Chronic administration of theophylline to rats induces a post-insulin binding defect in adipocyte glucose transport

Summary To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%–30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5±0.5 and 6.7±0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that ¹²⁵I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using ¹²⁵I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.     

Morbidity among employees engaged in the manufacture or formulation of chlorpyrifos.

The prevalence of selected illnesses and symptoms during 1977-85 was compared between 175 employees potentially exposed to the organophosphate insecticide chlorpyrifos and 335 matched controls with no history of exposure to organophosphates. Subjects were subdivided into three exposure intensity groups on the basis of job title and air monitoring data for dose response testing. This classification scheme was shown roughly to correlate with plasma cholinesterase inhibition in the workers. No statistically significant differences in illness or prevalence of symptoms were observed between the exposed and unexposed groups or among the three exposure subgroups. Potentially exposed employees did report symptoms of dizziness and of malaise and fatigue relatively more often than subjects from the comparison group; however, further analyses by exposure level, process area, or time did not support a relation with exposure. No cases of peripheral neuropathy were seen among the exposed workers. Although the sample size was small and the statistical power limited, the cumulative exposures likely to have been experienced by this workforce exceed those to be expected for individuals using the product as recommended. The absence of exposure related adverse effects, including neurological impairment, is reassuring.     

Comparative effects of pilocarpine in different vehicles on pupil diameter in albino rabbits and squirrel monkeys

Several commercial pilocarpine preparations have been compared for their efficacy of drug delivery as evaluated by changes in pupil diameter, and return to base-line pupil size, in rabbits and squirrel monkeys. Adsorbocarpine, Isoptocarpine, Pilocar, all at 2%, and Pilopine HS gel, 4%, were used. In albino rabbits the order of efficacy, as judged by area under the curve, or maximal pupil diameter change, was Pilopine greater than Isoptocarpine = Adsorbocarpine greater than Pilocar = saline (prepared in this laboratory). In general, greater areas under the curve were associated with greater changes in pupil diameter. Pupil diameter had returned to normal by a maximum of 5 hours after drop instillation. In squirrel monkeys, the maximum pupillary change was statistically (P greater than 0.05) the same for all preparations, as was the percentage change in pupil diameter at 6 hours since pupils were still somewhat constricted at this time after drop instillation. The differences in area under the curve were minor. The greater response in primates compared to rabbits may be due to differences in pigment, intraocular kinetics and a far more active ciliary muscle in primates. Also studied were newly developed, non-surfactant containing, preservative-free polymer- and microparticle-based vehicles. Some of the vehicles, based on cyanoacrylate, modified hyaluronate, anionic copolymers, polyvinyl-pyrrolidone, cross-linked gelatin and microparticles showed greater pupillary changes and areas under the curve in rabbits compared to saline vehicle. When compared to commercial preparations in the monkey eye cyanoacrylate block copolymer and modified hyaluronate showed an increase in efficacy. Polyvinylpyrrolidone, anionic copolymer and cross-linked gelatin were equal to the commercial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malignant histiocytosis. Complete remission in two pediatric patients

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.     

Systemic Vasculitis with Renal Involvement — A Review

Twenty five patients with renal vasculitis presenting over an eight year period were reviewed. Ten had microscopic polyarteritis, 6 classic polyarteritis, 5 overlap syndrome, 2 Churg-Strauss syndrome and 2 Wegener’s granulomatosis. Clinical features included hypertension, pulmonary involvement, neurological involvement and arthralgia. Serum creatinine was over 500 umol/1 in 13 patients, 10 of whom required dialysis. Visceral angiography was positive in 80% of those studied, Focal and segmental necrotising glomerulonephritis was the commonest renal lesion. Treatment consisted of corticosteroids and cytotoxic agents in most cases. Plasmapheresis was used for rapidly progressive renal failure, severe pulmonary haemorrhage or cerebral vasculitis. Improvement or stabilisation of renal function was seen in 68% of patients treated. There were 4 early deaths and one late death. The diagnosis, histology, treatment and outcome of renal vasculitis is discussed. The importance of early diagnosis and treatment is emphasised in this potentially reversible cause of acute renal failure.     

Evaluation of the Ca 1 monoclonal antibody in distinguishing oral squamous cell carcinoma from non-malignant or premalignant oral lesions

The Ca antigen has been reported to be present on the surface of malignant but not, with few exceptions, non-malignant cells. We investigated the potential usefulness of the monoclonal Ca 1 antibody in differentiating oral squamous cell carcinoma from non-malignant or premalignant oral neoplasms. Paraffin-embedded sections from 33 biopsy specimens of 12 hyperplastic and 21 neoplastic oral lesions were examined by immunohistochemical staining. Seven of the 33 specimens showed positive staining for Ca antigen. Fifteen of 21 specimens of oral squamous cell carcinoma were negative for Ca antigen, and one case of focal keratosis was positive. The results indicate that the use of the Ca 1 antibody to distinguish oral squamous cell carcinoma from non-malignant or premalignant oral lesions is highly unreliable.     

Long-term effects of cochlear implants in children.

OBJECTIVE: Since 1987, when the use of multichannel cochlear implants was initiated in children, candidacy has expanded; many thousands of children have received these devices, and results have revealed a wide range of performance. However, few long-term studies exist on a large population of these children. There have been concerns expressed that cochlear implant function might degrade over time, that devices and electrodes might migrate and extrude in the growing child, or that there might even be a deleterious effect of long-term stimulation of the cochlear nerve. The purpose of this study was to explore the long-term effects of implantation as a function of performance over time, reimplantation, and educational factors. STUDY DESIGN AND SETTING: We studied 81 children who received implants at a major academic medical center and were followed for 5 to 13 years. RESULTS: Results revealed significant gains in speech perception, use of oral language, and ability to function in a mainstream environment. There was no decrease in performance over time and no significant incidence of device or electrode migration or extrusion, and device failure did not cause a deterioration in long-term outcome. CONCLUSIONS: Multichannel cochlear implants in children provide perception, linguistic, and educational advantages, which are not adversely affected by long-term electrical stimulation.