Age-specific Doses Research Articles

Investigating Age-Specific Respiratory Deposition Doses of Traffic-Related Particles at Urban Intersections in Pune, India

Investigating Age-Specific Respiratory Deposition Doses of Traffic-Related Particles at Urban Intersections in Pune, India

Гострі респіраторні інфекції в дітей: сучасні тенденції противірусної терапії

The aim is тto study the clinical efficacy of Flavovir® in the treatment of acute respiratory viral infections (ARVI) in young children. Materials and methods. The study included 60 young children who received outpatient treatment at the primary health care centers of the Vinnytsia region in the period from 2019 to 2021. The inclusion criteria for the study were ARVI and age аfrom 1 month to 3 years; exclusion criteria were еaggravated premorbid background (immunodeficiency diseases, congenital malformations, etc.), the use of other antiviral drugs, influenza vaccination. According to this aim the children are divided into two groups. The first group consisted of 30 children with ARVI who received Flavovir® (Research and Production Company "Ecopharm" Ltd, Ukraine) in combination with symptomatic therapy. The second group consisted of 30 patients with ARVI who received only symptomatic therapy. The distribution of patients into groups was carried out randomly. The groups were representative for age, sex, structure and severity of disease. Results. During the study the drug Flavovir® showed an effective antiviral effect in the treatment of acute respiratory viral infections in young children. In ase of the introduction of Flavovir® in the treatment regimen of the examined patients, a positive dynamics of clinical disease was noted: the intoxication syndrome disappeared three times faster (Group I — duration on average 3.4±0.2 days; Group II — 10.4±0.6 days , p<0.05), catarrhal syndrome disappeared approximately two times faster (group I — duration on average 4.5±0.4 days; II group — 9.6±0.7 days, p<0.05); нthere was a reduction in the recovery time by almost two times (group I — on average 5.81±0.5 days, II group — 11.8±0.6 days, p<0.05). The drug is well tolerated by patients and safe for children. Conclusions. The results obtained allow to recommend Flavovir® in age-specific doses for the etiotropic therapy of modern acute respiratory viral infections in young children, taking into account the direct antiviral effect of the drug. The study was carried out in accordance with the principles of the Declaration of Helsinki. The informed consent of the parents of the children was obtained for the research. The author declares no conflicts of interest. Key words: children, treatment, acute respiratory viral diseases, Flavovir.

Coronavirus Disease 2019 Vaccine in Children

Coronavirus Disease 2019 Vaccine in Children

Effective doses and associated age-related risks for common paediatric diagnostic nuclear medicine and PET procedures at a large Australian paediatric hospital.

Effective dose alone cannot be used to specify and communicate the radiation risk for an individual as risks are dependent on many factors including age and gender. There are limited published data regarding age-specific effective doses and the associated lifetime risk of developing cancers for paediatrics. In this study, we have estimated the typical effective doses for six commonly performed paediatric nuclear medicine and positron emission tomography (PET) studies at the Royal Children's Hospital, Melbourne, Australia. Effective doses were used to estimate and categorise associated stochastic risks with commonly used risk terminology. Paediatric protocols for common nuclear medicine and PET studies and the World Health Organization (WHO) 50th percentile weight-for-age data for females and males aged up to 18 years were used to estimate typical organ and effective doses using ICRP dosimetric tables for radiopharmaceuticals and lifetime risk of cancer incidence using BEIR VII Phase 2 report data. Results were used to determine standardised levels of risk. Organ doses, effective doses, corresponding lifetime risk of cancer incidence and level of risk category from six common nuclear medicine and PET studies for paediatric patients were calculated and presented for ease of communication. Typical effective doses from common paediatric nuclear medicine and PET studies and the associated lifetime risk of cancer incidence and level of risk have been established for our institution. This can be used to convey risks to health professionals, patients and carers in ways that are easy to understand and compare with other everyday risks.

Dose Estimation for the European Epidemiological Study on Pediatric Computed Tomography (EPI-CT).

Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies.

DOSE ASSESSMENT OF NATURAL TERRESTRIAL RADIONUCLIDES IN COMMONLY CONSUMED FOODS IN NORTH INDIA.

