The function of adrenal glands in children and adolescents during and after oncological treatment.

The purpose of this work was to present the current state of knowledge on the effects of frequently used therapeutic forms, selected pharmacotherapy (including glucocorticosteroids, immune checkpoint inhibitors, mitotane, metyrapone, aminoglutetimide, etomidate, ketoconazole, fluconazole), but also radiation therapy on the functioning of the hypothalamic-pituitary-adrenal axis in children and adolescent during and after oncological treatment. The most common pediatric cancers, where complications of adrenal insufficiency occur, are presented. Moreover, current recommendations how to diagnose the function of the adrenal axis in oncological pediatric patients, as well during oncological treatment as after it, including patients treated with steroids and also patients in severe stages, are reported. The rules of the treatment of adrenal dysfunction in those patients are presented. This understanding is of key importance for oncologists and endocrinologists in the process of diagnosing, treating and developing patient health care, as well as during therapy as after it, offering safety and improving the quality of life.

Assessment of adrenal function in pediatric cancer survivors.

INTRODUCTION: Oncological therapy can temporarily or permanently disrupt adrenal gland function. The aim of our study was to assess the function of adrenal glands in cancer survivors and to find the best diagnostic tools for it. MATERIAL AND METHODS: Sixty patients aged 1.2-14.9 years (mean 8.3 ±3.5) with diagnosed malignancies and 45 healthy children as controls were recruited to the study. Patients were assessed 0-8 years (mean 2.4 ±2.0 years) after the oncological therapy. In all patients fasting blood samples were collected to measure: glucose, sodium, potassium, cortisol, aldosterone, plasma renin activity (PRA), dehydroepiandrostenedione-sulphate (DHEA-S), adrenocorticotropic hormone (ACTH) and antibodies against the adrenal cortex (AAA). Moreover, 24-hour urinary free cortisol (UFC) was assessed. Test with synthetic ACTH was carried out with 250 µg in neuroblastoma and nephroblastoma patients and with 1 µg in other oncological patients. RESULTS: The levels of morning cortisol and sodium were significantly lower and blood glucose were higher in cancer survivors than in controls (p = 0.006, p = 0.043, p = 0.008). Basal laboratory tests confirmed adrenal insufficiency (AI) in 1 patient with neuroblastoma. Low-dose ACTH revealed AI in 3 patients with acute lymphoblastic leukemia. In the study group, UFC correlated with evening and midnight cortisol (p = 0.001, p = 0.006). In the control group UFC correlated with DHEA-S (r = 0.623, p = 0.0001). None of assessed parameters correlated with the time since the completion of oncological therapy. CONCLUSIONS: The study confirmed possibility of developing asymptomatic AI in cancer survivors even several years after therapy. Instead of morning cortisol, classical diagnostic low-dose ACTH test seems to be an optimal tool for adrenal function's assessment.

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.

Cushing disease in children and adolescents - assessment of the clinical course, diagnostic process, and effects of the treatment - experience from a single paediatric centre.

INTRODUCTION: Adrenocorticotropic hormone-dependent Cushing syndrome, known as Cushing disease (CD), is a rare disease in paediatric patients, the signs and symptoms of which differ from those seen in adult patients. AIM OF THE STUDY: The objective of the study was to present the diagnostics and treatment results of CD in children and adolescents. MATERIAL AND METHODS: We included four consequent patients in the study, 7-15 years old, with CD confirmed by laboratory tests and finally by histology ex-aminations after surgery. The data were retrospectively retrieved from the medical records of all the patients from the years 2012-2018. RESULTS: The median time from the onset of clinical symptoms to CD diagnosis was 1.5 years. All patients presented with rapid weight gain ac-companying growth retardation, and behavioural, puberty, or menstruation disorders. The diagnostic process was carried out in accord-ance with the current standard. Diagnostic difficulties regarded the cyclic CD. All patients underwent transsphenoidal complete resection of the pituitary adenoma, and they all required transient glucocorticoid substitution for a period that correlated with the time from onset of symptoms to diagnosis. All subjects achieved normalisation of hormonal results and resolution of clinical symptoms, but all are still obese. Currently the patients are in remission, but there is a suspicion of the regrowth of the tumour mass in the eldest patient. CONCLUSIONS: In each case of the coexistence of growth velocity inhibition (not necessarily short stature) with the weight gain (not necessarily obesity) and the appearance of hyperandrogenism and depressive-anxiety disorders, biochemical diagnostics of CS should be performed. Obesi-ty could be a chronic complication of CD in childhood, even after effective neurosurgery treatment.

Cyclic Cushing's Disease in the Prepubertal Period-A Case Report and Review of Literature.

