Organ reserve, excess metabolic capacity, and aging.

"Organ reserve" refers to the ability of an organ to successfully return to its original physiological state following repeated episodes of stress. Clinical evidence shows that organ reserve correlates with the ability of older adults to cope with an added workload or stress, suggesting a role in the process of aging. Although organ reserve is well documented clinically, it is not clearly defined at the molecular level. Interestingly, several metabolic pathways exhibit excess metabolic capacities (e.g., bioenergetics pathway, antioxidants system, plasticity). These pathways comprise molecular components that have an excess of quantity and/or activity than that required for basic physiological demand in vivo (e.g., mitochondrial complex IV or glycolytic enzymes). We propose that the excess in mtDNA copy number and tandem DNA repeats of telomeres are additional examples of intrinsically embedded structural components that could comprise excess capacity. These excess capacities may grant intermediary metabolism the ability to instantly cope with, or manage, added workload or stress. Therefore, excess metabolic capacities could be viewed as an innate mechanism of adaptability that substantiates organ reserve and contributes to the cellular defense systems. If metabolic excess capacities or organ reserves are impaired or exhausted, the ability of the cell to cope with stress is reduced. Under these circumstances cell senescence, transformation, or death occurs. In this review, we discuss excess metabolic and structural capacities as integrated metabolic pathways in relation to organ reserve and cellular aging.

Curriculum mapping as a tool to facilitate curriculum development: a new School of Medicine experience.

BACKGROUND: Every curriculum needs to be reviewed, implemented and evaluated; it must also comply with the regulatory standards. This report demonstrates the value of curriculum mapping (CM), which shows the spatial relationships of a curriculum, in developing and managing an integrated medical curriculum. METHODS: A new medical school developed a clinical presentation driven integrated curriculum that incorporates the active-learning pedagogical practices of many educational institutions worldwide while adhering to the mandated requirements of the accreditation bodies. A centralized CM process was run in parallel as the curriculum was being developed. A searchable database, created after the CM data was uploaded into an electronic curriculum management system, was used to ensure placing, integrating, evaluating and revising the curricular content appropriately. RESULTS: CM facilitated in a) appraising the content integration, b) identifying gaps and redundancies, c) linking learning outcomes across all educational levels (i.e. session to course to program), c) organizing the teaching schedules, instruction methods, and assessment tools and d) documenting compliance with accreditation standards. CONCLUSIONS: CM is an essential tool to develop, review, improve and refine any integrated curriculum however complex. Our experience, with appropriate modifications, should help other medical schools efficiently manage their curricula and fulfill the accreditation requirements at the same time.

Diversity of Pediatric Workforce and Education in 2012 in Europe: A Need for Unifying Concepts or Accepting Enjoyable Differences?

OBJECTIVE: To evaluate differences in child health care service delivery in Europe based on comparisons across health care systems active in European nations. STUDY DESIGN: A survey involved experts in child health care of 40 national pediatric societies belonging both to European Union and non-European Union member countries. The study investigated which type of health care provider cared for children in 3 different age groups and the pediatric training and education of this workforce. RESULTS: In 24 of 36 countries 70%-100% of children (0-5 years) were cared for by primary care pediatricians. In 12 of 36 of countries, general practitioners (GPs) provided health care to more than 60% of young children. The median percentage of children receiving primary health care by pediatricians was 80% in age group 0-5 years, 50% in age group 6-11, and 25% in children >11 years of age. Postgraduate training in pediatrics ranged from 2 to 6 years. A special primary pediatric care track during general training was offered in 52% of the countries. One-quarter (9/40) of the countries reported a steady state of the numbers of pediatricians, and in one-quarter (11/40) the number of pediatricians was increasing; one-half (20/40) of the countries reported a decreasing number of pediatricians, mostly in those where public health was changing from pediatric to GP systems for primary care. CONCLUSIONS: An assessment on the variations in workforce and pediatric training systems is needed in all European nations, using the best possible evidence to determine the ideal skill mix between pediatricians and GPs.

Is there a "European Paediatrics"?

The journey from birth to adulthood is paved with threats to health and wellbeing, rendering this age group with its invaluable future potential particularly vulnerable. Therefore, children and adolescents deserve medical attention of the highest professional level based on solid, well founded training guidelines, the availability of a well-coordinated platform for the continuous acquisition of knowledge, exchange of ideas, and collaboration on research and clinical projects, and comprehensive continuing education. For the European region these crucial specifications are met to varying degrees by three major paediatric organisations: the European Academy of Paediatrics (EAP) with the European Board of Paediatrics (EBP) as the paediatric section of the European Union of Medical Specialists (UEMS PS), the European Paediatric Association (EPA/UNEPSA) and the European Confederation of Primary Care Paediatricians (ECPCP). A major goal of this paper is to call for the closest possible collaboration between these organizations in advocating for the health and rights of European children and adolescents and in effectively fostering the paediatric profession with a strong, unified voice.

