Pulmonary hypertension is ameliorated in mice deficient in thrombin‐activatable fibrinolysis inhibitor

Summary. Background: The fibrinolytic system has been implicated in the pathogenesis of pulmonary hypertension (PH). Thrombin‐activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and therefore its absence would be expected to increase fibrinolysis and ameliorate PH. Objective: The objective of the present study was to evaluate the effect of TAFI deficiency on pulmonary hypertension in the mouse. Methods and results: PH was induced in C57/Bl6 wild‐type (WT) or TAFI‐deficient (KO) mice by weekly subcutaneous treatment with 600 mg kg^?1 monocrotaline (MCT) for 8 weeks. PH was inferred from right heart hypertrophy measured using the ratio of right ventricle‐to‐left ventricle‐plus‐septum weight [RV/(LV+S)]. Pulmonary vascular remodeling was analyzed by morphometry. TAFI‐deficient MCT‐treated and wild‐type MCT‐treated mice suffered similar weight loss. TAFI‐deficient MCT‐treated mice had reduced levels of total protein and tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), transforming growth factor‐β (TGF‐β) and monocyte chemoattractant protein‐1 (MCP‐1) in bronchial alveolar lavage compared with wild‐type MCT‐treated mice. The ratio of RV to (LV+S) weight was significantly higher in WT/MCT than in KO/MCT mice. The pulmonary artery wall area and vascular stenosis were both greater in MCT‐treated WT mice compared with MCT‐treated TAFI‐deficient mice. Conclusions: TAFI‐deficient MCT‐treated mice had less pulmonary hypertension, vascular remodeling and reduced levels of cytokines compared with MCT‐treated WT animals, possibly as a result of reduced coagulation activation.     

Exact Location of the Branching Bundle in the Living Heart

Aims: The His bundle electrogram is believed to reflect the exact location of the His bundle. However, the distinction between distal His bundle potential and proximal right bundle branch potential is challenging. The aim of this study was to pinpoint the location of the branching point of the His bundle, and to compare that site with the site of recording of the largest His bundle electrogram (LH) during sinus rhythm.
Methods: We hypothesized that the site of earliest His activation (EH) during retrograde conduction via the left bundle branch is the branching point. We studied 15 nonconsecutive patients (mean age = 40 ± 22 years; eight men). We performed a programmed stimulation from right ventricular apex until retrograde right bundle branch block appeared. At that point we measured (1) the distance between antegrade LH site and retrograde EH site and (2) the atrial-to-ventricular amplitude ratio (A/V ratio) at both sites.
Results: EH was recorded at the proximal electrode of the His bundle catheter in all patients. Mean distance between EH and LH was 9.8 ± 2.5 mm. The mean A/V ratios at the EH site and the LH site were 1.01 ± 0.42 and 0.08 ± 0.06, respectively.
Discussion: This study showed that the EH site is located approximately 10-mm proximal to the LH site. The mean A/V ratio at the EH site during sinus rhythm is approximately 1.0. These observations suggest that the majority of His potentials reflect proximal right bundle activation. Before delivering radiofrequency energy in the para-Hisian area, attention should be paid to the presence of a His potential and to the A/V ratio, rather to the amplitude of the His electrogram.     

Step vs. progressive exercise: the kinetics of phosphocreatine hydrolysis in human muscle

It is well known that the VPO ₂ readjustment rate of the whole body is faster when carrying out a given constant work load starting from a baseline of moderate exercise than from rest. However, it has not been established whether the above change is the result of faster kinetics of the oxidative machinery or, alternatively, the consequence of a reduced involvement of confounding factors such as anaerobic glycolysis or tissue O₂ stores. The problem, earlier approached by chemical methods, was studied in man by ³¹P-NMRS assessment of the kinetics of phosphocreatine (PC) hydrolysis at the muscle level which is known to reflect the readjustment rate of the oxidative reactions. Twelve normal subjects carried out in a 90 cm bore modified Picker (1.5 T) magnet, a series of contractions by the plantar flexors reaching pre-set submaximal loads either in single steps (constant load, CL) or progressively (incremental exercise, I). If preceding exercise (I), compared to rest, influenced the rate of oxidations, the PC concentration at the target loads would be different for the two exercise modes, reflecting different energy deficits. This was not the case. Thus the present results show that the rate of readjustment of oxidations at the muscle level is not affected by priming exercise confirming previous findings and showing that theoretical models of VPO ₂ control are experimentally applicable to man.     

