A study on prostaglandin F2α in photodermatoses

Summary Prostaglandin F₂ (PGF₂) as a possible mediator was studied. Its plasma content was determined by radioimmunoassay. Changes in the DNA synthesis were followed by autoradiography. In active polymorphous light eruption (PLE) and porphyria cutanea tarda (PCT) a remarkable increase (over 300 pg/ml) in plasma content occurred, especially in cases involving large skin areas. Values returned to normal in remission. PGF₂ administered i.d., significantly increased the DNA synthesis of the epidermal cells 48 h after injection similar to the effect of three minimal erythema dosis UV-irradiation. This was more pronounced in PLE patients than in controls. These findings suggest some role of PGF₂ in producing the inflammatory and perhaps proliferative components of the skin symptoms in PLE. PGF₂ — in parallel to literary data concerning PGE — seems to be a mediator of UV-induced changes in DNA synthesis of the epidermal cells. Offprint requests to: Irene Horkay, MD (address see above)     

Revisiting the pathogenic mechanism of the GJB1 5’ UTR c.-103C > T mutation causing CMTX1

neurogenetics - The second most common form of Charcot-Marie-Tooth neuropathy (CMT), X-linked CMT type X1 (CMTX1), is caused by coding and non-coding mutations in the gap junction beta 1 (GJB1)...     

Age-dependent changes of K-elastin stimulated effector functions of human phagocytic cells: Relevance for atherogenesis

Effector functions of the elastin receptor on human phagocytic cells from young and older individuals were studied. In cells of young healthy subjects the elastin peptides, the agonists of receptor, stimulated both superoxide anion release from PMNs and phagocytosis of coated human red cells by monocytes. Elastin appeared to inhibit the cholesterol synthesis in monocytes, measured by the incorporation of ¹⁴C-acetate. In comparison with phagocytic cells of young (≤25 ± 6 years) subjects, PMNs of elderly donors (≥75 ±10 years) bore a similar number of binding sites for soluble elastin peptides, and the affinity of the elastin receptor was unchanged as shown by Scatchard analysis. The phagocytosis of coated human red cells stimulated by elastin peptides was also similar in the two age groups. However, several differences were found between phagocytic cells of young and elderly donors 1) PMNs of elderly released increased amounts of elastase from both resting and elastin peptide stimulated cells, and 2) monocytes of elderly showed a lack of inhibition of cholesterol synthesis by elastin peptides when maintained in cholesterol-free medium. These changes in effector functions of phagocytic cells from elderly donors might contribute to the age-dependent increase of susceptibility to the development of atherosclerotic lesions.     

A possible explanation of the germicide effect of carbon dioxide in supercritical state based on molecular-biological evidence

Supercritical carbon dioxide (CO₂) possesses germicide (bactericide and sporicide) effect. Despite of the fact, that this effect is used in industrial sterilization processes, the sterilization mechanism at molecular level is unclear. Our hypotheses can provide a molecular-biological explanation for the phenomenon.     

Interrelation between body composition and endocrine system in healthy elderly people

The body composition of 40 healthy aged and 20 healthy young people was determined using a multi-isotope method. At the same time their hormonal status was assessed. A correlation between the body composition and the endocrine status was investigated. Our results concerning the body composition and the hormonal values correlate with the findings of the literature. A strong correlation was found between the plasma volume and the renin-angiotensin-aldosterone system. The interrelation could explain the reciprocal age related changes of plasma volume and the renin-angiotensin-aldosterone system. No or weak correlation could be found between the body composition and other measured hormones.     

Cystatin C is a suitable marker of glomerular function in children with cancer

Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (S_Cr), the endogenous creatinine clearence ( C _Cr), and the calculated Counahan formula ( C _Counahan) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and S_Cr and between 1/cysC and C _Counahan. CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.     

Pharmacotherapy outcome in older pathological gamblers: a preliminary investigation

Although pharmacotherapy is often effective for pathological gambling, little is known about how it affects older populations. The present study examines the response to pharmacotherapy in a series of pathological gamblers age 60 years and older. Fourteen older patients who fulfilled DSM-IV criteria for pathological gambling were treated in an outpatient clinic. Subjects were assessed retrospectively with the Clinical Global Impressions scale (both severity and improvement measures) using information collected on gambling symptoms during clinic visits. Eight (57.1%) older patients achieved sustained response to pharmacotherapy. The present findings indicate that many older pathological gamblers respond to "off-label" use of pharmacotherapy. The present findings are preliminary. Further studies with larger samples are needed to confirm these findings.     

Use of helium-oxygen mixtures to relieve upper airway obstruction in a pediatric population

OBJECTIVES: Helium as a component of inspired gas decreases turbulent flow and airway resistance. Helium-oxygen mixtures have been used since the 1930s in the management of patients with upper airway obstruction. The objective of this study was to evaluate the efficacy of helium-oxygen mixtures in relieving upper airway obstruction in a pediatric population. STUDY DESIGN: Retrospective chart review of 42 pediatric patients who received helium-oxygen mixtures for upper airway obstruction within a 3-year period. METHODS: The study protocol included 42 pediatric patients, aged 1 week to 14 years, who were admitted to the Children's Hospital of Philadelphia from June 1997 to December 2000 and who received a total of 44 treatments of helium-oxygen therapy for upper airway obstruction. Response to treatment was determined by reduction in work of breathing noted on the chart. RESULTS: Thirty-two of 44 helium-oxygen treatments resulted in a positive response (73%). There were no significant differences in demographic characteristics between responders and nonresponders, except all of the premature infants were responders and 6 of the 9 patients with syndromes were nonresponders. CONCLUSIONS: Helium-oxygen therapy is a useful adjunct therapy for upper airway obstruction. Controlled clinical trials are necessary to better define the appropriate settings for use of helium-oxygen.     

Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia

The aim of this study was to see whether pleiotropic or myeloid hematopoietic growth factors, which do not stimulate normal lymphoid cells, can induce proliferation of blast cells of the acute lymphoid leukemia (ALL) of childhood. Bone marrow cells of 13 children with untreated ALL (nine common ALL, two myeloid antigen positive ALL and two early T-cell ALL) formed colonies of leukemic blast cells in primary methylcellulose cultures. Spontaneous growth was observed in three of 13 cases, whereas phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), a conventional source of various natural human cytokines, induced colony formation in ten of 13 cases. A similar rate of responsiveness was seen with recombinant human granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF); a combination of these three cytokines induced colony formation in all cases studied. The effect of these growth factors on colony formation seemed to be dose-dependent in some cases. Of the stimuli studied, GM-CSF induced the smallest number of colonies, whereas the effects of G-CSF, SCF and PHA-LCM were similar in this respect. Combination of cytokines proved to be even more efficient in inducing clonal proliferation of leukemic lymphoblasts. In double combinations, G-CSF and GM-CSF as well as G-CSF and SCF were able to potentiate each other's effects. Triple combination of these cytokines mediated the most potent growth stimulus. Our results demonstrate that myeloid and pleiotropic cytokines are able to stimulate clonal proliferation of pediatric leukemic lymphoblasts. This may present a potential hazard to children with ALL while on adjuvant therapy with hematopoietic growth factors. In vitro colony assays performed prior to or in parallel with the administration of hematopoietic growth factors to ALL patients may help to forecast their possible effects on leukemic cells in vivo.