We report on the adherence experience of a group of people living with HIV on ART over six years in Uganda.
Between 2005 and 2009, we followed up 41 participants who were also part of a clinical trial comparing home and facility based delivery of ART in Jinja, eastern Uganda. We conducted qualitative in-depth interviews at enrolment, 3, 6, 18 and 30 months to capture experiences with adherence over time. In 2011 we returned to these participants to find out how they were fairing with long term adherence. We managed to retrace 24 participants and interviewed them about their experience. We thematically analysed the data and compared findings over time.
Initially there were few barriers to adherence and many followed the adherence guidance closely. By year six, relaxation of these rules was noticeable although self-reported adherence continued to be high. Alcohol consumption was more common than before. Some relatives of the participants who had died claimed that some deaths were a result of alcohol. While participants reported that ART had allowed them to reclaim independence and return to work the changes in work and social routines created new challenges for adherence. Side effects like lipodystrophy were not only causing some stigma but for some tested their faith in the drugs. Many participants reported resumption of sexual lives but apart from those who selected same status partners, disclosure to new partners was minimal.
Good adherence practice to ART wanes over the long-term, and people who may have disclosed at initiation find it difficult to do so to new partners once they are healthy. Further adherence interventions and support with disclosure over the course of therapy may need to be considered. (Words: 283)
It is uncertain whether multiple micronutrients benefit the mental and psychomotor development of young children in developing countries. We conducted a randomised double-blind controlled trial to evaluate the effect of a richly micronutrient-fortified v. a basal fortified porridge on mental and psychomotor development in Zambian infants. Infants (n 743) were randomised at age 6 months to receive either the richly fortified or the basal fortified infant food and were followed up until 18 months of age. All the infants were evaluated monthly for achievement of a series of developmental milestones. The Bayley scales of infant development II were administered to a subsample of 502 infants at 6, 12 and 18 months. Rich micronutrient fortification had no significant benefit on the following: (a) number of developmental milestones achieved (rate ratio at 12 months = 1·00; 95 % CI 0·96, 1·05; P=0·81, adjusted for sex, socio-economic status and maternal education, with similar results at 15 and 18 months); (b) ages of walking unsupported (hazard ratio (HR) 1·04; 95 % CI 0·88, 1·24; P=0·63, adjusted for the above covariates) and of speaking three or four clear words (HR 1·01; 95 % CI 0·84, 1·20; P=0·94, adjusted for the above covariates); (c) mental development index (MDI) and psychomotor development index (PDI) of the Bayley scales (scores difference adjusted for baseline scores, age at the assessment, sex, socio-economic status, maternal education, language, age and HIV status: MDI 0·3 (95 % CI −0·5, 1·1), P=0·43; PDI −0·1 (95 % CI −0·9, 0·7), P=0·78). In conclusion, the results do not support the hypothesis that rich micronutrient fortification improves Zambian infants’ mental and motor development.
Micronutrient-fortified food; Mental and psychomotor development; Bayley scales of infant development; Developmental milestones
Cryptococcal meningitis (CM) in Africa is associated with up to 70% mortality at 3 months and 500,000 deaths annually. We examined strategies to improve on fluconazole monotherapy: addition of flucytosine (5-FC); and/or addition of short-course amphotericin B (AmB).
In step 1, previously reported, patients were randomized to receive FLU 1200 mg/d with or without 5-FC 100 mg/kg/day for 14 days. In step 2, 43 patients were similarly randomised, with addition of AmB 1 mg/kg/d for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality.
40 patients (25% with Glasgow Coma Scale < 15) were analyzed. EFA for the triple combination arm was greater than for AmB+FLU: −0.50 ± 0.15 log CFU/day vs. −0.38 ± 0.19 log CFU/day (p = 0.03); and greater than step 1 with FLU+5-FC (−0.28 ± 0.17) or FLU alone (−0.11 ± 0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, p = 0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, p = 0.1).
Addition of 5-FC and short course AmB to high-dose FLU significantly enhance EFA and may be associated with favourable trends in survival. Both these strategies should be tested in a larger phase III study.
