PBPK model for radioactive iodide and perchlorate kinetics and perchlorate-induced inhibition of iodide uptake in humans.

Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)-iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I- and cold ClO4- in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the measured levels of serum and urinary ClO4- from drinking water exposures, ranging from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid 131I- uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I- in serum from various tracer studies, are also successfully simulated. This model's parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I- provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to I- incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins.     

Successful treatment of pediatric plasmacytoid dendritic cell tumors with a contemporary regimen for acute lymphoblastic leukemia

Dendritic cell leukemia (DCL) or hematodermic tumor is an uncommon subtype of acute leukemia. In contrast to adult cases, children tend to have a less aggressive course. The diagnosis of DCL should be considered when its characteristic morphologic features are present and leukemic cells co‐express CD4 and CD56. Cases of DCL among pediatric patients have been reported to respond to therapeutic regimens for acute lymphoblastic leukemia, but details regarding the specifics of therapy are lacking. Pediatr Blood Cancer 2013; 60: E38–E41. © 2013 Wiley Periodicals, Inc.     

Opioid-based micro and nanoparticulate formulations: alternative approach on pain management

Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids.     

Trends in the safety of inpatient hysterectomy for benign conditions in California, 1991-2004

OBJECTIVE: To assess the utilization rates of and complications associated with inpatient hysterectomy in California between 1991 and 2004. METHODS: We used the California Patient Discharge Database to analyze International Classification of Diseases, 9th Revision, Clinical Modification diagnostic and procedure codes for 649,758 women undergoing inpatient hysterectomy in California between 1991 and 2004 using multiple logistic regression models. RESULTS: Between 1991 and 2004, the incidence of any type of inpatient hysterectomy for benign gynecologic conditions declined 17.6%. The rates of laparoscopically assisted vaginal hysterectomy and subtotal hysterectomy increased substantially. The year of hysterectomy was a factor associated with both medical and surgical complications; the odds of inpatient complications between 1991 and 2004 steadily declined. CONCLUSION: In California between 1991 and 2004, the incidence of inpatient hysterectomy for benign gynecological conditions and the adjusted odds of complications declined substantially. Changes in practice and shorter hospital stays may have affected the changes in inpatient hysterectomy rates and associated inpatient complications.     

Intimate partner violence screening and brief intervention: experiences of women in two New Zealand Health Care Settings

The identification of intimate partner violence (IPV) against women as a public health problem has led to routine health care site– based screening and brief intervention policies. However, there is a lack of evidence supporting the usefulness and safety of such policies. Our objective was to ascertain the acceptability, usefulness, and harm of a brief health care site– based screening intervention. In this qualitative study, semistructured interviews were conducted with 36 women several weeks after a standardized screening intervention in either an emergency department (adult and paediatric) or primary health care setting. The majority of women (97%) welcomed the IPV screening intervention and perceived it as nonthreatening and safe. The women reported no increased risk of harm because of the screening. The responses showed that the intervention had a therapeutic and educational quality, and the attitude and approach of the person asking the intervention questions was critical to a positive outcome. Women without a history of violence cautioned that IPV screening may be offensive to those who are abused, whereas those who reported abuse thought IPV screening was essential “to stop it [from] happening.” Our findings challenge concerns that IPV screening is offensive to women and increases their potential for danger. Participants were appreciative of the opportunity to tell their abuse stories in a safe and supportive context, and challenged the health care system to implement IPV screening, asking “What took you so long?”     

Postnatal development of pups from nursing rats treated with Gingko biloba

The Gingko biloba extract is contraindicated during pregnancy and lactation due to the lack of information about its effects on these reproductive phases. Previous studies have shown that G. biloba extract contains components with estrogenic and antiestrogenic activities, thus nursing dams treated with the extract of this plant could show reduction in milk production, resulting in malnutrition and poor development of pups. This work analyzes the postnatal development of pups, whose mothers were treated with G. biloba extract during the lactation period. Nursing Wistar rats received 3.5 mg/kg/day of G. biloba aqueous extract, corresponding to the highest human dose. Clinical signs of maternal toxicity were evaluated. The growth rate, viability, survival during treatment and lactation indices of the pups were calculated. The physical, motor and sensorial development of the pups was also evaluated. No maternal signs of toxicity were observed. As there were no biological differences between control and G. biloba treated pups, it is possible to assume that, in this experimental design, the administration of G. biloba aqueous extract to nursing rats during the lactation period seems to be devoid of toxic effect to mothers and to the physical, motor and sensory development of the pups.     

Do ventilated neonates require pain management?

Mechanical ventilation is a stressful experience in neonates resulting in changes in neuroendocrine parameters, pain scores, and physiologic responses. Assisted ventilation in neonates is presumed to be associated with chronic repetitive pain, which in turn is associated with adverse long-term sequelae. Reasons to routinely sedate ventilated neonates include improved ventilator synchrony, improved pulmonary function, and decreased neuroendocrine responses, including cortisol, beta-endorphine, and catecholamines. Reasons not to treat include the well-known adverse side effects of pain medication, especially the opiates, including hypotension from morphine, chest wall rigidity from fentanyl, and tolerance, dependence, and withdrawal from both opiates and benzodiazepines. Additionally, adverse effects such as death and IVH are not improved with preemptive treatment. Chronic pain assessment is poorly validated and difficult to assess in this population, and most studies have evaluated only acute pain scores. If patients are treated, opiates are the most common class of drugs, with morphine the most well studied. Fentanyl may be advantageous in hypotensive, younger neonates because it has fewer cardiovascular effects. The benzodiazepines, midazolam and lorazepam, have been used in ventilated neonates, but midazolam has been associated with adverse effects in one small study so concern remains regarding its use. Significant gaps in our knowledge exist, especially in regard to long-term effects of treatment, or lack thereof, and in the assessment of the chronic pain associated with assisted ventilation.     

Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active sle

Thirty-seven patients with criteria for systemic lupus erythematosus (SLE) and 18 normal controls were studied for their spontaneous background IgM antibody plaque-forming cell number to specific chemical haptens. Active SLE patients had significantly more plaque-forming cells in their peripheral blood to a total of five chemical determinants than did patients with inactive disease or controls. This increased number of plaque forming-cells correlated with depressed serum C3 levels by Spearman rank-order analysis. The finding of elevated numbers of spontaneous IgM plaque-forming cells to defined chemical haptens supports the concept that active SLE demonstrates a generalized increase in B-cell activity toward a variety of antigens.