Understanding and improving the diagnosis of dementia with Lewy bodies

PhD ThesisBackground Accurate diagnosis of dementia with Lewy bodies (DLB) has important implications for treatment and prognosis, but it is not currently clear how frequently DLB is diagnosed in routine clinical practice, nor how frequently they are assigned an alternative dementia diagnosis. 123I-metaiodobenzylguanidine (MIBG) may be capable of improving DLB diagnostic accuracy but it has not been investigated in clinically representative populations that include patients with comorbidities or interfering medications. Methods We conducted a cross-sectional survey of 5 569 patients attending three Psychiatry of Old Age services. From this cohort, 51 DLB and 51 matched non-DLB cases consented to extraction of data relating to the diagnostic process from their clinical case notes. We enrolled a clinically representative cohort of 17 patients with DLB and 16 with Alzheimer’s disease (AD) to a MIBG utility study. Each patient underwent detailed clinical examination, cardiac MIBG and FP-CIT SPECT imaging. Results DLB represented 5.6% of dementia cases but prevalence varied across services (3.5-5.9%). DLB cases were often given a different dementia subtype diagnosis (39%) and experienced a longer time from referral to diagnosis (265 days) than non-DLB patients (154 days). MIBG had a sensitivity and specificity of 71% and 75% for differentiating DLB from AD, but a lower HMR threshold enhanced specificity (100%) without compromising sensitivity. No significant relationships between HMR and either myocardial infarction, or medication prescription, were identified. ii Conclusions Variation in DLB prevalence across services may suggest differences in detection rather than in the true prevalence of the disease. The higher frequency of clinical contacts seen in DLB may provide opportunities to improve both diagnostic accuracy and time to diagnosis. Our findings support the use of representative cohorts in further MIBG research, particularly in determining appropriate HMR cut-offs. Our finding that three DLB patients had normal MIBG, but abnormal FP-CIT results challenges the Braak hypothesis of DLB pathogenesi

Clozapine-induced liver injury and pleural effusion

Clozapine, whilst associated commonly with a transient and benign increase in liver enzymes, has also been associated with varying presentations of hepatitis in existing case reports. This report describes what we believe to be the first documented case of acute liver injury and pleural effusion associated with clozapine, resolving after cessation of the agent. The case supports existing literature in advocating a high index of suspicion, particularly in the 4-5 weeks following clozapine initiation, when considering nonspecific clinical symptoms and signs

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM

Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

The Grizzly, December 6, 1985

Contemporary Women Playwrites Recent Lecture Focus • Faculty Carries Heavy Work Load • A Radio Station in the Making • Letters: RA System not Fair for Anyone; Does our School Paper Have a Monopoly? • Campus Memo: Learn to say no Effectively • In Search of Success: Mary Lou Happy as Claims Adjuster • Campus Briefs: Financial Aid Office Sends out Survey; Davidson Conducts Workshop on Athletic Tech.; Open Dailog Considers Scrapping U.S. Constitution • CPP Offers Lecture on Careers in Sales • Lady Bears Battle Tough Division II Competition • Matmen Finish Third in Invitational • Women\u27s Gymnastics Drops to Montclair State • Final Exam Schedule • Boxing Brother: Hammerin\u27 Hankhttps://digitalcommons.ursinus.edu/grizzlynews/1154/thumbnail.jp

The Grizzly, January 31, 1986

Nursing Homes: A Solution for the Elderly? Investigation 1 • Fetterolf Nears Completion • Smokers and Non-Smokers Must Meet Half Way • Horrible Hunger Continues • A Look at a Better Ursinus • Can a Dream Become a Reality? • The Limelight Shines on Lynne Edwards • Profile: John French Adds a Musical Twist • Pain Brings Gain for the Swimmin\u27 Women • Gymnasts Vaulting Into a New Season • Track Season Starts at the Gun • Basketball Hall of Fame Cites Women\u27s Team as Second in All-Time Victories • Wellness Bear Spotted! • Applications Being Taken for St. Andrew\u27s Scholarship • Women\u27s Studies Program Seeks Campus Wide Interest • Profile: Mr. Rue Keeps Records Straight • Ursinus Professor Publishes Books on Pennsylvania Dutch • Ursinus Professor\u27s Philosophy Text Publishedhttps://digitalcommons.ursinus.edu/grizzlynews/1155/thumbnail.jp