Cryptococcal; Meningitis; AIDS; Fluconazole; Flucytosine; Amphotericin B
Stigma is a barrier to HIV prevention and treatment. There is a limited understanding of the types of stigma facing people living with HIV (PLHIV) on antiretroviral therapy (ART). We describe the stigma trajectories of PLHIV over a 5-year period from the time they started ART.
Longitudinal qualitative in-depth interviews were conducted with 41 members of The AIDS Support Organisation (TASO) from 2005 to 2008 in Jinja, Uganda, who were part of a pragmatic cluster-randomised trial comparing two different modes of ART delivery (facility and home). Participants were stratified by gender, ART delivery arm and HIV stage (early or advanced) and interviewed at enrolment on to ART and then after 3, 6, 18 and 30 months. Interviews focused on stigma and ART experiences. In 2011, follow-up interviews were conducted with 24 of the participants who could be traced. Transcribed texts were translated, coded and analyzed thematically.
Stigma was reported to be very high prior to starting ART, explained by visible signs of long-term illnesses and experiences of discrimination and abuse. Early coping strategies included: withdrawal from public life, leaving work due to ill health and moving in with relatives. Starting ART led to a steady decline in stigma and allowed the participants to take control of their illness and manage their social lives. Better health led to resumption of work and having sex but led to reduced disclosure to employers, colleagues and new sexual partners. Some participants mentioned sero-sorting in order to avoid questions around HIV sero-status. A rise in stigma levels during the 18 and 30 month interviews may be correlated with decreased disclosure. By 2011, ART-related stigma was even more pronounced particularly among those who had started new sexual relationships, gained employment and those who had bodily signs from ART side-effects.
This study has shown that while ART comes with health benefits which help individuals to get rid of previously stigmatising visible signs, an increase in stigma may be noticed after about five years on ART, leading to reduced disclosure. ART adherence counselling should reflect changing causes and manifestations of stigma over time.
Stigma; Antiretroviral therapy; Disclosure; Uganda; Side effects; Sero-sorting
Background. Vancomycin-resistant enterococci (VRE) are significant nosocomial pathogens worldwide. There is one report about the epidemiology of VRE in Saudi Arabia. Objective. To determine the risk factors associated with VRE infection or colonization in intensive care unit (ICU) settings. Design. This is a descriptive, epidemiologic hospital-based case-control study of patients with VRE from February 2006 to March 2010 in ICU in a tertiary hospital in Saudi Arabia. Methods. Data were collected from hospital records of patients with VRE. The main outcome measure was the adjusted odds ratio estimates of potential risk factors for VRE. Results. Factors associated with VRE included ICU admission for multiorgan failure, chronic renal failure, prior use of antimicrobial agents in the past three months and before ICU admission, gastrointestinal oral contrast procedure, and hemodialysis. Being located in a high risk room (roommate of patients colonized or infected with VRE) was found to be protective. Conclusions. Factors associated with VRE acquisition are often complex and may be confounded by local variables.
Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1) in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation.
The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA) and internal (ICA) carotid arteries over the cardiac cycle in vivo.
Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semi-automatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and stress-induced stiffness of the arterial wall (stiffening in response to intraluminal blood pressure fluctuation) for each patient.
The diameter and wall thickness of the segments (CCA, ECA and ICA) of the carotid bifurcation were found to decrease and stress-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25±7 to 63±23 kPa (CCA), from 22±7 to 57±19 kPa (ECA) and from 28±8 to 67±23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40±0.25 to 1.50±2.05 MPa (CCA), from 0.49±0.34 to 1.14±0.52 MPa (ECA) and from 0.68±0.31 to 1.51±0.69 MPa (ICA). The stress-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared to end-diastole.
The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries – CCA, ECA and ICA – exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.
common carotid artery; external carotid artery; internal carotid artery; in vivo mechanical properties; circumferential stress; stiffening
Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.
Inclusion of infectious disease (ID) physicians in the care of patients with possible infection can favorably affect antibiotic usage. The aim of this study was to evaluate the role of the ID consultations in reducing inappropriate antibiotic usage.
