Sublingual Immunotherapy To House Dust Mite As An Immunological Intervention In Refractory Atopic Dermatitis

Sublingual immunotherapy (SLIT) with house dust mite (HDM) preparation has been shown to reduce disease severity in patients with atopic dermatitis (AD). A 5-year-old girl with severe Atopic Dermatitis refractive to all possible pharmacotherapy was put on SLIT for dust mite and followed up for a period of one year. SLIT to dust mite proved highly effective in reducing the disease severity score as well as prevention of exacerbations in this patient.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

Significant impact of +105 A>C promoter polymorphism in IL-18 cytokine in patients with kidney stone disease.

Background: Inflammation may be one cause of nephrolithiasis and the interleukin-18 (IL-18) encoding gene polymorphisms at +105 A>C has been implicated in several inflammation related diseases. The aim of this study was to test whether IL-18+105 A>C polymorphisms could act as genetic marker for renal stone disease. A case-control study was conducted to observe the genotype distribution of IL-18+105 A>C, to elucidate the possible role of this SNP as risk factor in renal stone development and to examine its correlation with the clinico-pathologic variables. Methods: Using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique, we tested the genotype distribution of 160 nephrolithiasis patients in comparison with 200 disease free controls from the same geographical region. Results: We observed significant differences of IL-18+105 A to C between the controls and patients with odds ratio 5.4 (P = 0.001). The prevalence of the variant genotypes AC + CC in the patients was higher than that in the controls (45% v/s 30%) and showed a significant association (P = 0.003). Moreover, the frequency per copy of the C allele of IL-18+105 A>C was found to be implicated more in patient group 0.27 as against only 0.16 in controls (P = 0.0003). Further, males and subjects with <45 years of age in patient group were significantly associated with variant genotype (P <0.05). Conclusion: Thus, it is evident from our study that IL-18+105 A>C is implicated in renal stone disease, and that the rare, C related allele is connected with higher susceptibility to nephrolithiasis.

Study of serum interleukin (IL) 18 and IL-6 levels in relation with the clinical disease severity in chronic idiopathic urticaria patients of Kashmir (North India)

BACKGROUND: Chronic urticaria is termed as idiopathic if there is an absence of any identifiable causes of mast cell and basophil degranulation. Various cytokines have been found to be involved in inflammatory processes associated with chronic idiopathic urticaria, including interleukin (IL) 18 and IL-6. OBJECTIVE: To evaluate any possible correlation of IL-18 and IL-6 cytokines with the clinical disease severity in chronic idiopathic urticaria (CIU). METHODS: IL-18 and IL-6 levels of CIU patients (n = 62) and healthy controls (n = 27) were assessed by commercially available enzyme linked immunosorbent assay kits following the manufacturer's protocols. RESULTS: Serum IL-18 concentration (mean ± standard deviation [SD], 62.95 ± 36.09 pg/mL) in CIU patients and in healthy controls (54.35 ± 18.45 pg/mL) showed no statistical significance (p > 0.05). No statistically significant difference (p > 0.05) was observed between autologous serum skin test (ASST) positive and ASST negative patients with regard to the serum IL-18 levels either. Similarly, serum IL-6 concentration (0.82 ± 4.6 pg/mL) in CIU patients and in healthy controls (0.12 ± 1.7 pg/mL), showed no statistical significance (p > 0.05). Also, comparison between positive and ASST negative patients with regard to the serum IL-6 levels was statistically nonsignificant (p > 0.05). However, statistical significance was found both in IL-18 and IL-6 concentrations in certain grades with regard to the clinical disease severity of urticaria. CONCLUSION: There is no significant association as such found between IL-18 and IL-6 levels with CIU, however, these cytokines may help in predicting the clinical disease severity in CIU. Hence, these cytokines may indicate a potential role as a biomarker to assess the disease severity in CIU.

