The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos.

BACKGROUND: Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive. OBJECTIVE: To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. METHODS: The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin. RESULTS: In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample). CONCLUSION: Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.

Unusual features associated with cranial openings of optic canal in dry adult human skulls.

One hundred and eighty six dry adult human skulls (372 sides) were studied in order to reveal the presence of unusual features--such as recess, fissure and notch--in the cranial opening of the optic canal. Recess, an extension of the lateral wall, was found in 229 (61.5%) sides. Fissure, an irregular discontinuity above the lateral recess, was observed in 158 (42.4%) sides. Notch, a gap in the posterior-most limit of the roof, was seen in 66 (17.7%) sides. These were commonly seen bilaterally. The etiology of these was attributed to the development of the optic canal. During intrauterine life the optic canal is in the form of a large keyhole shaped foramen, which slowly transforms into the adult canal. A developmental arrest at an early stage may lead to the formation of recesses and fissures.

Dengue shock syndrome in newborn: a case series.

Four cases of dengue shock syndrome were seen during an epidemic of dengue fever. Three cases recovered following appropriate management.

Incidence and morphological study of zygomaticofacial and zygomatico-orbital foramina in dry adult human skulls: the non-metrical variants.

Morphological diversity in the form of multiple zygomaticofacial (ZF) foramina was studied in 165 dry, unsexed adult human skulls. Zygomatic bones revealed variation in the number of foramina on their orbital and facial aspects. These were absent in 72 (21.8%) sides. A single ZF foramen was seen in 148 (44.9%) sides. Two ZF foramina were found in 92 (27.9%) sides, out of which 29 (8.8%) sides had one zygomatico-orbital (ZO) foramen, while 63 (19.1%) sides had two ZO foramina. Three ZF foramina, a relatively uncommon occurrence, were found in 17 (5.1%) sides, which included eight (2.4%) sides with one less and nine (2.7%) sides with the same number of ZO foramina. Four ZF foramina were seen in one (0.3%) side with three on the orbital aspect, a feature not reported before. The zygomatic nerve may be disrupted on elevating periorbita from the lateral wall during orbital surgery, and care should be taken to prevent injury to the nerve during the lateral orbitotomy approach to access intraorbital soft tissue tumors.

Unusual facets on the acetabulum in dry adult human coxal bones: a morphological and radiological study.

A smooth facet was found antero-inferior to lunate surface of 48 acetabula, in a study conducted on 315 dry adult coxal bones, 26 of which (13 pairs) were of articulated pelves. Three different shapes of the facet were oval (56.3%), piriform (22.9%) and elongated (20.8%). The prevalence of the oval facet was higher in both sexes. In 37.5% bones it extended to superior ramus of pubis and in 62.5% it was limited within the acetabular margin. They were either discrete (58.3%) or continuous with the lunate surface (41.7%). The surface configuration was flat (29.2%), concave (43.7%) or grooved (27.1%). One male articulated pelvis showed a bilateral presentation. Measured along the long axis the size varied between 11 to 17 mm. The radiographs showed notching, antero-inferior to acetabular margin in grooved facets whereas concave and flat facets were seen as areas of rarefaction. It is postulated that this facet could be a consequence of a particular posture which results in traction of the ligaments attached to this area. This unusual feature has not been reported earlier.

CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.

Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas the expanded alleles contain a pure uninterrupted stretch of 34 to 59 CAG repeats. We have previously reported the presence of a limited pool of 'ancestral' or 'at risk' haplotypes for the expanded SCA2 alleles in the Indian population. We now report the identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene and their characterization in 215 normal and 64 expanded chromosomes. The two biallelic SNPs distinguished two haplotypes, GT and CC, each of which formed a predominant haplotype associated with normal and expanded SCA2 alleles. All the expanded alleles segregated with CC haplotype, which otherwise was associated with only 29.3% of the normal chromosomes. CAA interspersion analysis revealed that majority of the normal alleles with CC haplotype were either pure or lacked the most proximal 5' CAA interruption. The repeat length variation at SCA2 locus also appeared to be polar with changes occurring mostly at the 5' end of the repeat. Our results demonstrate that CAA interruptions play an important role in conferring stability to SCA2 repeat and their absence predisposes alleles towards instability and pathological expansion. Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus.

Management of atypical epicapsular star.

An 18-year-old woman had brown pigment deposits on the central anterior capsule of the lens associated with poor visual acuity and significant anisometropia. Surgical removal of the deposits, phacoemulsification, and intraocular lens implantation resulted in visual improvement. Epicapsular stars are formed by the confluence of multiple fine pigmentary deposits. Although they cause amblyopia, this does not appear to be dense. Surgical removal of these central deposits may improve vision, even if the patient presents as an adult.

Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12.

Spinocerebellar ataxia 12 (SCA12) is a recently identified form of autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' untranslated region of the gene PPP2R2B. We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members. The sizes of the expanded alleles ranged from 55 to 69 CAG repeats, and the sizes of the normal alleles ranged from 7 to 31 repeats. We believe our study is the first to demonstrate that SCA12 may not be as rare in some populations as previously thought.

Molecular analysis of Friedreich's ataxia locus in the Indian population.

