Phenotypes and spontaneous cell cytotoxicity of mononuclear cells from patients with seronegative spondyloarthropathies: Ankylosing spondylitis,psoriatic arthropathy and pauciarticular juvenile chronic arthritis — Analysis of mononuclear cells from peripheral blood,synovial fluid and synovial membranes

Summary T-cell subpopulations and natural killer (NK) cells from peripheral blood, synovial fluid and synovial membranes from patients with seronegative spondyloarthropathies were investigated. Thirty-four patients with ankylosing spondylitis, sixteen patients with psoriatic arthropathy and six patients with pauciarticular juvenile chronic arthritis were studied. All the patient groups had normal proportions of T4⁺ and T8⁺ cells as well as normal T4/T8 ratios in peripheral blood. In the synovial fluids the T4/T8 ratios were reduced in ankylosing spondylitis and psoriatic arthropathy (p<0.05). Although both the T4 and T8 subpopulations were reduced, the T4/T8 ratios in the synovial membranes of patients with these two disorders tended to be within the normal range of that of peripheral blood. Increased numbers of T-cells in the synovial fluid from patients with ankylosing spondylitis expressed class II MHC antigens. The natural killer cell activity was normal in peripheral blood and synovial fluids of patients with ankylosing spondylitis and psoriatic arthropathy while it tended to be reduced, although not significantly, in pauciarticular juvenile chronic arthritis. Synovial membranes were almost devoid of NK cell activity. The number of Leu 7⁺ cells were reduced in synovial fluid of patients with psoriatic arthropathy (p<0.04), but not as significantly as in the two other patient groups.     

Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment

Summary The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p<0.05). Plasma oestrone was suppressed by a mean of 40.6% (p<0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p<0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.     

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.     

The effect of quinidine on the analgesic effect of codeine

Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l^–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l^–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results.     

Bronchial response to breathing dry gas at 3.7 MPa ambient pressure

In diving, pulmonary mechanical function is limited by the increased density of the gas breathed. Breathing cold and dry gas may cause an additional increase in airways resistance. We have measured forced vital capacity, forced expired volume in 1 s (FEV₁) and forced midexpiratory flow rate (FEF_25%–75%) before and after breathing dry or humid gas at 29–32°C during a standardized exercise intensity on a cycle ergometer at an ambient pressure of 3.7 MPa. The atmosphere was a helium and oxygen mixture with a density of 6.8 kg · m^–3. Six professional saturation divers aged 26–37 years participated in the study. There were no significant differences in convective respiratory heat loss between the exposures. The mean evaporative heat loss was 67 W (range 59–89) breathing dry gas and 37 W (range 32–43) breathing humid gas, corresponding to water losses of 1.7 g · min^–1 (range 1.5–2.2) and 0.9 g · min^–1 (range 0.8–1.1), respectively. There was a significant reduction in FEV₁ of 4.6 (SD 3.6)% (P<0.05), and in FEF_25%–75% of 5.8 (SD 4.7)% (P<0.05) after breathing dry gas. There were no changes after breathing humid gas. By warming and humidifying the gas breathed in deep saturation diving bronchoconstriction may be prevented.     

Physical activity is associated with a low prevalence of musculoskeletal disorders in the Royal Norwegian Navy: a cross sectional study

Background  

Despite considerable knowledge about musculoskeletal disorders (MSD) and physical, psychosocial and individual risk factors there is limited knowledge about physical activity as a factor in preventing MSD. In addition, studies of physical activity are often limited to either leisure activity or physical activity at work. Studies among military personnel on the association between physical activity at work and at leisure and MSD are lacking. This study was conducted to find the prevalence of MSD among personnel in the Royal Norwegian Navy and to assess the association between physical activity at work and at leisure and MSD.     

Fluctuations in tumor blood perfusion assessed by dynamic contrast-enhanced MRI.

Temporal heterogeneity in blood perfusion is a common phenomenon in tumors, but data characterizing the nature of the blood flow fluctuations are sparse. This study investigated the occurrence of blood flow fluctuations in A-07 melanoma xenografts by using gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced MRI (DCE-MRI). Each tumor was subjected to two DCE-MRI acquisitions separated by 1 hour. The data were processed by Kety analysis and resulted in two E.F images (E is the initial extraction fraction of Gd-DTPA and F is the perfusion) and two lambda images (lambda is the partition coefficient of Gd-DTPA) for each tumor. The E . F images were used to determine the changes in blood perfusion arising in the time between the two imaging sequences. The lambda images were used to control the reproducibility of the experimental procedure. The study showed that DCE-MRI with subsequent Kety analysis is a useful method for detection of blood flow fluctuations in A-07 tumors, and strongly suggested that the peripheral regions of A-07 tumors are more exposed to temporal changes in blood perfusion than are the central regions.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Frequency and causes of shunt revisions in different cerebrospinal fluid shunt types

Summary Shunt complications and revisions are common in hydrocephalic patients treated with a ventriculo-atrial or a ventriculo-peritoneal shunt. The reported revision rate differs very much but the rate of revision is close to 50% in many papers. Data from 884 hydrocephalic patients treated with various shunt types in the period 1958–1989 were recorded retrospectively in order to evaluate the frequency of revision for various shunt types and secondly to analyse the specific reasons for the shunt revisions.The rate of shunt revision was 45%. The Pudenz shunt was revised more often (62%) than the remaining shunt types. The Hakim and the Orbis-Sigma shunts had fewer revisions (35% and 27%, respectively) than the other observed shunt types. A defect of or an obstruction in the ventricular catheters was a frequent cause of revision followed by a defect or an obstruction of the distal catheter, a displacement of the distal catheter and an acute infection. Because of the higher rate of revision for the Pudenz shunt the rate of the above mentioned specific complications is also higher in most of the subgroups for that specific shunt type. Driven by these experiences it is reasonable to seek to develop and introduce new shunt types in an attempt to reduce the complication rate.     

Electromyography of the internal anal sphincter performed under endosonographic guidance description of a new method

PURPOSE: The aim of our study was to investigate internal anal sphincter electromyographic signals. METHODS: Electromyography of the internal anal sphincter was performed with platinum wire electrodes in six healthy volunteers (three males and three females), inserted under endosonographic guidance. Platinum wire electrodes were also inserted into the external anal sphincter. Activity of both the internal and external anal sphincter in a 40-second period was measured. RESULTS: Internal anal sphincter median activity was 22.1 (range, 5.5–67.6) μ V. Slow-wave activity was 47 cycles/minute (range, 34–55 cycles/minute). After inflation of a rectal balloon with air until a constant relaxation of the anal canal was obtained, a decrease in internal anal sphincter activity to 15.9 (1.2–31.3) μV as well as a decrease in slow-wave activity to 34 cycles/minute (range, 27–40 cycles/minute) was found. The original internal anal sphincter EMG was resumed after deflation of the rectal balloon. External anal sphincter median activity was 31 (range, 0.77–18.6)μV. During inflation of the rectal balloon, a reflex increase in external sphincter EMG activity was found. With the rectal balloon fully inflated a part of this increase was still present, 11.0 (1.9–24.6)μV. In some of the subjects, this increased activity was superimposed on the internal anal sphincter recordings as well. During a voluntary squeeze it was not possible to identify internal anal sphincter activity due to activity of the external anal sphincter totally overriding the internal anal sphincter signal. CONCLUSION: Precise EMG recordings from the internal anal sphincter is possible with endosonographic guidance of the electrodes, except during voluntary squeezing of the external anal sphincter.