Materials and Methods:
This is a prospective study evaluating all adult ID consultations from January 2006 to December 2009. A total of 1444 consultation requests were recorded during the 4-year period.
The most frequent consultations were from cardiology (23.1%), orthopedics (8.2%), general medicine (7.8%), hematology-oncology (7.8%), gastroenterology (7.3%), and pulmonary/critical care (7.1%). The main reason for consultation was for the choice of antibiotics (75%). The commonest diagnoses prior to consultation were fever (14.7%), bacteremia (9.1%), and urinary tract infection (8.4%). Bacteremia was documented in 21.4% of cases and 12.9% were found to have no identifiable focus of infection. Antimicrobial therapy was changed in 58.7% and antimicrobials were discontinued in 14.7% of cases. The number of antimicrobial therapy was one (49.7% and 49.9%) and two (24% and 17.6%, P = 0.0001) before and after the consultation, respectively. In addition, 17.3% and 26.9% (P = 0.0001) received no antimicrobial agents before and after ID consultation.
ID consultation is important to reduce inappropriate antimicrobial therapy and to limit the number of dual therapy.
Antibiotic use; Antimicrobial stewardship; Consultation; Infectious disease
More than 500,000 deaths are attributed to rotavirus gastroenteritis annually worldwide, with the highest mortality in India. Two successive, naturally occurring rotavirus infections have been shown to confer complete protection against moderate or severe gastroenteritis during subsequent infections in a birth cohort in Mexico. We studied the protective effect of rotavirus infection on subsequent infection and disease in a birth cohort in India (where the efficacy of oral vaccines in general has been lower than expected).
We recruited children at birth in urban slums in Vellore; they were followed for 3 years after birth, with home visits twice weekly. Stool samples were collected every 2 weeks, as well as on alternate days during diarrheal episodes, and were tested by means of enzyme-linked immunosorbent assay and polymerase-chain-reaction assay. Serum samples were obtained every 6 months and evaluated for seroconversion, defined as an increase in the IgG antibody level by a factor of 4 or in the IgA antibody level by a factor of 3.
Of 452 recruited children, 373 completed 3 years of follow-up. Rotavirus infection generally occurred early in life, with 56% of children infected by 6 months of age. Levels of reinfection were high, with only approximately 30% of all infections identified being primary. Protection against moderate or severe disease increased with the order of infection but was only 79% after three infections. With G1P, the most common viral strain, there was no evidence of homotypic protection.
Early infection and frequent reinfection in a locale with high viral diversity resulted in lower protection than has been reported elsewhere, providing a possible explanation why rotavirus vaccines have had lower-than-expected efficacy in Asia and Africa. (Funded by the Wellcome Trust.)
It is difficult to longitudinally characterize cognitive impairment in amyotrophic lateral sclerosis (ALS) due to motor deficits, and existing instruments aren’t comparable with assessments in other dementias.
The ALS Brief Cognitive Assessment (ALS-BCA) was validated in 70 subjects (37 with ALS) who also underwent detailed neuropsychological analysis. Cognitive predictors for poor survival were then analyzed in a longitudinal cohort of 171 ALS patients.
The ALS-BCA was highly sensitive (90%) and specific (85%) for ALS-dementia (ALS-D). ALS-D patients had shorter overall survival, primarily due to the poor survival among ALS-D patients with disinhibited or apathetic behaviors after adjusting for demographic variables, ALS site of onset, medications, and supportive measures. ALS-D without behavioral changes was not a predictor of poor survival.
ALS-D can present with or without prominent behavioral changes. Cognitive screening in ALS patients should focus on behavioral changes for prognosis, while non-behavioral cognitive impairments may impact quality of life without impacting survival.
Shah Ebrahim and colleagues argue that more research on non-communicable diseases (NCDs) in both high-income countries and low- and middle-income countries can result in mutual benefits and will help better address the growing burden of NCDs.
Infection with Chikungunya alphavirus (CHIKV) can cause severe arthralgia and chronic arthritis in humans with persistence of the virus in perivascular macrophages of the synovial membrane by mechanisms largely ill-characterized.
