A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

A profile of invasive cutaneous malignant melanoma in Malta: 1993–2002

BACKGROUND: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. OBJECTIVE: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. RESULTS: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100,000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100,000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (< or = 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. CONCLUSION: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.     

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.     

Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model. METHODS: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. CONCLUSIONS: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.     

How does fast track affect quality of care in the emergency department?

STUDY OBJECTIVES: Use of fast track has been shown to improve the emergency department flow of less urgent patients. It has been speculated, however, that this could negatively affect the care of urgent patients. The objective of this study was to determine whether a dedicated fast track for less urgent patients [Canadian Triage and Acuity scale category 4/5 (CTAS 4/5)] affected (1) the time to assessment for urgent patients (CTAS 3), (2) the length of stay for less urgent patients (CTAS 4 and 5), and (3) the left-without-being-seen rate. METHODS: In June 2003, fast track was opened in our emergency department from 13:00 to 19:00 h. A before-after intervention comparison analysis was completed for 1 week in Aug 2002 and the same week in Aug 2003. Data collected included (1) time to assessment of CTAS 3 patients, (2) the length of stay for CTAS 4/5 patients, and (3) percentage of patients who left without being seen. RESULTS: A total of 368 patients were reviewed for 2002 and 380 patients were reviewed for 2003. Median time to assessment of CTAS 3 patients presenting from 13:00 to 19:00 h was reduced from 66 min (Interquartile range: 40, 94 min) in 2002 to 60 min (IQR: 38, 108 min) after fast track was open in 2003 (P = 0.95). Median length of stay of CTAS 4 and 5 patients was reduced from 170 min (IQR: 111, 256 min) to 110 min (IQR: 69, 185 min) (P < 0.001). The overall left-without-being-seen rate decreased from 5% (20/368) to 2% (9/380). CONCLUSION: A dedicated fast track for CTAS 4/5 patients can reduce the length of stay and the left-without-being-seen rate with no impact on CTAS 3 patients seen in the main emergency department.     

Revascularized fibula for tibia replacement in adamantinoma

Adamantinoma of long bones is one of the rarest of malignant bone tumors; it is commonly located in the middle or lower third of the diaphysis of the tibia. A case with multiple occurrences affecting both the tibia and fibula is presented. En bloc resection with wide operative margins was performed, and a large tibial defect of 23 cm was effectively bridged by a revascularized free fibular flap. At 13 months follow-up, there was no sign of local recurrence or metastasis, and the patient was mobile.     

Sexual function in patients presenting to a urogynecology practice

The purpose of this study was to evaluate sexual function in women referred to a urogynecology practice. All new patients were mailed an optional female sexual function index (FSFI) in conjunction with their history forms; other sexual function information was obtained during the physician interview. Over 6 months, four hundred fifty new patients were enrolled. Of these, 243 (54%) were not sexually active. Reasons listed for sexual inactivity included partner problems/no partner (32%), low desire (14%), prolapse (10%), and pain (10%). There were several differences between sexually active and non-sexually active participants; however, after a multivariate analysis, only age, marital status, and stage/grade 1–2 of prolapse remained significant. One hundred nine sexually active patients completed the FSFI; the majority was sexually active two to four times per month. Female sexual dysfunction was noted in 70 (64%) patients. Lowest scores were noted for the domain of desire, followed by arousal, orgasm, lubrication, satisfaction, and pain. Reduced frequency of intercourse was the only factor significantly associated with dysfunction. Ninety-four percent were not embarrassed by the survey. Overall, sexual inactivity is common in patients presenting for urogynecologic care. Those that are sexually active report low rates of sexual activity and high rates of sexual dysfunction. Most sexually active patients will accept a sexual function questionnaire as part of their routine assessment.This research was presented at the American College of Obstetricians and Gynecologists annual clinical meeting, May 10, 2005, San Francisco, CA, USA.