The present study aimed to record natural radionuclide content in branded food samples representative of a typical North Indian diet. Forty samples of various food items falling into three categories namely, cereal grains, pulses and beverages were collected from the local markets of Punjab. The radiometric analysis was performed using NaI(Tl) scintillator detector. The activity concentrations ranged between 10±1 and 20±5Bqkg-1 for 226Ra, Below Detectable Limit (BDL) and 10±2Bqkg-1 for 232Th and 440±56 and 562±70Bqkg-1 for 40K. The radium equivalent (Raeq) varied from 55Bqkg-1(corn) to 70Bqkg-1 (tea) with an average of 62Bqkg-1. Internal hazard index (HI) was also calculated (0.18-0.24), which was well below the prescribed threshold of one (24). Age-specific annual effective doses were estimated for infants, children and adults. Children were the most sensitive group of population to radionuclide doses from cereal grains. The annual effective doses were further used to calculate the lifetime cancer risk which exceeded the world average of 2.9$\times$10-4 (24). However, the overall results showed that the intake of these dietary products by the general public did not pose any serious health risk.

Efficacy of Pandughni Vati & Punarnavadi Mandura Vati in the managment of Pandu w.s.r. iron deficiency anemia in children- An open labelled comparative clinical trial

Background:Anemia is a public health problem worldwide, and its prevalence in India is higher than any other south asian countries. Iron deficiency anemia (IDA) is having larger share out of all types of anaemia’s. Symptomatology of IDA resembles with Kapha dominant variety of Pandu. Pandughni Vati (PV) and Punarnavadi Mandura (PM) Vati mentioned in Ayurveda are being used in clinical practice since long.Aim:To assess the efficacy of Pandughni Vati and compare its clinical efficacy with Punarnavadi Mandura Vati in the management of Pandu ws.r. iron deficiency anemia in children.Materials and methods:Present clinical study was a randomized trial for management of iron deficiency anemia aged 2–16 years. Out of total 91 patients enrolled, 60 completed the study and divided into two groups. In group A, Pandughni Vati (trial drug) and in group B, Punarnavadi Mandura Vati in the management of Pandu ws.r. iron deficiency anemia in children. (standard drug) were given to 30-30 patients respectively for a duration of 90 days in age specific doses. Patients were assessed by clinical signs and symptoms of Pandu and investigation parameters like complete blood count, serum iron, serum ferritin and total iron binding capacity (TIBC) on baseline and after 90 days of treatment. Statistical analysis was carried out by Sigma Stat software.Results:On comparison, highly significant difference was found between two groups in subjective parameters such as Panduta (pallor), Daurbalya (weakness), Hriddrava (palpitation), Akshikuta Shotha (periorbital oedema), Pindikodweshtana (leg cramps) and Shwasa (breathlessness) whereas objective and saturation percentage except serum ferritin.Conclusion:The study revealed that, both the drugs; Pandughni Vati and Punarnavadi Mandura Vati were equally effective in the management of IDA so, it could be concluded that Pandughni Vati, can be used as mineral-free, safe, easily obtainable, palatable, cost-effective alternative drug of choice in alternative of Punarnavadi Mandura in iron deficiency anemia in children.

PECULIARITIES OF ANTIBIOTIC-ASSOCIATED DIARRHEA DEVELOPMENT IN CHILDREN WITH ACUTE RESPIRATORY INFECTIONS

Introduction: Acute respiratory infections (ARI) are the main cause of morbidity in most countries. The probability of complications and age determine antibiotics administration. Antibiotic associated diarrhea (AAD) is one of the side effects of antibiotics. The aim: The study of the prevalence rate of AAD and the characteristics of its development in children with ARI. Materials and methods: The study included 75 children aged from 1 to 12 y diagnosed with ARI, who were treated with age-specific doses of antibiotics. The influence of children's anamnesis, parents' health on the development of AAD was studied with odds ratio calculation (OR). Results: In general, AAD incidence was 52%. The highest frequency 59.3% was observed in children under 3 y. AAD most often developed in children treated with amoxicillin - 92%. The greatest dependence of AAD development was connected with breastfeeding less than 6 months - OR was 7.65, preterm birth - 2.9, functional GIT disorders in anamnesis - up to 3.14, allergy - 2.33. The risk of AAD development increased with the age of parents more than 35 y - 5.03, at the age of parents less than 18 and older than 35 y - 4.09, parents' allergies - 3.74 and parents smoking - 2.43. Conclusions: The most important factors of AAD development on antibiotics therapy in children with ARI are breastfeeding less than 6 months, functional GIT disorders and allergic conditions in anamnesis. Suboptimal age and parents' health (GIT disorders, allergic conditions and unhealthy habits) also increase the risk of AAD development.

