Eosinophilic granulomatous lymphadenopathy: association with hyper-IgE and eosinophilia

Cervical lymph node enlargement is probably the most frequently detected childhood lymphadenopathy. We report 2 cases of cervical lymphadenopathy in children associated with hyper-IgE and eosinophilia, displaying the features of necrotizing eosinophilic granulomatosis. Immunohistochemical analysis and a serological work-up failed to elucidate the underlying etiology. We would like to call the attention of physicians and pathologists to this unusual clinical picture, different from the fatal form of necrotizing eosinophilic granulomatosis, and we suggest a role for the eosinophils in the pathologic appearance of the lymph nodes.     

Transdermal penetration of physostigmine: Effects of oleic acid enhancer

The efficiency of the transdermal penetration of physostigmine through the guinea-pig skin, in a vehicle containing propionic acid, was studied in the course of developing a transdermal physostigmine pad for the potential treatment of Alzheimer's disease patients. In an attempt to improve drug penetration, the addition of various concentrations of oleic acid(0.5–5%) was tested. The study included histological examination of skin biopsies from application site. The addition of 0.5% oleic acid to the vehicle enhanced the permeation of physostigmine and shortened the time needed to reach steady state levels of blood cholinesterase inhibition, without any damage to the skin. Stable values of physostigmine concentration and of cholinesterase inhibition were measured both in blood and in brain up to 72 h. A high correlation was found between physostigmine concentration in the plasma and cholinesterase inhibition in whole blood samples (r = 0.99 for the values measured up to 48 h). A lower correlation was found between physostigmine concentration and cholinesterase inhibition in the brain (r = 0.57). In a vehicle containing up to 1% oleic acid, physostigmine was stable for at least one month. Oleic acid concentrations higher than 1%, while increasing the flux of the drug through the skin, resulted in considerable skin damage. © Wiley-Liss, Inc.     

Psycho-Social Factors and Blood Pressure During Pregnancy and Delivery

This research investigates the relationship between repression and blood pressure by using an objective and well-known test for classifying subjects as repressors (Byrne's R-S scale), and examines the relationships among socio-economic level, ethnic origin, and blood pressure. Subjects were 461 Israeli pregnant women who gave birth in urban hospitals. The physiological measures were the highest blood pressure a woman had during pregnancy, as well as blood pressure, heart rate and temperature measured immediately after her admission to the hospital. The women's anxiety level was ranked before and after delivery. No confirmation was found for the psychoanalytically based hypothesis held by several investigators, that subjects with repressive personality type would have higher blood pressure. No significant relationship was found between socio-economic level and any physiological measure. Israeli Jews of Oriental origin had lower blood pressure than those of European origin, even though the former were of lower socio-economic level.     

Fatal liver infarction after transjugular intrahepatic portosystemic shunt procedure

Hepatic infarction is a rare disease. We describe here a cirrhotic patient with end-stage renal failure and recurrent tense ascites with fatal hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Abdominal ultrasound, radionuclide liver scan, abdominal computed tomography scan, and finally liver biopsy established the diagnosis. The mechanism causing the infarct is not clear. However, as the infarct appeared after the patient had an episode of shock and disseminated intravascular coagulation, it could well be that the concomitant hepatic arterial insufficiency contributed to the infarct. Physicians should be aware of this possible catastrophic complication.     

Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication

A 5-year-old child with desmoplastic small round-cell tumor was treated with a protocol of very-high-dose, short-term chemotherapy, containing HD-CAV (cyclophosphamide, doxorubicin, vincristine, and mesna), ifosfamide, and etoposide. Two days after the initiation of ifosfamide, he exhibited new-onset lethal encephalopathy manifested by subacutely progressive cerebellar and then temporal and frontocortical degeneration leading to a vegetative state and eventually to death. A full work-up, including brain biopsy, was negative, excluding infections and metabolic or vascular causes. Ifosfamide is known to be capable of causing acute encephalopathy that can be severe but is generally reversible. This child showed a very atypical progressive, lethal course of ifosfamide toxicity. The possibility of this complication should be considered when high-dose ifosfamide treatment is planned for children.     

