New perspectives on use of thymic factors in immune deficiency.

Current knowledge on the role of thymic factors in the immune response is inadequate and remains relatively primitive when compared with present technical possibilities for assessing lymphocyte subsets or cytokine interaction. New studies support the potential importance of thymic factors as regulators of immune interactions. Indirect evidence supports the concept that thymic factors may work at the level of IL-2. The functional identity of cells responsive to thymic factors and the relation of observed effects to cytokine network interactions need to be established. The use of thymic factors in the future will depend on the development of criteria to identify appropriate settings in which to use such factors and the implementation of appropriate measures of immune functional response.

Characterization of thermosensitive chitosan gels for the sustained delivery of drugs.

The aim of this study was to investigate the physical properties of a chitosan/glycerophosphate (GP) thermosensitive solution which gels at 37 degrees C and evaluate the in vitro release profiles of different model compounds. The gelation rate was dependent on the temperature and on the chitosan deacetylation degree. The solution containing 84%-deacetylated chitosan could be stored 3 months at 4 degrees C without apparent change in viscosity. The in vitro release profiles of the model compounds depended on the presence of GP in the chitosan solution, on their molecular weight and on the presence of lysozyme in the release media. They were not affected by the electrostatic charge of the model compound when present at low concentrations. During the first 4 h, the release was accompanied by a substantial loss of the gel weight which was mainly attributed to the leaching of water and excess GP. Scanning electron micrographs revealed that the solutions yield gels with a highly porous structure after 24 h of exposure to a continuous flow of phosphate buffered saline. These results indicate that the chitosan/GP thermosensitive solutions gel rapidly at body temperature, can remain in the sol state at 4 degrees C and can sustain the delivery of macromolecules.

Pigmented villonodular synovitis in a child.

The authors present a case of pigmented villonodular synovitis (PVNS) in an adolescent with monarticular involvement of the ankle and without congenital anomalies or sibling involvement. Its rarity in the ankle and in childhood is discussed; a review of the clinical, radiological, and pathological features of PVNS is presented.

Neurobehavioral tests as a medical surveillance procedure: applying evaluative criteria.

Neurobehavioral impairment is among the earliest indicators of a toxic insult on the nervous system. Neurobehavioral tests measure behavior impairment by noninvasive procedures that assess various performance and personality changes. Neurobehavioral tests have been used on groups of workers included in epidemiologic research studies; however, their suitability for an ongoing medical surveillance program for workers exposed to neurotoxic agents has not been evaluated. In Ontario, Canada, a set of validity criteria must be met to determine whether a medical procedure may be prescribed for a specific medical surveillance program. The evaluative criteria are standards for judging the desirability of a procedure based on social values and scientific considerations. In this paper, various studies using neurobehavioral tests are reviewed, and the validity of using these procedures for medical surveillance is evaluated by applying the Ontario evaluation criteria. The conclusion is that neurobehavioral tests are useful for well-controlled, cross-sectional studies, but they do not yet meet the validity criteria for procedures prescribed in an ongoing medical surveillance program for workers exposed to neurotoxic agents.

Unemployment and health: physicians' role.

Unemployment has been documented to have detrimental impacts on a person's mental, physical and social well being. When unemployment or being out of work is due to injury or sickness, the effects are compounded by mental and social factors. In an effort to prevent prolonged unemployment due to injury or sickness, changes were made to existing disability income supplement plans to redirect their focus from basic income support to active employment measures. This is intended to reduce individual's dependency on financial assistance and encourage individuals to take personal responsibility for getting back to work. The various disability insurance plans require primary care physicians to provide opinion and participate in the recovery and safety return to work of injured or sick persons. The physician approach to medical care of the injured/sick person with employment problems should focus on return to work as a goal of treatment. The patient should be seen as part of a social or environmental system and not as an isolated individual. The physician has a significant role to play in the diagnosis, determining functional abilities and participation in the return to work plan. The physician positive participation, not only provides an intrinsic cost saving value in insurance costs, but more important, helps patients maintain gainful employment. Work often helps in regaining health. Many factors are involved in a return to work outcome and physicians need to know how to identify and track the factors that facilitate or impede return to work. The challenge for the physician is to utilize the available resources to facilitate the recovery and communicate with other parties involved in the return to work process. This paper discusses the disability insurance plans in Canada and the community expectations from physicians dealing with patients who are out of work because of injury or sickness. It is acknowledged that primary care physicians' skills are not adequate in this area and that there is a need for continuing medical education to prepare them for this new role. Relevant topics should be introduced in medical curricula.

Follow-up of a group of workers intoxicated with 4,4'-methylenedianiline.

