TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease

A subgroup of common variable immunodeficiency (CVID) patients have distinct clinical features, particularly granulomata splenomegaly, characteristic blood lymphocyte phenotype, and elevated circulating TNF levels. To investigate the genetic basis for this phenotype, 150 CVID patients and 200 controls were genotyped for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms and eight class I and II HLA loci using PCR and sequence specific primers (PCR-SSP) sequence-specific primers. Clinical and immunophenotypic data were collected for 90 patients to examine associations with CVID patient subgroups. The presence of granulomata (22% of patients) was strongly associated with splenomegaly, T and B lymphopenia, reduced CD4+ CD45RA+ T cells, and CD8+ CD57+ lymphocytosis, confirming the concept of a subgroup of patients with distinct clinical and laboratory features. The uncommon TNF +488A allele was strongly associated with this subgroup (p = 0.0005). The association between "granulomatous" CVID and TNF +488A was independent of HLA class I and II associations. We postulate that the presence of the TNF +488A allele, or alleles in linkage disequilibrium with it, contributes to the high levels of TNF and granulomatous complications characteristic of this subgroup of patients.     

Excimer laser photorefractive keratectomy for the correction of hyperopia using an erodible mask and axicon system

PURPOSE: The purpose of the study is to evaluate photorefractive keratectomy for the correction of hyperopia using the erodible mask and Axicon system. METHODS: Forty-three patients (43 eyes) with a mean refraction (spherical equivalent) of +4.54 diopter (D) (range, +1.75 to +7.50 D) were treated using a Summit Technology "Apex Plus" excimer laser. This system uses an erodible mask to create a 6.50-mm diameter hyperopic correction over the axial cornea. An Axicon then is used to fashion a 1.50-mm "blend zone" around the correction. On the basis of preoperative refractions, patients were assigned to 3 groups: 2 groups of 14 patients underwent either "+2.00 D" or "+3.00 D" corrections and 15 patients had "+4.00 D" corrections. RESULTS: All patients had a reduction in their hyperopia with an overcorrection, especially in the first month after surgery and some stability in the refractive change at 3 to 6 months. The mean manifest refraction (n = 43) at 6 months was -0.17 D (range, +4.50 D to -3.125 D). Patient satisfaction was high. At 6 months, all eyes had an improvement in unaided near visual acuity. Unaided distance acuity was improved in 37 eyes (86%). A ring of haze 6.5 mm in diameter appeared in all eyes 1 month after surgery. Night halo measurements at 6 months showed no differences from preoperative levels. Flicker contrast sensitivity and forward light scatter (glare) measurements showed no differences after surgery. CONCLUSIONS: In this short-term study, photorefractive keratectomy for hyperopia using the erodible mask and Axicon system appeared to be a promising procedure. Visual performance, in terms of flicker contrast sensitivity, forward light scatter, and night halos, was not compromised. There was an overcorrection based on the manufacturer's algorithms. Manipulation of the treatment algorithms should improve future predictability.     

Georges Guillain's neurologic exploration of America

This is a study of the status of American neurology at the beginning of the 20th century as perceived by European neurologist Georges Guillain. Guillain trained in Paris, the international "Mecca" of neurology at that time. Whereas many Americans traveled and studied in Europe, very few European neurologists made the reverse journey to the United States. In 1902 Georges Guillain, age 26, traveled to the United States with the specific aim of evaluating neurologic services in America. Recent access to Guillain's personal travel journal and an article in French that he wrote after his return to Europe provide first-hand documentation of American neurology at the turn of the century from a European perspective. Using introductory references from his teacher, Pierre Marie, Guillain visited New York, Chicago, Boston, Philadelphia, and Baltimore. He studied hospitals, outpatient departments, laboratories, and universities, comparing them with institutions in his native France and other European capitals. Guillain was particularly struck by the creative energy of American neurologists, the broad-ranging programs in research and patient care, and the strong financial support provided by local philanthropists, universities, and governments. Guillain clearly foresaw the rising international role of American neurology and the prominence it would gain by the end of his career in the 1950s.     

Studies on the secondary metabolites from the Indian gorgonian Subergorgia suberosa: isolation and characterization of four analogues of the cardiotoxin subergorgic acid

OBJECTIVE: The authors examined whether striatal dopamine transporters were altered in acutely (96 hours or less) abstinent cocaine-abusing subjects, as suggested by postmortem studies. METHOD: [123I] beta-CIT and single photon emission computed tomography were used to assess striatal dopamine transporter levels in 28 cocaine-abusing subjects and 24 comparison subjects matched as a group for age and gender. RESULTS: Results showed a significant (approximately 20%) elevation in striatal V3" values in acutely abstinent cocaine-abusing subjects relative to comparison subjects. An inverse correlation between dopamine transporter level and Hamilton Depression Rating Scale score was also observed. CONCLUSIONS: These findings indicate more modest elevations in striatal dopamine transporters in cocaine-abusing subjects than noted in previous postmortem reports and suggest a possible relationship between cocaine-related depression and dopamine transporter binding.     