Brown tumour of hyperparathyroidism in the mandible associated with atypical parathyroid adenoma

The brown tumour of hyperparathyroidism is a localized bone tumour and an uncommon manifestation of hyperparathyroidism. A 27-year-old woman presented with a mandibular 8 x 10 cm solid mass diagnosed as central giant cell granuloma. Chemical blood analysis revealed increased serum calcium levels of 12.46 mg/dL and the parathyroid hormone level was 124 pg/dL. The patient underwent surgery with removal of a parathyroid mass. Histologically, this parathyroid tissue was seen to be limited by a fibrous capsule with morphological features consistent with atypical parathyroid adenoma. The mandibular tumour has receded and the patient declined further procedures. This is the first case reported of brown tumour as the primary manifestation of an atypical parathyroid adenoma, a lesion that shares some features with parathyroid carcinoma without the unequivocal properties of malignancy.     

Distinct cytogenetic pathways of advanced-stage neuroblastoma tumors,detected by spectral karyotyping

Molecular studies of advanced-stage neuroblastoma (NBL) have revealed a marked genetic heterogeneity. In addition to MYCN amplification and chromosome 1 short-arm deletions/translocations detected by conventional cytogenetics, application of fluorescence in situ hybridization has disclosed a high prevalence of 17q gain, whereas allelotyping and comparative genomic hybridization techniques also have revealed loss of 11q and of other chromosomal material. Using the recently developed technique of spectral karyotyping (SKY), we sought to refine the cytogenetic information, identify hidden recurrent structural chromosomal abnormalities, and compare them to the molecular findings. Thirteen samples of metaphase spreads from 11 patients with advanced-stage NBL were analyzed by SKY. Most of them were found to have complex karyotypes (more than three changes per metaphase) and complex unbalanced rearrangements. Recurrent aberrations leading to 17q gain, deletion of 1p, MYCN amplification, and loss of 11q appeared in 7, 4, 4, and 5 patients, respectively, in simple and complex karyotypes. Chromosome 3 changes and gain of 1q and 7q appeared in 6, 5, and 4 patients, respectively, in complex karyotypes only, reflecting later changes. A strikingly high prevalence of the unbalanced translocation der(11)t(11;17), leading to concomitant 11q loss and 17q gain in 4 patients, delineated a distinct cytogenetic group, none having 1p deletion and/or MYCN amplification. der(11)t(11;17) was associated with complex karyotypes with changes in chromosomes 3 and 7q. The 17q translocations with partners other than 11q were associated with 1p deletion and/or MYCN amplification. The distinct cytogenetic subgroups identified by SKY confirm and extend the recent molecular observations, and suggest that different genes may interact in the der(11)t(11;17) pathway of NBL development and progression.     

The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy-induced adrenocorticotropic hormone hypersecretion

To examine the role of IL-1 in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis, mice with knockout of the IL-1 receptor type I (IL-1rKO) were exposed to psychological and metabolic stressors. When exposed to mild stressors (auditory stress or a low dose of 2-deoxyglucose), IL-1rKO mice displayed a significantly diminished corticosterone secretion, compared with wild-type (WT) controls. In response to more severe stressors (60-min restraint or a high dose of 2-deoxyglucose), both groups exhibited a similar increase in corticosterone secretion. To examine the role of IL-1 in HPA axis feedback regulation, serum ACTH levels were measured after adrenalectomy (ADX) in IL-1rKO mice and in mice with transgenic overexpression of IL-1 receptor antagonist within the brain (IL-1raTG). As expected, WT controls exhibited ADX-induced ACTH hypersecretion, whereas IL-1rKO and IL-1raTG mice showed no increase in ACTH levels, suggesting that brain IL-1 has a critical role in ADX-associated ACTH hypersecretion. Similarly, WT mice that were chronically exposed to IL-1ra in utero displayed a diminished ADX-induced ACTH hypersecretion, compared with vehicle-treated controls, suggesting a developmental role of IL-1 in HPA axis regulation. In conclusion, our results suggest that endogenous IL-1 plays a critical role in HPA axis activation after stress and ADX.