Telemedicine for the International Space Station.

The medical care for the integrated crew of the International Space Station (ISS) will require close co-operation between the partner agencies in the areas of selection, medical surveillance, countermeasures, and handling of acute medical problems. Based on a commonly accepted policy of shared care and responsibilities medical guidelines, procedures, and standards for medical data and communication need to be harmonised under the responsibility of the Multilateral Medical Operations Panel (MMOP). A supporting telemedical network connecting the partners on an organisational and technical level will facilitate the harmonisation process and provide new tools for effective co-operation between medical professionals. Earth bound projects with similar application areas can profit from and contribute to this development and need to be considered for efficient implementation and exploitation.

A rapid fluorometric enzyme immunoassay for the determination of neonatal TSH from blood spots.

We describe a novel method for the detection of thyrotropin from dried blood spots using a horseradish peroxidase-labelled sandwich enzyme immunoassay with fluorometric detection. The detection limit of the present assay is 1.25 mIU/l with within-run and between-run imprecision being in the range 5.2 to 11.4%. The results of the assay correlate well with two commercial methods: an enzyme immunoassay (r = 0.93) and a time-resolved fluorescence assay (r = 0.90). The blood spot values also show a good correlation (r = 0.93) with respective values obtained from plasma using a commercial immunoradiometric method. The assay may also be performed colorimetrically with sensitivity similar to the fluorometric assay. However, the latter provides a wider dynamic range with an upper limit of 400 mIU/l while the colorimetric method reaches a plateau at 25 mIU/l. Due to its simplicity and rapid performance (3 h), the fluorometric assay is suitable for the routine screening of congenital hypothyroidism.

Diagnostic value of cerebrospinal fluid adenosine deaminase determination.

We measured the activity of adenosine deaminase (ADA) in the cerebrospinal fluid of 3 patients with tuberculous meningitis, 38 with viral meningitis, 15 with bacterial meningitis, 5 with malignant lymphoma, 11 with cerebrovascular diseases and 13 with miscellaneous neurological disorders. The highest ADA activities were observed in patients with tuberculous meningitis (median 21.3 U/l, range 20.0-23.0) and lymphoma (13.0 U/l, range 4.0-25.0). The sensitivity of the test for diagnosing tuberculous meningitis was 100% and the specificity 99% when a cut-off value of 20.0 U/l was used. We conclude that determination of ADA in cerebrospinal fluid is useful for the diagnosis of tuberculous meningitis, but that high activity also can be seen in some other CNS disorders, e.g. lymphoma with meningeal involvement.

Endogenous interference in immunoassays in clinical chemistry. A review.

The increasing availability and use of immunoassays in clinical chemistry have revealed a number of endogenous interferences. Solid-phase sandwich immunoassays based on monoclonal antibodies are particularly sensitive to any factor able to bridge immunoglobulins together. Heterophilic immunoglobulin antibodies have been demonstrated in up to 40% of patient samples and to cause spuriously elevated results unless certain precautions are taken. Rheumatoid factors belong to the same category, but their affinity is usually too low to cause significant interference. Immunoscintigraphy generates high-titre anti-immunoglobulin responses causing serious interferences in immunoassays. Recently interfering factors of unknown nature causing nonspecific binding of enzyme-labelled antibodies have been observed. Spuriously decreased values can be caused by complement, which may interfere with antigen-binding to solid phase antibody. The aforementioned and other endogenous interferences in immunoassays are reviewed and methods for their elimination discussed.

Immunocatalytic assay of pancreatic alpha-amylase in serum and urine with a specific monoclonal antibody.

In this immunocatalytic assay for alpha-amylase (EC 3.2.1.1) of pancreatic origin, a highly specific monoclonal antibody coupled to plastic beads is used to extract pancreatic amylase from samples, leaving salivary amylase in solution. The catalytic activity of the bound pancreatic amylase is then determined with blocked p-nitrophenyl maltoheptaoside as substrate. The method shows no cross-reactivity with salivary amylase, analytical recovery is 89-109% for pancreatic amylase, and interassay imprecision is 7.1-7.7%. We used the method to determine pancreatic amylase in serum and urine from healthy controls and different patient groups. The reference intervals for 34 supposedly healthy controls were: serum, 10-48 U/L (mean 27 U/L); urine, less than 20-435 U/L (mean 104 U/L). Results by the present assay correlated well with a salivary amylase inhibition assay (Boehringer Mannheim). We conclude that the described immunocatalytic assay is clinically useful for detecting increased activities of pancreatic amylase in serum and urine.

Adenosine deaminase activity in joint effusions.