The role of colonoscopy in coloproctological practice

OBJECTIVE: To determine how well MRI can detect tarsal coalition compared with CT, the current imaging standard. MATERIALS AND METHODS: Coronal and axial CT and MRI were performed within 3 weeks of each other on 40 feet in 20 consecutive patients referred with symptoms of possible tarsal coalition. Scans were read independently in blinded fashion by different imagers. Coalitions were either complete (osseous) or incomplete (non-osseous). Results were compared with available surgical data and clinical follow-up. RESULTS: Both modalities prospectively identified 15 coalitions (9 patients) and each missed 1 calcaneonavicular coalition. Twenty-three of the remaining 24 feet were negative for coalition on both CT and MRI. An atypical incomplete talocalcaneal coalition seen on CT was not identified prospectively on MRI. CONCLUSION: MRI is very good for detecting tarsal coalition and has a high rate of agreement with CT, the imaging "gold standard." When clinical suspicion for coalition is high, CT remains a more cost-effective diagnostic modality. If other causes for ankle pain are also entertained, MRI can be performed and provide nearly equivalent diagnostic accuracy for detecting tarsal coalition.     

Senile dementia of the Binswanger's type

Senile dementia of the Binswanger's type is a term used to describe a dementia syndrome characterized by onset in the sixth or seventh decade of life, subcortical neurologic deficits, psychiatric disorders and evidence of hypertension or systemic vascular disease. The status of senile dementia of the Binswanger's type as a distinct entity is a matter of some controversy. The array of neuroimaging abnormalities and clinical findings attributed to this condition overlap with a number of other neuropathologies. Leukoaraiosis, or attenuation of subcortical white matter, seen on computed tomographic scans or magnetic resonance imaging of the brain, is a hallmark of senile dementia of the Binswanger's type. The clinical findings associated with Binswanger's disease are varied but typically include a progressive dementia, depression and "subcortical" dysfunction such as gait abnormalities, rigidity and neurogenic bladder. Treatment is largely supportive and includes a discussion about advanced directives, social support and antidepressant therapy. Control of hypertension and aspirin prophylaxis may help prevent further progression of white matter disease.     

Analysis of the role of variation of major histocompatibility complex class II expression on nonobese diabetic (NOD) peripheral T cell response

The current paradigm of major histocompatibility complex (MHC) and disease association suggests that efficient binding of autoantigens by disease-associated MHC molecules leads to a T cell-mediated immune response and resultant autoimmune sequelae. The data presented below offer a different model for this association of MHC with autoimmune diabetes. We used several mouse lines expressing different levels of I-Ag7 and I-Ak on the nonobese diabetic (NOD) background to evaluate the role of MHC class II in the previously described NOD T cell autoproliferation. The ratio of I-Ag7 to I-Ak expression correlated with the peripheral T cell autoproliferative phenotype in the mice studied. T cells from the NOD, [NOD x NOD. I-Anull]F1, and NOD I-Ak transgenic mice demonstrated autoproliferative responses (after priming with self-peptides), whereas the NOD.H2(h4) (containing I-Ak) congenic and [NOD x NOD. H2(h4) congenic]F1 mice did not. Analysis of CD4(+) NOD I-Ak transgenic primed lymph node cells showed that autoreactive CD4(+) T cells in the NOD I-Ak transgenic mice were restricted exclusively by I-Ag7. Considered in the context of the avidity theory of T cell activation and selection, the reported poor peptide binding capacity of NOD I-Ag7 suggested a new hypothesis to explain the effects of MHC class II expression on the peripheral autoimmune repertoire in NOD mice. This new explanation suggests that the association of MHC with diabetes results from "altered" thymic selection in which high affinity self-reactive (potentially autoreactive) T cells escape negative selection. This model offers an explanation for the requirement of homozygous MHC class II expression in NOD mice (and in humans) in susceptibility to insulin-dependent diabetes mellitus.     

Efficient registration of 2D points to CAD models for real-time applications

Efficient registration is a major challenge for real-time machine vision applications. Modern acquisition hardware can produce data at extremely high rates. Thus, efficient registration algorithms are required to align data to reference models to detect deviations and take correcting actions if needed. In this work, an efficient registration procedure of 2D points to CAD (computer-aided design) models is proposed. Recent developments in the field are reviewed and evaluated in terms of accuracy, speed and robustness. Efficient algorithms are proposed for the most computationally expensive parts of the registration, including an estimation of the rigid transform, a calculation of the closest point to geometric primitives, and an estimation of the surface normal. Furthermore, a novel primitive caching procedure is proposed that, when combined with an R-tree, greatly improves the execution speed of the registration. The result is a very accurate registration procedure, since geometric primitives are treated analytically with no point sampling required. At the same time, the proposed procedure is robust, very fast, and can achieve the correct registration in less than one millisecond.