Background: Cyclic Cushing's disease (CD) has been described in about 15% of adult patients with CD. In the pediatric population, diagnosis of CD is rare and cyclic presentations of the disease are not adequately understood or described. Moreover, prepubertal patients usually do not present with the typical signs and symptoms of CD, which can obscure or delay diagnosis. In this paper, we report a case of cyclic CD in a prepubertal age girls whose etiology was a pituitary corticotropinoma. Case presentation: A Caucasian 7.8 year old girl was admitted to pediatric endocrinology for the evaluation of short stature and prior obesity. The patient remained overweight despite significant lifestyle modifications, resulting in 6 kg weight loss during the prior 6 months. The physical exam was notable for precocious adrenarche and thelarche, but difficult to differentiate from steatomastia. Hypothalamo-pituitary-adrenal axis diagnostics, including single diurnal excretion of urinary cortisol, morning ACTH, and serum cortisol levels, were all within normal limits, and MRI of the pituitary gland showed no deviations at this time. Because of the clinical suspicion of cyclic hypercortisolemia, she was referred to our outpatient clinic for follow-up. After 6 months, the patient returned with rapid weight gain, accompanied by nocturnal anxiety, exacerbation of depressive behavior, insomnia and excessive sweating, and was readmitted to the ward for testing. Standard diagnostics confirmed CD and repeat MRI at 8.6 years old showed a microadenoma of 3 × 4 mm in the right side of the anterior pituitary gland. Histopathologic examination described an atypical, densely-granulated pituitary corticotroph adenoma with Ki-67 expression above 3%. Conclusion: Cyclic presentations of CD in the prepubescent age group could cause difficulties in diagnosis because of atypical signs and symptoms, which can be absent in the remission phase. Decreases in height percentiles and velocities obtained from the growth chart, as well as fluctuations in weight, and signs of androgenization can allow the clinician to suspect cycling CD in prepubertal patients. Confirmation of cyclic CD diagnosis is only possible during periods of relapse (hypercortisolemic state) and should be investigated according to the current diagnostic standard.

Local complex permittivity measurements of porcine skin tissue in the frequency range from 1 GHz to 15 GHz by evanescent microscopy.

The near-field evanescent microwave microscope is based on a coaxial transmission line resonator with a silver plated tungsten tip protruding through an end-wall aperture. The sensor is used to measure the local dielectric properties of porcine skin in the frequency range from 1 GHz to 15 GHz. The dielectric property of the skin within the near field of the tip frustrates the electric field and measurably changes the transmission line's resonant frequency and quality factor (Q). The shift of the resonator's frequency and Q is measured as a function of tip-sample separation, and a quantitative relationship between the real and imaginary parts of the local dielectric constant using the method of images is established. The associated changes in quality factor image scans of subsurface tissue structure and dielectric properties of skin surface lesions are presented.

Case study: enhancing effective and efficient congestive heart failure management at Columbus Regional Hospital.

For left ventricular function assessment, angiotensin converting enzyme inhibitor at discharge, smoking cessation education, and congestive heart failure (CHF) discharge instructions, a CHF team developed interventions to improve current practices.

Inflammatory cytokines and cell adhesion molecules in a rat model of decompression sickness.

To characterize early blood and tissue markers predictive of decompression sickness (DCS), this study focused on identifying changes in inflammatory mediators during the 24-h period immediately following compression-decompression of female Sprague-Dawley rats. Early blood and tissue markers predictive of DCS include inflammatory cytokines and cell adhesion molecules (CAMs). Increased levels of inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon-gamma (IFN-gamma), were detected in the circulation 6 h after decompression. Increased levels of only IL-6 were observed at 24 h. Compared with control animals maintained at 1 atmospheres absolute pressure ATA (101 kPascal), significant increases in expression of E-selectin, and L-selectin, as well as intercellular adhesion molecule-1 (ICAM-1), were observed immunohistochemically in the lungs and brains of the rats 6 h after exposure to 2 (203 kPascal), 3 (303 kPascal), or 4 (404 kPascal) ATA, followed by rapid decompression. These levels drop by 24 h. In contrast to the observations in brain, greater increases in expression of E-selectin and L-selectin around vessels and connective tissue were seen at 24 h after decompression in the quadriceps of rats exposed to either 3 or 4 ATA. Significant increases in expression of the A(2A) receptor, which modulates inflammation by downregulating production of these cytokines, were detected only in the quadriceps removed at 24 h after decompression from 4 ATA. This study demonstrated that rapid decompression induces the release of mediators of inflammation and resulting tissue inflammation cascades, as well as a protective anti-inflammatory response.