We herein analysed the innate immune response (cytokine and programmed cell death) of RAW264.7 mouse macrophages following CHIKV infection. We found that the infection was restrained to a small percentage of cells and was not associated with a robust type I IFN innate immune response (IFN-α4 and ISG56). TNF-α, IL-6 and GM-CSF expression were upregulated while IFN-γ, IL-1α, IL-2, IL-4, IL-5, IL-10 or IL-17 expression could not be evidenced prior to and after CHIKV exposure. Although CHIKV is known to drive apoptosis in many cell types, we found no canonical signs of programmed cell death (cleaved caspase-3, -9) in infected RAW264.7 cells.
These data argue for the capacity of CHIKV to infect and drive a specific innate immune response in RAW264.7 macrophage cell which seems to be polarized to assist viral persistence through the control of apoptosis and IFN signalling.
Chikungunya virus; Macrophage; Apoptosis; Viral persistence; Inflammation
Attention-deficit hyperactive disorder (ADHD) is a psychiatric illness commonly diagnosed during the early years of childhood. In many adolescents with undiagnosed ADHD, presentation may not be entirely similar to that in younger children. These adolescents pose significant challenges to parents and teachers coping with their disability. Often adolescents with behavioural problems are brought to medical attention as a last resort. This case describes an adolescent who presented to a primary care clinic with school truancy. He was initially treated for depression with oppositional defiant disorder and sibling rivalry. Only following a careful detailed history and further investigations was the diagnosis of ADHD made. He showed a positive improvement with the use of methylphenidate for his ADHD and escitalopram for his depression. The success of his management was further supported by the use of behavioural therapy and parenting interventions. There is a need to increase public awareness of ADHD, especially among parents and teachers so that early intervention can be instituted in these children.
attention-deficit hyperactive disorder; primary care; school truancy
γδ T cells rapidly produce cytokines and represent a first line of defence against microbes and other environmental insults at mucosal tissues and are thus thought to play a local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing γδ T (γδ-17) cells that expressed the αEβ7 integrin and were closely associated with the airway epithelium. Importantly, prostaglandin (PG)I2 and its receptor IP, which downregulated airway eosinophilic inflammation, promoted the emergence of these intraepithelial γδ-17 cells into the airways by enhancing IL-6 production by lung eosinophils and dendritic cells. Accordingly, a pronounced reduction of γδ-17 cells was observed in the thymus of naïve mice lacking the PGI2 receptor IP, as well as in the lungs during allergic inflammation, implying a critical role for PGI2 in the programming of “natural” γδ-17 cells. Conversely, iloprost, a stable analog of PGI2, augmented IL-17 production by γδ T cells but significantly reduced the airway inflammation. Together, these findings suggest that PGI2 plays a key immunoregulatory role by promoting the development of innate intraepithelial γδ-17 cells through an IL-6-dependent mechanism. By enhancing γδ-17 cell responses, stable analogs of PGI2 may be exploited in the development of new immunotherapeutic approaches.
Lung; inflammation; Th2 cells; γδ T cells; IL-17
Cannabinoid CB2 receptor has emerged as a very promising target over the last decades. We have synthesized and evaluated a new fluorescent probe designated NMP6 based on 6-methoxyisatin scaffold, which exhibited selectivity and Ki value at hCB2 of 387 nM. We have demonstrated its ability to be an effective probe for visualization of CB2 receptor binding using confocal microscopy and a flow cytometry probe for the analysis of CB2 protein expression. Furthermore, NMP6 was easily obtained in two chemical steps from commercially available building blocks.
Chikungunya virus (CHIKV) is an arthritogenic member of the Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is now known to target non hematopoietic cells such as epithelial, endothelial cells, fibroblasts and to less extent monocytes/macrophages. The type I interferon (IFN) response is an early innate immune mechanism that protects cells against viral infection. Cells express different pattern recognition receptors (including TLR7 and RIG-I) to sense viruses and to induce production of type I IFNs which in turn will bind to their receptor. This should result in the phosphorylation and translocation of STAT molecules into the nucleus to promote the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the capacity of CHIKV clinical isolate to infect two different human fibroblast cell lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune response.
