Identification of FUS p.R377W in essential tremor.

BACKGROUND AND PURPOSE: Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma (FUS) segregating with essential tremor (ET) within a large French-Canadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated. METHODS: The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing. RESULTS: Sequencing of FUS identified a previously reported non-pathogenic mutation p.G174_G175del in one ET patient and two healthy controls, and a novel p.R377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis. CONCLUSION: This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.

Naming the Dead - Confronting the Realities of Rapid Identification of Degraded Skeletal Remains.

The Armed Forces DNA Identification Laboratory (AFDIL) is one of the leading laboratories in the world for the processing of degraded skeletal remains. Extended efforts have been made to develop protocols and standards that will hold up to the intense scrutiny of both the scientific world and the U.S. legal system. Presented in this paper are the specifics of the in-house systems and procedures that have allowed AFDIL to streamline the processing of degraded skeletal remains and family references for mitochondrial DNA (mtDNA) analysis. These include the development of our in-house bioinformatics systems by which every package and sample that passes through the laboratory is tracked; protocols designed specifically for both questioned and reference samples; and the difficulties inherent in this type of organization. Two case studies presented involve one of ancient remains and one on the recent event of September 11, 2001. Finally, future directions available to both AFDIL and the DNA analysis community as a whole are discussed.

Silicon migration from oxygen to carbon and decarbonylation in methoxytriphenylsiloxycarbene.

[reaction: see text] Thermolysis of 2-methoxy-2-triphenylsiloxy-5,5-dimethyl-Delta(3)-1,3, 4-oxadiazoline affords methyl triphenylsilylformate and methyl triphenylsilyl ether via methoxytriphenylsiloxycarbene. Kinetics show that the carbene undergoes reversible 1,2-triphenylsilyl migration (Brook rearrangement) as well as irreversible decarbonylation. Computed transition states and activation energies (B3LYP/6-31+G) suggest that the migration of the silyl group from oxygen to carbon occurs through an "in plane" transition state with the carbene lone pair forming a new bond to silicon. Decarbonylation involves a four-membered ring, achieved by nucleophilic attack of the oxygen atom of the methoxy group at silicon.

Herniation of the hepatic flexure through the foramen of Winslow: a case report.

Herniation through the foramen of Winslow is among the rarest of internal hernias. Predisposing factors include an enlarged epiploic foramen, a mobile cecum and ascending colon, and an abnormal length of small bowel mesentery. Obstruction, strangulation, and perforation with associated metabolic and septic sequelae are the major complications associated with this disease. We report a case of herniation through the foramen of Winslow in which the diagnosis was established preoperatively.

A validation study for the extraction and analysis of DNA from human nail material and its application to forensic casework.

A validation study was conducted to demonstrate that deoxyribonucleic acid (DNA) could be successfully extracted from human nail material and analyzed using short tandem repeat (STR) profiling and/or mitochondrial DNA (mtDNA) sequencing. This study involved the development of a DNA extraction protocol that includes a cleaning procedure designed to remove external contaminants (e.g., biological, chemical). This protocol was used to test human nail material that had been soaked in whole blood from a second donor and coated with gold-palladium to simulate scanning electron microscopic analysis. The results showed no indication of a mixture and were consistent with that of the nail donor. Fresh human nail material usually yielded both STR profiles and mtDNA sequence information; however, aged human nail material (approximately eight years old) yielded only mtDNA sequence information. Upon completion of the validation study, the extraction protocol was used for the analysis of a torn fingernail fragment recovered from the scene of a violent homicide in 1983. A partial STR profile and mtDNA sequence information indicated that the fingernail fragment was excluded as originating from the suspect and was, in fact, consistent with originating from one of the victims.

Imipramine overdose complicated by toxic megacolon.

Tricyclic antidepressants are a class of drugs commonly used for the treatment of depression. Tricyclic antidepressants account for approximately 20 to 25 per cent of drug overdoses that require acute medical admission. The most common cause of mortality is cardiovascular toxicity (e.g., arrhythmia, heart block, or hypotension). Other morbidities include conditions secondary to anticholinergic effects (central and peripheral) and respiratory complications. Ileus, constipation and urinary retention are common peripheral anticholinergic sequelae, whereas unusual complications include pancreatitis, intestinal pseudo-obstruction with cecal perforation, and sigmoid colon gangrene. We report a case of imipramine overdose that was complicated by toxic megacolon with an associated perforation.