Liquid Room Temperature Stable Glucagon—Glucose Response in Pediatric Type 1 Diabetes Patients

Objective: The International Society for Pediatric and Adolescent Diabetes recommends age-specific dosing of glucagon for the rescue of severe hypoglycemia. A novel ready-to-use stable liquid glucagon auto-injector (GAI; Xeris Pharmaceuticals) was evaluated for the treatment of hypoglycemia in pediatric subjects with two age-specific doses. Research Design and Methods: A sequential efficacy and safety study was conducted involving 31 children with T1D (ages 2-17 years) to evaluate two subcutaneous doses of GAI (0.5 mg or 1 mg) for treatment of hypoglycemia (PG < 80 mg/dL), induced via IV insulin or insulin pump. The primary efficacy endpoint was increase in mean plasma glucose from baseline at 30 minutes following administration of an age-appropriate glucagon dose. As secondary endpoints, subjects were assessed for time from dosing to achieve a 25 mg/dl increase in plasma glucose and other PD and PK parameters. Results: Statistically significant increases in mean plasma glucose from baseline to 30 minutes post administration of glucagon were observed across the 3 pediatric age groups (81.4±18.3 mg/dL, 84.2±25.3 mg/dL, and 54.0±27.3 mg/dL in the 2 to < 6 years [n=7, 0.5 mg dose], 6 to < 12 years [n=13, 0.5 mg dose], and 12 to < 18 years [n=11, 1 mg dose] age groups, respectively). All evaluable subjects achieved the target glucose elevation of ≥25 mg/dL from baseline. Across age groups there were no notable differences with regards to mean glucose AUC0-90m, Cmax, and Tmax or median time to achieve a 25 mg/dl glucose increase. Plasma glucagon AUC0-240m, Cmax, and Tmax were similar across the age groups. Nausea (36.4%) and vomiting (18.2%) were the most commonly reported AEs. Conclusions: To prevent medical complications and their sequalae, prompt management of severe hypoglycemia emergencies is critically important. These results demonstrate that age-appropriate doses of GAI were effective in treating hypoglycemia, safe, and well tolerated in pediatric subjects ages 2 through 17 years old. Disclosure B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. P. Strange: Other Relationship; Self; AstraZeneca. Consultant; Self; Valeritas, Inc.. Stock/Shareholder; Self; Valeritas, Inc..

CLINICAL EFFICACY OF PELARGONIUM SIDOIDES EPS® 7630 IN COMPLEX THERAPY OF CHILDREN WITH CHRONIC ADENOIDITIS, WHO HAS UNDERGONE ADENOIDECTOMY

200 children aged 4 to 12 years diagnosed with grade 3 adenoids, chronic adenoiditis, admitted for routine surgical intervention – adenoidectomy, have been examined and treated in the Pediatric ENT-pathology Department of the Moscow Department of Health L.I. Sverzhevskiy Otorhinolaryngology Healthcare Research Institute. 2 groups of patients were formed depending on the treatment performed in the postoperative period. Group I (active treatment): 100 children who underwent conservative treatment after adenoidectomy, including: tested/investigational drug – Umckalor solution (per os), dosing regimen: children aged from 4 to 6 years – 5–10 drops 3 times a day, aged from 6 to 12 years – 10 to 20 drops 3 times a day; topical decongestants (in the age-related dosage); silver proteinate (nasal drops in age-specific doses); secondand third-generation antihistamines (in the age-specific doses). Group II (control): 100 children, who received conservative therapy after adenoidectomy, including: antibacterial therapy (in the age-specific doses) (third-generation cephalosporins); topical decongestants (in the age-specific doses); silver proteinate (nasal drops in age-specific doses); secondand third-generation antihistamines (in the age-specific doses). In both groups, the course of postoperative therapy amounted to 7 days. The clinical studies have shown that in the early postoperative period the clinical efficacy of Umckalor as part of combined therapy in children, who underwent adenoidectomy, involves reducing the duration of reactive events, accelerating the healing of the postoperative nasopharynx wound. The combined antiviral, antibacterial, immunomodulatory, anti-inflammatory, mucolytic and secretory-motor effect of the drug allows Umckalor to be used as an alternative to antibacterial drugs as part of combined therapy in children who underwent adenoidectomy.

