Diagnosing abuse: a systematic review of torn frenum and other intra-oral injuries.

INTRODUCTION: A torn labial frenum is widely regarded as pathognomonic of abuse. METHODS: We systematically reviewed the evidence for this, and to define other intra-oral injuries found in physical abuse. Nine studies documented abusive torn labial frena in 27 children and 24 [corrected] were fatally abused: 22 were less than 5 years old. Only a direct blow to the face was substantiated as a mechanism of injury. RESULTS: Two studies noted accidentally torn labial frena, both from intubation. Abusive intra-oral injuries were widely distributed to the lips, gums, tongue and palate and included fractures, intrusion and extraction of the dentition, bites and contusions. CONCLUSIONS: Current literature does not support the diagnosis of abuse based on a torn labial frenum in isolation. The intra-oral hard and soft tissue should be examined in all suspected abuse cases, and a dental opinion sought where abnormalities are found.     

Controversies in tuberculosis

Tuberculous infection among children continues to be a significant cause of morbidity. The symptom complex are so variable among children that the final diagnosis often rests on the laboratory tests. Proper interpretation of the tests, specially tuberculin test and radiographic studies, are necessary for establishing correct diagnosis. The usefulness of tuberculin test in both unimmunized and BCG vaccinated children is highlighted. BCG accelerated response as a test should be reserved for identifying serious form of pulmonary disease or CNS tuberculosis when the tuberculin test is negative. Radiographic assessment may be sensitive in some instances but not always specific and hence needs cautious interpretation. Tuberculosis among BCG vaccinated children though not uncommon, needs proper documentation. Current trends in the management of tuberculosis including CNS forms are briefly outlined.     

Comparative evaluation of commonly used laboratory tests for post-mortem diagnosis of rabies

Animal brain samples received at WHO Collaborating Centre laboratory at National Institute of Communicable Diseases (NICD) during the years 1991-2002 were tested by Seller's stain, Fluorescent Antibody Test (FAT) and Mouse Innoculation Test (MIT) as methods of rabies diagnosis. Negri bodies on Seller's staining could be detected in 52.5% of MIT positive brains, the concordance of this test with MIT was found to be 77.8%. FAT was positive in 91.5% of MIT positive brains, though it showed concordance of 95.7% with MIT results in the total samples. 12.2% of the samples were found positive by FAT of which 1/3rd also showed the presence of Negri bodies when MIT was negative i.e. showing that the virus is present in inactivated form. Thus emphasizing the need for timely and proper collection and transportation of specimens for testing. Seller's stain and FAT give reliable diagnosis of rabies in the brain samples in majority of the cases. MIT being time-intensive test, is of academic value only in decision making as regards initiation of Post Exposure Treatment (PET), it is recommended that in cases where Seller's stain and FAT have yielded negative results the decision to initiate PET should give due consideration to the nature and circumstances of the animal bite and other epidemiological features.     

Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia

The aim of this study was to determine which human immunodeficiency virus type 1 (HIV-1) subtypes were circulating in Australia and to correlate the subtypes with risk factors associated with the acquisition of HIV-1 infection. DNA was extracted from peripheral blood mononuclear cells, and HIV-1 env genes were amplified and subtyped using heteroduplex mobility analysis, with selected samples sequenced and phylogenetic analysis performed. The HIV-1 env subtypes were determined for 141 samples, of which 40 were from female patients and 101 were from male patients; 13 samples were from children. Forty-seven patients were infected by homosexual or bisexual contact, 46 were infected through heterosexual contact, 21 were infected from injecting drug use (IDU), 13 were infected by vertical transmission, 8 were infected from nosocomial exposure, and 6 were infected by other modes of transmission, including exposure to blood products, ritualistic practices, and two cases of intrafamilial transmission. Five subtypes were detected; B (n = 104), A (n = 5), C (n = 17), E (CRF01_AE; n = 13), and G (n = 2). Subtype B predominated in HIV-1 acquired homosexually (94% of cases) and by IDU (100%), whereas non-subtype B infections were mostly seen in heterosexually (57%) or vertically (22%) acquired HIV-1 infections and were usually imported from Africa and Asia. Subtype B strains of group M viruses predominate in Australia in HIV-1 transmitted by homosexual or bisexual contact and IDU. However, non-B subtypes have been introduced, mostly acquired via heterosexual contact.     

Cytokines: the yin and yang of vitiligo pathogenesis

Introduction: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients.

Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes.

Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo.     