Effects of PCB 126 on primary immune organs and thymocyte apoptosis in chicken embryos.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyl (PCB) 126 produce thymic atrophy and immunosuppression. This study explored the hypothesis that the thymic atrophy produced by developmental exposure to PCB 126 is associated with an increase in apoptotic thymocytes at the end of incubation in chicken embryos. Eggs were injected via the air cell with PCB 126 (0.05, 0.13, 0.32, 0.64, and 0.80 ng/g egg) on d 0 of incubation, and tissues were collected on d 20. Controls included noninjected and vehicle-injected (sunflower oil) eggs. Thymocytes were cultured for 6 h and analyzed by flow cytometry for decreased DNA content (propidium iodide staining) and cell size (forward scatter), which indicate apoptosis. PCB 126 induced dose-dependent mortality with an LD50 of 1.01 ng/g and lowest-observed-effect concentration (LOEC) of 0.32 ng/g. Teratogenic effects commonly associated with TCDD and planar PCBs, including cranial and foot deformities and subcutaneous edema, tended to increase with dose of PCB 126. PCB 126 reduced thymus mass by approximately 20% at 0.64 and 0.8 ng/g, the number of viable thymocytes by approximately 20-24% at and above 0.13 ng/g, and the number of bursal lymphoid cells by 57% at 0.64 ng/g. The percentage of apoptotic thymocytes increased with dose, reaching levels 2 times greater than controls at 0.8 ng/g. Electrophoresis of low-molecular-weight DNA from thymocytes of all doses demonstrated fragments in multiples of 180 bp. This DNA laddering is a hallmark of apoptosis. At all doses, thymocytes exhibited caspase-3 activation, another indicator of apoptosis. The results of this experiment supported the hypothesis that the thymic atrophy produced by developmental exposure to PCB 126 in chicken embryos is associated with an increase in apoptotic thymocytes on embryonic d 20.

The effect of m-xylene on cytotoxicity and cellular antioxidant status in rat dermal equivalents.

Exposure of the skin to volatile organic chemicals (VOCs) can lead to irritation, inflammation and cytotoxicity. Since VOCs are used in industrial, commercial and military applications, concern is mounting with respect to VOC safe exposure limits. Although traditional toxicological assessment of VOCs has utilized animal models, the use of alternative in vitro models is becoming more widespread. We have previously developed a sealed exposure system that prevents chemical loss through evaporation and enables calculation of target cell chemical dose. The present study utilized this in vitro exposure method to assess m-xylene-induced cytotoxicity and antioxidant status in dermal equivalents (dermal fibroblasts in a collagen matrix). At the end of a 1- or 4-h exposure, cytotoxicity was measured using the MTT assay and the EC50 values determined were 1481 +/- 88 and 930 +/- 33, respectively. Decreases in cellular thiols and catalase activity were observed, which occurred in a time and dose-dependent manner. Treatment of dermal equivalents with the antioxidants N-acetylcysteine (NAC) and catalase provided some protection against m-xylene-induced cytotoxicity. When compared to m-xylene exposures, treatment with either 1.0 or 5.0 mM NAC led to increases in the EC50 values at 1 and 4 h. Increases in these EC50 values ranged from 1.22- to 1.32-fold at 1 h and 1.27- to 1.54-fold at 4 h. Although treatment with catalase (1000 U/ml) led to a 1.35-fold increase in cell viability at 1 h, no significant differences were observed at either 1 or 4 h when compared to dermal equivalents exposed to m-xylene alone. These results suggest that exposure to m-xylene leads to a time- and dose-dependent decrease in cellular antioxidants and that cellular thiols may provide protection against the cytotoxic properties of m-xylene.

Knowledge, attitudes and practices of Caribbean laboratory workers: adoption of bio-safety guidelines - abstract

Biomedical laboratories are work environments which pose special infectious disease risks to personnel who work in them. With the advent of the AIDS pandemic, emphasis has been placed on adoption of Universal Precautions Policy by all health care workers. In order to assess the extent of safety management, knowledge of, and compliance with established safety standards, laboratory workers in the English-speaking Caribbean were surveyed via an anonymous, self-administered, pre-coded questionnaire. One hundred and thirty-one questionnaires were returned from 16 laboratories in 13 countries (50 percent response rate). Responses indicated that there were universal deficiencies in safety management. Only 38 percent of respondents indicated that a safety manual was readily available. Most staff indicated some familiarity with Universal Precautions but there was inadequate awareness (60 percent affirmative responses) regarding the possibility of contracting infections in the laboratory. There were instances of eating, drinking, smoking, mouth pipetting and recapping of needles. The preliminary survey indicates that there is inadequate compliance with safety standards among laboratory workers in the English-speaking Caribbean. Safety management needs to be improved with intervention strategies designed to heighten laboratory workers' perception of the real risk of infection, in order to accomplish the neccessary behaviour modification. (AU)