Cumulative Effective Dose and Cancer Risk of Pediatric Population in Repetitive Whole-Body Scan Using Dual-Energy X-Ray Absorptiometry

This study aims to quantitatively evaluate the cumulative effective dose and associated cancer risk of pediatric patients of US and Hong Kong population undergoing repetitive whole-body scans with dual-energy X-ray absorptiometry (DXA) during their diagnosis and follow-up periods. Organ-absorbed doses of pediatric patients undergoing DXA whole-body scan have been computer simulated using patient imaging parameters input to the Monte Carlo software PCXMC. Gender- and age-specific effective doses have been calculated with the simulated organ-absorbed doses using the ICRP-103 approach. The associated radiation-induced cancer risk, expressed as lifetime attributable cancer risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Mathematical fitting for effective dose and for LAR, as a function of age at exposure, has been analytically obtained to quantitatively estimate the cumulated effective dose and LAR for pediatric patients of US and Hong Kong population with repetitive DXA whole-body scan during their follow-up period. The effective dose of a single DXA whole-body scan for patients exposed at the age between 5 and 18 years was calculated as 8.47–17.68 µSv. The corresponding LAR for US and Hong Kong population was between the range of 4.57 × 10−7 and 7.14 × 10−7. The cumulative effective dose of DXA whole-body scan for patients exposed annually at age between 5 and 18 years was calculated as 180 µSv for girls and 168 µSv for boys. The corresponding cumulative LAR for US and Hong Kong population was calculated as 3.77 × 10−6 to 5.48 × 10−6. Girls would be at a statistically significant higher cumulated cancer risk than boys under the same whole-body DXA protocol (p = 0.03). The probability of cumulative LAR for pediatric populations undergoing annual DXA whole-body scan is regarded as minimal. We demonstrate the use of computer simulation and analytic formulation to quantitatively obtain the cumulated effective dose and cancer risk at any age of exposure, which are useful information for medical personnel to track patient radiation dose and to alleviate patients' parents concern about radiation safety in repetitive whole-body scan using DXA.

Phasing out of the Universal Mega Dose of Vitamin-A Prophylaxis to Avoid Toxicity.

Childhood blindness due to corneal ulceration was prevalent among poor Indian children. To tackle this situation, the National Institute of Nutrition (NIN), Hyderabad, India, Vitamin-A (Vit-A) prophylaxis programme was launched nationally in 1970 after field testing. Research of Indian Council for Medical Research (ICMR) documented that prevalence of Vit-A deficiency signs such as Bitot's spot decreased among children, over a period of time. However, this decrease cannot be ascertained is due to mass Vit-A prophylaxis programme. This is because coverage was low and patchy. Improved nutrition status, wider vaccination coverage, increased rate in breast feeding and improvement of healthcare services played a crucial role. Rather many studies revealed that (mass prophylaxis to the child who is having adequate Vit-A level) it may be harmful to certain group of children as a result of acute toxic symptoms. High dose of Vit-A is capable of loss of bone density-hence retarded growth may be observed in susceptible individuals. To tackle this issue food based approach should be promoted (which includes breast feeding) along with timely measles vaccination. The children who have signs of Vit-A deficiency (e.g. night blindness, xeropthalmia, Bitot's spot) or post measles children should receive Vit-A in age specific daily doses for two weeks along with Vit-A rich food, like green leafy vegetables, red palm oil, liver etc. Public spirited citizens, together with scientific community in India, should discourage this “one size fit to all” approach. It will not only avoid the ill effects of high dose of Vit-A but also it will help us optimal utilization of health resources in a resource poor country like India.

A practical guideline for the release of patients treated by I-131 based on Monte Carlo dose calculations for family members

We recently published effective doses per time-integrated activity (mSv MBq−1 s−1) for paediatric and adult family members exposed to an adult patient released from hospital following I-131 therapy. In the present study, we intend to provide medical physicists with a methodology to estimate family member effective dose in daily clinical practice because the duration of post-radiation precautions for the patient–family member exposure scenario has not been explicitly delineated based on the effective dose. Four different exposure scenarios are considered in this study including (1) a patient and a family member standing face to face, (2) a patient and a family member lying side by side, (3) an adult female patient holding a newborn child to her chest and (4) a one-year-old child standing on the lap of an adult female patient following her I-131 therapy. The results of this study suggest that an adult female hyperthyroidism (HT) patient who was administered with 740 MBq should keep a distance of 100 cm from a 15-year-old child for six days and the same distance from other adults for seven days. The HT female patient should avoid holding a newborn against her chest for at least 16 days following hospital discharge, and a female patient treated with 5550 MBq for differentiated thyroid cancer should not hold her newborn child for at least 15 days following hospital discharge. This study also gives dose coefficients allowing one to predict age-specific effective doses to family members given the measured dose rate (mSv h−1) of the patient. In conclusion, effective dose-based patient release criteria with a modified NRC two-component model provide a site medical physicist with less restrictive and age-specific radiation precaution guidance as they fully consider a patient’s iodine biokinetics and photon attenuation within both the patient and the exposed family members.

