Electrical remodeling in cardiac hypertrophy

In recent years, electrical remodeling has emerged as an important pathophysiologic mechanism in many types of cardiac pathology. Because clinical heart disease often involves both hypertrophic and failure phenotypes, identification of disease-specific mechanisms is essential. This review focuses on mechanisms of electrical remodeling in cardiac hypertrophy, emphasizing transmembrane Ca²⁺ fluxes and Ca²⁺-responsive signaling pathways. Where information is available, the remodeling of hypertrophy is contrasted with what is known about heart failure.     

Breaking the rules: the unconventional recognition of HLA-B27 by CD4+ T lymphocytes as an insight into the pathogenesis of the spondyloarthropathies

Despite extensive research, it remains unclear why a small proportion of HLA- B27(+) individuals develop spondyloarthropathies (SpA). Because the function of HLA-B27, as a major histocompatibility complex (MHC) class I molecule, is peptide presentation to CD8(+) T cells, research has concentrated on the role of HLA-B27 as a restriction element for CD8(+) cytotoxic T lymphocytes in pathogenesis. However, findings in the B27-transgenic animal models, together with the identification of unusual processing and presentation features of HLA-B27, have raised alternative hypotheses for the pathogenic role of HLA-B27. One such hypothesis is that HLA-B27 can be recognized by CD4(+) T lymphocytes. Here we report the identification of such unusual cells, which break the conventional rules of MHC restriction, and propose a model for the role of such CD4(+) T cells in SpA.     

Perianal rhabdomyosarcoma presenting as a perirectal abscess: A report of 11 cases

Background Purpose: The organs and soft tissues of the pelvis are some of the most common primary sites for rhabdomyosarcoma (RMS) in children and adolescents. In most cases a mass is detectable on clinical examination, and the initial concern is focused on the possibility of a neoplasm. The current report concerns 11 patients, each presented with a painful perineal-perianal mass suggesting an abscess to the extent that each one of these patients was treated initially with antibiotics or incision and drainage for several weeks to months before the pathologic diagnosis of RMS was established. Methods: The authors reviewed the clinical histories of all patients with perirectal/perianal RMS from their respective institutions to identify cases in which the initial clinical diagnosis or impression was that of a perirectal abscess. Pathologic material was reviewed in all cases. Results: Eleven patients, 7 of whom were girls, ranged in age from 1 to 16 years at diagnosis (median age, 14 years). Fever accompanied the clinical presentation in 2 patients. None of the patients had a past medical history of illness that may have predisposed them to a perirectal abscess, although one patient had a family history of inflammatory bowel disease. Duration of symptoms ranged from 1 month to 1 year (mean, 4.6 months). Each patient presented with a tender perianal/perineal nodule or mass. Inguinal adenopathy was present in 6 patients at diagnosis. White blood cell counts ranged from 6,600/mm³ to 24,500/mm³. LDH levels ranged from 414 to 3,432 U/L. The average time from presentation to pathologic diagnosis of RMS was 2.1 months. Nine of the 11 cases showed an alveolar pattern. All were high-stage disease. Of 7 patients with follow-up longer than 1 year, 2 (29%) are alive without disease. Conclusion: This report presents the need to consider the possibility of a malignant neoplasm, in this case RMS, in a child or adolescent with a putative perirectal abscess that fails to respond in the expected manner to incision and drainage and antibiotic therapy.     

Gangrenous intestine in a hernia can be reduced

A 3-month-old former 31-week premature triplet presented with a perforated terminal ileum 36 hours after complete reduction of an incarcerated inguinal hernia. Classic pediatric surgery teaching asserts that gangrenous bowel in an inguinal hernia will not reduce. In this case, gangrenous bowel was reduced and proceeded to perforate after reduction. Though extremely rare, it is possible to reduce gangrenous bowel, and disposition requires reliable observation at home or hospitalization, if circumstances warrant. J Pediatr Surg 37:919-920.     

Prevalence of domestic violence and associated factors among women on a trauma service

BACKGROUND: Despite the increasing recognition of the problem of domestic violence (DV), it has not been studied in surgical populations. METHODS: Eligible patients underwent screening for a recent history of DV and alcohol abuse (AA). Other demographic, health, and injury-related data were also collected. RESULTS: Of 127 subjects entered into the study, 18% screened positive for DV and 21% screened positive for AA. Of those screening positive for DV, 65% screened positive for AA compared with 12% of those screening negative for DV (p < 0.001.) Screening for DV was recommended by a vast majority of subjects, with only 6% of subjects responding that it was not appropriate. CONCLUSION: Both DV and AA have a high prevalence among female trauma patients admitted to trauma centers. Nearly all subjects recommended screening for DV. Screening for DV should be incorporated into the routine care of female trauma patients.     

Giggle incontinence in children: a manifestation of detrusor instability

PURPOSE: To our knowledge the prevalence and cause of giggle incontinence in children is not known. We hypothesized that laughter may induce unstable detrusor contractions in children susceptible to detrusor instability. We evaluated the prevalence of diurnal voiding symptoms of urinary urgency, urge incontinence, pelvic withholding maneuvers and hesitancy in patients with giggle incontinence, the prevalence of giggle incontinence in patients with diurnal voiding symptoms, the prevalence of the 2 conditions in first degree relatives of patients with giggle incontinence, the influence of treatment for detrusor instability on the frequency of giggle incontinence and the prevalence of diurnal voiding symptoms in control children with giggle incontinence. MATERIALS AND METHODS: Of 1,421 children 5 to 15 years old referred to the pediatric nephrology department for various problems 109 were diagnosed with giggle incontinence and 460 had diurnal voiding symptoms. A total of 627 children visiting the pediatrician office whose parents completed a survey questionnaire served as controls. RESULTS: Diurnal voiding symptoms were noted in 95% of the patients with giggle incontinence, while giggle incontinence was noted in 23% of those with diurnal voiding symptoms. Of the patients with giggle incontinence a positive family history for that entity and diurnal voiding symptoms was noted in 13% and 28%, respectively. Giggle incontinence improved in all patients after treatment for detrusor instability and it resolved completely in 89%. Giggle incontinence recurred with a relapse of diurnal voiding symptoms in 28 cases and improved with improved diurnal voiding symptoms during modification of therapy. Diurnal voiding symptoms were present in 43% of the 157 controls with giggle incontinence. CONCLUSIONS: Giggle incontinence results from detrusor instability induced by laughter and it improves with effective treatment of detrusor instability.     

Outcome of relapse in lupus nephritis: roles of reversal of renal fibrosis and response of inflammation to therapy

BACKGROUND: Renal relapse in lupus nephritis has been shown to have ominous prognostic significance with the majority of patients progressing to doubling of serum creatinine (CRX2). However, not all patients do so. This report explores the roles of response of inflammation to therapy and of glomerular scarring and interstitial fibrosis and their potential reversal to outcome of renal relapse. METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy, as well as subsequent biopsies for clinical indications, were studied. The relationships of morphologic factors to renal relapse and its outcome as well as to CRX2 and end-stage renal disease (ESRD) were analyzed. Cox proportional hazards modeling was used to assess association of morphologic variables with outcomes. RESULTS: Renal interstitial fibrosis and glomerular segmental scarring were partially reversible in 17 and 11 patients, respectively. This decline was associated with an excellent prognosis, with only one patient in each group (5.9% and 9.1% respectively) progressing to CRX2. All 18 patients who progressed to CRX2 either failed to respond to therapy (7 patients) as defined by normalization of serum creatinine (SCr) and reduction of proteinuria to < or =1 g/day, or relapsed after initial response (11 patients), as defined by recent rise of SCr > 50% and/or proteinuria > 3.5 g/day. However, relapse also occurred in 11 of 47 other patients without progression to CRX2. These patients showed a greater initial response of inflammation and deposits to therapy and fibrous lesions partially reversed in the period prior to relapse, so that active lesions were superimposed on a lower level of chronic lesions. By contrast, chronic lesions mounted steadily in those who progressed to CRX2. Cox proportional hazards modeling indicated a strong association of inflammatory variables with renal relapse, CRX2 and ESRD. However, the extent of immunoglobulin deposits was not significantly associated with any outcome. Finally, we found that failure of disease to remit also is associated with a high rate of CRX2 (64.8% vs. 13.0%, P = 0.00034). CONCLUSIONS: Interstitial fibrosis and glomerular scarring in systemic lupus erythematosus are partially reversible, and this reversal is attended by an excellent outcome. The outcome of renal relapse is determined by the initial response of inflammatory and chronicity elements to therapy, those with prior partial reversal of interstitial and glomerular scarring having a good outcome, and those in whom fibrotic lesions have continued to increase and have a poor outcome. Inflammatory variables appear to be more important in determining outcome than immunoglobulin deposits.     

Endogenous postmenopausal hormones and carotid atherosclerosis: a case-control study of the atherosclerosis risk in communities cohort

Studies examining the relation between endogenous postmenopausal hormone levels and cardiovascular disease have yielded conflicting results. After excluding women with a history of hormone replacement therapy (HRT) use, the authors conducted a US case-control study in 1987-1992 comparing endogenous postmenopausal hormone levels in women with and without significant carotid atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) cohort. Atherosclerosis was assessed by using B-mode ultrasound to measure carotid artery intimal-medial thickness (IMT). Cases (n = 182) were postmenopausal women with average IMT measurements greater-than-or-equal the 95th percentile. Controls (n = 182) were frequency matched to cases on age and ARIC center and had IMT measurements < the 75th percentile. After adjustment for cardiovascular risk factors, no association was found between the odds of atherosclerosis and increasing quartiles of estrone, dehydroepiandrosterone sulfate, or androstenedione. Compared with participants in the lowest quartile of sex hormone-binding globulin (SHBG), those in the highest quartile had a significantly lower odds of atherosclerosis (odds ratio = 0.48, 95% confidence interval: 0.24, 0.97). Similarly, participants in the highest quartile of total testosterone had a lower odds of atherosclerosis (odds ratio = 0.38, 95% confidence interval: 0.20, 0.74). The authors found higher total testosterone and SHBG to be inversely related to carotid atherosclerosis, suggesting their potential importance in reducing atherosclerotic risk in postmenopausal women not using HRT.     

Haptoglobin genotypes are not associated with resistance to severe malaria in The Gambia

The influence of haptoglobin polymorphisms on severe malaria occurrence was assessed in 1183 individuals from The Gambia. No significant association was found between severe malaria and either haptoglobin genotypes or phenotypes. The advantages of using a deoxyribonucleic acid-based haptoglobin typing method are discussed.