Epidemiology of HIV infection and AIDS in Antigua - abstract

In December 1985, the first case of AIDS in Antigua occurred in a homosexual male. As of March 1991, Antigua recorded 43 cases of HIV infection. Seven of these, (16.3 percent) were donors. Apart from one donor, a female, the remaining six donors had unprotected sex with prostitutes. Thirteen (30 percent) of the 43 cases were prostitutes, 10 (1.6 percent) of whom were diagnosed in a serosurvey of 622 prostitutes between January 1988 and March 1991. Despite the heterosexual/prostitute linkage, the male homosexual/bisexual group is significant: 12 (28 percent) of the 43 cases were in this category. There were 13 cases of AIDS with 6 cases (46 percent) in the male homosexual/bisexual group. This figure should be interpreted cautiously since all 13 of the HIV prostitutes returned home to Santo Domingo and the status of 12 of them was unknown. The homosexual/bisexual group does not seem to be closely associated with the heterosexual-prostitute group (AU)

An alternative test strategy for confirmation of HIV serology - abstract

Conventional HIV confirmatory testing algorithms use Western Blot (WB), radioimmunoprecipitation assay (RIPA) or immunofluorescence assay (IFA). All are costly and require well-trained staff. An alternative confirmatory test strategy was evaluated. This involved testing of a panel of 231 stored frozen samples with known WB results with a first generation enzyme linked immunosorbent assay, ELISA (Pharmacia HIV-I E ELISA) and a second generation ELISA (Abbott Recombinant HIV-I ELISA). The panel consisted of 122 WB positive, 37 WB indeterminate and 72 WB negative results. Ninety-six percent of the WB positive samples were positive by both ELISAs; 4 percent gave inconclusive results. Twenty-five (67.6 percent) of the WB indeterminate samples gave inconclusive results by the 2 ELISAs, 11 (29.7 percent) were negative by 2 ELISAs and were probably from truly negative patients. One sample (2.7 percent) was positive by both ELISAs, 53 (74 percent) gave inconclusive results. No WB negative samples gave positive results in both ELISAs. This alternative test strategy could be adopted with results being reported only for samples found clearly positive by both ELISAs (51 percent of samples tested). Other samples should be tested using conventional algorithms. For 51 percent of samples, the cost of confirmatory tests will be reduced from US$70.00 to US$4.00 per samples (AU)

Bacterial-aetiology of neonatal conjunctivitis in Trinidad - abstract

This prospective, consecutive survey of 3,645 babies delivered at the Mount Hope Women's Hospital from March 1 to November 8, 1990 was to determine the aetiology of neonatal conjunctivitis and to compare 3 methods for detection of Chlamydial infection in material from affected eyes. One hundred and twenty babies presented with purulent conjunctivitis within the first four weeks of life and were investigated for bacterial infection including chlamydia trachomatis. Material from infected eyes was examined for the presence of aerobic bacteria by standard bacteriological methods and for chlamydial infection by fluorescein antibody (FA) test, ELISA method and tissue culture. Staphylococcus aureus (40 percent) and Chlamydia trachomatis (11 percent) were the commonest organisms isolated. The prevalence rate of chlamydia trachomatis was 3.84 percent per 1,000 live births. Tissue culture and ELISA methods were more sensitive than the immuno-fluorescence technique. The cost per test for chlamydia trachomatis by the 3 methods varied from a minimum of TT$37.44 to a maximum of TT$63.11. In spite of the cost, it is recommended that testing for Chlamydial as well as bacterial infections should be a routine part of investigating neonatal conjunctivitis (AU)

Yellow fever studies in Trinidad, 1988-1989: attempts to demonstrate Transovarial Transmission of yellow fever virus in Haemagogus mosquitoes collected in nature

Subsequent to an epizootic of yellow fever (YF) in monkeys and the isolation of yellow fever (YF) virus from sylvatic mosquitoes in December, 1988 and January, 1989 in south-east Trinidad, ovitrapping for mosquito eggs was started in January, 1989, in an attempt to demonstrate transovarial transmission of the virus. Multi-paddle ovitraps were used. From a total of 52,632 eggs collected in various parts of the country, the following species of mosquitoes were reared: Haemagogus janthinomys (54 percent), Hg. leucocelaenus (32 percent), Aedes insolitus (12 percent), Hg. equinus (1 percent). When mosquito eggs were removed from the hard board paddles then vacuum-treated for hatching, the process proved very economical in storage space. Most eggs were obtained at the start of the wet season, four to five months after the isolation yellow fever virus from wild caught adult mosquitoes and monkey carcasses. When adult mosquitoes reared from eggs were processed for yellow fever virus, no virus was detected from any of the mosquito pools to indicate that transovarial transmission had occurred (AU)