The activity of adenosine deaminase (ADA) was determined in serum and synovial fluid of 98 patients with joint effusions of various causes. Compared with osteoarthritis, there were significantly higher mean synovial fluid ADA activities in seropositive rheumatoid arthritis (p less than 0.01), chronic seronegative polyarthritis (p less than 0.001), juvenile chronic arthritis (p less than 0.001) and reactive arthritis (p less than 0.001). In inflammatory joint diseases higher mean ADA activities in synovial fluid than in serum were observed, indicating a local release of ADA by cells within the joints. ADA activity in synovial fluid correlated with general disease activity as measured by haemoglobin concentration and erythrocyte sedimentation rate, and may provide an additional measure of the degree of inflammation in joint diseases.

Serum angiotensin converting enzyme in pneumonias.

Serum concentrations of angiotensin converting enzyme (ACE) were studied in pneumonias caused by different pathogens and in cases in which the aetiology could not be defined. In all aetiological groups, except in viral pneumonia, there was a significant increase in ACE during recovery (p less than 0.001). In several patients the lowest values during the acute phase of disease and the highest values during recovery were outside the reference limits. In cases with known aetiology the highest ACE values and the difference between the lowest and the highest values correlated positively with C-reactive protein concentrations at admission (p less than 0.001). The pathophysiology behind the fluctuations of the ACE concentrations is unknown.

Serum lipids in viral and bacterial meningitis.

The changes in serum triglycerides (Tg), cholesterol and high density lipoprotein (HDL) cholesterol were examined in 17 patients with viral (VM) and in 7 patients with bacterial (BM) meningitis. In VM, there were low values of cholesterol (p less than 0.001) and HDL cholesterol (p less than 0.01) on admission to hospital and a rise in Tg after 1 week (p less than 0.01). In BM, caused in 4 cases by meningococci and in 3 cases by various streptococci, both cholesterol and HDL cholesterol were decreased during the acute phase (p less than 0.001 and less than 0.02, respectively). Corresponding changes were observed when the meningococcal cases were treated as a separate group (p less than 0.02 and less than 0.05, respectively). On admission cholesterol and HDL cholesterol levels in BM were lower than those in VM (p less than 0.05 in each case). In VM, the changes in serum lipids did not correlate with the changes of protein and glucose levels or leucocyte counts in cerebrospinal fluid (CSF). In BM, protein concentration in CSF correlated negatively with serum Tg (p less than 0.01) and positively with HDL cholesterol (p less than 0.05); glucose concentration in CSF correlated positively with Tg (p less than 0.01). Our results emphasize the need for further investigation of the pathophysiological role of lipids in various infections.

Carcinoembryonic antigen (CEA) in blood in cases of pneumonia.

Serum levels of carcinoembryonic antigen (CEA) were analysed in patients with pneumonia of different etiology. Significant (p less than 0.01) increases in blood CEA levels occurred in all groups of pneumonia of bacterial etiology, i.e., pneumococcal, gram-negative or chlamydial. In viral pneumonia similar increases were observed, but the changes were not statistically significant, probably due to the small number of patients. In pneumonia of unknown etiology CEA behaved as in bacterial pneumonias. Maximal values between 5 and 15 micrograms/l CEA were common in pneumonia, the basal level usually being less than 5 micrograms/l. The severity of pneumonia, as judged by maximal erythrocyte sedimentation rate, correlated weakly with CEA levels in the bacterial group (p less than 0.05). In pneumonias of unknown etiology white blood cell counts and C-reactive protein levels correlated significantly with maximal CEA (p less than 0.01). In conclusion we have demonstrated, that in pneumonias of different etiology strongly but transiently increased blood CEA levels are the rule. The severity of pneumonia is not clearly correlated with CEA levels.

Diagnostic significance of pleural fluid lactate concentrations.

Lactate concentrations in the pleural fluid and plasma of 57 patients with pleural effusions were measured by an enzymatic method. The mean pleural fluid lactate concentrations were significantly higher in patients with empyemas and rheumatoid arthritis than in patients with tuberculosis, cancer, non-specific pleural effusions and congestive heart failure. Pleural fluid lactate concentrations correlated significantly with pleural fluid lactate dehydrogenase activities and inversely with pleural fluid glucose concentrations. An elevated pleural fluid lactate concentration is not diagnostic for empyema, as most patients with rheumatoid arthritis and some with tuberculosis and cancer also show high values.

Peripheral blood lymphocyte subsets in radiologists exposed to ionizing radiation.

To investigate whether low dose ionizing radiation caused perturbation of peripheral blood lymphocytes in radiology unit staff, the T-helper/suppressor ratio was examined in eight radiologists exposed to low dose radiation over a period of 6 to 27 years (mean 12 years). No significant difference was noted in the T-cell subsets between exposed radiologists and non-exposed control subjects. The effect of low dose ionizing radiation on peripheral blood lymphocyte subsets seems to be virtually negligible. Further, measurement of the T-helper/suppressor ratio is not a reliable way of demonstrating any damage to bone marrow caused by low dose ionizing radiation.