Autoimmune thyroid disease in Libyan children and young adults with type 1 diabetes mellitus.

UNLABELLED: Diabetes mellitus is a common autoimmune endocrine disorder associated with organ-specific autoantibodies which are frequently detected at the time of diagnosis. Some of these antibodies are specific to the pancreas (GAD, IA2, ICA) while others are related to different autoimmune diseases. AIM OF THE STUDY: To define the prevalence of thyroid autoimmune disease in Libyan patients with type 1 diabetes mellitus (T1DM) since no similar studies have been performed in Libya. MATERIALS AND METHODS: Blood samples were collected from 218 patients with T1DM who are followed by the Pediatric Department, Tripoli Medical Center, Libya. All sera were analyzed in Italy (Laboratory of Immunopathology and Allergy, Udine). The patients were composed of 123 females (56.4%) and 95 males (43.6%), mean age 12.2 ± 4.6 years (range 2.1-24.5 years), mean duration of diabetes 4.7 ± 4.0 years (range 0.1-17.5 years). Sera were tested for anti-thyroperoxidase (TPO) and anti-thyroglobulin antibodies (TG). TSH and FT4 concentrations were measured in all subjects. GAD, IA-2 was also measured. RESULTS: Of the diabetic children, 23.4% were positive for anti-microsomal peroxidase antibodies (TPO-Ab) and 7.8% for antithyroglobulin antibodies (TG-Ab); whereas 6.9% of the patients were positive for both TPO-Ab and TG-Ab. Of the T1DM patients who were positive for TPO-Ab, 66.6% were females. The majority (57%) of the patients who were positive for TPO had diabetes for longer than 5 years. Five patients (2.3%) had evidence of subclinical hypothyroidism whereas two patients (0.9%) had overt hypothyroidism. Two patients had subclinical hyperthyroidism and two (0.9%) had overt hyperthyroidism. Interestingly, 16.2% of patients were positive for both thyroid and pancreatic antibodies. CONCLUSIONS: The prevalence of autoimmune thyroid disease in type 1 diabetic patients is higher than in the general population. A routine screening strategy should be implemented with the determination of anti-thyroid antibodies and TSH in type 1 diabetic patients, particularly in girls, and in patients with diabetes of more than 5 years duration. Patients who have positive TPO antibodies may need the assessment of thyroid function at shorter intervals.

[Kangaroo Mother Care and conventional care: a review of literature]. / Kangaroo Mother Care ed assistenza convenzionale: una revisione della letteratura.

Low birth weight is one of the major health problems throughout the world. All such neonates can benefit from an effective and efficient human care model - Kangaroo Mother Care. A review of the literature was performed to compare the short and long-term outcome of Kangaroo Mother Care to those of conventional care (incubator). Short-term outcome considered heart and breathing frequency, percutaneous oxygen saturation , transcutaneous oxygen pressure , body temperature, sleep-wake cycles, stress and pain. Long-term outcome considered mortality, somatic, psycho-motor and cognitive development, the incidence of infections and duration of hospitalization. Studies including pre-term neonates were also included. 19 of the 80 studies corresponded to the study criteria and demonstrated that Kangaroo Mother Care is important because it reduces pain and infections, shortens hospitalization, favors breast-feeding: in comparison to neonates treated conventionally, this method results in an earlier and better cognitive and motor development . Concerning body temperature, there were no differences with respect to traditional care. The literature shows that the Kangaroo Mother Care method can be a useful "adjunctive" strategy although further studies are necessary to clarify aspects such as heart and breathing rate and oxygen saturation that appear contradictory.

Effect of different starting doses of levothyroxine on growth and intellectual outcome at four years of age in congenital hypothyroidism.

