Screening for early cognitive impairment in multiple sclerosis patients using the clock drawing test

The clock drawing test (CDT) is a complex task assessing integrative functions, abstract thinking and visuospatial organization. In the present study we evaluated the CDT as a possible screening instrument for early cognitive impairment in multiple sclerosis (MS) patients. In total, 107 MS patients completed the CDT as well as a battery assessing five cognitive domains. There were 73 female and 34 male participants (mean age 45.4+/-11.6 years, range 19-69). The majority (76/107) were diagnosed with a relapsing-remitting disease course. Mean expanded disability status scale (EDSS) score was 4.3+/-2.4 (range 0-8). The CDT was scored on a 1-6 point scale with "1" being a perfect score and "6" reflecting severe disorganization. Mean CDT score was 2.6+/-1.4. In 53% of patients the CDT was normal while in 11.2% dementia was apparent. The CDT score did not correlate with the total EDSS. Significant correlations were obtained with the mental functional system score of the EDSS (r = 0.78; p = 0.0001), visual learning and recall, sustained attention and concentration. Our findings demonstrate the sensitivity of the CDT to several cognitive domains. The absence of correlation with total EDSS score coupled with significant correlation with the mental functional system suggests that the CDT may be useful for screening MS patients.     

Childhood and adolescent thyroid carcinoma

OBJECTIVES: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. METHODS: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years. There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease confined to the thyroid, 34 (60%) had additional lymph node metastasis to the neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4 patients, and a lobectomy in 4 patients. All 56 patients received postoperative thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of patients after their initial surgery. RESULTS: The overall survival rate was 98% with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The one death that occurred in this patient population was the result of a congenital heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their thyroid carcinoma. The time to first recurrence of disease ranged from 8 months to 14.8 years (mean, 5.3 years). None of those with disease confined to the thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in patients with lymph node metastasis and 29% (2 of 7) in patients with lung metastasis (P = 0.02). Tumor characteristics were evaluated for time to first recurrence utilizing the logistic likelihood ratio test to predict disease recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03), positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02) were significant for developing recurrent disease. Patients younger than 15 years old at diagnosis were more likely to have more extensive tumor at diagnosis than patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma of the thyroid in children and adolescents has little risk of mortality but a high risk of recurrence. Younger patients present with a more advanced stage of disease and are more likely to have disease recurrence. Total thyroidectomy and lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone replacement (suppressive) administration, and diligent surveillance are warranted.     

Increased maternal serum human chorionic gonadotropin concentrations are an independent risk factor for SGA in dichorionic twin gestations.

OBJECTIVE: To determine maternal and neonatal complications among dichorionic and monochorionic twins with isolated midtrimester elevated maternal serum human chorionic gonadotropin (MShCG). MATERIAL AND METHODS: MShCG was determined in 247 women with dichorionic twins and 32 women with monochorionic twins between 16-18 weeks gestation. Among the dichorionic twins 219 patients had MShCG < 2.5 MoM, 14 between 2.5-3.0 MoM and 14 above 3.0 MoM. Of the patients with monochorionic twins 15 had MShCG < 2.5 MoM, nine between 2.5-3.0 MoM and 8 above 3.0 MoM. All patients had maternal serum alpha fetoprotein < 2.5 MoM. Karyotype was normal among all neonates. Statistical analysis was performed with SPSS package. RESULTS: Patients with monochorionic twins had higher rates of cesarean section when MShCG was > 3.0 MoM (100% vs. 44%; p = 0.03) and of preterm delivery when MShCG was > 2.5 MoM (87.5% vs. 46.7%; p = 0.04). A non significant higher rate of small for gestational age (SGA) neonates was found when MShCG was > 2.5 MoM among first twin (37.5% vs. 13.3%; p = 0.08). In contrast, patients with dichorionic twins had higher rates of SGA neonates and low 1 minute Apgar scores in the second twin when MShCG was > 2.5 MoM (23.1% vs. 10%; p = 0.04, 15.4% vs. 11.9%; p < 0.01). A multivariate logistic regression model with forward stepwise selection was performed with SGA as outcome variable. The model included the following variables: MShCG, hypertensive disorders, gestational age at delivery, chorionicity, twin order, cesarean section (CS) and preterm delivery. MShCG levels were the only significant factor predicting SGA among bichorionic twins (OR 1.76, 95% CI 1.2-2.5). CONCLUSIONS: (1) Increased concentrations of MShCG are an independent risk factor for SGA among dichorionic twins. (2) MShCG > 2.5 MoM are associated with adverse maternal outcome among monochorionic twins.     