4,4'-Methylenedianiline (MDA), an aromatic amine, is a known human hepatotoxin and an animal carcinogen but there is little information regarding its chronic effects in humans. Between 1967 and 1976, 10 workers at a plant in Ontario that used MDA as an epoxy hardener developed acute jaundice. We followed this group from the date of intoxication through to the end of 1991 for cancer incidence by matching with the Ontario Cancer Registry. To date, one cancer, a pathologically confirmed bladder cancer has developed (expected number based on provincial incidence rates: 0.64 for all cancers, 0.05 for bladder cancer). This finding may be important because bladder cancer was a site of interest a priori; bladder cancers have been observed in two other occupationally exposed groups (significantly higher than expected in one of these); in the National Toxicology Program bioassay, urinary bladder tumors occurred in exposed animals but not in controls; and MDA has structural similarity to known human bladder carcinogens such as benzidine.

Occupational chemical exposures in artificial organic fiber industries.

This review discusses artificial organic fibers that are produced from materials of natural origin such as rayons, cellulose triacetates and proteins; or made from polymerised chemicals such as polyamides, polyesters, polyvinyls, modacrylics, carbon fibers, polyolefins, polyurethane and polytetrafluoroethylene. Chemicals involved include monomers, solvents, flame retardants, pigments and other additives. Occupational exposure to chemicals in the production stages are discussed and also the potential health hazards involved are reviewed. Current exposure levels, engineering controls and work practices for some of the chemicals used in the Ontario artificial fiber industry are discussed. Recommendations are made for areas that need further study and/or investigation.

Active calcium ion transport Xenopus laevis skin.

The skin of intact, free-swimming Xenopus laevis transports Ca2+ inwardly in a manner that is proportional to the external [Ca2+] up to about 0.3 mmol.l-1, saturates above 0.3 mmol.l-1, and is opposed to the electrochemical gradient. Efflux is relatively constant at external concentrations between 0.016 and 0.6 mmol.l-1; net flux which is negative below 0.125 mmol.l-1 becomes positive above this external [Ca2+]. Allometric analysis suggests that both Ca2+ influx and efflux scale to the 2/3 power approximately like surface area. There were no significant differences in influx between summer and fall animals; however, efflux was greater in the fall and this resulted in a change from positive balance in the summer to negative balance in the fall. Isolated skins were shown to support a Ca2+ uptake rate of nearly 30 nmol.cm-2.h-1. The phenylalkylamine verapamil in the apical bathing solution significantly inhibited this at 25 mumol.l-1. The benzothiazepine diltiazem was also effective at 50 mumol.l-1 while the dihydropyradine nifedipine was ineffective up to 100 mumol.l-1. The inorganic ion La3+ was effective at blocking Ca2+ uptake at 300 mumol.l-1; Ni2+ was also effective at 500 mumol.l-1 but Co2+ was ineffective up to 500 mumol.l-1. These results suggest that apical calcium channels in Xenopus laevis skin have properties similar to mammalian L-channels and fish gill Ca2+ channels.

A review of health risks in acrylonitrile industry.

The Occupational Health Branch of the Ontario Ministry of Labour began a study in 1978 for the evaluation of health risks associated with acrylonitrile (AN) exposure. Detailed hygiene and medical investigations were conducted in fourteen plants for evaluating AN exposure in various industrial processes. For companies were also studied in relation to mixed chemical exposure representing acrylic fibres, nitrile rubber, ABS-resin, and acrylic emulsions production. The possible interaction between AN and other coexisting chemical exposures was reviewed since dimethyl formamide, styrene, and butadiene have similar pharmacokinetics and possible synergistic effects. Exposure in acrylic fibre production may be synergistic and carcinogenic. Results of air monitoring indicated exposure levels to AN below 2 ppm (TWA) in most cases. Exposure to other co-existing chemicals was evaluated. Results of medical tests indicated no significant abnormalities in chest x-rays or liver function tests in currently exposed workers.

Health effects associated with exposure to anaesthetic gases in Ontario hospital personnel.

In a retrospective study (by questionnaire) of 8032 personnel exposed to anaesthetic gases in operating and recovery rooms in Ontario hospitals, and 2525 non-exposed hospital staff, the response was 78.8% for the exposed and 87.2% for the unexposed personnel during the period 1981-5. Logistic regression analysis, with age and smoking standardised, showed that women in the exposed group had significantly increased frequencies of spontaneous abortion and their children had significantly more congenital abnormalities (p less than 0.05). No chronic disease was significantly associated with the exposed group. These findings, together with similar ones from other studies, suggest that it is prudent to minimise exposure to waste anaesthetic gases.

Hygiene aspects of occupational exposure to waste anaesthetic gases in Ontario hospitals.

