Atrial Capture Detection with Endocardial Electrodes

A new method of evoked response detection, previously demonstrated in the ventricle, has been studied in the atrium at the time of routine pacemaker implant in 16 patients. The atrial evoked response was readily detectable in all patients due to excellent recovery from poststimulus polarization. In six patients, as experimental threshold- tracking pacemaker was used to automatically verify atrial capture and to generate strength-duration curves. It is concluded that this pacing technique is both simple and reliable, and that automatic atrial threshold tracking is feasible.     

A pilot study on the effects of the transition of paediatric to adult health care in patients with haemophilia and in their parents: patient and parent worries,parental illness‐related distress and health‐related Quality of Life

Summary. The aim of this pilot study was to investigate the effects of the transition from paediatric to adult health care services in haemophilia patients and their parents. We compared pretransition children (n = 9) and their parents (n = 18) to posttransition patients (n = 8) and their parents (n = 21). Pre‐ and posttransition patients did not differ in self‐rated health‐related quality of life (QoL) or worries about the transition. Fathers of posttransition patients rated their son’s QoL as poorer than those of pretransition patients (P = 0.034) and indicated higher levels of illness‐related distress than fathers of pretransition patients (P = 0.034). The findings indicate that the transition affects parents more than patients. Moreover, we found gender differences in parental worries about the transition. The findings indicate that programmes designed to facilitate the transition in haemophilic patients should also address the patients’ parents.     

Extracellular protein disulfide isomerase regulates feedback activation of platelet thrombin generation via modulation of coagulation factor binding

Summary. Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue‐factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: To investigate the involvement of surface thiol isomerases and especially PDI, in thrombin‐mediated thrombin amplification on human platelets. Methods/results: Using a newly developed thrombin‐dependent platelet thrombin generation assay, we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti‐TF antibodies inhibiting TF‐induced thrombin formation in platelet‐depleted plasma had no effect compared with vehicle‐treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase‐inhibitors bacitracin and anti‐PDI antibody RL90, respectively. Platelet thrombin formation depends on binding of coagulation factors to the platelet surface. Therefore, involvement of thiol isomerases in this binding was investigated. As shown by confocal microscopy and flow cytometry, thrombin‐stimulated platelets exhibited increased surface‐associated PDI as well as extracellular disulfide reductase activity compared with unstimulated platelets. Flow cytometric analysis revealed that membrane impermeant thiol blockers or PDI inhibitors, which had been added after platelet stimulation and after phosphatidylserine exposure to exclude their influence on primary platelet activation, significantly inhibited binding of all coagulation factors to thrombin‐stimulated platelets. Conclusions: Thus, surface‐associated PDI is an important regulator of coagulation factor ligation to thrombin‐stimulated platelets and of subsequent feedback activation of platelet thrombin generation. Cell surface thiol isomerases might be therefore powerful targets to control hemostasis and thrombosis.     

The burden of HCV treatment in patients with inherited bleeding disorders

Summary. Many patients with inherited bleeding disorders are infected with hepatitis C virus (HCV). Antiviral treatment, consisting of pegylated interferon and ribavirin, has many side‐effects. The aim of the study was to prospectively assess the occurrence and course of side‐effects and changes in health‐related quality of life (HRQoL) during antiviral treatment in patients with inherited bleeding disorders and chronic HCV. Forty‐seven patients were followed during antiviral treatment. Side‐effects of treatment were recorded, and the Beck Depression Inventory and the RAND‐36 HRQoL questionnaire were administered at regular intervals. Frequently reported side‐effects were fatigue (100%), headache (94%), pruritus and skin rash (94%), concentration problems (89%), decreased appetite (89%), fever, irritability and hair loss (all 85%). Many side‐effects disappeared soon after end of treatment, but 4 weeks after cessation fatigue, concentration problems and sleeping problems were still present in more than 30% of patients. Dose reduction was necessary in 21 patients (45%), mostly because of decreasing weight or haemoglobin levels. Two patients stopped treatment prematurely because of side‐effects. Depression was present in 28 patients (60%). HRQoL decreased significantly during treatment in all RAND‐36 domains, and increased again within 4 weeks after treatment. Major side‐effects were similar in patients with successful (n = 31, 66%) and unsuccessful antiviral treatment. In patients with inherited bleeding disorders and chronic HCV, antiviral treatment has many, but mostly transient side‐effects and a significant impact on quality of life. Careful follow‐up and management of side‐effects will ensure optimal compliance and treatment results.     