Mechanisms of cell signaling by nitric oxide and peroxynitrite: from mitochondria to MAP kinases

Many of the biological and pathological effects of nitric oxide (NO) are mediated through cell signaling pathways that are initiated by NO reacting with metalloproteins. More recently, it has been recognized that the reaction of NO with free radicals such as superoxide and the lipid peroxyl radical also has the potential to modulate redox signaling. Although it is clear that NO can exert both cytotoxic and cytoprotective actions, the focus of this overview are those reactions that could lead to protection of the cell against oxidative stress in the vasculature. This will include the induction of antioxidant defenses such as glutathione, activation of mitogen-activated protein kinases in response to blood flow, and modulation of mitochondrial function and its impact on apoptosis. Models are presented that show the increased synthesis of glutathione in response to shear stress and inhibition of cytochrome c release from mitochondria. It appears that in the vasculature NO-dependent signaling pathways are of three types: (i) those involving NO itself, leading to modulation of mitochondrial respiration and soluble guanylate cyclase; (ii) those that involve S-nitrosation, including inhibition of caspases; and (iii) autocrine signaling that involves the intracellular formation of peroxynitrite and the activation of the mitogen-activated protein kinases. Taken together, NO plays a major role in the modulation of redox cell signaling through a number of distinct pathways in a cellular setting.     

Comparison of nasal pressure transducer and thermistor for detection of respiratory events during polysomnography in children

STUDY OBJECTIVES: The results of small studies have suggested that a nasal-cannula pressure transducer has a higher sensitivity than a thermistor in detecting hypopneas and diagnosing sleep-disordered breathing in both adults and children. We compared a thermistor alone, and in conjunction with a pressure transducer, for detection of sleep-disordered breathing in children during in-home polysomnography. DESIGN: Retrospective analysis of a subsample of a prospective cohort study. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: A subsample of the Tucson Children's Assessment of Sleep Apnea study population. MEASUREMENTS AND RESULTS: Polysomnographic recordings of 40 children (24 girls and 16 boys, mean age 9.2 +/- 1.7 years; range 6-11 years) were analyzed to compare the detection of sleep-disordered breathing events by 2 different methods of measuring airflow: thermistor alone and thermistor with nasal-cannula pressure transducer (transducer) used simultaneously. The transducer detected all the respiratory events detected by the thermistor, but the thermistor detected only 84% of the transducer-defined events. Consequently, the transducer-derived mean respiratory disturbance index was higher than that detected by the thermistor (7.0 +/- 3.8 vs 5.9 +/- 3.4, P < .001). The bias error between transducer respiratory disturbance index and thermistor respiratory disturbance index on a Bland-Altman plot was 1.08 (95% confidence interval, 0.8 - 1.4). There was good agreement between the thermistor and the transducer for making the diagnosis of sleep apnea using a cutoff of a respiratory disturbance index greater than 5 (kappa = 0.69). The quality of the tracings with the transducer was comparable to that of the thermistor, but the transducer dislodged more frequently. CONCLUSION: The use of a nasal transducer in conjunction with a thermistor was more sensitive than the thermistor alone in detecting sleep-disordered breathing in children during unattended polysomnography.     

Conformation of O6-alkylguanosines: molecular mechanism of mutagenesis

The O⁶-alkylation of guanine residues in DNA treated with alkylatingagents induce mutations due to mis-pairing resulting from thedeprotonation of N1. In addition to the deprotonation of N1,the conformation of the O⁶-alkyl group with respect to N7 ofguanine is very important. Here, we present X-ray crystallographicevidence that shows that the methyl group in O⁶-methylguanosinehas a preference for the distal conformation, blocking the Watson-Cricksites. This distal conformation persists in the solid statefor several analogs of O⁶-alkylguanosine also. This preferredconformation agrees with the result that poly(O⁶-methyl GMP)does not form any stable complex with poly(U). However, themispairing of O⁶-methylguanine with thymine and the resultantGA transition is known from in vitro studies. The above twoopposite results strongly indicate that the conformation ofthe O⁶-alkyl group and the base pairing properties of O⁶-alkylguanineat the monomer and polymer levels must be different from thesituation when the modified base is embedded with a small frequencyin a duplex. It is interesting to note that the sterical blockingof the Watson-Crick site at the monomer level and the alteredbase pairing properties when present as occasional bases ina duplex emerge as a common property for several mutagenic baseslike O⁶-alkylguanmes, O⁴ -methyluracil and N⁴-hydroxycytosine.