Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.      

Facteurs associés aux perdus de vue des patients sous traitement antirétroviral dans un centre de traitement ambulatoire du VIH à Conakry,Guinée

Background

Late or inadequate therapeutic management increases the risk of mortality associated with HIV/AIDS. The aim of this study was to analyze the proportion and factors associated with loss of follow-up in HIV patients who receiving antiretroviral therapy at Conakry.

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Hilar masses: evaluation with CT-guided biopsy after negative bronchoscopic examination

Computed tomography (CT)-guided biopsies of 20 patients with hilar masses were performed after non-diagnostic bronchoscopic examination. Bronchoscopy included washings, brushings, routine biopsy, and, in many cases, transbronchial biopsy. In all but one case (95%), biopsy with a 22-gauge needle permitted a cytologic diagnosis of malignancy. In 14 of the 19 cases (74%), a diagnosis of primary lung carcinoma involving the hili was made, and in the remaining five of the 19 (26%), metastatic hilar adenopathy from an extrathoracic primary tumor was identified. A pneumothorax rate consistent with our average rate for CT-guided biopsies (25%) was obtained, and only one patient required chest tube placement. In this series, CT-guided biopsies of hilar masses were more consistently successful in obtaining tissue for diagnosis than were bronchoscopic biopsies. Transthoracic needle aspiration biopsy may be the preferred initial diagnostic procedure in many patients with hilar masses.