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE SPINE: A CAUSE OF BACK PAIN? A CONTROLLED STUDY

This is the first controlled study of the frequency of backpain in a European caucasian population with diffuse idiopathicskeletal hyperostosis (DISH). Elderly patients admitted to hospital for reasons other thanback pain were assessed for the presence of spinal DISH usingthe routine lateral chest radiograph films. A total of 106 probands(82 males, 24 females) with a mean age of 70 years fulfilledthe criteria for DISH as defined previously. One hundred andseventyeight patients (117 males, 61 females) not meeting thesecriteria were used as controls. The prevalence of back painwas assessed by a blinded interviewer using a structured questionnaire.Our primary hymthesis was that spinal DISH positive probandshad not had back pain more often than controls. The controlledstudy showed no statistically significant difference in painfrequency between spinal DISH positive probands and controlsat any spinal level. We conclude that back pain does not occur more often in radiographicallydefined DISH positive probands than in controls. The radiologicalfinding of spinal DISH, as far as it does not lead to stenosisof the spinal canal or dysphagia, thus seems to be a findingwithout clinical relevance. KEY WORDS: Spine, Radiographs, Pain, Osteoarthritis, Forestier's disease, Ankylosing vertebral hyperostosis     

Active surfactant in pharyngeal aspirates of term neonates: lipid biochemistry and surface tension function

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air–liquid interface to values below 5 mN m^?1. In addition, it has been suggested that surfactant is also present in the airways, particularly in the perinatal period. We isolated surfactant from pharyngeal aspirates obtained from 33 neonates immediately after delivery and analysed it for both phospholipid (PL) composition and surface tension function. PL classes and phosphatidylcholine (PC) molecular species were determined by normal and reversed-phase high-performance liquid chromatography (HPLC), respectively. Static and dynamic surface properties of the surfactant were studied in a pulsating bubble surfactometer. Sample volume was 1.3 ± 0.5 mL (mean ± SD) with a total amount of 2.5 ± 1.3 μmol of PL and a concentration of 2.1 ± 1.0 μmol mL^?1 PL. HPLC analyses of PL classes revealed a composition identical with surfactant prepared from alveolar washes, i.e. PC 83.6 ± 2.1%, sphingomyelin 1.4 ± 0.5%, phosphatidylglycerol 8.1 ± 1.6%, phosphatidylethanolamine 2.1 ± 0.5% and phosphatidylinositol 2.6 ± 1.1%. Thin-layer chromatography showed almost identical results but was more time-consuming and needed more material for analysis. Analysis of PC molecular species revealed a composition typical of human alveolar surfactant with 54.7 ± 3.9% dipalmitoyl PC, 10.3 ± 1.9% palmitoyloleoyl PC and 9.1 ± 1.5% palmitoylmyristoyl PC. Minimal surface tension fell to values below 5 mN m^?1 within 5 min of cycling in all subjects. The methods used in this study allowed for complete PL and surface tension analyses of surfactant obtained during routine pharyngeal suctioning after delivery at term. Whether they are also applicable to preterm neonates with respiratory distress remains to be determined.     

The 13C-mixed triglyceride breath test in healthy adults: determinants of the 13CO2 response

