Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.     

A review of animal models for portal vein embolization

Background

Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE.

Materials and methods

We performed a systematic literature search in Medline and Pubmed, from 1993–June 2013, using search headings “PVE” and “portal vein ligation”. Articles were included when meeting the selection criteria: experimental animal study on PVE or portal vein ligation and experiments described in 5 animals or more.

Results

Sixty-one articles were selected, describing six different animal models. Most articles reported experiments with rats, rabbits, and pigs. In rats, the increase in wet-weight ratio of the non-occluded liver or total liver weight is greatest in the first 7 d with values ranging from 75%–80.5% on day 7. The volume increase of FRL in the rabbit model is greatest in the first 7 d with values ranging from 33.6%–80% on day 7. In pigs, the largest gain in volume of the FRL was seen in the first 2 wk.

Conclusions

The choice of the model depends on the specific aim of the study. Evaluating the increase in liver volume and liver function after PVE, larger animals as the pig, rabbit, or the dog is useful because of the possibility to apply computed tomography volumetry. To evaluate mechanisms of regeneration after PVE, the rat model is useful, because of the variety of antibodies commercially available.     

Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes

Aims

Evidence of ethnic disparities in the conversion of prediabetes to type 2 diabetes is scarce. We studied the association of impaired fasting glucose (IFG) and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2 diabetes in three ethnic groups.

Methods

We analyzed data for 90 South-Asian Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in the periods 2001–2003 and 2011–2012. We excluded those with type 2 diabetes or missing FPG data. We defined baseline IFG as FPG of 5.7–6.9 mmol/L. We defined type 2 diabetes at follow-up as FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%), or self-reported type 2 diabetes.

Results

10-Year cumulative incidences of type 2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic Dutch, 4.5% (p < 0.05). The adjusted association of baseline IFG and FPG with the 10-year cumulative incidence of type 2 diabetes was stronger for South-Asian Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to normoglycaemia) ORs were 11.1 [3.0–40.8] for South-Asian Surinamese, 5.1 [2.0–13.3] for African-Surinamese, and 2.2 [0.5–10.1] for ethnic Dutch.

Conclusions

The 10-year cumulative incidence of type 2 diabetes was higher and associations with baseline IFG and FPG were stronger among South-Asian Surinamese and African-Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2 diabetes in South-Asians and suggest more rapid conversion in populations of South-Asian origin and (to a lesser extent) African origin than European origin.     

Paternal influences on treatment outcome of behavioral parent training in children with attention-deficit/hyperactivity disorder

This study aims to explore the influence of paternal variables on outcome of behavioral parent training (BPT) in children with attention-deficit/hyperactivity disorder (ADHD). 83 referred, school-aged children with ADHD were randomly assigned to BPT plus ongoing routine clinical care (RCC) or RCC alone. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Moderator variables included paternal ADHD symptoms, depressive symptoms, and parenting self-efficacy. We conducted repeated measures analyses of variance (ANOVA) for all variables, and then analyzed the direction of interaction effects by repeated measures ANOVA in high and low scoring subgroups. Paternal ADHD symptoms and parenting self-efficacy played a moderating role in decreasing behavioral problems, but not in decreasing ADHD symptoms. Paternal depressive symptoms did not moderate either treatment outcome. BPT is most beneficial in reducing children’s behavioral problems when their fathers have high levels of ADHD symptoms or high-parenting self-efficacy.     

Diabetes Patients' Experiences With the Implementation of Insulin Therapy and Their Perceptions of Computer-Assisted Self-Management Systems for Insulin Therapy

Background

Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems.

Objective

Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients’ perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system.

Methods

In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd.

Results

When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression, and some were ignorant of treatment targets. Patients who never used a computer-assisted insulin self-titration system felt they had enough knowledge to know when their insulin should be adjusted, but still believed that the system advice would be useful to confirm their reasoning. Furthermore, the time and effort saved with automated insulin advice was considered an advantage. Patients who had used PANDIT found the system useful if their glycemic regulation improved. Nevertheless, for some patients, the absence of personal contact with their caregiver was a drawback. While guidelines state that adjustment of basal insulin dose based on fasting plasma glucose values is sufficient, both patients who had and those who had not used PANDIT felt that such a system should take more patient data into consideration, such as lifestyle and diet factors.

Conclusions

Patients encounter multiple obstacles when implementing insulin therapy. Computer-assisted insulin self-titration can increase patient awareness of treatment targets and increase their confidence in self-adjusting the insulin dose. Nevertheless, some barriers may still exist when using computer-assisted titration systems and these systems could also introduce new barriers.     

The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience

IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.     

Development and psychometric properties of the “Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales” in adolescents

European Child & Adolescent Psychiatry - Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and...     

Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study

Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.