Blurred vision as the sole initial presentation of disseminated lung malignancy

Symptomatic choroidal metastasis [CM] is a rare presenting feature of disseminated lung malignancy. Detection of the primary malignancy usually precedes ocular findings. We report a rare case of blurred vision secondary to bilateral CM as the sole initial manifestation of disseminated lung malignancy in a female patient. Pulmonary symptoms appeared 2 months later. She received radiotherapy and palliative chemotherapy and survived for 7 months after the initial presentation.

Kikuchi-Fujimoto disease in fine needle aspiration smears: A clinico-cytologic study of 18 pediatric cases and correlation with 68 adult patients.

Objective: Kikuchi-Fujimoto disease (KFD) is a self-limiting disorder which usually affects young women. There are only a few studies on pediatric KFD patients and their fine-needle aspiration (FNA) cytodiagnosis. We report a series of pediatric KFD patients diagnosed by FNA cytology and compare them with adults. Materials and Methods: By routine FNA cytology and through retrospective review smears initially diagnosed as reactive hyperplasia of lymph node during the years 2004-2009, 18 pediatric and 68 adult KFD cases were detected. The clinico-cytologic features of these two groups were compared. Results: The age of the pediatric patients ranged from 6 to 18 years with a median of 13.5 years and adult cases were aged 19 to 54 years with a median of 30 years. Only 1 pediatric case (5.6%) and 20 (29.4%) adult cases were initially diagnosed as KFD (P = 0.0604). Arab:non-Arab ratios were 4.3:1 among the pediatric patients and 1:1.5 for the adults (P = 0.0043). FNA smears were highly cellular in 4 (22.2%) pediatric cases and 37 (54.4%) adult cases (P = 0.0180). More than 5% Kikuchi histiocytes was present in 8 (44.4%) pediatric and 49 (72.1%) adult cases (P = 0.0474). No significant difference was observed in male: female ratio, frequency of head & neck lymphadenopathy, time (season) of presentation, and presence of neutrophils and capillary networks, etc. Conclusions: Besides observation and interpretation errors, a significant difference between the two groups in respect of some clinico-cytomorphological features could have influenced the routine cytodiagnosis leading to lower pickup rate of pediatric KFD cases as compared to adults.

Papillary thyroid carcinoma: How much should the surgeon read from Fine needle aspiration cytology reports.

Objective: During routine fine needle aspiration cytodiagnosis of papillary thyroid carcinoma (PTC), a number of cases are diagnosed as suspicious; or it is suggested that PTC or a neoplasm be ruled out by histopathology. Since these diagnostic labels are likely to put the clinicians in a difficult situation while planning the management, this study aims to find out how much the surgeon should read from these reports. Materials and Methods: The patients were divided into two groups. Group A included 38 cases diagnosed as PTC or suspicious of PTC. Group B included 40 cases in which it was suggested that PTC/a neoplasm to be ruled out and non-neoplastic lesions with one or more cytologic features of PTC. The two groups were compared with clinical, imaging and cytomorphologic features. Results: A significant difference was observed with respect to age between Group A and Group B (P<0.001). The frequency of the following five cytologic features was significantly higher in Group A: papillary formation (P<0.001), psammoma bodies (P=0.054), fine nuclear chromatin (P=0.010), frequent nuclear grooves (P<0.001) and intra-nuclear cytoplasmic inclusion (P<0.001). Three or more of the five cytologic features were also reported in significantly higher number of Group A cases (P<0.001). Majority (81.8%) of the cases with subsequent histology in Group A were confirmed as PTC as opposed to 7.7% in Group B (P<0.001). Conclusions: Thus, cases with definitive cytodiagnosis of PTC and suggestive of PTC (Group A) should be taken much more seriously by the surgeons as compared to Group B cases.