Indirect immunofluorescence and quantitative RT-PCR were used to test for the susceptibility of both fibroblast cell lines to CHIKV.
Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently susceptible to CHIKV infection and the former producing at least 30-fold higher viral load at 48 h post-infection (PI). We found that the expression of antiviral genes (RIG-I, IFN-β, ISG54 and ISG56) was more robust in the more susceptible cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere with the nuclear translocation of pSTAT1 in both cell lines.
Critically, CHIKV can control the IFN response by preventing the nuclear translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the relative resistance of HT-1080 cells to CHIKV infection could not be attributed to more robust innate IFN- and ISG-dependent antiviral responses. These cell lines may prove to be valuable models to screen for novel mechanisms mobilized differentially by fibroblasts to control CHIKV infection, replication and spreading from cell to cell.
CHIKV; Type I IFN; HS 633T; HT-1080; RIG-I; TLR7; STAT-1
The QuantiFERON®-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test utility. To assess variability, we compared results from the same subjects when QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different laboratories.
Subjects were recruited at two sites and blood was tested in three labs. Two labs used the same type of automated ELISA workstation, 8-point calibration curves, and electronic data transfer. The third lab used a different automated ELISA workstation, 4-point calibration curves, and manual data entry. Variability was assessed by interpretation agreement and comparison of interferon-γ (IFN-γ) measurements. Data for subjects with discordant interpretations or discrepancies in TB Response >0.05 IU/mL were verified or corrected, and variability was reassessed using a reconciled dataset.
Ninety-seven subjects had results from three labs. Eleven (11.3%) had discordant interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled results. After correction of manual data entry errors for 9 subjects, and exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the manufacturer's recommended cutoff. Non-uniform error of measurement was observed, with greater variation in higher IFN-γ measurements. Within-subject standard deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement ranged from −0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25 IU/mL of the cutoff.
Greater interlaboratory variability was associated with manual data entry and higher IFN-γ measurements. Manual data entry should be avoided. Because variability in measuring TB Response may affect interpretation, especially near the cutoff, consideration should be given to developing a range of values near the cutoff to be interpreted as “borderline,” rather than negative or positive.
According to extensive epidemiological data, infertility is associated with increased ovarian cancer risk. Previous studies showed that both women with infertility and those with ovarian cancer have autoantibodies to ovarian antigens. The objective was to determine if women with infertility have antibodies to mesothelin, a well characterized ovarian cancer antigen.
Sera were obtained from women with infertility (n=109), ovarian cancer (n=28), benign ovarian tumors or cysts (n=24) and from healthy women (n=152). Infertility included those with a risk for ovarian cancer; endometriosis (n=23), ovulatory dysfunction (n=17), premature ovarian failure (n=25) and unexplained infertility (n=44). Sera were assayed for mesothelin antibodies and for circulating mesothelin antigen by immunoassay and compared to assay control sera (n=16) to determine a positive result.
Mesothelin antibodies were significantly more frequent in women with prematurely reduced ovarian function including ovulatory dysfunction (59%), ovarian failure (POF) (44%) and unexplained infertility (25%) compared to controls. In contrast, women with endometriosis, who also have a high risk for ovarian cancer, did not have mesothelin antibodies. Serum levels of mesothelin were rarely elevated in women with infertility but were high in most patients with ovarian cancer.
Conclusions and Significance
We show for the first time that antibodies to mesothelin, a well characterized ovarian cancer antigen, occur in some women with epidemiologic risk for ovarian cancer. The results suggest it may be possible to identify which women with infertility have ovarian cancer risk.
Autoantibodies; Mesothelin; Infertility; Ovarian Cancer
Neonatal diabetes is a rare cause of hyperglycemia, affecting 1: 500,000 births, with persistent hyperglycemia occurring in the first months of life lasting more than 2 weeks and requiring insulin. This condition in infants less than 6 months of age is considered as permanent neonatal diabetes mellitus.
