Review of the cutaneous manifestations of autoimmune connective tissue diseases in pediatric patients

Autoimmune connective tissue diseases are chronic inflammatory disorders associated with complex genetic and environmental interplay resulting in a variety of cutaneous and systemic manifestations. Pediatric onset of these disorders carries a unique diagnostic pressure for the clinician due to the potential years of disease burden and complications. Mortality and morbidity from these disorders has fallen dramatically over the past fifty years due to increasing awareness of these disease sequelae and utilization of systemic treatment modalities when necessary. This review highlights the clinicalfeatures that are unique to pediatric presentations of lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, juvenile onset systemic sclerosis and morphea. Each of these disorders has a distinct appearance corresponding to a particular cutaneous and systemic clinical course and prognosis. Awareness of the associated potential systemic complications can also alert the clinician to make astute management decisions when confronted with a probable rheumatologic case. Cutaneous symptoms may predate onset of systemic symptoms and by keeping the rheumatologic differential diagnoses in mind, the dermatologist can play a key role in potentially offsetting autoimmune disease burden in children.     

Genotypic analysis of human immunodeficiency virus type 1 env V3 loop sequences: bioinformatics prediction of coreceptor usage among 28 infected mother-infant pairs in a drug-naive population

We sought to predict virus coreceptor utilization using a simple bioinformatics method based on genotypic analysis of human immunodeficiency virus types 1 (HIV-1) env V3 loop sequences of 28 infected but drug-naive women during pregnancy and their infected infants and to better understand coreceptor usage in vertical transmission dynamics. The HIV-1 env V3 loop was sequenced from plasma samples and analyzed for viral coreceptor usage and subtype in a cohort of HIV-1-infected pregnant women. Predicted maternal frequencies of the X4, R5X4, and R5 genotypes were 7%, 11%, and 82%, respectively. Antenatal plasma viral load was higher, with a mean log(10) (SD) of 4.8 (1.6) and 3.6 (1.2) for women with the X4 and R5 genotypes, respectively, p?=?0.078. Amino acid substitution from the conserved V3 loop crown motif GPGQ to GPGR and lymphadenopathy were associated with the X4 genotype, p?=?0.031 and 0.043, respectively. The maternal viral coreceptor genotype was generally preserved in vertical transmission and was predictive of the newborn's viral genotype. Infants born to mothers with X4 genotypes were more likely to have lower birth weights relative to those born to mothers with the R5 genotype, with a mean weight (SD) of 2870 (±332) and 3069 (±300) g, respectively. These data show that at least in HIV-1 subtype C, R5 coreceptor usage is the most predominant genotype, which is generally preserved following vertical transmission and is associated with the V3 GPGQ crown motif. Therefore, antiretroviral-naive pregnant women and their infants can benefit from ARV combination therapies that include R5 entry inhibitors following prediction of their coreceptor genotype using simple bioinformatics methods.     

Human Immunodeficiency Virus (HIV) types Western blot (WB) band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare,Zimbabwe

Background

Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression.

Methods

HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV gag antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy.

Results

Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7%) had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants.

Conclusion

Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease diagnosis, WB test could also be used in conjunction with simpler tests like full blood counts and patient clinical assessment as a relatively cheaper disease monitoring tool required prior to accessing antiretroviral therapy for poor resource settings. However, there is also need to factor in the role of host-parasite genetics and interactions in disease progression.

     

Malignant disease of the appendix

The authors shows case report 81 old patient, underwent surgical treatment on Surgical Clinic KBC DR Dragisa Misovi? because of malignant appendix. Primary symptoms of illness was acute abdomen. Histology confirm nature of illness. The authors discusses about different types of malignant appendix and ways of their treatment, and propose operative procedures which are need to be done in these cases.     