U.S. suburbanization in the 1980s.

"This paper measures and analyzes differences in rates of suburbanization during the 1980s among U.S. metropolitan areas which fit a monocentric urban model. Three findings are of interest: (1) the average rate of suburbanization for U.S. metropolitan areas was the same in the 1980s and the 1970s; (2) the monocentric urban model provides a good description of population distribution for a diminishing number of urban areas; and (3) variables that characterize the entire metropolitan area as well as those that measure disparities between the central city and its suburban ring are important in explaining differences in rates of decentralization."

Severe Burkholderia (Pseudomonas) gladioli infection in chronic granulomatous disease: report of two successfully treated cases.

Chronic granulomatous disease (CGD) is characterized by a defect in phagocytic cells that leads to recurrent superficial and deep pyogenic infections. Burkholderia (Pseudomonas) gladioli is a gram-negative bacillus in the pseudomallei group of pseudomonads that is known primarily as a plant pathogen. We report two cases of pneumonia, one accompanied by septicemia, caused by B. gladioli in patients with CGD and their successful treatment with antibiotics. We believe these represent the first reports of human disease caused by this organism. We conclude that B. gladioli should be considered a potential pathogen in patients with CGD.

Distal wound complications following pedal bypass: analysis of risk factors.

Wound complications of the pedal incision continue to compromise successful limb salvage following aggressive revascularization. Significant distal wound disruption occurred in 14 of 142 (9.8%) patients undergoing pedal bypass with autogenous vein for limb salvage between 1986 and 1993. One hundred forty-two pedal bypass procedures were performed for rest pain in 66 patients and tissue necrosis in 76. Among the 86 men and 56 women, 76% were diabetic and 73% were black. All but eight patients had a history of diabetes and/or tobacco use. Eight wounds were successfully managed with maintenance of patent grafts from 5 to 57 months. Exposure of a patent graft precipitated amputation in three patients, as did graft occlusion in an additional patient. One graft was salvaged by revision to the peroneal artery and one was covered by a local bipedicled flap. Multiple regression analysis identified three factors associated with wound complications at the pedal incision site: diabetes mellitus (p = 0.03), age > 70 years (p = 0.03), and rest pain (p = 0.05). Ancillary techniques ("pie-crusting") to reduce skin tension resulted in no distal wound problems among 15 patients considered to be at greatest risk for wound breakdown. Attention to technique of distal graft tunneling, a wound closure that reduces tension, and control of swelling by avoiding dependency on and use of gentle elastic compression assume crucial importance in minimizing pedal wound complications following pedal bypass.

Chemically sensitized erythrocytes for hemagglutination reactions.

The use of chemically modified indicator erythrocytes for hemagglutination reactions can result in increased sensitivity. Treatment of erythrocytes with polyvinylpyrrolidone (PVP) or dextran T40 (10% weight/volume) induces changes in the cell surface in the form of extensions and blebbing, thereby increasing the surface area. These sensitized cells can be used in forensic science when detection or quantitation of erythrocyte surface reacting antibodies is important. The effect of altering membrane lipid fluidity on erythrocyte surface antigens has also been investigated. Treatment of cells with a reagent that increases the membrane ratio of cholesterol to phospholipid results in enhanced hemagglutination capacity despite the lack of extensive spiculation.

Free fatty acid scintigraphy in patients with successful thrombolysis after acute myocardial infarction.

Twenty-three patients with successful intracoronary thrombolytic therapy in the acute stage of infarction underwent scintigraphy with radioiodinated heptadecanoic acid two weeks after myocardial infarction and three to 12 months later. In patients with normal or slow elimination rates in the infarct area, ejection fractions were significantly higher than in patients with fast elimination (70 +/- 6% vs 47 +/- 13%, P less than 0.05). Consequently, left ventricular damage score was lower in patients with normal and slow elimination rates (1.7 +/- 1.6 vs 4.9 +/- 2.4, P less than 0.05). Repeated scintigraphy showed normalization of the elimination rates in patients with previously slow elimination, except in one patient in whom the elimination rate remained slow, patients with fast elimination rates remained unaltered. It is concluded that scintigraphy with radioiodinated heptadecanoic acid is an appropriate method to assess myocardial viability in patients with successful thrombolytic therapy.