Effect of macular photocoagulation on visual acuity of Omani patients with clinically significant macular edema

The aim of this study was to determine the effect of macular laser treatment on the visual acuity [VA] of Omani diabetic patients with clinically significant macular edema [CSME]. Visual outcome was also correlated with duration and control of diabetes and presence or absence of hypertension and hyperlipidemia. This is a retrospective noncomparative cohort study involving 101 eyes of 72 Omani diabetic patients. Change in VA was determined using Snellen's VA chart. The mean duration of follow-up was approximately 21 months [range, 16-24 months]. 29.7% of the patients maintained their vision, 35.6% showed improvement, whereas 34.7% showed a decrease in their vision. Positive visual outcome showed a statistically significant direct relationship with tight control of diabetes and absence of hypertension and an inverse relationship with the duration of diabetes. Presence of hyperlipedemia did not show a statistically significant relationship with positive visual outcome. However, it showed a trend to better visual outcome in the absence of hyperlipedemia. Peak incidence of macular edema was seen at the age of 52.3 years. Macular photocoagulation was found to be an effective method of treatment for CSME among Omani diabetic patients, which has resulted in a positive visual outcome in 65.3% of the patients [stable and improved vision]. Effective control of diabetes, duration of diabetes, and hypertension are the factors which influence the postlaser visual outcome

Metallo-beta-lactamase-producing clinical isolates of Acinetobacter species and Pseudomonas aeruginosa from intensive care unit patients of a tertiary care hospital.

Prompt detection of metallo-beta-lactamase (MBL) producing isolates is necessary to prevent their dissemination. Frequency of MBLs producing strains among multidrug resistant (MDR) Acinetobacter species and Pseudomonas aeruginosa was evaluated in critical care patients using imipenem-EDTA disk method. One hundred MDR Acinetobacter spp. and 42 Pseudomonas aeruginosa were checked for MBL production, from January to June 2001. MBL was produced by 96.6 % of imipenem-resistant Acinetobacter isolates, whereas 100% imipenem-resistant Pseudomonas aeroginosa isolates were MBL producers. Carbapenem resistance in MDR Acinetobacter spp. and Pseudomonas aeruginosa isolates in this study was due to MBLs. This calls for strict infection control measures to prevent further dissemination.

Effect of highly active anti-retroviral therapy on CD3+/CD4+/CD8+ T lymphocyte counts in HIV seropositive Kashmiri patients: a follow up study.

Antiretroviral therapy has played an important role in improving the quality of life and extending the life span of HIV positive patients. In the present study 17 naive HIV positive patients out of a total of 23 positive cases from local population who had absolute CD4+ counts below 300 were given ARV therapy and followed for 1 year. The patients showed an overall improvement in CD4+T lymphocyte counts at one year survival. The values of CD3+ & CD8+ T lymphocytes also changed as expected.

Luteinizing hormone-Releasing hormone analogue-Induced cataract in a patient with prostate cancer

To report a case of right posterior subcapsular cataract induced by 3-monthly depot luteinizing hormone-releasing hormone [LHRH] analogue therapy in a patient with early prostate cancer. A 52-year-old male with static myopia of several years' duration was given a 3-month depot LHRH analogue [goserelin 10.8 mg] as part of neoadjuvant treatment for early prostate cancer. Four weeks after the treatment, the patient developed right posterior subcapsular cataract commonly associated with steroid treatment. The patient had right eye cataract extraction followed by insertion of a new lens. This report shows a case of a posterior subcapsular cataract as an adverse reaction to depot goserelin acetate. This is a feature commonly seen in steroid-induced cataract. Patients with prostate cancer and poor vision if due to cataract may not be ideal patients for depot preparations of LHRH analogues

Studies on resistance / sensitivity pattern of bacteria related with urinary tract infections

In order to determine the resistance pattern against five different groups of antimicrobial agents, six different species of bacteria were isolated from among two hundred cases of UTIs. The front line antibiotics for treating urinary tract infection due to Escherichia coli, Klebsiella species, Staphylococcus aureus and Proteus species should include Cephradine, Ofloxacin, Cefaclor, Cephalothin and Pipemidic acid. However, for treating UTI due to Pseudomonas species, the drug of choice must be a member of fluoroquinoline group [norfloxacin, ofloxacin and ciprofloxacin]

