Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.     

Quality of life following surgery for recurrent fistula-in-ano

Background  

The management of fistula-in-ano remains a major surgical challenge and carries a significant morbidity affecting the quality of life (QOL) due to the disease and repeated operations. The aim of the study was to assess the QOL before and after successful surgical treatment of recurrent fistula-in-ano using the gastrointestinal quality of life index (GIQLI) which is a validated instrument consisting of 36 questions for measuring quality of life in patients with gastrointestinal disorders including fistula-in-ano.     

Serum insulin patterns and the relationship between insulin sensitivity and glycaemic profile in women with polycystic ovary syndrome

Objective  To evaluate serum insulin levels and insulin sensitivity in women with polycystic ovary syndrome (PCOS) in relation to their glycaemic status.
Design  An observational study.
Setting  A tertiary-level reproductive health centre in Sri Lanka.
Sample  Infertile women diagnosed as having PCOS ( n  = 168) on the basis of the Rotterdam criteria were included in the study.
Methods  Glycaemic status and serum insulin values were assessed at fasting and at 2 hours after a 75-g oral glucose load and stratified as diabetes mellitus (DM) (10.12%), impaired glucose tolerance (IGT) (23.21%) and normoglycaemia (66.67%). The normoglycaemic group was restratified as groups A (10.7%), B (79.5%) and C (9.8%) on the basis of serum insulin levels, with group A having the lowest and group C the highest values. The Quantitative Insulin Sensitivity Check Index (QUICKI) scores of women with DM and IGT and those in groups A, B and C in the normoglycaemic category were compared.
Main outcome measures  Insulin sensitivity in these groups of women.
Results  Body mass index (BMI) exceeded 23 kg/m² in 77.38% of the women. In normoglycaemic women with PCOS, insulin sensitivity was highest in group A. In groups B and C, insulin sensitivities corresponded to those found for women with IGT and DM respectively. This pattern was also reflected in the BMI.
Conclusions  Normoglycaemic women with PCOS are heterogeneous regarding insulin sensitivity. The treatment offered to those with DM and IGT could be extended to subgroups B and C of normoglycaemic subjects. Normoglycaemic women with PCOS with high insulin sensitivity (group A) would not qualify for this treatment.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Community lifestyle of Candida in mixed biofilms: a mini review

Candida is the most common human fungal pathogen that causes a variety of afflictions from superficial mucosal infections to deep mycoses . Biofilm formation is a major virulence factor of Candida , and more than 300 articles have been published on Candida biofilms over the past two decades. However, most of these data are on monospecies biofilms of Candida , and information on mixed-species Candida biofilms or bacteria– Candida combinations is still scarce. Yet, in nature, the yeast exist in a mixed milieu either in the oral cavity or in other habitats with a multitude of bacteria colonising mucosal surfaces within a shared community. This mini review describes the current knowledge on candidal–candidal or bacterial–candidal interactions in mixed-species biofilms. The underlying mechanisms of these interactions appear to depend on several factors relating to biofilm development, such as species and strains of organisms, nutritional factors, aerobiosis and related environmental factors. Although the fundamental nature of these interactions appears to be commensalism and antagonism, the emerging evidence based on novel molecular, proteomic and imaging tools indicates these biological mechanisms to be far more complex than hitherto recognised. Demystifying the mechanisms underlying the growth and development of mixed-species communities involving Candida will undoubtedly yield useful data for the effective management of microbial infections in general.     

Colposcopic genital findings in prepubertal girls assessed for sexual abuse

After the introduction of the colposcope for the examination of children suspected of being sexually abused in Leeds, a study was undertaken to describe the findings in detail. A total of 109 consecutive prepubertal girls, mean age 70.4 months were assessed including colposcopic genital and anal examination, and peer group review of reports and photographs. Fifty nine children had signs consistent with blunt force penetrating trauma (hymenal transection/major notch, scar, or hymenal attenuation). Transections were encountered most commonly at 6 o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh abduction only and in 47 the hymenal orifice transverse diameter was greater than 4 mm on labial separation. Overall, physical findings were commonly present and in only two cases were no signs recorded. Non-specific and frequent findings included patterns of labial and introital reddening. Supportive hymenal signs including swelling, rounding of edge, thickening, distortion, and loss of symmetry were common. Labial fusion was present in 20. Urethral dilatation with labial separation was noted in 14. Physical findings including normality are consistent with abuse and even minor anogenital signs as well as negative findings should be documented. Colposcopy and photography are valuable tools in peer review, teaching, and case management.