Orofacial Muscle Weakening in Facioscapulohumeral Muscular Dystrophy (FSHD) Patients.

BACKGROUND: Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. METHODS: Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman's correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. RESULTS: A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. CONCLUSIONS: Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype-phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients.

New-onset atrial fibrillation and clinical outcome in non-cardiac intensive care unit patients.

BACKGROUND: Data regarding new onset atrial fibrillation (nAF) in general, non-cardiac, intensive care unit (ICU) patients are limited. However, it has been suggested that nAF is associated with worse clinical outcome in these patients. OBJECTIVE: The purpose of the present work was to study the prognostic impact of nAF, in this setting. METHODS: We prospectively studied all patients admitted to a single ICU for a period of 12 months. Patients admitted for brief post-operative monitoring, patients with chronic, intermittent atrial fibrillation and atrial fibrillation present upon admission, were excluded. Death during ICU stay (ICUD) was the pre-specified study end-point. Length of stay (LOS) for survivors was also reported. A number of factors related to the occurrence of nAF and the present disease were recorded for each patient. RESULTS: The study population was comprised of 133 patients. Twenty (15%) of them manifested nAF. The end-point of ICUD was observed in 27.1% of the patients. The median LOS reported was 8 days. Patients with nAF seemed to have significantly worse prognosis, compared to those who did not manifest nAF (OR=3.35, 95%CI:1.26-8.92; P=0.016). Additionally, nAF patients appear to require significantly extended LOS (P=0.01). Nevertheless, when the effect of nAF on ICUD was adjusted for sepsis, there was no statistically significant difference between those that manifested nAF and the rest of the patients. CONCLUSION: Patients suffering nAF seem to have worse prognosis during ICU stay. However, a direct impact of nAF on mortality was not documented.

Incidence and predictors of new-onset atrial fibrillation in noncardiac intensive care unit patients.

BACKGROUND: Atrial fibrillation (AF) is thought to be a relatively common arrhythmia in the setting of noncardiac intensive care unit (ICU). However, data concerning AF deriving from such populations are scarce. In addition, it is unclear which of the wide spectrum of AF predictors are relevant to the ICU setting. OBJECTIVES: The aim of our study was to evaluate the incidence of new-onset AF and investigate the factors that contribute to its occurrence in ICU patients. METHODS: We prospectively studied all patients admitted to our ICU during a 1-year period. Patients admitted for brief postoperative monitoring and patients with chronic or intermittent AF and AF present upon admission were excluded. A number of conditions incriminated as AF risk factors or "triggers" from demographics, medical history, present disease, and cardiac echocardiography as well as circumstances of AF onset were recorded. RESULTS: The study population consisted of 133 patients (90 males). Atrial fibrillation was observed in 15% of them. Age older than 65 years (P=.001), arterial hypertension (P=.03), systemic inflammatory response syndrome (P<.001), sepsis (P=.001), left atrial dilatation (P=.01), and diastolic dysfunction (P=.04) were significantly associated with the occurrence of AF. By multivariate analysis, it was demonstrated that only older than 65 years (odds ratio, 7.0; 95% confidence interval, 2.0-24.6; P=.003) and sepsis (odds ratio, 6.5; 95% confidence interval, 2.0-21.1; P=.002) independently predict new-onset AF. Patients manifesting AF were frequently hypovolemic (30%) and had electrolyte disorders (40%) as well as elevated and rising serum C-reactive protein (70%). CONCLUSION: A significant fraction of ICU patients manifest AF. The predictors of interest for the ICU patients might be considerably different than those of the general population and other subgroups with systemic inflammation possibly having a pivotal role.

Arguments for a left lateral predisposition of endometrioma.

OBJECTIVE: To analyze a hypothesis regarding the pathogenesis of endometriosis. DESIGN: Retrospective study. SETTING: Two academic endometriosis referral centers. PATIENT(S): We evaluated operative and pathologic reports of 251 women who underwent laparoscopic or laparotomy treatment of endometrioma from August 1996 to February of 2002 at Yale University School of Medicine and at the University of Crete Department of Obstetrics and Gynecology. INTERVENTION(S): Laparascopic examination. MAIN OUTCOME MEASURE(S): Statistical methods included chi(2) and Mann-Whitney U tests measuring incidence of right- vs. left-sided endometria. RESULT(S): One hundred seventy patients from Yale University and 81 Greek patients participated in this study. Endometrioma was significantly more frequent in the left ovary (139 of 206 [67.4%]) than in the right ovary (67 of 206 [32.6%]; odds ratio [OR] = 4.3; 95% confidence interval [CI) 2.9-6.5; chi(2) = 48.9) and significantly different from the expected proportion of 50% (chi(2) = 25.2). When bilateral endometriomas were included, 62.1% (184 of 296) were left-sided and 37.15 (112 of 296) were right-sided (OR = 17.5; 95% CI 1.9-3.8; chi(2) = 34.1). Dilated ovarian veins in were found in 22 (68.7%) of 32 Greek cases with endometrioma. All 20 women with left endometrioma had left ovarian vein dilated. CONCLUSION(S): We suggest a new mechanical theory of implication, the female varicocele theory, which could play an important role in the development of ovarian endometriosis or endometriomas.

Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy.

PURPOSE: To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three cycles of "intensified" CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. RESULTS: HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. CONCLUSIONS: For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.