Association between smoking and genital warts: longitudinal analysis

ObjectivesTo assess the association between smoking and the reported clinical diagnosis of genital warts.MethodsA sample of 58 094 women (aged 18–45) randomly drawn from the general female population of Denmark,...

Once‐Daily Gentamicin Dosing in Pediatric Patients Without Cystic Fibrosis

To estimate an appropriate once-daily gentamicin dose and dosing interval for non-critical care pediatric patients older than 3 months of age without cystic fibrosis. Pharmacokinetic analysis of data from a retrospective medical record review. Large academic children's hospital. One hundred fourteen non-critical care pediatric patients older than 3 months of age without cystic fibrosis who received multiple-daily dosing regimens of gentamicin between September 2007 and April 2008. Patient-specific pharmacokinetic parameters were calculated using drug concentrations obtained at steady state. Once-daily doses were extrapolated for each patient to achieve goal peak and trough concentrations. Using the average of these doses and the patient-specific pharmacokinetic parameters, theoretical once-daily peak and trough concentrations were calculated for each patient. Patient characteristics were analyzed to determine differences between patients who did and those who did not achieve adequate peak concentrations. Mean +/- SD pharmacokinetic parameters were as follows: elimination rate constant 0.32 +/- 0.06 hour(-1), half-life 2.28 +/- 0.54 hours, and volume of distribution 0.24 +/- 0.08 L/kg. The only patient demographic characteristic found to have a significant effect on the extrapolated peak concentration was age. The following age-specific once-daily doses were calculated: 3 months to less than 2 years, 9.5 mg/kg; 2 years to less than 8 years, 8.5 mg/kg; and 8-18 years, 7 mg/kg. Age was the primary factor in determining the once-daily dose of gentamicin in our pediatric population. Further prospective research is necessary to determine the safety and efficacy of these age-based, once-daily doses for gentamicin.

Age-specific effective doses for pediatric MSCT examinations at a large children’s hospital using DLP conversion coefficients: a simple estimation method

There is a need for an easily accessible method for effective dose estimation in pediatric CT. To estimate effective doses for a variety of pediatric neurological and body CT examinations in five age groups using recently published age- and region-specific dose length product (DLP) to effective dose conversion coefficients. A retrospective review was performed of 1,431 consecutive CT scans over a 12-week period using age- and weight-adjusted CT protocols. Age- and region-specific DLP to effective dose conversion coefficients were applied to console-displayed DLP data. Effective dose estimates for single-phase head CT scans in neonatal, and 1-, 5-, 10- and 15-year-old age groups were 4.2, 3.6, 2.4, 2.0 and 1.4 mSv, respectively. For abdomen/pelvis CT scans the corresponding effective doses were 13.1, 11.1, 8.4, 8.9 and 5.9 mSv. The range of pediatric CT effective doses is wide, from ultralow dose protocols (<1 mSv) to extended-coverage body examinations (10-15 mSv). Age- and region-specific pediatric DLP to effective dose conversion coefficients provide an accessible and user-friendly method for estimating pediatric CT effective doses that is available to radiologists working without medical physics support.

Head-and-neck organ doses from an episode of orthodontic care

The high prevalence of orthodontic treatment in young people makes the associated radiation to the head and neck of potential public-health significance. In this study, we estimated secular changes (1963-2003) in age-specific organ doses associated with orthodontic care and collective organ doses in the United States in 1999. A survey of radiographic records at 1 university clinic was combined with published estimates to provide organ-specific radiation doses. Collective organ doses were estimated from the 1999 US Nationwide Evaluation of X-ray Trends and published orthodontic utilization surveys. Before 1992, orthodontic care in a university setting was associated with mean doses of 7.0 milligrays (mGy) to the thyroid, 0.8 mGy to the red bone marrow, 2.7 mGy to the brain, 13.2 mGy to the salivary glands, and 5.1 mGy to the bone. After 1992, the doses decreased to 2.8 mGy to the thyroid, 0.3 mGy to the red bone marrow, 0.7 mGy to the brain, 6.2 mGy to the saliva glands, and 2.4 mGy to the bone. Around 1999, the collective doses associated with orthodontic care in the United States in patients less than 19 years of age were 400 Gy to the red bone marrow and 3800 Gy to the thyroid. Orthodontic care, in part due to its high prevalence, potentially contributes significantly to the diagnostic radiation burden in those less than 19 years old in the United States.