OBJECTIVES: Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by expansion of GAA repeats in the frataxin gene. We have carried out the first molecular analysis at the Friedreich's ataxia locus in the Indian population. MATERIALS AND METHODS: Three families clinically diagnosed for Friedreich's ataxia were analyzed for GAA expansion at the FRDA locus. The distribution of GAA repeats was also estimated in normal individuals of Indian origin. RESULTS: All patients clinically diagnosed for Friedreich's ataxia were found to be homozygous for GAA repeat expansion. The GAA repeat in the normal population show a bimodal distribution with 94% of alleles ranging from 7-16 repeats. CONCLUSION: Indian patients with expansion at the FRDA locus showed typical clinical features of Friedreich's ataxia. The low frequency of large normal alleles (6%) could indicate that the prevalence of this disease in the Indian population is likely to be low.

Variation in shape of the lingula in the adult human mandible.

The lingulae of both sides of 165 dry adult human mandibles, 131 males and 34 females of Indian origin, were classified by their shape into 4 types: 1, triangular; 2, truncated; 3, nodular; and 4, assimilated. Triangular lingulae were found in 226 (68.5%) sides, truncated in 52 (15.8%), nodular in 36 (10.9%) and assimilated in 16 (4.8%) sides. Triangular lingulae were found bilaterally in 110, truncated in 23, nodular in 17 and assimilated in 7 mandibles. Of the remaining 8 mandibles with different appearances on the 2 sides, 6 had a combination of triangular and truncated and 2 had nodular and assimilated. The incidence of triangular and assimilated types in the male and female mandibles are almost equal. In the truncated type it was double in the male mandibles while the nodular type was a little less than double in the female mandibles.

Comparison of tissue harmonic imaging with conventional US in abdominal disease.

Harmonic waves are generated from nonlinear distortion of an acoustic signal as an ultrasound wave insonates tissues in the body. These beams are integer multiples of a fundamental transmitted frequency. Potential advantages of harmonic imaging include improved axial resolution due to higher frequencies and better lateral resolution due to narrower beams. Decreased noise from side lobes improves signal-to-noise ratios and reduces artifacts. Deleterious effects of the body wall are also reduced. The authors prospectively studied ultrasonographic (US) findings in 100 adult patients with 202 abdominal lesions by comparing harmonic US images with conventional US images. The results were subjected to statistical analysis. Harmonic imaging was superior to conventional US in regard to lesion visibility and diagnostic confidence. Harmonic imaging was particularly useful for depicting cystic lesions and those containing echogenic tissues such as fat, calcium, or air. In patients with a body mass index of 30 or more, harmonic imaging was clearly better for lesion visibility and confidence of diagnosis. The authors recommend routine use of harmonic imaging for abdominal US studies in all adult patients.

Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation.

Expansion of CTG/CAG trinucleotide repeats has been shown to cause a number of autosomal dominant cerebellar ataxias (ADCA) such as SCA1, SCA2, SCA3/ MJD, SCA6, SCA7, SCA8 and DRPLA. There is a wide variation in the clinical phenotype and prevalence of these ataxias in different populations. An analysis of ataxias in 42 Indian families indicates that SCA2 is the most frequent amongst all the ADCAs we have studied. In the SCA2 families, together with an intergenerational increase in repeat size, a horizontal increase with the birth order of the offspring was also observed, indicating an important role for parental age in repeat instability. This was strengthened by the detection of a pair of dizygotic twins with expanded alleles showing the same repeat number. Haplotype analysis indicates the presence of a common founder chromosome for the expanded allele in the Indian population. Polymorphism of CAG repeats in 135 normal individuals at the SCA loci studied showed similarity to the Caucasian population but was significantly different from the Japanese population.

Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors.

Immune reconstitution in acquired immunodeficiency syndrome (AIDS) patients on highly active anti-retroviral therapy (HAART) with cytomegalovirus (CMV) retinitis manifested as posterior segment intraocular inflammation has been reported. We report an adult HIV-positive Indian male with clinically inactive CMV retinitis who developed panuveitis with hypopyon. This was related to immune recovery mediated by combination anti-retroviral treatment, including protease inhibitors.

Morphologic and imaging studies of duplicate optic canals in dry adult human skulls.

Three dry adult human skulls, two with bilateral and one with unilateral duplication of the optic canal were found. Their gross morphologic features were studied. Optic canals were separated by a septum of variable thickness dividing the posterior part of the canal into a large canal in the usual position and a smaller one inferior to it. The skull with unilateral duplication of the right side had a bony bar forming the carotico-clinoid canal. One of the skulls was disarticulated and its sphenoid had bilaterally duplicated optic canals divided by thin septa, both having a slit. Conventional radiography and CT scans for the optic canal were performed on two of these skulls but not on the disarticulated bone, and the imaging representations of these features were correlated with the anatomic findings on the dry skull.

Anatomical description and frequencies of bony projections on the cerebral aspect of the petromastoid part of the temporal bone in dry adult human skulls.

A morphological peculiarity was observed in the form of bony projections on the upper part of the medial border of the groove for the sigmoid sulcus on the internal surface of the mastoid part of the temporal bones. In a study on 636 temporal regions of 318 dry unsexed adult human skulls of Indian origin, 101 (15.9%) temporal bones exhibited these elevations. These ranged from being inconspicuous tubercles to well-defined sharp spines. In 73 (72.3%) cases, a projection was present unilaterally, more commonly on the right side and in 28 (27.7%) it was bilateral. A subjective assessment of the size showed the projections to be small (70; 69.3%), medium (16; 15.8%) and large (15; 14.8%).