Defects in lipolysis due to pancreatic insufficiency can be diagnosed by the mixed triglyceride (MTG) ¹³CO₂ breath test. However, the effects of various test conditions on the ¹³CO₂ response have only been partially elucidated. In healthy adults, we performed the ¹³CO₂ mixed triglyceride breath test and we compared (a) the inter- and intra-individual variation in the ¹³CO₂ response; (b) the effect of two different test meals; (c) the effect of an additional meal during the test; and (d) the effect of physical exercise during the test. Upon repeating the test in the same individual (test meal cream), repeatability coefficients were large, with respect to either time to maximum ¹³C excretion rate (3.8 h), maximum ¹³C excretion rate (4.9% ¹³C dose h^?1) or cumulative recovery of ¹³C over the 9-h study period (22.7% ¹³C dose). The cumulative ¹³C expiration over 9 h obtained with the test meal composed of cream was quantitatively similar to that obtained with bread and butter: 42.2 ± 8.4% and 47.7 ± 6.3% respectively. Fasting for 9 h during the test resulted in similar ¹³C expiration rates and cumulative ¹³C expiration (43.4% ± 7.2%) when compared with consumption of an additional meal 3 h after the start of the test (38.3 ± 5.3%). The ¹³CO₂ response increased in five out of seven subjects, but decreased in the other two, when moderate exercise was performed (bicycle ergometer, 50 W for 5 h). We conclude that the repeatability of the MTG test in healthy adults is low. The present results indicate that a solid and a liquid test meal, containing a similar amount of fats, give similar cumulative ¹³CO₂ responses, and that stringent prolonged fasting during the test is unnecessary. Standardization of physical activity seems preferable, since the unequivocal effects of moderate exercise on the ¹³CO₂ response were observed in the individuals studied.     

Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38–57%), right 45% (2–62%) vs. control subjects 59% (38–70%), P  < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1–25%)] was lower than in the patients with right hemicolectomy [19% (0–69%)] and control subjects [24% (7–50%)], P  < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 μmol g⁻¹) than in those with left hemicolectomy (0.048 μmol g⁻¹), which coincided with a higher cytolytic [right 49% (3–93%), left 2% (1–37%)] and alkaline phosphatase activity [right 6.7 U mL⁻¹ (1.2–40.1 U mL⁻¹), left (2.0 U mL⁻¹ (1–25.7 U mL⁻¹), both P  < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.     

Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man

Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first- and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic glucose clamp. Twelve healthy male subjects, age (mean ± SEM) 22.5 ± 0.5 years, body mass index (BMI) 21.7 ± 0.6 kg m^?2, were studied in a randomized, double-blind study design. Glibenclamide 10 mg or placebo was taken before a 4-h hyperglycaemic clamp (blood glucose 8 mmol L^?1 during the first 2 h and 32 mmol L^?1 during the next 2 h). During hyperglycaemic clamp at 8 mmol L^?1, the areas under the Δinsulin curve (AUC_Δinsulin , mean ± SEM) from 0 to 10 min (first phase) were not different: 1007 ± 235 vs. 1059 ± 261 pmol L^?1 × 10 min (with and without glibenclamide, P = 0.81). However, glibenclamide led to a significantly larger increase in AUC_Δinsulin from 30 to 120 min (second phase): 16 087 ± 4489 vs. 7107 ± 1533 pmol L^?1 × 90 min (with and without glibenclamide respectively, P < 0.03). The same was true for AUC_ΔC-peptide: no difference from 0 to 10 min but a significantly higher AUC_ΔC-peptide from 30 to 120 min on the glibenclamide day (P < 0.01). The M/I ratio (mean glucose infusion rate divided by mean plasma insulin concentration) from 60 to 120 min, a measure of insulin sensitivity, did not change: 0.26 ± 0.05 vs. 0.22 ± 0.03 μmol kg^?1 min^?1 pmol L^?1 (with and without glibenclamide, P = 0.64). During hyperglycaemic clamp at 32 mmol L^?1, the AUC_Δinsulin from 120 to 130 min (first phase) was not different on both study days: 2411 ± 640 vs. 3193 ± 866 pmol L^?1 × 10 min (with and without glibenclamide, P = 0.29). AUC_Δinsulin from 150 to 240 min (second phase) also showed no difference: 59 623 ± 8735 vs. 77389 ± 15161 pmol L^?1 × 90 min (with and without glibenclamide, P = 0.24). AUC_ΔC-peptide from 120 to 130 min and from 150 to 240 min were slightly lower on the glibenclamide study day (both P < 0.04). The M/I ratio from 180 to 240 min did not change: 0.24 ± 0.04 vs. 0.30 ± 0.07 μmol kg^?1 min^?1 pmol L^?1 (with and without glibenclamide, P = 0.25). In conclusion, glibenclamide increases second-phase insulin secretion only at a submaximally stimulating blood glucose level without enhancement of first-phase insulin release and has no additive effect on insulin secretion at maximally stimulating blood glucose levels. Glibenclamide did not change insulin sensitivity in this acute experiment.