Changing spectrum of squamous cell abnormalities observed on papanicolaou smears in Mubarak Al-Kabeer Hospital, Kuwait, over a 13-year period

The aim of this study was to determine the incidence of squamous cell abnormalities in cervical cytology in Mubarak Al-Kabeer Hospital, Kuwait, and to document any change in the pattern of these lesions. Over a 13-year period [1992-2004], 86,434 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional Pap smears were first examined by cytotechnicians and finally reported by cytopathologists. The smears were classified according to the modified Bethesda system. The age of presentation of squamous cell abnormalities in Kuwaiti women was analyzed. Smears from 83,052 [96.09%] patients were found satisfactory for reporting while the remaining 3.9% was unsatisfactory. Atypical squamous cells of undetermined significance [ASCUS] were seen in 1,790 [2.2%] cases, atypical glandular cells of undetermined significance [AGUS] in 630 [0.8%] cases, low grade squamous intraepithelial lesion including human papillomavirus changes [LSIL] in 824 [1.0%] cases, high grade squamous intraepithelial lesion [HSIL] in 189 [0.2%] cases, and carcinoma in 79 [0.1%] cases of which 44 [0.05%] were squamous cell carcinoma. A comparison of average cases/annum during the study period revealed a significant increase in ASCUS from 1.13 to 2.83% [p < 0.001] and AGUS from 0.33 to 1.08% [p < 0.001]. However, the percentage of LSIL, HSIL and carcinoma detected in Pap smears remained the same. A significant linear trend [p < 0.001] was observed in satisfactory smears, ASCUS and AGUS over the years. However, no significant change was found in the detection of LSIL, HSIL and carcinoma. A reduction in the age of LSIL/HSIL and an increasing trend in the number of Kuwaiti women over the years was also observed which makes screening of young women essential in Kuwait

Management of opportunistic infections in pediatric HIV.

Human immunodeficiency virus (HIV) causes a chronic infection that leads to profound immunosuppression. A hallmark of this process is the depletion of CD4+ lymphocytes, which predisposes the patient to develop a variety of opportunistic infections and certain neoplasms. The CD4+ lymphocyte count is the best validated predictor of the likelihood of developing opportunistic infections (OI). Susceptibility to OI increases as HIV induced immunosuppression becomes more severe. The management of HIV infection hence involves not only inhibiting viral replication using antiretroviral drugs, but also treating OI. This article focuses on the management of such commonly occurring OI in HIV infected patients.

High density lipoproten cholesterol [HDL] metabolism and its role in chemic heart disease

Case control and prospective epidemiology studies have found a striking, consistently negative association between High Density Lipoprotein [HDL] levels and coronary vascular events. As a result, the genetic and environmental determinants of HDL levels are being studied intensively. These investigationS and their potential clinical applications require a fundamental understanding of the structure, function and metabolism of HDL and its components. Of the special interest are the means by which it exerts its apparently protective effect. In this report we characterize the structure of HDL and describe its components, particularly the protein component. We discuss HDL metabolism in light of the relationship of HDL to other lipoprotein classes and relate what little is known of the functions of HDL. We also review the biochemical mechanism by which HDL may protect against cardiovascular disease and discuss further biochemical research that will be necessary for a better understanding of HDL. Interest in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related to coronary artery disease. Case-control and prospective observations of the striking, consistent and independent negative association between HDL levels and coronary vascular have in turn generated new interest in the structure, competitive and metabolism of these fascinating lipoproteins. Several studies carried out in Pakistan also reveal the inverse relation of HDL to HDL1,2. This article contains a tremendous amount of information on HDL and its relationship to genetic and environmental factors which should be useful to investigators and clinicians in their evaluation and use of HDL cholesterol measurements to assess heart disease risk. A knowledge of the structure, function and metabolism of HDL and its components is essential to understand what is being measured, and by what molecular mechanisms HDL may prevent or retard vascular disease

Conduction disturbances in acute myocardial infarction: incidence, site-wise relationship and the influence on in-hospital prognosis.