To evaluate the effect of different initial levothyroxine (LT4) replacement doses on growth and intellectual outcome in patients with congenital hypothyroidism (CH) detected by neonatal screening program, the longitudinal growth and intelligence quotient (IQ) were assessed and compared at 4 years of age in 83 patients with CH. The patients were divided into three groups according to the initial LT4 dose used: (1) group 1 (n = 42) received the previously recommended dose of 6.0-8.0 microg/kg per day; (2) group 2 (n = 21) received a dose of 8.1-10.0 microg/kg per day; (3) Group 3 (n = 20) a dose of 10.1-15.0 microg/kg per day. The IQ, evaluated by the Wechsler Preschool and Primary Scale of Intelligence test at 4 years of age, was significantly higher in group 3 (IQ 98 +/- 9) compared to group 1 (IQ 88 +/- 13; p < 0.05) but not compared to group 2 (IQ 94 +/- 13). However, the IQs were below the normal range (< 85) in six patients from group 2 (28%), but in none of the patients from group 3 (p = 0.03). Patients from group 3, with severe CH at diagnosis, had an IQ (97 +/- 9) at 4 years of age, which was not different from that of patients from the same group with moderate CH at diagnosis (IQ 99 +/- 9). Similar results were also observed in patients from group 2 however, mean IQ scores in these patients (93 +/- 12) were several points lower than those observed in patients from group 3 (95 +/- 15). After the first month of treatment, optimal serum levels of thyroxine (T4) and free thyroxine (FT4) were achieved in all groups, however, only patients from group 3 were able to normalize thyrotropin (TSH) (group 1, 16.0 +/- 12.0; group 2, 9.2 +/- 10.0; and group 3, 2.4 +/- 3.3 mU/L; p < 0.0001). Twelve patients from group 2 treated with an initial LT4 dose above 9 microg/kg per day were able to normalize TSH levels within the first 3 months of life and this resulted in a better IQ (97 +/- 16) compared to the remaining patients from the same group (IQ 90 +/- 9). In the whole group of 83 patients the IQ at 4 years of age was positively correlated to both initial LT4 dosage (r = 0.27, p < 0.02) and FT4 concentrations after the first month of treatment (r = 0.29, p < 0.02), and negatively correlated to TSH concentrations after the first month of treatment (r = -0.27, p < 0.02). No significant differences were observed in height, weight, head circumference, and bone age maturation among the three groups of patients. No clinical signs or symptoms of overtreatment were observed during follow-up in patients receiving the higher LT4 dosage. Our results indicate that high LT4 starting doses rapidly normalize serum TSH concentrations resulting in an improvement of the IQ at 4 years of age, even in patients with severe CH at diagnosis. Growth and bone age maturation are not affected by such a high dose.

A pathophysiologic approach to growth problems in children with attention-deficit/hyperactivity disorder.

In recent years there has been an increasing trend in the diagnosis and treatment of children with attention-deficit/hyperactivity disorder (ADHD) worldwide. One of the most frequently discussed side effects of these treatments is related to problems of growth. In order to better understand what ADHD is and the mechanisms by which it could affect growth, this article reviews relevant data from a clinical and neurophysiologic perspective to improve understanding of this controversial issue.

HLA-DQ types of celiac disease in Libyan children with type 1 diabetes mellitus.

OBJECTIVE: To determine the genetic profile of celiac disease (CD) in Libyan children with type 1 diabetes as there are no data on the frequency of human leukocyte antigen (HLA)-related CD-predisposing genes in diabetic patients in Libya. METHODS: We randomly studied 218 Libyan type 1 diabetic children. The mean age was 12.2±4.6 years; 56% were female patients. The mean duration of diabetes was 4.7±4.0 years. All patients were screened for CD with IgA tissue-transglutaminase (tTG) and endomysium antibodies. Patients with positive immunological screen were programmed for a small-bowel biopsy. HLA-DRB1* and HLA-DQB1* were genotyped in all tTG-positive patients. RESULTS: Twenty-seven (12.4%) out of 218 patients with type1 diabetes had positive tTG, and 20 (9.2%) of these patients were positive for endomysium antibodies. Five patients (5/27) were already known cases of biopsy-proven CD. Biopsy was not performed in two patients. One biopsy result was normal, whereas 19 biopsies demonstrated morphological changes consistent with CD. Forty-eight percent of the anti-tTG-positive group were homozygous for HLA-DQ2, whereas 75% of biopsy-proven CD patients had HLA-DQ2, 21% had HLA-DQ2/DQ8, and 4% had HLA-DQ8. In addition, the majority (70%) carried HLA-DQ2 linkage with HLA-DRB1*03. CONCLUSION: Overall, biopsy-confirmed prevalence of CD was 11% (24 of 218). The present study confirms that CD in the Libyan type 1 diabetic population is high when compared with European and US studies, and for the first time we document that this population shares similar HLA-DQ2 genotype. This supports the theory regarding the role of the environment as an important factor in CD development in this part of the world.

Genomics in pediatric endocrinology-genetic disorders and new techniques.

In the last few years, there have been remarkable advances in the development of new and more sophisticated genetic techniques. These have allowed a better understanding of the molecular mechanisms of genetically determined pediatric endocrine disorders and are paving the way for a radical change in diagnosis and treatment. This article introduces some of these concepts and some of the genetic techniques being used.