Adenosine deaminase in the diagnosis of pleural effusions.

The activity of adenosine deaminase (ADA) was determined in serum and pleural fluid of 90 patients with pleural effusions of various aetiology. Tuberculous pleural effusions, empyemas and rheumatoid pleural effusions demonstrated significantly higher activities of ADA than parapneumonic , nonspecific and malignant pleural effusions and effusions in systemic lupus erythematosus and congestive heart failure. In tuberculosis, empyema and rheumatoid arthritis ADA activity was significantly higher in pleural fluid than in serum, indicating a local synthesis of ADA by cells within the pleural cavity in these diseases.

The differential diagnosis of bacterial and aseptic meningitis using cerebrospinal fluid laboratory tests.

The lactate, lysozyme, C-reactive protein and serum amyloid-A protein concentrations in cerebrospinal fluid were measured in 11 patients with bacterial meningitis, 27 patients with aseptic meningitis and in 31 control patients. The mean concentration of each parameter was significantly higher (p less than or equal to 0.0001) in patients with bacterial meningitis than in those with aseptic meningitis or those without meningitis. The reliability of these tests in the differential diagnosis of bacterial and aseptic meningitis was compared with leucocyte counts in cerebrospinal fluid. Gram staining for bacteria, and protein and glucose levels. The cerebrospinal fluid lactate level proved to be more sensitive than lysozyme. C-reactive protein or serum amyloid-A protein and had a high degree of specificity.

Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and parathyroid hormone in patients with femoral neck fracture in southern Finland.

Serum concentrations of 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D] and immunoreactive parathyroid hormone (PTH) were determined in elderly patients with fracture of the femoral neck and in age-matched controls during summer, winter and early spring in southern Finland. The expected seasonal variation in 25-OHD values was observed in both patients and controls, though the patient group had significantly lower values during winter (P less than 0.02) and spring (P less than 0.01). The 24,25(OH)2D:25-OHD ratio remained constant in both patients and controls throughout the study. A significant negative correlation between PTH and 25-OHD values was found in the patient group. Thus, vitamin D deficiency may contribute to the high incidence of femoral neck fractures in elderly people, and the increased PTH activity, observed in many patients with these fractures, is secondary to vitamin D deficiency.

In vitro production of leucocyte migration inhibitory factor by lymphocytes in exudative pleural effusions.

The indirect leucocyte migration inhibition test was used to investigate production of leucocyte migration inhibitory factor (LIF) by lymphocytes from pleural fluid and peripheral blood. The samples were taken from 19 patients with exudative pleural effusion resulting from malignant disease (n = 9), tuberculosis (n = 5) and nonspecific causes (n = 5). The lymphocytes were cultured in the presence of leucoagglutinin (LA) and purified protein derivative (PPD) and without mitogen or antigen. Although LIF production varied widely, pleural fluid lymphocytes from patients with benign diseases produced significantly more LIF in response to LA than pleural fluid lymphocytes from patients with malignant disease. In comparison to peripheral blood, the LA induced LIF production by pleural fluid lymphocytes was significantly enhanced in patients with nonspecific pleural effusion and significantly reduced in patients with malignant disease. However, pleural fluid lymphocytes from four patients with malignant disease produced LIF spontaneously, suggesting that they were already stimulated in vivo. In tuberculous pleural effusions the percentage of macrophages correlated negatively with the LIF production induced by LA and PPD. Lymphokines produced by sensitized lymphocytes in pleural fluid may be important in the local response to infectious agents and tumour growth by affecting the cellular composition of the effusion.

Leucocyte migration inhibition assay from clotted plasma droplets.

Two different techniques for performing leucocyte migration inhibition factor (LIF) assays were compared. A clotted plasma droplet LIF assay gives similar results as the conventional capillary tube method, but it is more sensitive and technically simpler to perform, and less blood is required for the assay. The plasma droplet method is suitable for particulate (BCG) as well as soluble (PPD) antigens, provided that the culture medium is supplemented with horse or human serum. If foetal calf serum is used no inhibition can be demonstrated with soluble antigen. Defibrinated blood gives the most clear-cut results and LIF activity can still be detected even after 24 hours storage of samples. EDTA anti-coagulated blood can alternatively be used, but it is less stable. The assay can still be performed after 3 hours storage of the blood, although the migration inhibition is decreasing. After 24 hours storage EDTA anticoagulated blood cannot be used for LIF assays.