The impact of parental death versus separation from parents on the mental health of Israeli adolescents

Early research suggested that the loss of a parent during childhood can lead to depression and other psychopathology in children and adults. More recent research has differentiated between loss due to death and separation from parents and has questioned the link between early parental death and psychopathology. We examined the hypothesis that separation from parents has a more detrimental effect than the death of a parent on the mental health of adolescents in the community. Israeli adolescents (N = 844) with a mean age of 16.7 +/- 1.0 years (mean +/- SD) participated in this study. Seventy reported that a parent did not live at home during one of three 5-year periods until they reached the age of 15; 37 reported the death of a parent and 777 were from intact families. All participants completed the Brief Symptom Inventory (BSI), General Well Being Schedule (GWB), Parental Bonding Instrument (PBI), and Perceived Social Support Family/ Friends Scales (PSS-Fam and PSS-Fr). Adolescents who had experienced separation from parents had more psychiatric symptoms (BSI), expressed a lower sense of well-being (GWB), experienced less support from their family (PSS-Fam), and felt less cared for and more controlled by their parents (PBI) compared with those belonging to intact families. The death of a parent was not associated with significantly different scores on these variables. When we controlled for parental bonding (PBI) and perceived social support from family (PSS-Fam), the differences between the separation group and the intact family group were no longer significant. The psychological impact of separation from parents involves a greater risk for psychopathology than the death of a parent. The quality of the relationship with the parents moderates the negative impact of separation from them.     

RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients.

Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation-dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men.     

Apoptosis induction of human myeloid leukemic cells by ultrasound exposure

Therapeutic ultrasound (ULS) and the resulting cavitation process has been shown to induce irreversible cell damage. In this study, we wanted to further investigate the mechanism of ULS-induced cell death and to determine whether apoptosis is involved. High intensity focused pulsed ULS sonication at a frequency of 750 KHz was delivered to HL-60, K562, U937, and M1/2 leukemia cell line cultures. ULS exposure used with induction of transient cavitation in the focal area was delivered with an intensity level of 103.7 W/cm2 and 54.6 W/cm2 spatial-peak temporal-average intensity. As a control, ULS of lower intensity was delivered at 22.4 W/cm2 spatial-peak temporal-average intensity, presumably without generation of cavitation. Our results indicated that DNA damage induced by ULS cavitation did not involve generation of free radicals in the culture media. Morphological alterations observed in cells after exposure to ULS included: cell shrinkage, membrane blebbing, chromatin condensation, nuclear fragmentation, and apoptotic body formation. Apoptotic cells were evaluated by fluorescence microscopy and detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, which identifies DNA breaks, and by the leakage of phosphatidylserine from the inner to the outer side of the membrane layer of treated cells. Some bioeffects induced on sonicated HL-60 cells, such as inhibition of cell proliferation, DNA repair, and cell-dependent apoptosis, were found to be similar to those produced by gamma-irradiation. Thus, much of the cell damage induced by therapeutic ULS in leukemia cells surviving ULS exposure appears to occur through an apoptotic mechanism.     

Comparative study of Hebrew University-Hadassah Medical School participation in education council ofr foreign medical graduates (ECFMG) examination.

The achievements of the 874 (55%) medical graduates of Hebrew University-Hadassah School who took the ECFMG examination from 1962, when it was introduced in Israel, to 1972, were compared with those of candidates from other schools during the same period. The achievement level of candidates was high: usually above the 90th percentile rank position; 80 to 85% of its candidates passed the examination (compared to about 40% from all other schools); and the frequency distribution of ECFMG examination scores of HUHMS candidates in 1965 revelas a similarity to the achievements in American medical schools. The difference between the percentage of candidates passing the ECFMG examination from year to year supports the contention that the level of difficulty of the examinations varies. Candidates taking the examination after several years of clinical experience do not perform better. Since only 19% of all HUHMS graduates have gone abroad for postgraduate training, and only 11% have remained abroad for 4 or more consecutive years, participation in ECFMG has not been reflected in an increase in 'brain drain'.