Exposure of workers to waste anaesthetic gases in the operating and recovery rooms of hospitals is an ongoing concern because a number of epidemiological and mortality studies have reported significant adverse effects. To evaluate the health risks if any, and to assist in the development of guidelines or regulations for the hospital sector in Ontario, the Health and Safety Support Services Branch of the Ontario Ministry of Labour conducted this extensive study. The results of the hygiene study show that exposure to waste anaesthetic occurs because of leaks in the anesthetic equipment. The three major sources of leaks (i.e. exhalation valves, masks and high-pressure fittings) produced concentrations above the limit of detection of nitrous oxide (1000 ppm of N2O) in a significant number of samples. Of the samples taken at leak sources those taken at the exhalation valve had the highest percentage of samples above 1000 ppm, which suggested that scavenging systems were not receiving proper service and maintenance. Only 23% of the operating rooms surveyed met the Ontario Ministry of Health Criterion of 24 air changes per hour. Dilution ventilation was less effective than scavenging in keeping down concentrations of air contaminants. The sampling data show that the anaesthetists have the highest time-weighted average exposure (median value range 56-79 ppm) of the major group of occupations surveyed and that the general surgeons' TWA is much lower (28 ppm). It was concluded that the dilution ventilation rate of 24 air changes per hour should be maintained in all operating rooms and that there should be no recirculation of exhaust air when operations are in progress. To keep down concentrations of anaesthetic gases scavenging systems should be provided in all operating rooms. In each hospital maintenance should be the responsibility of a qualified staff member who has been adequately trained in the repair and maintenance of anaesthetic delivery systems. Finally, a qualified staff member should be responsible for conducting periodic personal monitoring in operating rooms (ORs) and recovery rooms (RRs) and the sampling strategy should include individuals and the exhaust grilles.

The capillary transport system for free fatty acids in the heart.

The nature of the process by which free fatty acids, which are tightly bound to albumin, traverse the endothelium of cardiac capillaries to reach the cardiac muscle cells, so that they are extracted to a net extent of approximately 40%, needs clarification. Previous studies have indicated that a membrane fatty acid-binding protein provides for carrier-mediated uptake of free fatty acids by isolated hepatocytes, cardiomyocytes, and jejunal mucosal cells. A monoclonal monospecific antibody was prepared against purified membrane fatty acid-binding protein from rat liver. Multiple-indicator dilution experiments were carried out in the isolated rat heart with labeled albumin, sucrose, and palmitate in the presence of control perfusate or perfusate containing either specific antibody or comparable nonspecific myeloma cell supernatant (each of the latter containing additional albumin, in identical concentrations). Analysis of the labeled-sucrose curves provided a permeability-surface area product for sucrose to which that for palmitate could be compared. In comparison with control supernatants, myeloma supernatant produced a minor inhibition of palmitate uptake, as a result of the increase in albumin concentration. The specific antibody, which contained identical albumin concentrations, produced a major inhibition of palmitate uptake, significantly greater than with the myeloma supernatant. The data indicate that the membrane fatty acid-binding protein mediates the transfer of free fatty acid across the endothelial cells of cardiac capillaries for presentation to heart muscle. Passive intramembrane lateral diffusion of palmitate could not provide an explanation for the findings.

Flow-limited tracer oxygen distribution in the isolated perfused rat liver: effects of temperature and hematocrit.

We used the multiple-indicator dilution technique to examine the kinetics of tracer oxygen distribution and uptake in the rat liver perfused in a nonrecirculating fashion with blood. 51Cr-labeled 18O2-saturated erythrocytes, labeled albumin, sucrose and water (the tracers for oxygen and vascular, interstitial and cellular references) were injected simultaneously into the portal vein. Timed anaerobic samples were collected from the hepatic vein and analyzed by mass spectrometry for relative 18O2 enrichment and radioactivity. In a set of experiments performed at 32 degrees C, oxygen uptake was substantially diminished; tracer oxygen profiles approached those expected for a completely recovered, flow-limited substance. At 37 degrees C, much larger tracer oxygen sequestration occurred. Experiments were carried out at each temperature at higher and lower hematocrit, and oxygen consumption at each temperature was found to be independent of hematocrit. The tissue space of distribution for tracer oxygen relative to the total sinusoidal vascular content was influenced by the hematocrit: it was smaller at higher hematocrit and larger at lower hematocrit, as expected. The derived partition coefficient of oxygen for liver cells relative to plasma (expressed in terms of the liver and plasma water spaces) was, on average, 2.62 ml/ml; it was independent of the hematocrit. Analysis of the indicator dilution experiments indicates that the tracer oxygen is distributed into tissue in a flow-limited rather than a barrier-limited fashion, and that with this, an ongoing concomitant intracellular sequestration of tracer can be seen.

Respiratory variables and exposure-effect relationships in isocyanate-exposed workers.

Respiratory variables in 95 isocyanate workers and 37 control workers were compared. The exposed workers had a slightly higher frequency of cough and shortness of breath than the controls and a significantly lower frequency of family history of asthma, hay fever, and bronchitis. The isocyanate workers had slightly lower baseline lung function than the control workers but demonstrated significantly larger declines in their pulmonary function over the work shift. Both groups showed some intraday and intraweek variation in lung function. The changes in lung function over the work shift varied with different job categories, the largest changes occurring in finishing-area workers. A gradation of response was observed when exposure was categorized as nil, low, or high, but no exposure-effect relationships could be demonstrated by regression analysis of either area or personal results.