Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I‐MIBG accompanied by ASCT for high‐risk and relapsed neuroblastoma: A pilot study

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant ¹³¹I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day ?30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m²), carboplatin (1500 mg/m²), and melphalan (210 mg/m²). Non‐MIBG‐avid subgroup received etoposide (600 mg/m²), carboplatin (1200 mg/m²), and melphalan (150 mg/m²). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.     

Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy

Citation Moravej A, Jeddi‐Tehrani M, Salek‐Moghaddam AR, Dokouhaki P, Ghods R, Rabbani H, Kazemi‐Sefat GE, Shahbazi M, Zarnani AH. Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy. Am J Reprod Immunol 2010; 64: 97–103 Problem In pregnant women with antithyroglobulin antibody, prevalence of abortion is 2–4 fold higher compared to normal controls. Direct effect of such harmful autoantibodies on female reproductive organs may serve a role in pregnancy loss. Method of study Expression of thyroglobulin in decidua, placenta, and ovary of pregnant Balb/c mice ((Balb/c×Balb/c and Balb/c×C57BL/6) during early, middle, and late stages of pregnancy was evaluated. Expression of thyroglobulin was investigated in these tissues by semi‐quantitative RT‐PCR. In addition, polyclonal antithyroglobulin antibody was produced, and expression of thyroglobulin protein in aforesaid tissues was evaluated by immunohistochemistry and dot‐blot analysis. Results The results showed that thyroglobulin message is not expressed in placenta, decidua, or ovary in any stages of pregnancy. The same results were obtained at the protein level. Conclusion It is likely that antithyroglobulin antibodies have no direct detrimental effect on such organs in patients with thyroid autoimmunity suffering from recurrent abortion.     

Comparative evaluation of two fixed doses of 185 and 370 MBq 131I, for the treatment of Graves' disease resistant to antithyroid drugs

Radioiodine (131I) treatment is often applied for the treatment of Graves' disease (GD). The optimal dose of 131I for Graves' hyperthyroidism is debated. Various techniques suggest either fixed doses or varying doses based on elaborate calculations of the gland size, 131I uptake, and 131I turnover. Fixed dose regimens avoid dose calculations but there is no consensus on the actual dose to be administered. We compared two routinely recommended fixed 131I doses of 185 and 370 MBq for this purpose. Fifty nine patients with GD who had not been previously treated with 131I were randomized in two groups. Group A consisted of 33 patients who were treated with 185 MBq of 131I. Group B consisted of 26 patients who were treated with 370 MBq of 131I. Group A patients were 21% male and 78% female, mean age 38.1+/-14.4, range 15 to 77 y. Group B patients were 27% male and 73% female, mean age 40.7+/-11.7, range 27 to 72 y. All patients were reexamined every six months for two years. The following clinical outcomes were noticed: a) Persistent hyperthyroidism, which was considered as failure to treatment, requiring further 131I treatment. b) Hypothyroidism; requiring life-long replacement treatment. c) Euthyroid state. Euthyroid and hypothyroid states were considered as a response to treatment of hyperthyroidism. In Group A, 10 patients (30.3%) became euthyroid and 6 (18.2%) hypothyroid (an overall response of 48.5%), while 17 (51.5%) remained hyperthyroid by the end of the follow-up period. In Group B, 10 patients (38%) became euthyroid and 13 (50%) hypothyroid, an overall response of 88.5%. Non responders were 3 patients (11.5%). No correlation was noted between the outcome of treatment and age, sex, size of the thyroid gland or thyroid uptake in each Group of patients, while a significant correlation was noted between the disease outcome and the amount of administered 131I (P<0.003). The incidence of hypothyroidism by the end of two years of follow up was less in Group A than in Group B and the incidence of non responders to treatment was lower in Group A. In view of the higher cost of treatment, the longer time elapsing to treatment, the number of office visits by the patients and the higher number of patients with persistent hyperthyroidism in Group A, we conclude that a fixed dose of 131I of 370 MBq is more useful and effective for the treatment of GD as compared to 185 MBq of 131I.     

Laparoscopic surgery in Crohn's disease

Laparoscopic surgeons attempting to treat Crohn's disease must have experience working with inflammatory bowel disease and advanced laparoscopic skills. Nonetheless, laparoscopy is dramatically changing all aspects of gastrointestinal surgery and inflammatory bowel disease, including Crohn's disease, is likely to benefit, as well. This article defines the role of laparoscopy in treating Crohn's disease and outlines surgical therapy.     