Sylvatic yellow fever activity in Trinidad 1988-1989

Of a total of 18,068 mosquitoes (361 pools) collected in south-eastern Trinidad forests from December, 1988 to May, 1989, 47 species belonging to 14 genera were identified. Five yellow fever virus isolates were made from Haemagogus janthinomys and one from Sabethes chloropterus. All the other pools of mosquitoes examined were negative for the virus. The mosquito isolates were made in December and January. In addition, in late February and early March, two infected howler monkeys (Alouatta sp.) were detected. Since March, despite continued surveillance, no yellow fever virus has been detected in mosquitoes or monkeys. There has been no reported human infection (AU)

The 1988-1990 epizootic of yellow fever in Trinidad: virological aspects

Sylvatic yellow fever virus activity occurred in Trinidad between December, 1988 and January, 1990. It was first detected in the Trinity Hills area of Guayaguayare in the south eastern forest of the island and subsequently spread west to Moruga and north to Fishing Pond. Surveillance activities in these areas resulted in the collection of over 18,000 mosquitoes and seven monkeys which were referred to the CAREC laboratories for viral investigation. Six pools of mosquitoes yielded yellow fever virus in December, 1988 and January, 1989. Isolations were made from Haemagogus janthinomys (five pools) and Sabethes chloropterus (one pool). Extensive collections in other areas failed to yield virus. Three Alouatta monkeys proved to be infected with yellow fever. These were all Alouatta sp. and were submitted to the laboratory in February and March of 1989 and January of 1990. Thorough virological investigation of febrile persons, with and without liver involvement, showed no evidence to spread to the human population either before or during the epizootic. This was attributed to the high level of immunization achieved in the population following the yellow fever outbreak of 1978-1980 (AU)

Studies on yellow fever in inter-epizootic period in Trinidad

Following an outbreak of yellow fever in Trinidad in 1978-1979, a study was undertaken to investigate the jungle reservoirs and vectors of yellow fever virus in the inter-epizootic period, to seek evidence of natural transovarial transmission of yellow fever virus in Haemagogus collected. These were made four months after the last detection of virus in that area of the island and could not positively be attributed to transovarial transmission. None of the 42,815 progeny of wild mosquitoes yielded virus. No yellow fever virus was isolated from 34,300 mosquitoes other than Haemagogus nor from 15 vertebrates collected in areas of former virus activity. Good progress was made in optimizing the use of the AP-61 cell line resulting in rapid isolation and identification of dengue and yellow fever viruses from Caribbean countries (AU)

Entomological activities during the yellow fever epidemic in Trinidad, 1978-1980

An epidemic of sylvan yellow fever occurred in Trinidad during the period 1978 to 1980. Entomological activities were initiated at various localities where monkey (Alouatta spp.) mortalities were reported. A total of 5,468 Haemagogus janthinomys was collected and tested which resulted in the isolation of 17 strains of yellow fever virus. Two strains of the virus were isolated from a total of 49 Haemagogus leucocelaenus and these constituted the first isolations of yellow fever virus from this species of mosquito from Trinidad. Attempts to demonstrate transovarial transmission of yellow fever virus from adults feared from eggs and larvae collected in the field were unsuccessful. However, from two locations virus isolations were made at the end of rainy season (January) and at the beginning of the successive rainy season (June) (AU)

A clinico-pathological study of yellow fever with demonstration of the virus in the human liver

The clinical histopathological and serological findings in three patients who developed yellow fever after entering the Guayaguayare forest in south-east Trinidad in January and February 1979 are described in this report. The patients were all previously healthy young males and the clinical features of the disease varied from fulminant viral hepatitis with hepato-renal failure to a self-limiting anicteric viral illness. The first patient died, and histopathological examination of the liver was done post-mortem. Needle biopsy of the liver was done on case 2 which presented with the clinical picture of infective hepatitis, and on case 3 with the features of an anicteric viral illness. The histopathological hallmarks of midzonal necrosis, granular eosinophilic degeneration (Councilman bodies) and fatty change in the parenchymal cells of the liver were seen in three cases. The electron microscopic study demonstrated the presence of the yellow fever virus in the liver of the patient who died (AU)