Mechanism of ventricular tachycardia in a patient with double-outlet left ventricle

We report the case of ventricular tachycardia (VT) ablation procedure in a patient with history of surgically repaired double-outlet left ventricle. The electrophysiology procedure revealed a re-entry pattern between the right-ventricle to main-pulmonary-artery conduit and the tricuspid annulus. The re-entrant mechanism was most likely promoted by a fibrous remodeling of this area, related to the surgical repair. This case is the first to describe a re-entry mechanism between fixed anatomical barriers in a repaired right ventricle of a double-outlet left ventricle. A pace mapping technique was used to highlight the VT isthmus.     

Surgical treatment of piles

PURPOSE: The present prospective, randomized clinical trial compares the outcome of surgical hemorrhoidectomy according to Parks and Milligan-Morgan in terms of hospital stay, duration of incapacity to work, symptom relief, length of morbidity, and patient convenience. METHODS: Thirty-four consecutive patients with third or fourth degree internal hemorrhoids were randomly allocated to the two groups. Before surgery, all patients were interviewed using a standard questionnaire, followed by rectal examination. All patients underwent a follow-up interview and examinations 1, 2, 4, 8, and 12 weeks after the operation. RESULTS: No serious postoperative complications were seen. Length of hospital stay (3.2 days for Parks hemorrhoidectomyvs. 4.6 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 0.2 and 2.6, respectively;P=0.02) and mean duration of incapacity to work (12.3 days for Parks hemorrhoidectomyvs. 20.2 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 5.7 and 10.2, respectively;P<0.001) differed significantly between the Milligan-Morgan and Parks patients. Until two weeks after the operation, Milligan-Morgan hemorrhoidectomy patients experienced significantly more pain. CONCLUSIONS: Our study confirms that both operations are safe, easy to perform, and lead to satisfactory results. However, the Parks procedure is the preferred option, because it minimizes patients' postoperative discomfort, is more economic, has a significantly reduced hospital stay, and has a shorter time for return to work.     

Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens

PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.     

Does continuous positive airway pressure by face mask improve patients with acute cardiogenic pulmonary edema due to left ventricular diastolic dysfunction?

OBJECTIVE: Continuous positive airway pressure (CPAP) by face mask is an effective method of treating severe cardiogenic pulmonary edema (CPE). However, to our knowledge, no study has provided a precise evaluation of the effects of CPAP on cardiac function in patients presenting with CPE and preserved left ventricular (LV) function. DESIGN: Prospective observational clinical study. SETTING: A 14-bed, medical ICU at a university hospital. PATIENTS: Nine consecutive patients presenting with hypoxemic acute CPE. INTERVENTIONS: All patients were selected for 30 min of CPAP with 10 cm H(2)O by mask with fraction of inspired oxygen adjusted for a cutaneous saturation > 90%. Doppler echocardiography was performed before CPAP application and during the last 10 min of breathing with CPAP. Two-tailed, paired t-tests were used to compare data recorded at baseline (oxygen alone) and after CPAP. MEASUREMENTS AND RESULTS: Four patients presented CPE with preserved left ventricular (LV) function (a preserved LV ejection fraction [LVEF] > 45%, and/or aortic velocity time integral > 17 cm in the absence of aortic stenosis or hypertrophic cardiomyopathy). Oxygenation and ventilatory parameters were improved by CPAP in all patients. Hemodynamic monitoring and Doppler echocardiographic analysis demonstrated that in patients with preserved LV systolic function, mean arterial pressure and LV end-diastolic volume were decreased significantly by CPAP (p < 0.04). In patients with LV systolic dysfunction, CPAP improved LVEF (p < 0.05) and decreased LV end-diastolic volume (p = 0.001) significantly. CONCLUSION: CPAP improves oxygenation and ventilatory parameters in all kinds of CPE. In patients with preserved LV contractility, the hemodynamic benefit of CPAP results from a decrease in LV end-diastolic volume (preload).     

High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency

We have described a child suffering from Mendelian susceptibility to mycobacterial disease (MSMD) due to autosomal recessive, complete T-bet deficiency, which impairs IFN-γ production by innate and innate-like adaptive, but not mycobacterial-reactive purely adaptive, lymphocytes. Here, we explore the persistent upper airway inflammation (UAI) and blood eosinophilia of this patient. Unlike wild-type (WT) T-bet, the mutant form of T-bet from this patient did not inhibit the production of Th2 cytokines, including IL-4, IL-5, IL-9, and IL-13, when overexpressed in T helper 2 (Th2) cells. Moreover, Herpesvirus saimiri–immortalized T cells from the patient produced abnormally large amounts of Th2 cytokines, and the patient had markedly high plasma IL-5 and IL-13 concentrations. Finally, the patient’s CD4⁺ αβ T cells produced most of the Th2 cytokines in response to chronic stimulation, regardless of their antigen specificities, a phenotype reversed by the expression of WT T-bet. T-bet deficiency thus underlies the excessive production of Th2 cytokines, particularly IL-5 and IL-13, by CD4⁺ αβ T cells, causing blood eosinophilia and UAI. The MSMD of this patient results from defective IFN-γ production by innate and innate-like adaptive lymphocytes, whereas the UAI and eosinophilia result from excessive Th2 cytokine production by adaptive CD4⁺ αβ T lymphocytes.     

Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker

A prerequisite to dephosphorylation at Ser–Pro or Thr–Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker.