HISTOPATHOLOGIC FINDINGS IN THE LYMPHOID AND RETICULOENDOTHELIAL SYSTEM IN PEDIATRIC HIV INFECTION: A Postmortem Study

The present report describes the histopathological features of lymphoreticular tissues in 29 pediatric autopsies of human immunodeficiency virus (HIV)-infected patients. Mean age for the whole group was 1.77 years; 68.9 and 62 of the cases were 2 years old or less and 1 year old or less at the time of death, respectively. Twenty-one cases were categorized as acquired immunodeficiency syndrome (AIDS) and the rest included seven HIV-positive newborns and infants and two infants belonging to a high-risk group. The thymus (24 cases) showed severe lymphoid depletion (atrophy) in 16 (66.6 ) cases, microcystic transformation of Hassall's corpuscles (HCs) in 4, calcified HCs in 3, absence of HCs in 3, and plasmacytic infiltrates and Warthin-Finkeldey-type multinucleated giant cells (also found in lymph nodes and bowel lymphoid aggregates in the same case) in 1. Lymph nodes (25 cases) revealed extensive lymphocyte depletion (68 ); selective follicular (2 cases) or paracortical (3 cases) atrophy; hemophagocytosis (44 ); some type of hyperplasia (plasmacytosis, enlarged follicles) in 5 cases; some type of lymphadenitis (12 cases), 5 cases of which were due to opportunistic infections (cytomegalovirus, 2; histoplasmosis, cryptococcosis, Mycobacterium avium-intracellulare, 1 each). Main findings in the spleen (28 cases) were extensive lymphocyte depletion (10 cases), limited to the white pulp in 4 and including the red pulp in 7; some type of lymphoid hyperplasia (limited to white pulp in 6 cases and involving the red pulp in 5); hemophagocytosis (7 cases); and foci exhibiting a peculiar arrangement of spindle-shaped cells combined with capillaries, plasma cells, and occasionally siderophages in 11. These we have termed kaposiform areas due to the resemblance to the so-called inflammatory variant of Kaposi's sarcoma. This pattern was also recognized in lymph nodes of two cases. Although atrophy was the main theme, cases with hyperplasia were also noticed. The possible relationship, if it exists at all, between kaposiform areas and Kaposi's sarcoma remains to be established. No tumor was found in this series. No specific histopathologic pattern of lymphoid tissues atributable to HIV emerged form this study aside from kaposiform areas, a microscopic feature not previously reported in this circumstance in pediatrics.     

VIRAL INFECTIONS OF THE RESPIRATORY TRACT IN HOSPITALIZED CHILDREN A Study from Oslo during a 90 Months'Period

ABSTRACT. A diagnosis of 979 respiratory viral infections was made in hospitalized children. Respiratory syncytial virus greatly outnumbered the other viruses: it caused 58% of the total virus infections and occurred in winter epidemics. Influenza A and B virus occurred during late winter and spring, rhinovirus had a seasonal distribution towards spring and autumn, whereas adenovirus types 1, 2 and 5 had no distinct seasonal distribution. Whereas respiratory syncytial virus were mainly associated with bronchiolitis and adenovirus type 7 with pneumonia, rhinovirus infections were most often found in children with episodes of acute bronchial asthma. The influenza A and B and adenovirus types 1, 2 and 5 infections often occurred with extrarespiratory symptoms, especially febrile convulsions.     

Time to diagnosis of retinoblastoma in Latin America: A systematic review

Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has been associated with extraocular disease, metastasis and mortality. However, the relationship between TTD and prognosis is complex and not simply a linear correlation, particularly if TTD is <6?months. This systematic review aims to identify studies reporting TTD of retinoblastoma in Latin America, highlighting factors affecting TTD, alongside proposals and initiatives to obtain shorter intervals. The review also aims to discuss the methodology linked to cancer pathways studies. The study respected PRISMA recommendations, was registered on Prospero, an international database for systematic review registries under number CRD42017076777. MEDLINE/PUBMED, LILACS and SCIELO databases were searched. Studies from Latin America and the Caribbean, published between 1997 and 2017, reporting TTD and age at diagnosis of patients with retinoblastoma were selected. Nine studies were selected, concerning 1560 patients from Argentina, Brazil, Chile, Honduras, Mexico and Peru. The median TTD ranged from 3 to 5?months and the median age at diagnosis ranged from 16.5 to 22.2?months. A prolonged TTD was observed and was associated to damaging results on retinoblastoma outcomes, particularly increasing extraocular disease, and mortality rates. Methodological heterogeneity was observed and reiterates the importance of standardization of TTD studies, allowing more reliable comparisons and greater knowledge about retinoblastoma pathways before diagnosis. Reports on successful initiatives against delayed diagnosis were scarce, emphasizing a need for further studies.     

The Urinary System in Down Syndrome: A Study of 124 Autopsy Cases

We examined 124 autopsy cases of Down syndrome for the presence of renal and urinary tract abnormalities. The cases were divided into three groups: (I) fetuses of 16-22 weeks gestation (n = 18), (II) stillborns or newborns who died on the first day of life (n = 9), and (III) Down patients 1 day to 25 years of age (n = 97). Kidney weight was reduced by a mean of 14.4% compared with expected values. Renal hypoplasia, defined as kidney weight less than two-thirds expected, was found in 18 cases. Glomerular microcysts were found in 23 of 97 cases in group III. Focal dilatation of tubules was found in 10, simple cysts in 7, and immature glomeruli deep in the renal cortex in 18 cases. Obstructive uropathy occurred in 2 of 18 (11.1%) in group I, 2 of 9 (22.2%) in group II, and 4 of 97 (4.1%) in group III. Obstructive uropathy with bilateral cystic dysplastic kidneys resulted in Potter's sequence. We suggest that obstructive uropathy is associated with Down syndrome. When severe, it results in Potter's sequence and an early perinatal death. A chromosomal analysis is recommended in any case of obstructive uropathy in the fetal or neonatal period.     

Infections in Children with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: An Autopsy Study of 30 Cases in South Florida, 1990-1993

Thirty autopsies performed on infants and children with HIV infection and/or AIDS were reviewed for the presence and type of infection. Twenty-six (87%) demonstrated evidence of infection in addition to HIV at the time of postmortem examination. Pathogenic bacterial infections were the most frequently encountered, seen in 15 of the cases. Nine of the 15 (60%) were due to gram-negative rods, most commonly Pseudomonas aeruginosa. Infections with gram-negative organisms often involved multiple organ systems and were frequently undiagnosed both pre -and postmortem because of variability in culture results and difficulties in identification both clinically and in tissue sections. Discussion is presented of unusual staining characteristics and filamentous morphology found with these pathogens. Other pathogenic bacteria encountered were Klebsiella pneumoniae, Escherichia coli, Enterobacter sp., and Staphylococcus. Fungal infections due to Candida species were present in nine cases (31 %) but were invasive in only two of these. One instance of Aspergillus meningo-encephalitis was noted. Proven viral infections were present in five children (three cytomegalovirus, one herpes simplex, and one adenovirus). Pneumocystis carinii pneumonia was diagnosed in five of the patients (17%), and one instance of disseminated Mycobacterium avium-intracellulare was encountered.     

Pathology of Suspected Acquired Immune Deficiency Syndrome in Children: A Study of Eight Cases

Biopsy and/or autopsy material from lymphoreticular and other organs was studied in 8 children with suspected acquired immune deficiency syndrome (AIDS). One or both parents of each of these children had one or more of the recognized risk factors for AIDS, such as intravenous drug abuse, prostitution, Haitian origin. The following histologic patterns were noted in the lymph nodes: (1) follicular hyperplasia with normocellular paracortex, (2) follicular hyperplasia with depletion of paracortex, and (3) atrophy of follicles with depletion of paracortex. Lymphoid interstitial pneumonitis (LIP), a previously unreported lesion in AIDS, was present in 4 cases. It is suggested that the pulmonary lymphoid lesion may be part of a more generalized lymphoid hyperplasia involving B cells. The gross and microscopic features of the thymus, available in 2 of the 8 cases, indicated that the immunologic defect in these children was not of congenital type. Pathologic findings can be helpful in the diagnosis of the syndrome when correlated with clinical and immunologic features of suspected cases and of the pulmonary lesion. The latter is of importance in deciding the type of therapy to be given for the pulmonary disease process.     

