during dialysis with regional citrate anticoagulation

Hemodynamic effects related to changes in serum ionized calcium (iCa) are difficult to determine during conventional hemodialysis (HD) using a fixed dialysate concentration of calcium. Regional citrate anticoagulation (RCA) allows the study of the effects of predefined iCa changes on arterial stiffness and blood pressure (BP) during a single dialysis session. In a crossover study, 15 patients with end-stage renal disease underwent two HD sessions with RCA. Each session was divided into two study phases in which iCa was titrated either to 0.8-1.0 mm or to 1.1-1.4 mm. The sequence of phases was randomly chosen and alternated for the second session. After reaching a stable iCa level, pulse wave velocity (PWV), arterial BP, and heart rate were measured. iCa levels were modified during sequence 1 (iCa low-high) from a predialysis baseline value of 1.15 ± 0.09 mm, first to 0.92 ± 0.05 mm (time point 1; P < 0.001 vs. baseline) and then to 1.18 ± 0.05 (time point 2; ns). During sequence 2 (iCa high-low), iCa levels were modified from 1.15 ± 0.12 mm first to 1.20 ± 0.05 mm (time point 1; ns vs. baseline) and then to 0.93 ± 0.03 (time point 2; P < 0.001). Assuming a basic linear repeated measures model, PWV was positively related to iCa levels (P < 0.03) independent of systolic or diastolic BP, heart rate, or ultrafiltration rate. PWV is closely related to acute changes in serum iCa levels in HD patients using RCA. RCA provides an interesting opportunity to study the effects of acute iCa changes during one dialysis procedure.

Diastolic dysfunction of the cardiac allograft and maximal exercise capacity

BACKGROUND: Peak oxygen uptake (peak Vo(2)) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx) peak Vo(2) remains reduced despite normal systolic left ventricular function, which highlights the relevance of diastolic function. In this study we aim to characterize the predictive significance of cardiac allograft diastolic function for peak Vo(2). METHODS: Peak Vo(2) was measured using a ramp protocol on a bicycle ergometer. Left ventricular (LV) diastolic function was assessed with tissue Doppler imaging sizing the velocity of the early (Ea) and late (Aa) apical movement of the mitral annulus, and conventional Doppler measuring early (E) and late (A) diastolic transmitral flow propagation. Correlation coefficients were calculated and linear regression models fitted. RESULTS: The post-transplant time interval of the 39 HTxs ranged from 0.4 to 20.1 years. The mean age of the recipients was 55 +/- 14 years and body mass index (BMI) was 25.4 +/- 3.9 kg/m(2). Mean LV ejection fraction was 62 +/- 4%, mean LV mass index 108 +/- 22 g/m(2) and mean peak Vo(2) 20.1 +/- 6.3 ml/kg/min. Peak Vo(2) was reduced in patients with more severe diastolic dysfunction (pseudonormal or restrictive transmitral inflow pattern), or when E/Ea was > or =10. Peak Vo(2) correlated with recipient age (r = -0.643, p < 0.001), peak heart rate (r = 0.616, p < 0.001) and BMI (r = -0.417, p = 0.008). Of all echocardiographic measurements, Ea (r = 0.561, p < 0.001) and Ea/Aa (r = 0.495, p = 0.002) correlated best. Multivariate analysis identified age, heart rate, BMI and Ea/Aa as independent predictors of peak Vo(2). CONCLUSIONS: Diastolic dysfunction is relevant for the limitation of maximal exercise capacity after HTx.

Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease

OBJECTIVE To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. DESIGN Prospective study in consecutive individuals. SETTING University hospital. METHODS Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. RESULTS Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. CONCLUSIONS Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.

Interdisciplinary Cardiovascular and Neurologic Outpatient Rehabilitation in Patients Surviving Transient Ischemic Attack or Stroke With Minor or No Residual Deficits

Objective To evaluate the feasibility and effectiveness of a comprehensive outpatient rehabilitation program combining secondary prevention and neurorehabilitation to improve vascular risk factors, neurologic functions, and health-related quality of life (HRQOL) in patients surviving a transient ischemic attack (TIA) or stroke with minor or no residual deficits. Design Prospective interventional single-center cohort study. Setting University hospital. Participants Consecutive consenting patients having sustained a TIA or stroke with 1 or more vascular risk factors (N=105) were included. Interventions Three-month hospital-based secondary prevention and neurorehabilitation outpatient program with therapeutic and educational sessions twice a week. Patients were evaluated at entry and program end. Main Outcome Measures Impact on vascular risk factors, neurological outcome, and HRQOL. Results A total of 105 patients entered the program and 95 patients completed it. Exercise capacity (P<.000), smoking status (P=.001), systolic (P=.001) and diastolic (P=.008) blood pressure, body mass index (P=.005), low-density lipoprotein cholesterol (P=.03), and triglycerides (P=.001) improved significantly. Furthermore, the 9-Hole-Peg-Test (P<.000), Six-minute Walking Test (P<.000), and One Leg Stand Test (P<.011) values as well as HRQOL improved significantly. The program could be easily integrated into an existing cardiovascular prevention and rehabilitation center and was feasible and highly accepted by patients. Conclusions Comprehensive combined cardiovascular and neurologic outpatient rehabilitation is feasible and effective to improve vascular risk factors, neurologic functions, and HRQOL in patients surviving TIA or stroke with minor or no residual deficits.