Polymorphisms in the genes of cytochrome oxidase P450 2D6 (CYP2D6), paraoxonase 1 (PON1) and apolipoprotein E (APOE) as risk factors for Parkinson's disease

BACKGROUND/AIM: The presence of Parkinson's disease (PD) among the members of a family is a clear indication of the significance of genetics in its development. In spite of that, the majority of patients with PD shows a sporadic form of the disease induced as a result of interaction of both environmental and genetic factors. The aim of this study was to examine the effects of polymorphisms in the genes of cytohrome P450 2D6(CYP2D6), paraoxonase 1 (PON 1) and apolipoprotein E (APOE), as risk factors for PD. METHODS: We examined 106 patients with PD (65 men and 41 women) and 75 ethnically matched control subjects. The mean age at onset of PD in the patients was 46.9+/-9.4 years (ranging from 30 to 70 years). Genotyping was performed using standard PCR amplification and restriction endonuclease digestion protocols described for known polymorphism in the candidate genes under study. RESULTS: The genotype A/A polymorphisms 2D6* gene of CYP2D6 and genotype M/M polymorphisms L54M gene of PON1 were significantly more frequent in the patients with PD than in the control group. The patients with genotypes A/A and M/M had 3.4 and 3.2 higher risk of PD, respectively than the control group (p = 0.01). The relation between genotypes A/A gene of CYP2D6 and M/M gene of PON1 was modified by the age at onset. The genotypes were associated with early onset of PD (P = 0.001, p = 0.004). The carriers of the A and M alleles in homozygote had 2.4 and 4.2 years respectively earlier onset of PD than carriers of other genotypes with these polymorphisms. The frequency allele e4 gene of APOE was higher in the PD patients with early onset (20%) than in PD with later onset (7.4%), while the genotype epsilon3/epsilon3 was associated with PD late onset (p = 0.024). Combined genotype I (carriers of the two risk allels in homozygote and one alleles risk in heterozygote) and combined genotype II (carriers of the three alleles risk in homozygote) caused early PD. Combined genotype II was detected in 12.7% of the patients in the group of early onset, and in 2.4% of the patients with the onset after 45 years. CONCLUSION: The results of our study suggest that the genotypes A/A and M/M genes of CYP2D6 and PON1, and allele epsilon4 gene are an important risk for the development of PD, causing its early onset. The cumulative effects of the risk genes cause an early onset of PD.     

Expression of alphasmooth muscle actin in lens epithelia from human donors and cataract patients

In order to re-evaluate functional implications of alphasmooth muscle actin (alphaSMA) expression in lens epithelial cells (LECs), we assessed its presence in donor lenses without visible opacities (DON), lenses with mature cataract (CAT), and cataractous lenses with posterior subcapsular opacities (PSO) or anterior subcapsular fibrosis (ASF). The levels of alphaSMA and transforming growth factor-beta2 (TGFbeta2) mRNAs were measured by classical and real-time PCR. Expression and structural organisation of alphaSMA protein and beta-catenin were monitored by Western blotting and confocal microscopy. All DON analysed contained measurable amounts of alphaSMA mRNA. In CAT without and with PSO, mRNA expression was increased and, again more than doubled in ASF. TGFbeta2 mRNA expression varied widely between the individual samples but was slightly increased in ASF. No correlation existed between alphaSMA or TGFbeta2 expression and the age of the donors in any of the lens categories. Confocal microscopy revealed that, in DON and CAT, alphaSMA was preferentially expressed in a simple granular pattern in single or small clusters of LECs within a normally shaped cobblestone epithelium. Locally, the granules were merged into short stretches at the cell margin. In CAT, a few abnormally shaped cells contained polygonal alphaSMA structures and short stress fibres. In CAT with PSO and ASF, polygons and stress fibre bundles predominated in spindle-shaped cells. Expression patterns of different complexity were often present in the same epithelium. Apical polygons and basal stress fibres were detected within the same cell and may reflect instability of the interface between epithelium and cortical fibres and changes in adhesion to the capsule, respectively. High levels of betacatenin mRNA and protein were present in all lens types. However, with increasing complexity of alphaSMA organisation, betacatenin staining disappeared from the cell margin and basal infoldings and was shifted towards the cytoplasm and nucleus. The presence of alphaSMA in DON, the absence of any correlation between mRNA level and age, and the modest increase in complexity of alphaSMA-containing structures in CAT argue against an inevitable link between alphaSMA expression and the development of age-related cataract. Low levels of alphaSMA expression may reflect repair of normal wear and tear. In pathologic situations such as PSO and ASF, persisting stimulation and additional incentives may induce increased alphaSMA expression and more elaborate patterning, eventually leading to completion of EMT.