Seizures in the Developing Brain Cause Adverse Long‐term Effects on Spatial Learning and Anxiety

Seizures in the developing brain cause less macroscopic structural damage than do seizures in adulthood, but accumulating evidence shows that seizures early in life can be associated with persistent behavioral and cognitive impairments. We previously showed that long-term spatial memory in the eight-arm radial-arm maze was impaired in rats that experienced a single episode of kainic acid (KA)-induced status epilepticus during early development (postnatal days (P) 1-14). Here we extend those findings by using a set of behavioral paradigms that are sensitive to additional aspects of learning and behavior. On P1, P7, P14, or P24, rats underwent status epilepticus induced by intraperitoneal injections of age-specific doses of KA. In adulthood (P90-P100), the behavioral performance of these rats was compared with that of control rats that did not receive KA. A modified version of the radial-arm maze was used to assess short-term spatial memory; the Morris water maze was used to evaluate long-term spatial memory and retrieval; and the elevated plus maze was used to determine anxiety. Compared with controls, rats with KA seizures at each tested age had impaired short-term spatial memory in the radial-arm maze (longer latency to criterion and more reference errors), deficient long-term spatial learning and retrieval in the water maze (longer escape latencies and memory for platform location), and a greater degree of anxiety in the elevated plus maze (greater time spent in open arms). These findings provide additional support for the concept that seizures early in life may be followed by life-long impairment of certain cognitive and behavioral functions. These results may have clinical implications, favoring early and aggressive control of seizures during development.

Predictive value of pretransplantation cyclosporine pharmacokinetic studies on initial post-transplantation dosing in pediatric kidney allograft recipients.

Despite the introduction of a variety of new immunosuppressive agents, cyclosporine A (CsA) has maintained a strong position in pediatric transplantation (Tx). Post-Tx dosing with CsA is a challenging task because of the narrow therapeutic window of the drug, the great individual variability of metabolism and the lack of consensus about the optimal dosage and targeted blood concentration. Sufficient administration of CsA may be protective against acute rejections and other early complications after Tx, which is crucial for the long-term survival of the graft. Individual doses based on pre-Tx pharmacokinetic studies might be helpful in achieving optimal early concentrations of CsA. To asses the usefulness of pharmacokinetic studies, we retrospectively compared the post-Tx doses administered with the individually predicted doses between 1988 and 1998. Multiple regression of data on 65 de novo renal transplant recipients, 1.1-15.5 yr old, was used to analyze the significance of the predicted dose, trough blood concentration of CsA (B-CsA), serum creatinine and age at the time of Tx in explaining the doses used during the first three post-Tx weeks. Patients were grouped according to age (<2, 2-8 and >8 yr), according to the predicted dose (within or outside +/-25% of age-group average), and according to the oral formulation of CsA. Standard dosing scheme was simulated by using age-specific average doses in the place of the individual predicted doses. Administered doses of CsA were high [averaging 22.6 (504), 20.7 (484), and 12.4 mg/kg/d (329 mg/m2/d) for patients <2, 2-8, and >8 yr old] but the average B-CsA remained in the target range of 250-450 microg/L. The predicted dose and age were significant parameters in explaining the administered doses during the first 3 wk after Tx. B-CsA and S-creatinine were non-significant. The predicted doses were used to initiate the dosing of CsA after Tx (R2 = 0.70) and adjustments to dosing were made during the next weeks (R2 = 0.59, 0.52). Multiple regression model showed better fit for 60% of our patients, who had atypical predicted doses (R2 = 0.74, 0.60, 0.64 for first, second and third post-Tx weeks, respectively), most remarkably in patients <2 yr of age, than for the study population as a whole. A simulated standard dose was not able to explain the administered doses of CsA. In conclusion, pre-Tx pharmacokinetic studies are valuable for determining individual post-Tx starting doses, especially for those patients who need high or low doses of CsA. Individual dosing led to relatively high initial CsA doses, which could be significant for the long-term survival of the graft.

The relationship of thyroid cancer with radiation exposure from nuclear weapon testing in the Marshall Islands.

The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radio-iodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population. The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and 137Cs deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid.