In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei

Background  

Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism.     

Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin

CONTEXT: Metformin therapy for adults and children with type 2 diabetes is well established. However, its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined. OBJECTIVE: We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity. DESIGN AND SETTING: Patients referred to a pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover trial. PATIENTS: Twenty-eight patients (13 males) aged 9-18 yr participated in the study. INTERVENTION: Patients received metformin (1 g twice daily) and placebo for 6 months, each with a 2-wk washout period. MAIN OUTCOME MEASURES: Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal magnetic resonance imaging), and insulin sensitivity (Si; minimal model, fasting insulin and glucose) were measured at baseline and 6 and 12 months. RESULTS: Mean age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score 2.54 (range, 1.93-2.85). Metformin had a greater treatment effect over placebo for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in 45% of subjects while on metformin and 27% of subjects while on placebo (P = 0.21). CONCLUSIONS: Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin. Although improvement in Si was noted in many individuals, Si was a less useful parameter for analysis of group data, possibly because of effects of variable compliance and changing Si during puberty.     

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9- 7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).      

Psoriatic alopecia - fact or fiction? A clinicohistopathologic reappraisal

Background: The incidence of psoriatic alopecia in psoriatic patients is underwhelming, given the prevalence of psoriasis in the North American population. Recently, a 60-year-old Albanian female, lacking a significant medical history for psoriasis, presented to our clinic with a 1-year history of "dandruff" associated with itch, hair thinning, and histopathologic evidence consistent with prior reports of "psoriatic alopecia." Aims: The absence of preceding or concomitant psoriasis suggests that the patient's alopecia is an antecedent manifestation of psoriasis, thus prompting this retrospective study to ascertain better the relationship between alopecia and psoriasis. Methods: We performed a retrospective review of 33 scalp biopsies on 31 patients having histopathologic diagnosis of psoriasis belonging to 31 patients seen between 2007 and 2010. Results: Alopecia was a presenting feature in 48% of cases with definitive clinical and/or histopathologic diagnosis of psoriasis (scale crust with neutrophils, psoriasiform epidermal hyperplasia, and hypogranulosis). The most common follicular-related changes were infundibular dilatation (87%) followed by perifollicular fibrosis (77%), perifollicular lymphocytic inflammation (68%), thinning of the follicular infundibulum (55%), and fibrous tracts (28%). Of interest, sebaceous glands were absent in 60% and atrophic in 25% of cases. Conclusion: While a major limitation of this study is that it is a retrospective one, given that these changes are common to varying degrees in all lymphocytic scarring alopecias, we posit that psoriatic alopecia likely represents a secondary clinical change to a primary process and is not a unique histopathologic entity. A prospective study with a control group that includes lymphocytic scarring alopecias from non-psoriatic patients is required to support our findings.     

Protein selectivity: a prognostic index in IgA nephritis

Among 98 patients with IgA nephritis who had protein selectivity studies performed, 54% had nonselective proteinuria and the remaining 46% had selective proteinuria. Patients with nonselective proteinuria had a higher incidence of glomerulosclerosis. At the end of a 4-year follow-up period, patients with nonselective proteinuria had lower creatinine clearance, higher incidence of hypertension and chronic renal failure when compared to patients with selective proteinuria. Six out of eleven patients (55%) in the study who had the nephrotic syndrome had selective proteinuria. Among these 6 patients, 1 had spontaneous remission and 5 responded to steroid or cyclophosphamide therapy. The remaining 5 patients with nonselective proteinuria did not respond to therapy. In the patients who had selectivity studies repeated, the data showed that the selectivity index (SI) can fluctuate depending on the clinical course of the patients. SI can therefore be used to monitor the progress of patients on long-term follow-up. Protein selectivity appears to be a useful prognostic index in IgA nephritis. For patients with the nephrotic syndrome it may serve as a guide to therapy.     