The Grizzly, January 31, 1986

Nursing Homes: A Solution for the Elderly? Investigation 1 • Fetterolf Nears Completion • Smokers and Non-Smokers Must Meet Half Way • Horrible Hunger Continues • A Look at a Better Ursinus • Can a Dream Become a Reality? • The Limelight Shines on Lynne Edwards • Profile: John French Adds a Musical Twist • Pain Brings Gain for the Swimmin\u27 Women • Gymnasts Vaulting Into a New Season • Track Season Starts at the Gun • Basketball Hall of Fame Cites Women\u27s Team as Second in All-Time Victories • Wellness Bear Spotted! • Applications Being Taken for St. Andrew\u27s Scholarship • Women\u27s Studies Program Seeks Campus Wide Interest • Profile: Mr. Rue Keeps Records Straight • Ursinus Professor Publishes Books on Pennsylvania Dutch • Ursinus Professor\u27s Philosophy Text Publishedhttps://digitalcommons.ursinus.edu/grizzlynews/1155/thumbnail.jp

The Grizzly, November 8, 1985

Snyder Holds New Chair of Physics • Internships Problematic, but Necessary • Founder\u27s Day Filled with Science • Letters: The Good and Bad of Security • Science Makes its Stand in Liberal Arts Programs • In Search of Success: Jackson • Parsons Adds a Touch of Dutch Country • Playing Red/Gold in Recruitment • Freshman Urged to Begin Career Planning • Key Issues • Booters Play the Bridesmaid Again • Lady Bears Off to ECAC for Another Time • Bad Luck Strikes the Grizzlies • Box Lacrosse Popularity Grows • Successful Search for Liberal Arts Students • The Stand • Athlete of the Week • Education Department Offers Teaching Internshiphttps://digitalcommons.ursinus.edu/grizzlynews/1151/thumbnail.jp

The Grizzly, February 28, 1986

Dormitory Damages are Repaired and Billed Immediately • Irish Gives Advice to Those in Job Market • Dean Whatley, There is a Parking Problem!!! • Letters: End Frat Prejudice; Case of Poor Taste; Where Were You on Thursday Night?; Pledging Plagues a Few • Alcohol Policy: A Case Study in the Liberal Arts Education • Student Volunteers Making a Difference at Norristown • Gramm-Rudman Will Hit U.C. • Epps not Opposed to Proposed Alcohol Policy • Parking: Still First Come First Served • Haverford Steals Show at MAC\u27s • Gymnasts Take Second at PAIAWs Breaking Team Scoring Record • The Lantern is Still Waiting for You • Little Known Ursinusiana • New Pipe Organ to be Installed in Bomberger • Aerobics: The Solution to Fat • Magnificent Noise • Campus Briefs: Faculty Bowled Over by Frontal Lobotomies; Wickersham to Speak at Classical Association; Open Dialog: Street People are Inevitable in a Free Society ; Spanish Student Finds New Home at Ursinus • Faculty Discusses Science for the Non-Scientific • Sculpture Exhibit by Klaus Ihlenfeldhttps://digitalcommons.ursinus.edu/grizzlynews/1159/thumbnail.jp

Sparticle Spectra and LHC Signatures for Large Volume String Compactifications

We study the supersymmetric particle spectra and LHC collider observables for the large-volume string models with a fundamental scale of 10^{11} GeV that arise in moduli-fixed string compactifications with branes and fluxes. The presence of magnetic fluxes on the brane world volume, required for chirality, perturb the soft terms away from those previously computed in the dilute-flux limit. We use the difference in high-scale gauge couplings to estimate the magnitude of this perturbation and study the potential effects of the magnetic fluxes by generating many random spectra with the soft terms perturbed around the dilute flux limit. Even with a 40% variation in the high-scale soft terms the low-energy spectra take a clear and predictive form. The resulting spectra are broadly similar to those arising on the SPS1a slope, but more degenerate. In their minimal version the models predict the ratios of gaugino masses to be M_1 : M_2 : M_3=(1.5 - 2) : 2 : 6, different to both mSUGRA and mirage mediation. Among the scalars, the squarks tend to be lighter and the sleptons heavier than for comparable mSUGRA models. We generate 10 fb^{-1} of sample LHC data for the random spectra in order to study the range of collider phenomenology that can occur. We perform a detailed mass reconstruction on one example large-volume string model spectrum. 100 fb^{-1} of integrated luminosity is sufficient to discriminate the model from mSUGRA and aspects of the sparticle spectrum can be accurately reconstructed.Comment: 42 pages, 21 figures. Added references and discussion for section 3. Slight changes in the tex