A rare case of permanent neonatal diabetes mellitus presented with intrauterine growth retardation (IUGR; birth weight: 1460 grams; female), hyperglycemia, glycosuria, and mild dehydration, a normal Apgar score of 8 and 9 at 1 and 5 minutes, respectively. The parents, of consanguineous union, had no prior history of diabetes mellitus. Of their 4 children, the first child had a diagnosis similar to the patient (their last child). The patient was initially started on continuous infusion of insulin, and then switched to regular insulin subcutaneously, but response was sub-optimal. She was started on neutral protamine Hagedorn, following which her condition improved. She was discharged on neutral protamine Hagedorn with regular follow-up.
In view of widespread consanguinity in Saudi Arabia it appears prudent and pertinent to suspect permanent neonatal diabetes mellitus following diagnosis of hyperglycemia in small-for-age infants, especially those with positive family history of diabetes. Close blood glucose monitoring is essential as long as hyperglycemia persists. Prolong follow-up is imperative.
consanguinity; diabetes; hyperglycemia; insulin; neonatal; neutral protamine Hagedorn
Citation analysis is currently one of the most widely used metrics for analyzing the scientific contribution in different fields. The Islamic World Science Citation Center (ISC) aims at promoting technical cooperation among Muslim scientists and their respected centers based on these theories. It also facilitates the accessibility of knowledge and research contribution among them. This paper aims at revealing some of the outmost features of ISC databases, in order to give a fairly clear view of what it is and what are its products. The paper consists of three major parts. After an introduction about the Islamic World Science Citation Center, the paper deals with major tools and products of ISC. In the third part ISCs’ journal Submission system is presented as an automatic means, by which users can upload journals’ papers into the respected databases.
Some complementary remarks have been made regarding the current state of ISC and its future plans.
The Islamic World Science Citation Center; ISC; Scientific contribution; Research Journals.
While not an uncommon tumor, urothelial carcinoma of the urinary bladder is rare in bladders draining pancreatic allografts. A case of urothelial carcinoma directly involving a pancreatic allograft with metastasis that occurred in a 49-year-old pancreas and kidney transplant recipient is described. Her initial clinical presentation and findings of CT scan of the abdomen suggested pancreatitis with features worrisome for rejection. A biopsy of her pancreatic allograft contained poorly differentiated carcinoma and cystoscopic biopsy disclosed an invasive high grade urothelial carcinoma arising in the background of extensive urothelial carcinoma in situ. Exploratory laparotomy revealed that the tumor invaded the right ovary and fallopian tube, cecum, and allograft with extensive retroperitoneal involvement. She underwent en bloc resection of distal ileum and cecum, resection of transplant pancreas, partial cystectomy, ileocolostomy anastomosis, and right salpingo-oophorectomy. Postoperatively, the patient was treated with four cycles of carboplatin and gemcitabine. She ultimately succumbed to her disease approximately 1 year after diagnosis. This case should alert physicians and radiologists to be aware of atypical presentation of urothelial carcinoma in bladder-drained pancreas grafts, the aggressiveness of such lesions, and the need for early biopsy to avoid diagnostic confusion with rejection.
Bladder cancer; Nested variant of urothelial carcinoma; Pancreas and kidney transplantation
Given that micronutrient deficiency, neglected intestinal parasitic infections (IPIs) and poor socioeconomic status are closely linked, we conducted a cross-sectional study to assess the relationship between IPIs and nutritional status of children living in remote and rural areas in West Malaysia.
