Arrhythmias in Common Arterial Trunk (CAT): Uncommon Atrial Tachycardia in CAT with Anomalous Pulmonary Venous Connection and Re-entry Atrial Tachycardia in CAT with HIV Seropositive Mother

We show a brief report of two common arterial trunk cases (CAT) with different arrhythmias and discuss anatomy, clinical and diagnostic management. The burden of volume and pressure overload of this cardiac malformation may predispose to different types of arrhythmia before and after surgical repair. Because of labile hemodynamic state in this group of patients, prompt diagnosis of any arrhythmia is mandatory as the devastating factor on prognosis. The first patient with a diagnosis of CAT Type II Collett and Edwards (CE) had a particular history with HIV seropositive mother assuming antiretroviral therapy during pregnancy, who presented hyperbilirubinemia and liver dysfunction at birth, and re-entry atrial tachycardia after repair. The second patient had CAT Type I CE with a partial anomalous venous connection of left superior pulmonary vein and uncommon type of atrial tachycardia with dual AV nodal physiology.     

Transvaginal and transabdominal sonography: prospective comparison

Transvaginal (TV) and transabdominal (TA) sonography were compared in a prospective study. A total of 230 examinations (126 pelvic, 104 pregnancy) were performed on 215 patients, ranging in age from 14 to 80 years. The improved anatomic detail on TV scans yielded new information in 138 (60%) examinations and better visualization of pelvic structures in 51 (22%) examinations. There was no important difference in diagnostic information provided by the two imaging modalities in 36 (16%) cases, and TV images were worse in five (2%). The clinical diagnosis was altered on the basis of TV sonographic findings in 54 (24%) cases and confirmed with certainty in 166 (72%). Diagnostic problems posed by TA scanning were not resolved by TV scanning in ten (4%) instances. Statistical analysis indicated that TV scanning was significantly better than TA scanning in the visualization of gestational sac contents (P less than .005), detection of fetal heart motion (P less than .001), and evaluation of the endometrial canal in the retroverted or retroflexed uterus (P less than .001). TV scanning was significantly better than TA scanning in visualization of the ovaries in patients with uterine leiomyomas (P less than .005) but not significantly better in peri- and postmenopausal patients (P greater than .05).     

Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Introduction

The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.

Method

A total of 187 breast cancer patients with either early-onset breast cancer (at age ≤ 40 years) or a personal and/or family history of breast or ovarian cancer were comprehensively tested by full sequencing of both BRCA1 and BRCA2. Two algorithms to predict the presence of mutations, the Manchester Scoring System and BOADICEA, were evaluated.

Results

Twenty-seven deleterious mutations were detected (14 in BRCA1 and 13 in BRCA2), only one of which was found in two unrelated individuals (BRCA2 490 delCT). In addition, 47 variants of uncertain clinical significance were identified (16 in BRCA1 and 31 in BRCA2). Notably, many mutations are novel (13 of the 30 BRCA1 mutations and 24 of the 44 BRCA2). We report that while there were an equal proportion of BRCA1 and BRCA2 mutations in the Chinese population in our study, there were significantly more BRCA2 mutations among the Malays. In addition, we show that the predictive power of the BOADICEA risk-prediction model and the Manchester Scoring System was significantly better for BRCA1 than BRCA2, but that the overall sensitivity, specificity and positive-predictive value was lower in this population than has been previously reported in Caucasian populations.

Conclusion

Our study underscores the need for larger collaborative studies among non-Caucasian populations to validate the role of genetic testing and the use of risk-prediction models in ensuring that the other populations in the world may also benefit from the genomics and genetics era.     

Selection of Patients for Treatment of Brain Arteriovenous Malformations by the Transvenous Approach: Relationship with Venous Anatomy and Risk of Hemorrhagic Complications

BACKGROUND AND PURPOSE:Intracranial hemorrhage represents a severe complication of brain arteriovenous malformation treatment. The aim of this cohort was to report the rate of hemorrhagic complications after transvenous endovascular embolization and analyze the potential angioarchitectural risk factors as well as clinical outcomes.MATERIALS AND METHODS:During an 11-year period, 57 patients underwent transvenous endovascular embolization. All cases of hemorrhagic complications were identified. We analyzed the following variables: sex, age, hemorrhagic presentation, Spetzler-Martin grade, size of the AVM before the transvenous treatment, number of venous collectors, pattern of drainage, presence of dilated veins, and technical aspects. Univariate and multivariate multiple regression analyses were performed to evaluate the potential risk factors for procedure-related hemorrhagic complications.RESULTS:Hemorrhagic complications (either intraprocedural or periprocedural) unrelated to a perforation due to micronavigation occurred in 8 (14.0%) procedures. Significant (mRS > 2) and persistent neurologic deficits were present in 2 (3.5%) patients at 6-month control. Larger nidi, especially >3 cm (P = .03), and a larger number of venous collectors have shown a statistically significant correlation with hemorrhagic complications. Only the number of venous collectors was identified as an independent predictor of hemorrhagic complications in the multivariate analysis (OR, 8.7; 95% confidence interval, 2.2–58.2) (P = .006).CONCLUSIONS:Larger nidus sizes and an increased number of venous collectors may increase the risk of hemorrhagic complications when implementing transvenous endovascular treatment of AVMs. The technique is effective and promising, especially with small nidi and single venous collectors.