Refractory subacute cutaneous lupus erythematosus successfully treated with rituximab

A 48-year-old woman presented with pruritic, scaly, annular plaques over her upper back and chest that were clinically, serologically and histologically characteristic of subacute cutaneous lupus erythematosus (SCLE). She failed to respond to conventional treatment, which included high-dose hydroxychloroquine, methotrexate, prednisolone, chloroquine, acitretin, thalidomide, dapsone and azathioprine. Subsequently treated with intravenous rituximab 375 mg/m² weekly for 4 weeks, she remained on adjuvant oral hydrochloroquine 600 mg daily and topical clobetasol propionate 0.05% ointment as required. Clearing of annular plaques was noted 8 weeks after the initial course of rituximab. By 12 weeks there were no new lesions and only post-inflammatory hyperpigmentation remained. Both hyper- and hypopigmentation, which is more common, are consistent with SCLE lesion regression. Skin lesions recurred 11 months later; however, no further lesions occurred after re-introduction of rituximab therapy. The treatment was well tolerated. A maintenance regimen of rituximab, 375 mg/m² every 8 weeks for 2 years, was commenced 3 months after completing the second course of treatment, with ongoing disease remission. Rituximab appears to have activity in refractory SCLE and clinical trials are required to further assess this potential therapy.     

Urine microalbumin/creatinine ratios in Singapore children.

The random urine albumin:creatinine (Ua:Uc) ratio was measured in 139 healthy children from newborn to age 4 years using the immunonephelometric method. This was shown to vary with age, the mean for neonates being 5.24mg/mmol (2SD range: 0.54-14.95mg/mmol) decreasing to 1.34mg/mmol (2SD range: 0.55-3.29mg/mmol) for the 2-4 years age range. The values for newborn to 6 months was significantly higher than the older age group (p less than 0.000001). 14 children with structural renal disease were then studied to determine the value of the random Ua:Uc ratio in detecting glomerular injury. This was found to be abnormal in children with glomerular filtration rate (GFR) less than 80ml/min/1.73m2 as well as in some children with complex bilateral renal structural abnormalities. Further longitudinal studies are required to determine the usefulness of this ratio in predicting progressive glomerular injury in this group of patients.     

Effects of stabilization appliances on nocturnal parafunctional activities in patients with and without signs of temporomandibular disorders

This study was designed to investigate the short‐term effects of stabilization appliances on parafunctional oral motor behaviour (bruxing and clenching) during sleep in patients with and without signs of temporomandibular disorders (TMD). Results revealed that stabilization appliances do not stop nocturnal parafunctional activities in both groups of patients. Active wear facets on the guide ramps of appliances were created by bilateral mandibular excursions. The extension of these facets indicate that the mandible moves laterally far beyond the edge‐to‐edge contact relationship of the canines during eccentric bruxism. Results also indicate that, with the exception of temporomandibular joint (TMJ) clicks, stabilization appliance therapy is effective in eliminating the signs of TMD evaluated.     

The effect of light scattering on multifocal electroretinography

PURPOSE: Unclear ocular media is a very common condition of older eyes characterized by significant light scattering and image degradation. The multifocal electroretinography (MERG) is a useful objective technique to measure retinal activity but its validity in the presence of cloudy ocular media remains unclear. We tested the MERG under controlled light scattering conditions using a liquid crystal diffuser (LCD) that simulated different degrees of image degradation. METHODS: The MERG were taken from 13 normal young subjects seated behind a LCD set under two conditions: scatter (visual acuity approximately 6/18) and non-scatter (visual acuity approximately6/6). The pupils had been dilated and the eyes were optically corrected for the working distance. The first-order kernel MERG response was analysed. Three subjects underwent MERG measurement with two additional intermediate light scattering levels (i.e. visual acuity approximately 6/9 and 6/12). RESULTS: The macular MERG response density was reduced (p < 0.001), but the peripheral MERG response densities were increased (p < 0.001) under the scattering condition. A similar trend was also observed with intermediate degrees of light scattering. Comparing the MERG waveforms without light scattering, a new retinal response was identified with a characteristic latency of about 60 ms (P60), but it was diminished in size under the scattering conditions. CONCLUSIONS: The veiling luminance might have caused the reduction in the macular MERG response and an elevation in the peripheral retina with light scatter. The functional suppression of P60 observed under the influence of light scatter may be related to retinal adaptation. Unclear optical media will affect the interpretation of MERG results.     

Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C

This look-back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion-transmitted HCV infection acquired in the neonatal period. A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti-D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994–95; the past donations of five of the donors, who had received anti-D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994–95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined. Twenty-one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti-HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis. The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.