A correlative study comparing current different methods of calculating left ventricular ejection fraction

BACKGROUND: Left ventricular ejection fraction (EF) is a major determinant of survival in patients with coronary artery disease (CAD). Comparative accuracy of numerous modalities in calculating EF is not well investigated. METHOD: We compared EF as calculated by rest and post-stress Cedars automated quantitative gated SPECT (AQGS), rest and post-stress semi-automatically processed gated SPECT (MQGS), echocardiography and contrast ventriculography (LVG) to those determined by rest and post-stress cavity-to-myocardium ratio (CMR) in 109 patients. Gated SPECT was performed based on a 2-day protocol using Tc-MIBI. RESULTS: Mean EF in LVG, echo, post-stress CMR, rest CMR, post-stress AQGS, rest AQGS, post-stress MQGS and rest MQGS were 41.8%+/-12.1, 44.8%+/-11.8, 38.1%+/-10.7, 35.7%+/-12.1, 44.5%+/-15.1, 46.9%+/-14.7, 40.1%+/-14.3 and 43.5%+/-14.3 respectively. Although significant differences were observed between some of these methods, good and excellent linear correlations were present among values (all Pearson correlations >0.63). Considering LVG as the 'gold standard', we defined two groups: EF <35% (class 1) and >35% (class 2). Discriminant analysis showed that SPECT has the ability to predict patients' classes. In 4/18 of patients with normal SPECT (on both visual and quantitative analyses, SSS <4), EF on QGS showed a significant decrease on post-stress compared with rest. CONCLUSION: There is a good correlation in calculating EF by LVG, QGS and echocardiography, regardless of EF value. Whenever QGS is impossible, CMR is a reliable indirect indicator of EF. Gating of both phases (and when impossible, CMR of both phases) has an additional value in diagnosis of CAD.     

Association of Plasma Retinol Binding Protein-4 (RBP4) and Sonographic Grading of Fatty Liver in Obese Iranian Children

Background

The prevalence of obesity and its related comorbidities, such as fatty liver, in children is increasing worldwide mostly due to changes in diet and life-style. Many serological markers have been suggested for screening of fatty liver but investigations for finding more reliable factors are still in progress.

Objectives

This study aimed to investigate the correlation between the level of retinol binding protein-4 (RBP4) in the serum and sonographic grading of fatty-liver severity in obese Iranian children.

Patients and Methods

This case-control, double-blind study involved 51 obese children aged between five and 17 years as the case group. In addition, 35 healthy lean children with no liver problems were selected as the control group. Plasma RBP4 (using an ELISA), serum triglycerides (TG), low-density-lipoproteins (LDL), high-density-lipoproteins (HDL), total-cholesterol (Chol), and body mass index (BMI) were measured. Grading the severity of the fatty liver condition was done by an expert radiologist in the case group.

Results

RBP4 levels in obese children (19 482.9 ± 3 302.2 pg/ml) were higher than those found in the lean control group (14 295.68 ± 2 381.3 pg/ml) (P < 0.05). In the obese patients, RBP4 levels showed a significant correlation with the grade of fatty liver and BMI (P < 0.05).

Conclusions

It was found that the level of RBP4 had a strong correlation with the severity of fatty liver. Therefore, RBP4 may be considered as a useful, noninvasive predictive biomarker of intrahepatic lipid content in obese children prior to using radiological investigations. In particular, abdominal sonography, for the evaluation of intrahepatic lipid content in obese patients, as the sensitivity of a sonography is decreased due to the increased thickness of the abdominal wall as a result of fat deposits.     

Outcomes and recurrence rates in chronic subdural haematoma

The object of this study was to determine the relationship between outcome (assessed by Glasgow Outcome Scale) and recurrence in chronic subdural haematoma (CSDH). Eighty-two consecutive patients who underwent surgery for CSDH were included in this study. The relationship between the following variables and CSDH recurrence was studied: sex; age; history of trauma; Glasgow Coma Scale (GCS) at the time of admission (stage 1: GCS>12, stage 2: GCS: 8 - 12, stage 3: GCS<8); interval between head injury (when a history of trauma was present) and surgery; presence of a midline shift on CT scans; presence of intracranial air 7 days after surgery; haematoma density; haematoma width; presence of brain atrophy; and Glasgow Outcome Scale (GOS, both quantitative and non-quantitative) at the time of discharge. Throughout the analysis, p<0.05 was considered statistically significant. The results showed lower GCS (p<0.001), higher GOS (p<0.001), presence of intracranial air 7 days after surgery (p=0.002), and a high density haematoma (p<0.001) were significantly associated with recurrence of CSDH. It was concluded that GOS is related with recurrence in CSDH.     

Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial

Background

Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI).

Methods

As a randomized clinical trial, one hundred twenty patients (103 male and 17 female) with angiographically confirmed CAD who were on long-term beta blocker therapy (≥3 months) enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60) in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60) without discontinuation of beta-blockers prior to DMPI.

Results

No significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility) in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096). Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001); however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898). The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7%) was not statistically different from group B (90%).

Conclusion

Beta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.