A total of 550 children participated, comprising 520 (94.5%) school children aged 7 to 12 years old, 30 (5.5%) young children aged 1 to 6 years old, 254 (46.2%) boys and 296 (53.8%) girls. Of the 550 children, 26.2% were anaemic, 54.9% iron deficient and 16.9% had iron deficiency anaemia (IDA). The overall prevalence of helminths was 76.5% comprising Trichuris trichiura (71.5%), Ascaris lumbricoides (41.6%) and hookworm infection (13.5%). It was observed that iron deficiency was significantly higher in girls (p = 0.032) compared to boys. Univariate analysis demonstrated that low level of mother's education (OR = 2.52; 95% CI = 1.38–4.60; p = 0.002), non working parents (OR = 2.18; 95% CI = 2.06–2.31; p = 0.013), low household income (OR = 2.02; 95% CI = 1.14–3.59; p = 0.015), T. trichiura (OR = 2.15; 95% CI = 1.21–3.81; p = 0.008) and A. lumbricoides infections (OR = 1.63; 95% CI = 1.04–2.55; p = 0.032) were significantly associated with the high prevalence of IDA. Multivariate analysis confirmed that low level of mother's education (OR = 1.48; 95 CI% = 1.33–2.58; p<0.001) was a significant predictor for IDA in these children.
It is crucial that a comprehensive primary health care programme for these communities that includes periodic de-worming, nutrition supplement, improved household economy, education, sanitation status and personal hygiene are taken into consideration to improve the nutritional status of these children.
Micronutrient deficiency and intestinal parasitic infections (IPIs) share a similar geographical distribution. A conservative estimate indicated that almost 2 billion individuals suffer from anaemia due to iron deficiency (ID), corresponding to 24.8% of the world's population. Crucially, most of these individuals are children and women of reproductive age in developing countries. Intestinal parasitic infections, especially soil-transmitted helminthes (STH), are prevalent in areas where micronutrient deficiency is widespread and the relationship between them has been studied. Most studies have noted an association between iron deficiency and IPIs. Against this background we studied the association between micronutrient deficiency, IPIs and socioeconomic factors among rural children in West Malaysia. Overall, 26.2%, 54.9% and 16.9% of the participants had anaemia, ID and iron deficiency anaemia (IDA), respectively. The overall prevalence of STH infections was 76.5% with Trichuris trichiura (71.5%), Ascaris lumbricoides (41.6%) and hookworm (13.5%). Univariate analysis found that low level of mother's education, i.e., less than 6 years of formal education, non working parents, low house income, T. trichiura infection and A. lumbricoides infection were significantly associated with the odds of IDA. The final multivariate analysis indicated that low level of mother's education was a significant predictor for IDA in these children.
Streptobacillus moniliformis is a fastidious growing Gram-negative bacillus responsible of rat-bite fever. We describe here the first report of this disease in la Réunion and the first isolation using shell vial cell culture from a blood culture bottle with a bacterium suspected to be dead.
Background. There are scarce data on the long-termsurvival of human immunodeficiency virus (HIV)—infected children receiving antiretroviral therapy (ART) in lower-middle income countries beyond 2 years of follow-up.
Methods. Previously untreated children who initiated ART on meeting immunological and/or clinical criteria were followed in a prospective cohort in Thailand. The probability of survival up to 5 years from initiation was estimated using Kaplan-Meier methods, and factors associated with mortality were assessed using Cox regression analyses.
Results. Five hundred seventy-eight children received ART; of these, 111 (19.2%) were followed since birth. At start of ART (baseline), the median age was 6.7 years, 128 children (22%) were aged <2 years, and the median CD4 cell percentage was 7%. Median duration of follow-up was 53 months; 42 children (7%) died, and 38 (7%) were lost to follow-up. Age <12 months, low CD4 cell percentage, and low weight-for-height z score at ART initiation were independently associated with mortality (P < .001). The probability of survival among infants aged <12 months at baseline was 84.3% at 1 year and 76.7% at 5 years of ART, compared with 95.7% and 94.8%, respectively, among children aged ⩾1 year. Low CD4 cell percentage and wasting at baseline had a strong association with mortality among older children but weak or no association among infants.
Conclusions. Children who initiated ART as infants after meeting immunological and/or clinical criteria had a high risk of mortality which persisted beyond the first year of therapy. Among older children, those with severe wasting or low CD4 cell percentage at treatment initiation were at high risk of mortality during the first 6 months of therapy. These findings support the scale-up of early HIV diagnosis and immediate treatment in infants, before advanced disease progression in older children.