Genomics in pediatric endocrinology--genetic disorders and new techniques.

In the last few years, there have been remarkable advances in the development of new and more sophisticated genetic techniques. These have allowed a better understanding of the molecular mechanisms of genetically determined pediatric endocrine disorders and are paving the way for a radical change in diagnosis and treatment. This article introduces some of these concepts and some of the genetic techniques being used.

Age-related renal parenchymal lesions in children with first febrile urinary tract infections.

OBJECTIVE: The aim of this study was to define the association between age and the occurrence of acute pyelonephritis and renal scars. METHODS: Between 1999 and 2002, all children 0 to 14 years of age consecutively seen with a first febrile urinary tract infection were enrolled in the study. (99m)Tc-Dimercaptosuccinic acid renal scintigraphy was performed within 5 days after admission for the detection of renal parenchymal involvement. The presence of vesicoureteral reflux was assessed by using cystography performed 1 month after the infection. If the acute scan results were abnormal, then follow-up (99m)Tc-dimercaptosuccinic acid scanning was performed after 6 months, to assess the frequency of scars. RESULTS: A total of 316 children were enrolled in the study (190 children <1 year, 99 children 1-4 years, and 27 children 5-14 years of age). (99m)Tc-Dimercaptosuccinic acid scintigraphy revealed that 59% of the children had renal involvement in the acute phase of infection. The frequency of kidney involvement in infants <1 year of age (49%) was significantly lower than that in children 1 to 4 years of age (73%) and >5 years of age (81%). Of the 187 children with positive acute (99m)Tc-dimercaptosuccinic acid scan results, 123 underwent repeat scintigraphy after 6 months. Renal scars were found for 28% of children <1 year, 37% of children 1 to 4 years, and 53% of children 5 to 14 years of age. No significant differences in the frequency of scars and the presence or absence of vesicoureteral reflux were noted. CONCLUSIONS: Our findings confirm that acute pyelonephritis and subsequent renal scarring occur only in some children with first febrile urinary tract infections. Children <1 year of age with febrile urinary tract infections have a lower risk of parenchymal localization of infection and renal scarring.

Efficacy of serum procalcitonin in evaluating severity of community-acquired pneumonia in childhood.

Microbe-specific diagnosis of community-acquired pneumonia (CAP) in childhood is difficult in clinical practice. Chest radiographs and non-specific inflammatory markers have been used to separate presumably bacterial from viral infection but the results have been inconsistent. The aim of the present study was to evaluate the usefulness of procalcitonin (PCT) in assessing the severity as well as the bacterial or viral aetiology of CAP. Serum PCT was measured by an immunoluminometric assay in 100 patients with CAP; 26 were treated as inpatients and 74 as outpatients. The pulmonary infiltrate was considered to be alveolar in 62 and interstitial in 38 cases, according to the radiological diagnosis. The bacterial and viral aetiology of pneumonia was studied by an extensive serological test panel. No differences were found in PCT concentrations between the 4 aetiological (pneumococcal, atypical bacterial, viral, unknown) and the 3 age (< 2, 2-4 and > or = 5 y) groups. Serum PCT was >0.5 ng/ml in 69%, >1.0 ng/ml in 54% and >2.0 ng/ml in 47% of all patients. PCT was higher in patients that were admitted than as outpatients (medians 17.81 vs 0.72 ng/ml, respectively, p<0.01) and higher in alveolar than in interstitial pneumonia (medians 9.43 vs 0.53 ng/ml, respectively, p<0.01). In conclusion, serum PCT values were found to be related to the severity of CAP in children even though they were not capable, at any level of serum concentration, to differentiate between bacterial and viral aetiology.

A comparison study of the prevalence of overweight and obese Italian preschool children using different reference standards.

INTRODUCTION: The number of overweight children is constantly increasing in both developed and underdeveloped countries. Most epidemiological surveys consider school age children with little attention being given to preschool age children. This study was undertaken to define the prevalence of being overweight or obese in a population of children 3-6 years of age, living in North-East Italy. We also identified differences when comparing body mass index (BMI) data against three different national and international standards. SUBJECTS AND METHODS: The study involved 258 children (124 males and 134 females) with an average age of 4.8 years. Weight and height were obtained for each child and BMI was calculated according to the formula weight (kg)/height (m)(2). The prevalence of overweight and obese subjects was then determined using the growth curves of the Centers for Disease Control and Prevention (CDC), the growth curves of the International Obesity Task Force (IOTF) and the curves published in 2003 by Luciano et al. RESULTS: All three methods gave similar, but not identical, estimates of the prevalence of overweight in both boys and girls. However, when determining the prevalence of obesity, the use of the CDC curves led to a significantly higher prevalence of obesity in both males and females when compared to the growth charts of the IOTF and Luciano et al. BACKGROUND: The use of the CDC growth curves leads to an increase in the prevalence of obesity when evaluating children under 5 years of age. The lower cut-off values inherent in the CDC charts, in contrast to the ones proposed by the IOTF, allow for earlier identification of a larger number of subjects with weight problems and therefore provide the potential for earlier intervention.

