Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel

During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. Conclusion In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account. Received: 21 October 1997 and in revised form: 30 April 1998 /Accepted: 5 May 1998     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Clinical significance of abdominal scintigraphy using 99mTc-HMPAO-labelled leucocytes in patients with seronegative spondyloarthropathies

Abdominal scintigraphy shows silent gut inflammation in patients with spondyloarthropathies (Sp) without clinical evidence of gut inflammation. Abdominal scintigraphy images are different than those obtained in patients with ulcerative colitis or Crohn's disease and are not related to the anti-inflammatory drugs administered. The aim of this study was to examine the clinical associations of findings on abdominal scintigraphy in patients with Sp. A total of 204 Sp patients (European Spondylarthropathy Study Group 1991 criteria) and 54 non-Sp controls receiving non-steroidal anti-inflammatory drugs were studied. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO)-labelled leucocytes. ^99mTc-HMPAO-labelled leucocyte scans were positive in 104 Sp patients (50.9%) and in six non-Sp controls (2.9%) (P<0.001; OR=8.32; 95% CI=3.23-22.67). Silent gut inflammation was not associated with any of the following: age of onset, duration of evolution, sex, family history of Sp or psoriasis, articular manifestations, extra-articular manifestations, radiological findings or HLA-B27 positivity. Positive abdominal scintigraphy was associated with active disease (P<0.0001; OR=52.7; 95% CI=19-145.6) and an increase in the C-reactive protein (P<0.005; OR=3.4; 95% CI=1.5-7.4). It is concluded that (a) abdominal scintigraphy using ^99mTc-HMPAO-labelled leucocytes is of value in detecting the silent gut inflammation in Sp patients, and (b) silent gut inflammation is related to the clinical activity, but is not associated with any particular type of illness or with HLA-B27.     

Meconium and neurotoxicants: searching for a prenatal exposure timing.

BACKGROUND: Exposure to organochlorine compounds (OCs) has been a subject of interest in recent years, given their potential neurotoxicity. Meconium is easily available and accumulates neurotoxicants and/or metabolites from the 12th week of gestation. AIMS: To determine whether neurotoxicants, specifically OCs, could be detected in serially collected meconium, and to compare the results with those obtained in cord blood samples. METHODS: A sample of cord blood and three serial stool samples were analysed in 10 newborns. Pentachlorobenzene (PeCB), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane (p,p'-DDT) and its metabolite dichlorodiphenyl dichloroethylene (p,p'-DDE), and hexachlorocyclohexane isomers (alpha-, beta-, gamma-, and delta-HCH) were analysed by gas chromatography. RESULTS: From serial stool collection and analysis in newborns, there was an increase in the concentrations of HCB, p,p'-DDE, PCBs, and beta-HCH between the first and last stools of the newborn. Levels of DDT diminished as pregnancy progressed. Concentrations in cord blood were positively associated with concentrations in meconium for p,p'-DDE and beta-HCH. CONCLUSIONS: Meconium is a very useful instrument for the investigation of fetal exposure to neurotoxicants; serial collection and analysis of meconium should estimate the timing and degree of in utero exposure of the fetus to neurotoxicants. Analysis and interpretation of neurotoxicants in meconium results is a complex process. Measurement in meconium of a wide range of neurotoxic substances should facilitate early identification of harmful exposures, and enable rehabilitation and instigation of preventive measures.     

Epididymal metastases as the first sign of a colon cancer recurrence

Metastastic tumours involving the epididymis are rare and most often found in patients with disseminated disease. It is even more unusual when the metastasis of the epididymis is the first sign of tumour recurrence. We report a case of an asymptomatic recurrent colon carcinoma presenting as metastasis in the epididymis. Although metastatic cancer presenting as an intra-scrotal mass is extremely rare, it should be considered as a possibility in patients who present with a mass involving the testicle or epididymis.     

Heart arrest in cemented hip arthroplasty

Hip arthroplasty is a common surgical intervention in our hospital practice, involving high perioperative risk related to patients age and multiple concomitant diseases. Hemodynamic complications described vary from slight hypotension during surgery to heart failure and sudden death, particularly if the operation involves a cemented femoral component. Because of the type of patients undergoing such operations (elderly patients, with osteoporosis and scarce cardiopulmonary reserve), the unclear origin of complications and the lack of consensus on what constitutes adequate monitoring during surgery, hip arthroplasty is problematic for the specialists involved. We report on five deaths during cemented hip arthroplasty; after reviewing the case history and autopsy report of one, we believe the events leading to death were triggered by massive pulmonary embolism.     

Estudio de intervención formativa con miniensayos para mejorar la atención de las urgencias médicas en un centro de salud

ObjectiveTest effectiveness and acceptability of interventions short essay-type training in health emergency management (EM).DesignCombined case series and controlled study before and after training sessions.LocationHealth Center (HC).ParticipantsTeam on duty, two monitors-facilitators, and a mannequin.Main measuresVariables: response times, staff performance, resource usage and opinion. Structure: scenarios and key messages. Instrument development: 1. Initial/final questionnaire and events. 2. Essential/non-essential times; 3. Post-test opinion questionnaire. Performance of six consecutive 15 min tests fortnightly (including corrections) and poll after each test. A month later, repeat in random order and under similar conditions. Analysis: repeated measures.ResultsA total of 93 (2/3) workers completed the initial survey, and 74 the final, with 46 participants (25 doctors, 7 nurses, 21 non-health completed 95 direct interventions. Matching participants > 80% between series. A reduction was seen in the “detection of collapse to first defibrillation” interval (10 to 4 min). EM events improved 2-3 fold and “sense of security during a real EM” increased from 23% to 71% among participants. The vast majority of participants said “useful corrections made by the facilitator.” The proportions of those who “would like to see tests introduced” and those who said “re-training was needed in EM” were moderately increased (67.4% vs 85% in health care workers). The “would like to attempt basic life support” was unchanged.ConclusionDespite being reduced in number and duration, this model of intervention has shown positive trends in terms of use and acceptability for implementation in the HC.