The study was designed to assess the incidence of conduction disturbances, the relationship of the site of infarction with the type of conduction disturbances and the influence of conduction disturbances on the in-hospital prognosis. One hundred consecutive patients (M:F = 89:11) with a age range of 35-60 years with the history of first attack of acute myocardial infarction were included in the study. There were 45 anterior, 43 inferior and 12 combined anterior and inferior myocardial infarction patients. 44 of the patients had some type of conduction disturbances (Group A) and 56 had none (Group B). Inferior myocardial infarction patients showed higher incidence of conduction disturbances than anterior myocardial infarction (56.8% and 31.8% respectively) (Odd's ratio 2.98, 95% ci 1.14 to 7.9). Conduction disturbances were mostly (92%) atrio-ventricular in inferior myocardial infarction and mostly (72%) intraventricular in anterior myocardial infarction. Of the 13 cases of complete atrioventricular block, 8 had inferior, 2 anterior and 3 combined anterior and inferior infarction. In inferior infarction, complete atrioventricular block developed gradually through 1 degree and 2 degrees atrioventricular block but in the anterior infarction it developed suddenly. Patients with conduction disturbances developed more complications (84%) than those without conduction disturbances (54%). Mortality rate was higher in Group A (25%) than in Group B (3.6%) (Odd's ratio 9.0, 95% ci 1.76 to 86.73) with a overall rate of 13%. Mortality rate was higher in anterior myocardial infarction (50%) than in inferior myocardial infarction (25%) when complicated by complete atrioventricular block. It was concluded that conduction disturbances are predominantly atrioventricular in inferior and intra-ventricular in anterior MI; conduction disturbances are associated with increased risk of complications and death. Anterior location of MI may have an independent risk attribute.

Ruptured aneurysm of the sinus of Valsalva.

The objective of the present study was to assess the value of imaging techniques in the diagnosis of ruptured aneurysm of sinus of Valsalva (RASV). 38 patients were included in the study. 30 were male and 8 female. Their age ranged from 7 to 55 years (mean 25.8 years). Echocardiographic and doppler studies were done in all cases and 20 patients underwent catheterization and angiography. Two patients were asymptomatic, 20 (53%) had acute onset of symptoms and in the remaining 16 (42%) patients symptoms developed gradually. Twenty two (58%) patients were in NYHA functional class III or IV when first seen. Predominant symptoms were dyspnea (79%), palpitation (55%) and chest pain (52%). A continuous machinery murmur was detected in all the patients with associated thrill in 34 patients. Right coronary sinus (RCS) was the most common sinus involved (89%) followed by the noncoronary sinus (NCS) which was involved in 11% of patients. None of the patients in our series had aneurysm of the left coronary sinus. Twenty eight of the 34 RCS aneurysms ruptured into the right ventricular outflow tract (RVOT), 4 into right ventricular cavity (RVC), one into right atrium (RA) and one dissected into the ventricular septum and subsequently ruptured into the left ventricle. Of the 4 NCS aneurysms, 2 ruptured into RVC, one into RA and one into both the RA and RVC. Associated ventricular septal defect (VSD) was found in 10 (26%) patients and all of these patients had RCS aneurysm that ruptured into the RVOT. Aortic regurgitation (AR) was detected in 16 (42%) cases. Discrete subaortic stenosis was detected in one patient who also had associated VSD and AR. Vegetation of the aortic valve was detected in one patient who had RCS aneurysm. Twelve patients (11 male and one female) underwent surgical correction, 10 with and 2 without prior catheterization. Localization of the involved sinus, site of rupture and associated cardiac lesions by echocardiography and doppler study were found accurate at surgery and/or angiography in 22 cases of our series. Imaging techniques, thus appeared to be reliable tools for the diagnosis of RASV.