Endovascular treatment for brain arteriovenous malformations (bAVMs) was traditionally focused on targeting the nidus through an intra-arterial approach, whether as a means of curative treatment or targeted embolization as an adjunctive or emergency treatment. In an attempt to target parts of the nidus that lie in the deep brain areas or that are supplied by very thin or perforating arterial branches, transvenous endovascular embolization (TVE) has emerged and is becoming a new tool to target otherwise incurable brain AVMs.^1-3Even though TVE has several advantages, including a very high rate of angiographic cure up to 92.6%³ and a means of curing otherwise incurable bAVMs,^4,5 it still needs to be used very selectively, to reduce hemorrhagic complications (HC).Nevertheless, the technique is not exempt from intraprocedural or periprocedural complications. Hemorrhagic complications represent the most important and challenging procedure-related issues with this technique, which may lead to poor clinical outcomes.^6-9A greater understanding of the frequency and risk factors for HC may optimize patient selection for TVE. The aim of this study was to estimate the rates of intraprocedural and periprocedural hemorrhage after TVE for bAVMs, to assess the morbidity and mortality associated with bleeding, and to analyze the angioarchitectural risk factors linked with such complications.     

Discordant Left and Right Ventricular Optimal Atrioventricular and Interventricular Delays during Biventricular Pacemaker Optimization

Echocardiography‐guided optimization of atrioventricular (AV) delay (AVD) improves left ventricular (LV) filling, and optimized interventricular delay (VVD) leads to further improvement in cardiac output in patients with biventricular (Biv) pacing. Investigators use LV filling and ejection to optimize AV and VV delay in patients with Biv pacing. Effect of such optimization on right‐sided hemodynamics remains unknown. In our experience, few patients experience worsening of right ventricle (RV) hemodynamics when LV parameters are optimized. We present a series of cases where we observed suboptimal RV filling or ejection at optimal AVD and VVD for LV. This RV‐LV discordance may contribute to nonresponder rate to cardiac resynchronization therapy (CRT) and should be evaluated in a consecutive series of CRT nonresponder patients to help improve CRT response.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

DIAPHRAGMATIC PARALYSIS IN MOTOR NEURONE DISEASE: USE OF NON-INVASIVE INVESTIGATIVE AND THERAPEUTIC TECHNIQUES

SUMMARY Two cases of bilateral diaphragmatic weakness are described in which the condition was the presenting feature of motor neurone disease. Inspiratory muscle strength was assessed by a non-invasive technique involving measurements of pressures generated within the mouth. One patient with severe inspiratory muscle weakness is being treated with domiciliary nasal ventilation and has returned to a good-quality life. The other patient with less severe weakness has thus far required no ventilatory support.     

The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture

OBJECTIVES: To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals. DESIGN: Placebo-controlled, randomized, double-blind trial. SETTING: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers. PARTICIPANTS: One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity. INTERVENTION: Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy. MEASUREMENTS: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels. RESULTS: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant. CONCLUSION: Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.     

The role of MAP kinase kinase in interleukin-3 stimulation of proliferation

Expression of a dominant interfering mutant of MAP kinase kinase (MAPKK) inhibits interleukin-3 (IL-3) activation of MAP kinase in the murine bone marrow-derived cell line BAF3. This results in an increase in the level of IL-3 required to stimulate cell proliferation and suppress apoptosis. When apoptosis is constitutively inhibited by coexpression of bcl-2, the dominant interfering MAPKK inhibits IL-3 driven cell cycle progression. Thus, MAPKK function is necessary for optimal IL-3 inhibition of apoptosis and optimal IL-3 stimulation of entry into S phase. Expression of a constitutively activated mutant of MAPKK does not replace IL-3, but renders cells able to proliferate in a density-dependent manner. Cell contact is required to allow cell proliferation; such contact can be supplied by cells without activated MAPKK.