A pilot study evaluating a new questionnaire for prostatic symptom scoring, the SPSS, and its sensitivity as constructed to objective measures of outflow obstruction

AIM: To evaluate the extent to which our newly developed questionnaire, the Saitama Prostate Symptom Score (SPSS), for prostatic symptom scoring reflects objective findings in benign prostatic hyperplasia (clinical BPH) and to compare it with the International Prostate Symptom Score (IPSS) with regard to diagnostic sensitivity in clinical BPH. METHODS: In this study, both the SPSS and the IPSS were self-administered by patients. Free uroflowmetry, a pressure-flow study and the measurement of prostatic volume were carried out. RESULTS: There was no significant correlation between the results of the IPSS questionnaire and the urethral obstruction grade estimated by Schaefer or Abrams-Griffiths nomograms. The total score of the SPSS was correlated with these nomograms (P = 0.0487 and P = 0.0413, respectively). There was no significant correlation between the results of the IPSS questionnaire and the total volume or transition zone volume of the prostate, whereas the total score of the SPSS correlated with the total volume of the gland and transition zone volume (P = 0.0044 and P= 0.0051, respectively). CONCLUSION: This study revealed the SPSS to correlate with objective findings satisfactorily. However, there are still several aspects of the SPSS which need to be improved upon, and the questionnaire should be studied in larger numbers of patients suffering from lower urinary tract symptoms.     

Clinical Impact of Solifenacin on Generic and Symptom‐Specific Quality of Life for Females with Overactive Bladder: Using the Overactive Bladder Symptom Score and Rand Medical Outcomes Study 36‐Item Health Survey

Objectives: We evaluated the effectiveness of antimuscarinic treatment on disease‐specific and generic quality of life (QoL) in females with clinically diagnosed overactive bladder (OAB) by prospectively analyzing improvements in the overactive bladder symptom score (OABSS) and the Rand Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36). Methods: We prospectively recruited newly diagnosed female patients with OAB. Pretreatment disease‐specific symptoms were documented, and generic QoL questionnaires were administered. All subjects received solifenacin 5 mg/day for >8 weeks. Symptoms and general health‐related QoL (HRQoL) were assessed using the OABSS and SF‐36, respectively. Other objective variables, such as maximum urinary flow rate and postvoid residual urine volume, were also evaluated. Results: Seventy‐eight subjects met all inclusion criteria and no exclusion criteria. After 8 weeks, the mean OABSS decreased by approximately 50% compared with baseline (from 9.1 ± 2.8 to 4.5 ± 3.6). All individual scores in OABSS improved after administration of solifenacin. Before treatment, the scores of the study subjects in all SF‐36 domains were significantly worse than the age‐ and gender‐adjusted Japanese national norms (P < 0.01), except the vitality (VT) scale. Intra‐group comparisons between age groups showed worse mental health (MH) scores in all age groups. In the OAB group, three mean SF‐36 scales (physical function [PF], VT, and MH) significantly improved after treatment. Conclusion: Treatment of OAB with solifenacin is associated with significant improvement in generic HRQoL and disease‐specific symptoms at 8 weeks after drug administration. Particularly for generic HRQoL as measured by the SF‐36, solifenacin treatment effectively improves three SF‐36 scores: PF, VT, and MH.     

Hematoma with High Oxygen Partial Pressure Resulting from Injection Sclerotherapy for Esophageal Varices — Report of a Case

Abstract: Endoscopic injection sclerotherapy (EIS) was performed on a 44-year-old Japanese male, who had been suffering from risky esophageal varices due to cirrhosis of the liver. Blood gas analysis at the beginning of therapy showed that the partial pressure of oxygen at the variceal (PO2) and arterial blood (PaO2) were 47.2 mmHg and 64.1 mmHg, respectively. Sclerosant with contrast medium was injected into the varices and the left gastric vein was embolized; this was always confirmed by endoscopic varicealography during injection scleorotherapy (EVIS). During the fifth EIS session, there was evidence of pooling of contrast medium with sclerosant and an intramural hematoma had developed, which could not be reduced by puncture. The blood gas analysis showed a drastic increase in PO2 (107.9 mmHg), whereas PaO2 remained mostly unchanged (58.8 mmHg). To our knowledge, this is the first report of blood gas analysis during hematoma and the high PO2 compared with PaO2 indicated that there was a substantial inflow of oxygen-rich blood, possibly from the pulmonary vein into the varices. This inflow of blood into the varices may have contributed to the formation of the large hematoma in small varices following EIS. (Dig Endosc 1999; 11: 55–61)     

Long-term follow up of abdominal aortic aneurysm complicating Kawasaki disease: Comparison of the effectiveness of different imaging methods

A 2 month old boy with Kawasaki disease developed the rare complication of abdominal aortic aneurysm (AAA). He was followed up over 7 years by ultrasonography (2D-ECHO) with and without Doppler flow evaluation, angiography and computed tomography. Calcification was noted 33 months after the onset of the disease but the aneurysm did not decrease in size. 2D-ECHO was adequate for evaluating the size of an aneurysm, but did not show thrombus formation or calcification. Doppler flow studies did not show abnormally high blood flow velocities either at the inflow or outlet of aneurysms, which are indicative of stenosis. On the other hand an abdominal aortogram provided information regarding the luminal shape and abnormalities in flow pattern suggestive of thrombus formation. Fluoroscopy cannot demonstrate calcification in the early stages. Computed tomography (CT) was the imaging method of choice for the evaluation of obstructive or calcific changes; an organizing thrombus was clearly demonstrated and early detection of calcification was possible.