Aetiology of community-acquired pneumonia: serological results of a paediatric survey.

Serological methods are routinely used in the diagnosis of viral and atypical bacterial respiratory infections. Recently, they have also been applied to typical bacteria, such as Streptococcus pneumoniae. The aim of this study was to determine the aetiology of paediatric community-acquired pneumonia (CAP) in both ambulatory and hospitalized patients, by using antibody assays. During a 15-month prospective surveillance, paired sera were studied for antibodies to 14 microbes in 101 children with symptoms of acute infection and infiltrates compatible with pneumonia on chest radiographs. A potential causative agent was detected in 66 (65%) patients. Evidence of bacterial, viral and mixed viral-bacterial infection was demonstrated in 44%, 42% and 20% of the CAP cases, respectively. The most commonly found agents included Mycoplasma pneumoniae (27%), Pneumococcus (18%) and respiratory syncytial virus (17%). Human metapneumovirus (hMPV) was detected in 5 (5%) children. Pneumococcal infections were evenly distributed among the age groups studied. Our results confirm the role of S. pneumoniae in paediatric CAP at all ages, those of M. pneumoniae at >2 y of age and emphasize the emerging role of hMPV. The high proportion of mixed viral-bacterial infections highlights the need to treat all children with CAP with antibiotics.

Procalcitonin: a marker of severity of acute pyelonephritis among children.

OBJECTIVE: Febrile urinary tract infection (UTI) is a common problem among children. The diagnosis and management of acute pyelonephritis is a challenge, particularly during infancy. The distinction between acute pyelonephritis and UTI without renal involvement is very important, because renal infection may cause parenchymal scarring and thus requires more aggressive investigation and follow-up monitoring. However, this distinction is not easy among children, because common clinical findings and laboratory parameters are nonspecific, especially among young children. In an attempt to differentiate acute pyelonephritis from febrile UTI without renal lesions in a group of 100 children, we measured serum levels of procalcitonin (PCT), a new marker of infection. The objective of the study was to determine the accuracy of PCT measurements, compared with C-reactive protein (CRP) measurements, in diagnosing acute renal involvement during febrile UTI and in predicting subsequent scars, as assessed with 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. DESIGN: Serum CRP levels, erythrocyte sedimentation rates, leukocyte counts, and PCT levels were measured for 100 children, 1 month to 13 years of age, admitted for suspected febrile UTI (first episode). Renal parenchymal involvement was evaluated with DMSA scintigraphy within 5 days after admission. The DMSA study was repeated 6 months later if the initial results were abnormal. RESULTS: The mean PCT level was significantly higher in acute pyelonephritis than in UTI without renal lesions (4.48 +/- 5.84 ng/mL vs 0.44 +/- 0.30 ng/mL). In these 2 groups, the mean CRP levels were 106 +/- 68.8 mg/L and 36.4 +/- 26 mg/L, mean erythrocyte sedimentation rates were 79.1 +/- 33 mm/hour and 58.5 +/- 33 mm/hour, and leukocyte counts were 18 492 +/- 6839 cells/mm3 and 16 741 +/- 5302 cells/mm3, respectively. For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT measurements were 83.3% and 93.6%, respectively; CRP measurements had a sensitivity of 94.4% but a specificity of only 31.9%. Positive and negative predictive values for prediction of renal involvement with PCT measurements were 93.7% and 83% and those with CRP measurements were 61.4% and 83.3%, respectively. When inflammatory markers were correlated with the severity of the renal lesions, as assessed with DMSA scintigraphy, a highly significant correlation with both PCT and CRP levels was found. However, when the 2 parameters were correlated with renal scarring in follow-up scans, a significant positive association was found only for PCT levels. CONCLUSIONS: Serum PCT levels may be a sensitive and specific measure for early diagnosis of acute pyelonephritis and determination of the severity of renal parenchymal involvement. Therefore, this measurement could be useful for the treatment of children with febrile UTIs, allowing prediction of patients at risk of permanent parenchymal renal lesions.