Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.      

Elemental and Organic Carbon in Ambient Air of a Major Indian Urban Community

Recent epidemiological studies have demonstrated associations between residential proximity to traffic sources and adverse respiratory symptoms as the Diesel Exhaust Particulate surfaces act as a site for the concentration of thousands of organic compounds. Analysis of 24 h integrated samples of PM10 and PM2.5 collected at a kerb site in a major Indian urban community, heavily impacted by heavy commercial vehicles, showed elemental carbon concentrations higher (14.4–48.8 μg/m³) than organic carbon (1.7–9.2 μg/m³). The organic to elemental carbon ratio varied from 0.09 to 0.31. Average concentration of PM10 and PM2.5 ranged 133–492 μg/m³ and 87–160 μg/m³, respectively.     

Retino-hypothalamic-pineal hypothesis in the pathophysiology of primary headaches

Primary headaches include migraine, tension, cluster headaches, paroxysmal hemicrania and miscellaneous headaches unassociated with structural lesions. A putative role of the retino-hypothalamic-pineal (RHP) axis in the pathophysiology of primary headaches is reviewed in terms of (1) retinal dysfunction, (2) hypothalamic dysfunction and human circadian desynchrony, (3) pineal melatonin dysfunction and (4) rostral limbic dysfunction mediating the human stress response. Unified RHP hypothesis is proposed, suggesting that an acute, periodic or chronic, circadian desynchrony and dysfunction of the whole or part of the RHP axis is implicated in the pathophysiology of primary headaches. Supportive evidence for the RHP hypothesis, including recent PET studies showing changes in dorsal pons, hypothalamus and rostral limbic structures, is presented.     

Missing canines: a novel aetiology

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.     

Intra-articular hip injection: does pain relief correlate with radiographic severity of osteoarthritis?

Objective  

Intra-articular injection is being used widely for both diagnostic and therapeutic purposes in the hip. However, its efficacy is not always predictable in patients with hip osteoarthritis (OA). The purpose of this study was to determine whether the degree of radiographic severity of OA was predictive of the response to intra-articular injection of local anesthetic with corticosteroid and to determine the relationship between immediate pain relief resulting from the anesthetic and delayed pain relief resulting from corticosteroid administration.     

MRI features of tuberculosis of the knee

Objective  The objective of this study was to describe the magnetic resonance imaging (MRI) features of tuberculosis (TB) of the knee joint. Materials and methods  The MRI features in 15 patients with TB of the knee, as confirmed by histology of the biopsied joint synovium, were reviewed retrospectively. The images were assessed for intra-articular and peri-articular abnormalities. Results  All patients had florid synovial proliferation. The proliferating synovium showed intermediate to low T2 signal intensity. In the patients who were administered intravenous contrast, the hypertrophic synovium was intensely enhancing. Marrow edema (n = 9), osteomyelitis (n = 4), cortical erosions (n = 5), myositis (n = 6), cellulitis (n = 2), abscesses (n = 3), and skin ulceration/sinus formation (n = 2) were seen in the adjacent bone and soft tissue. Conclusion  Synovial proliferation associated with tuberculous arthritis is typically hypointense on T2-weighted images. This appearance, in conjunction with other peri-articular MRI features described, can help in distinguishing TB arthritis from other proliferating synovial arthropathies.     

Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.     

Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats

Agmatine, a polycationic amine synthesized via decarboxylation of l-arginine by arginine decarboxylase is reported to exhibit anti-hyperglycemic, antioxidant and memory enhancing effects. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze and object recognition paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with agmatine (5-10mg/kg, i.p. for 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. Further, memory improving effects of agmatine were independent of adrenal I(2) imidazoline receptors. In a separate set, agmatine treatment for an initial 15 days after diabetes confirmation also significantly reduced memory impairment during training trials after 30 days of diabetes confirmation. Moreover, treatment during training trials (30 days after diabetes) also significantly reduced memory impairment in diabetic rats. In conclusion, the present study demonstrates that treatment with agmatine prevents changes in oxidative stress and ChE activity, and probably consequent memory impairment in diabetic rats.