Rate-dependent AV delay optimization in cardiac resynchronization therapy

BACKGROUND: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT. METHOD: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise. RESULTS: The baseline AVD was optimized to 99 +/- 19 ms in the supine and 84 +/- 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT-VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT-VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation. CONCLUSIONS: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.     

Autoantibodies that bind glomeruli: cross-reactivity with bacterial antigen

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies. Anti-DNA antibodies are associated with glomerulonephritis in SLE. It has been shown that anti-DNA antibodies cross-react with bacterial polysaccharide and, thus, might be elicited by microbial exposure. Non-DNA-binding antibodies also contribute significantly to the pathogenesis of lupus nephritis. The goal of this study was to characterize non-DNA-binding, kidney-binding antibodies. METHODS: We generated a combinatorial library derived from spleen cells of a patient with SLE who had just previously received pneumococcal vaccine. The phage library was used in an in vivo biopanning technique to identify non-DNA-binding, kidney-binding antibodies. Antibodies were then analyzed for binding to bacterial polysaccharide and to renal antigens. RESULTS: Eight antibodies were characterized that bound glomeruli, but not DNA. All antibodies isolated by this protocol were IgG class, suggesting that there is affinity maturation for glomerular binding. Four of the antibodies cross-reacted with pneumococcal polysaccharide. Six of the antibodies bound to renal antigens that have previously been reported to be cross-reactive with DNA; the other 2 bound to histone. CONCLUSION: This study suggests that both DNA-binding and non-DNA-binding antibodies in SLE may be elicited by the same bacterial antigens.     

Research knowledge among parents of children participating in a randomized clinical trial

OBJECTIVE: Parental permission is required for child research, but parents' understanding of research aims and procedures has not been well documented. Parental research knowledge was assessed during a clinical trial in autism. METHOD: Parents of 101 children (age 5-17 years) with autism participating in a placebo-controlled trial of risperidone were given a questionnaire at the end of the study. RESULTS: Of the 95 parents completing the questionnaire, 99% knew of possible placebo assignment and that testing the medication efficacy was the main purpose of the investigators; 96% to 98% knew that research involved both risks and potential benefits, identified the study medication, and knew of their right to withdraw at any time; 90% to 95% knew of the medication's main side effects; 87% reported having been informed of possible alternatives to research participation; and 72% were aware that treatment was randomly assigned (whereas 27% reported that treatment was chosen based on individual needs to ensure best care). Parents with a college degree were more likely to recognize the random nature of treatment assignment. CONCLUSIONS: Overall, parents were highly knowledgeable of the main research components. About one fourth, however, seemed unaware that treatment was randomly determined and not personalized, suggesting that therapeutic misconception may affect some otherwise well-informed parents.     

Increasing incidence of childhood thyrotoxicosis in a population-based area of central Sweden

AIM: To study the incidence, prevalence and clinical characteristics of childhood thyrotoxicosis in a population-based area comprising five counties in central Sweden. METHODS: Retrospective analysis of the medical records of all children below 16 y of age with thyrotoxicosis during a 10-y study period. RESULTS: Forty-six children were identified with thyrotoxicosis. The median age at onset was 11.7 y and 85% were females. At the end of the study period on 31 December 1999, the prevalence was 0.08 per 1000. The mean annual incidence was four times higher in the second 5-y period than in the first (2.7 and 0.7 per 100000, respectively; p < 0.001). A first-degree relative with thyrotoxicosis was found in 21% of the children and 11/46 children (24%) showed autoimmune-related co-morbidity. Increased heart rate was observed in 95%, goitre in 67% and exophthalmos in 33% of the children. TSH was completely suppressed and free T4 was clearly above the upper reference limit in all children. TSH receptor-stimulating antibodies and peroxidase antibodies were observed in 80% and 71% of the children, respectively. CONCLUSION: This study indicates an increase in the incidence of childhood thyrotoxicosis in a population-based area of central Sweden. A prospective study aimed at identifying specific aetiological risk factors for development of thyrotoxicosis has been initiated.     

Endometriosis presenting as a urethral diverticulum: a case report

BACKGROUND: Pelvic pain is a common complaint among women of childbearing age. It has an extensive differential diagnosis that at times can make it difficult to determine its etiology. One must therefore rely on the characteristics of the physical examination, symptoms and imaging studies. However, in doing so, one should keep in mind that many diseases mimic one another. Physicians must be careful not to fall into the trap of simply assigning a specific disease to a given group of symptoms. CASE: A 35-year-old woman, gravida 2, para 0020, presented to a clinic complaining of left lower abdominal pain. She had a history of dyspareunia, dysmenorrhea, urinary frequency and numerous urinary tract infections. Previous laparoscopies had been negative for endometriosis. Physical examination demonstrated a 1.5-cm mass left of the midurethra. No pus was expressed through the urethra with cyst massage. Imaging showed a 1.1 x 1.1-cm lesion in the left posterolateral aspect of the urethra consistent with a urethral diverticulum. Uterine adenomyosis was also noted. Although clinical symptoms, physical examination and imaging suggested a urethral diverticulum, a vaginal endometriotic cyst was encountered at surgery. Pathologic evaluation of the surgically excised lesion revealed endometriosis, revealed endometriosis. CONCLUSION: In this case, clinical findings, location and imaging characteristics of a periurethral endometriotic lesion suggested a urethral diverticulum. Endometriosis should be considered in patients with a history of pelvic pain who present with urinary frequency and a periurethral lesion.