Severity of demyelination in vivo correlates with serum myelination inhibition activity in guinea pigs having a new form of experimental allergic encephalomyelitis

Guinea pigs received a suboptimal transfer of lymphocytes sensitized to myelin basic protein (BP) and were then immunized with guinea pig BP, BP plus chicken brain or chicken myelin, or chicken brain alone. Sera from these animals were tested for the presence of myelinotoxic antibodies, as detected by the myelination inhibition assay. Myelination inhibition activity correlated with the histologic severity of demyelination.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Phase II study of intravenous melphalan (NSC-8806) in the treatment of patients with advanced squamous carcinoma of the head and neck

The Illinois Cancer Center entered 25 patients on a phase II trial of intravenous melphalan treating patients with recurrent, metastatic or locally advanced and inoperable squamous cell carcinoma of the head and neck. All patients had bi-dimensionally measurable disease, at least a sixty day life expectancy, and adequate performance status (ECOG scale 2). All patients except one had received prior radiotherapy, chemotherapy or both. Melphalan dosage was 30 mg/m² every three weeks. Twenty-four patients were evaluable for response. One patient with laryngeal carcinoma had a clinical complete response of a nodal metastasis. Four patients had stabilization of disease for one to three months. There was formidable toxicity, including neutropenia (ANC < 1000/l 36%), and thrombocytopenia (< 50,000/l 32%). There were no drug-related deaths. Melphalan administered intravenously does not appear to be efficacious therapy in patients with previously treated advanced head and neck squamous carcinomas.     

Intercomparison of passive radon-detectors under field conditions in epidemiological studies

The Ardennes and Eifel region is a geologically distinct area covering parts of Germany, Belgium, France, and Luxembourg where enhanced concentrations of radon occur in some houses and other buildings. An international case-control study is being conducted to examine the role of radon in the etiology of lung cancer in this area. The radon detectors used are issued by different laboratories involving a variety of detector types and processes. A series of intercomparisons in houses was therefore conducted under similar conditions of exposure in the field. In most situations the different detectors gave similar results. Nevertheless, in some situations open and closed detectors yielded different results. Therefore, estimates of radon exposure have to be adjusted if results are to be pooled.     

Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.