Association of occupation and safety practices with work-injury absence among public hospital employees in Latin America: a study from Costa Rica.

BACKGROUND: Injury-related statistics in developing countries are rare. OBJECTIVE: To assess the relationship between occupational and safety-related risk factors and absences from work during the preceding 6 months due to work-related injury among public hospital employees in Costa Rica. METHODS: Data were used from a cross-sectional survey conducted in December 2000 among a stratified random sample of 1000 employees from 10 of the 29 public hospitals in Costa Rica. The questionnaire included sociodemographic data, occupational exposures, and organizational risk factors. A dichotomous variable was created to indicate work-injury absence. At-risk employees (n = 466) were classified as having had a work-injury absence if they reported having been absent for at least 1 day in the preceding 6 months because of a work-related injury. OR and 95% CI were calculated using unconditional logistic regression models. RESULTS: There is a greater likelihood of injury-related absence in non-professional occupational positions (ie, auxiliary personnel (OR = 2.29) and general services employees (OR = 5.55)) than in professional positions, and in employees who show poor compliance with safety practices (OR = 2.03) and have high interference from their job task (OR = 3.79) compared with their counterparts. CONCLUSIONS: Work-injury absence appears not only to be a function of work injury, but also a function of occupation and degree of compliance with safety practices.     

Feasibility of continuous temperature monitoring in pediatric immunocompromised patients: A pilot study

Early recognition of fever is paramount in reducing morbidity and mortality in immunocompromised patients. We performed a pilot study to determine the feasibility, safety, and tolerability of continuous temperature monitoring via TempTraq, a continuous temperature monitoring patch. Ten pediatric patients were enrolled and received continuous temperature monitoring over 5 days in addition to episodic monitor (standard of care). Episodic monitoring failed to detect fever in two patients and there was a significant delay (>12 h) of fever detection in two others that was detected with TempTraq. Additionally, caregivers reported TempTraq was tolerable and easy to apply.     

Respiratory illness during winter: a cohort study of urban children from temperate Australia

OBJECTIVE: To examine the epidemiology and burden of respiratory illness during winter in urban children from temperate Australia. METHODS: We conducted a cohort study of healthy Melbourne children, aged from 12 to 71 months. Parents kept a daily respiratory symptom diary and recorded resource use when an influenza-like illness (ILI) occurred. RESULTS: One-hundred and eighteen children had 137 ILI episodes over 12 weeks for a rate of 0.53 ILI episodes per child-month (95% CI 0.44-0.61). Risk factors for ILI included younger age, fewer people residing in the household, structured exposure to other children outside the home, and a higher household income. Episodes had a mean duration of 10.4 days with 64 visits to a general practitioner (46.7 GP visits per 100 episodes), 27 antibiotic courses prescribed (19.7 antibiotic courses per 100 episodes), and three overnight hospitalizations (2.2 admissions per 100 episodes). Parents reported an average of 11.7 h excess time spent caring for a child per episode. CONCLUSIONS: Respiratory illnesses are a common and largely neglected cause of illness in Australian children. Pathogen-specific data are required to better assess the likely impact of available and developing vaccines and other treatment options.     

A survey of resources and activities in the MISPHO family of institutions in Latin America: a comparison of two eras

BACKGROUND: In developing countries, implementation of effective pediatric cancer programs can reduce the overall rate of childhood mortality. To promote this objective, Monzas International School of Pediatric Hematology-Oncology (MISPHO)--for 14 countries with limited resources in Latin America--was launched in 1996. METHODS: A survey was conducted to evaluate the possible impact of MISPHO on the following areas: research, educational, and clinical activities, diagnostic services, transfusion medicine, supportive care, ancillary staffing complement, and parents' associations--before and after 1996. RESULTS: No institution lost resources or activities after 1996 and there were overall gains, in particular in educational activities, diagnostic capabilities, creation of single and multiple institutional treatment protocols. CONCLUSIONS: Although notable improvements have occurred, there are still important needs that have to be satisfied.     

Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: A pilot study

Respiratory infections are very frequent in children. Bacillus clausii has been demonstrated to exert some immunomodulatory activities and to be safe. We conducted a study to investigate whether B. clausii administration in allergic children with recurrent respiratory infections might modulate cytokine pattern. Ten children (mean age 4.4 yr) attending the nursery school were enrolled at the end of school year (i.e. in the summer). Bacillus clausii spores (Enterogermina): 2 billion spores per vial) were administered at the dosage schedule of two vials a day for 4 wk. A panel of cytokines, including interleukin (IL)-1, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha, was measured by immunoassay in the fluid recovered from nasal lavage, performed before and after the treatment. Bacillus clausii treatment induced a significant decrease of IL-4 levels (p < 0.01) and a significant increase of IFN-gamma (p < 0.05), IL-12 (p < 0.001), TGF-beta (p < 0.05), and IL-10 (p < 0.05) levels. Other cytokines were not significantly modified. In conclusion, this study shows that the B. clausii may exert immunomodulating activity by affecting cytokine pattern at nasal level in allergic children with recurrent respiratory infections.     

CESSATION OF THERAPY IN CHILDHOOD LEUKEMIA A Survey of 160 Cases from the Nordic Countries

ABSTRACT. A Survey is presented of 160 children from the Nordic countries who had their antileukemic therapy discontinued prior to November 1976. Twenty-seven of the 160 cases (17%) had suffered a relapse before May, 1977. Sixty-nine cases had their therapy stopped in the first ten months of 1976. All cases have been reported as acute lymphocytic leukemia. Different types of therapy schedules have been used. Thirty-five cases in sustained remission for more than 3 years without cessation of therapy are also included in the report, seventeen of whom had relapsed while still on therapy. Central nervous system or testicular relapse occurred in 21 of the total 44 cases who relapsed after three or more years of continuous remission, and whether they were on therapy or not.     

Ten years after acquiring an HIV-1 infection: a study in a cohort of eleven neonates infected by aliquots from a single plasma donation

We present data from a 10-year follow-up study of 11 children who had been infected in the neonatal period by small aliquots of plasma from a single donation. Three of the children died within the first 2.5 years of life, 5 other children died between 6.2 and 11 years after infection and 3 are alive at present. The latter children are classified as P1B (asymptomatic), P2A (non-specific findings) and P2B (neurological changes). All infected children showed progressive decline of cellular immunity. Immunoglobulin levels in serum were increased in the majority of children for prolonged periods and homogeneous immunoglobulin components were present. The severity of the disease was related neither to the clinical condition of the infants in the neonatal period nor to the volume of transfused plasma, the interval between freezing and thawing of the plasma, gestational age at birth and age at transfusion. Coinciding infections with other viruses had no impact on disease progression during the follow-up period of 10 years.     

UROPATHIES DIAGNOSED IN THE NEONATAL PERIOD: SYMPTOMATOLOGY AND COURSE: A Report of 40 Cases

Abstract. Bensman, A., Baudon, J. J., Jablonski, J. P. and Lasfargues, G. (Chaire d'Hygiène de la Première Enfance, Service de Chirurgie Viscérale, Faculté de Médecine Saint-Antoine, Hôpital Trousseau, Paris, France). Uropathies diagnosed in the neonatal period: symptomatology and course: A report of 40 cases. Acta Paediatr Scand, 69:499, 1980.—Forty infants with a uropathy diagnosed during the first two months of life were studied. Presenting signs were urinary tract infection in one-half of the cases, disorders of micturition, pelvic or abdominal wall malformations, abdomino-pelvic mass, and macroscopic hematuria. Obstructive uropathy was observed in 17 children and vesicoureteric reflux in 29. We noted a high incidence of extrarenal malformations (14 of the 40 cases) in this series of uropathies diagnosed during the neonatal period. Despite early diagnosis, the course was not favorable in 11 cases with congenital anomalies of the renal parenchyma.     

Ethical issues in research on control of the HIV/AIDS epidemic: report from a workshop of the world federation of scientists, Erice, Sicily, Italy, 22-24 August 2003

In research on control of the HIV/AIDS epidemic there are many ethical issues to be considered. The problem of personal autonomy versus the interest of society to prevent the spread of the disease in various settings makes it difficult to follow the regulations of the Declaration of Helsinki in all respects. This is particularly clear in the evaluation of trials aimed at preventing mother-to-child transmission of HIV. The interest of the child does not always conform to the policy of avoiding stigmatization of the mother. Programmes for the implementation of antiretroviral therapy and vaccine trials may differ in countries with different mean incomes of the inhabitants, and are also influenced by local patterns. For this reason, the Declaration of Helsinki should be changed in such a way that it conforms with the ways in which it may be possible to combat such a disastrous epidemic as that caused by HIV.     

Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: A prospective study of allergy‐prone children from birth to six years

Thomson JA, Widjaja C, Darmaputra AAP, Lowe A, Matheson MC, Bennett CM, Allen K, Abramson MJ, Hosking C, Hill D, Dharmage SC. Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: a prospective study of allergy‐prone children from birth to six years.
Pediatr Allergy Immunol 2010: 21: 1076–1085.
© 2010 John Wiley & Sons A/S The role of early childhood infections and immunisation in the development of allergic diseases remains controversial. To examine these associations, six hundred and twenty infants with first‐degree relatives with allergic diseases were recruited into the Melbourne Atopy Cohort Study. Information on risk factors and outcomes was collected by interviewer administered questionnaire and was based on parental report and/or a physician’s diagnosis. Risk factors examined included early childhood infections (including gastroenteritis, otitis media and lower respiratory tract infections) and immunisations in the first 2 yr of life. Outcomes were current asthma, allergic rhinitis and eczema at 6 yr of age. Univariate and multivariate regression analysis were used to estimate relative risk (RR) and assess confounding. By 6 yr, 79% of the original cohort remained in the study. Those with at least three episodes of gastroenteritis showed an increased risk (crude RR 2.36, 95%CI 1.41 3.95; adjusted RR 2.03 95%CI 1.50 2.75) for the later development of asthma at age 6. Of the scheduled immunisations, Sabin immunisation in the second year had a reduced risk of asthma at 6 yr (crude RR 0.60, 95%CI 0.37 0.98; adjusted RR 0.63 95%CI 0.39 1.02). Combined diphtheria and tetanus (CDT) immunisation in the first year had an increased risk of asthma at 6 yr (RR 1.76, 95%CI 1.11 2.78; adjusted RR 1.88 95%CI 1.28 2.77). Recurrent gastroenteritis in early childhood is associated with a later risk of asthma. This may reflect a cause and effect relationship, or exposure to common risk factors. In contrast, Sabin immunisation in the second year is associated with a decreased risk of asthma in later childhood. CDT immunisation in the first year may be a risk factor for asthma, but the need for CDT immunisation may also be a marker of increased risk of asthma in later childhood.     

Diagnosis of Ovarian Follicular Cysts from Birth to Puberty: A Report of Twenty Cases

ABSTRACT. Twenty girls aged 1 day to 17 years have been studied for ovarian follicular cysts. Clinical features leading to the discovery of the follicular cyst were different in prepubertal girls and in girls whose cyst was discovered during puberty. Before seven years of age, four girls presented a precocious pseudopuberty where breast development was in contrast with very low pituitary gonadotropin levels; two girls in this age group were diagnosed after complaining about abdominal pain. In two cases the diagnosis was prenatal during routine ultrasonography of the mother. After ten years of age, abnormal menses (5 cases) or acute abdominal pain (5 cases) were the main clinical features. In only one case the cyst presented as an abdominal mass. Follow-up of the 20 patients showed: spontaneous disappearance of the cyst within 3 to 32 weeks in 9 cases; ovariectomy in 8 cases, due to a torsion of a large cyst (over 55 mm) in 7 children and because of the fear of a possible tumor in one; limited resection of the cyst in 4 cases. By systematic ultrasonography, discovery of an ovarian cyst as defined by a non-echogenic area over 20 mm may occur relatively often in young girls. Spontaneous disappearance is frequent when the cyst is small (under 55 mm). Torsion of large cysts remains the major complication.     

Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: A longitudinal birth cohort study

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population-based, birth-cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV-proven bronchiolitis. Outcomes considered were 12-month prevalence of wheeze at two ages (between 30-42 and 69-81 months), cumulative prevalence of doctor-diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30-42 months and 22.6% vs. 9.6% at 69-81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30-42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69-81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population-based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.     

PLURIPOTENTIAL MELANOBLASTOMA, A UNIFYING CONCEPT ON MALIGNANCIES ARISING IN CONGENITAL MELANOCYTIC NEVI: Report of Two Cases

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.