Limited junctional diversity of Vδ5-Jδ1 rearrangement in multiple sclerosis patients

T-cell receptor (TCR) δ gene repertoire, as assessed by Vδ-Jδ rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30 healthy individuals by seminested PCR technique. Among the Vδ-Jδ junctional diversities studied, the most striking result has been observed in Vδ5-Jδ1 rearrangement. The detection of repeated Vδ5-Jδ1 nucleotide sequences in all analyzed clones from seven out of nine patients studied proved the monoclonal nature of γ δ T-cells with Vδ5-Jδ1 rearrangement. The clonal nature of this rearrangement proved by PAGE and sequencing analysis may suggest an antigen-driven expansion of γδT cells and argues for a significant role of γδ T-cells with Vδ5-Jδ1 rearrangement in MS pathogenesis. However, it cannot be excluded that clonal expansion of these lymphocytes may represent secondary change to central nervous system damage.     

Muscle metabolism from near infrared spectroscopy during rhythmic handgrip in humans

The rate of metabolism in forearm flexor muscles (MO₂) was derived from near-infrared spectroscopy (NIRS-O₂) during ischaemia at rest rhythmic handgrip at 15% and 30% of maximal voluntary contraction (MVC), post-exercise muscle ischaemia (PEMI), and recovery in seven subjects. The MO₂ was compared with forearm oxygen uptake (O₂) [flow?×?(oxygen saturation in arnterial blood-oxygen saturation in venous blood, S _aO₂?S _vO₂)], and with the ³¹P-magnetic resonance spectroscopy-determined ratio of inorganic phosphate to phosphocreatine (P_I:PCr). During ischaemia at rest, the fall in NIRS-O₂ was more pronounced [76 (SEM 3) to 3 (SEM 1)%] than in S _vO₂ [71 (SEM 3) to 59 (SEM 2)%]. During the handgrip, NIRS-O₂ was lower at 30% compared to 15% MVC [58 (SEM 3) vs 67 (SEM 3)%] while the S _vO₂ was similar [29 (SEM 3) vs 31 (SEM 4)%]. Accordingly, MO₂ as well as P_I:PCr increased twofold, while V˙O₂ increased only 30%. During PEMI after 15% and 30% MVC, NIRS-O₂ fell to 9 (SEM 1)% and “0”, but the use of oxygen by forearm muscles was not reflected in S _vO₂. During reperfusion after PEMI, the peak NIRS-O₂ was lowest after intense exercise, while for S _vO₂ the reverse was seen. The discrepancies between NIRS-O₂ and S _vO₂, and therefore between the estimates of the metabolic rate, would suggest significant limitations in sampling venous blood which is representative of the flexor muscle capillaries. In support of this contention, S _vO₂ and venous pH decreased during the first seconds of reperfusion after PEMI. To conclude, NIRS-O₂ of forearm flexor muscles closely reflected the exercise intensity and the metabolic rate determined by magnetic resonance spectroscopy but not that rate derived from flow and the arterio-venous oxygen difference.     

Grip force behavior in Gilles de la Tourette syndrome.

We analyzed predictive and reactive grip force behavior in 15 patients with Gilles de la Tourette syndrome (GTS) and 15 sex- and age-matched healthy control subjects. Nine patients were without medication; six patients were on medication. In a first experiment, participants lifted and held instrumented objects of different weight. In a second experiment, participants performed vertical point-to-point and continuous arm movements at different frequencies with a hand-held object. In a third experiment, preparatory and reactive grip force responses to sudden load perturbations were analyzed when a weight was dropped into a hand-held cup either by the subject or unexpectedly by the experimenter. Compared to the healthy subjects, GTS patients had increased grip forces relative to the load force in all tasks. Despite this finding, they adjusted the grip force to changes in load force (due to either a change in the mass lifted or accelerating the mass during continuous movements) in the same way as healthy subjects. The temporal coupling between grip and load force profiles was also similar in patients and healthy controls, and they displayed normal anticipation of impact forces when they dropped a weight into a hand-held cup. We found no significant effect of medication on the performance of GTS patients, regardless of the task performed. These results are consistent with deficient sensory-motor processing in Gilles de la Tourette syndrome.     

Herzversagen nach Appendektomie

We report on a 5-year-old girl who developed heart failure after an initially uneventful clinical course following a noncardiac surgical procedure. Echocardiographic examination showed severe myocardial dysfunction of both ventricles. The patient died on the 3rd postoperative day in low output failure and electromechanical dissociation. At autopsy total absence of myocardial tissue of the right ventricular free wall with severe lipomatous transformation was found. This abnormality appears clinically as an "arrhythmogenic right ventricle" in most of the cases. Therefore, severe dysrhythmia or myocardial dysfunction may have been the leading factors in the development of congestive heart failure with a deleterious outcome.     

Neurotensin stimulates the growth and secretion of rat adrenal zona glomerulosa.

Within 2 days neurotensin (NT) and ACTH administrations markedly enhanced the average volume of zona glomerulosa (ZG) cells and plasma aldosterone concentration (PAC) in intact rats. In dexamethasone-treated rats, both NT and ACTH evoked a clearcut ZG-cell hypertrophy, but only NT was able to raise PAC. In conclusion, our findings indicate that NT is a potent stimulator of the growth and secretion of rat ZG in vivo, and suggest that the mechanism underlying this action of NT does not involve the well-known NT-induced stimulation of ACTH release.     

Influence of cyproheptadine on endotoxin-induced disseminated intravascular coagulation (DIC) in weaned pigs

Changes in the coagulation system typical of consumption reaction, microthrombosis in the lungs and other organs and haemodynamic disturbances caused by infusion of endotoxin in weaned pigs were prevented by treatment with the serotonin receptor antagonist cyproheptadine.     

Increased hydrogen peroxide in the exhaled breath of uraemic patients unaffected by haemodialysis.

BACKGROUND: Uraemia is accompanied by conditions favouring the rise of H2O2 activity in body fluids. This results from the increased release of H2O2 by polymorphonuclear leukocytes and decreased plasma glutathione peroxidase activity. The purpose of this study was to determine if patients on chronic haemodialysis (HD) exhale more H2O2 than healthy individuals, and if dialysis affects breath H2O2 content. METHODS: We studied 29 chronic HD patients (mean age 49 +/- 11 years) and 40 healthy persons (mean age 44 +/- 9 years). H2O2, which is volatile, was measured fluorimetrically with the homovanillic acid method in the exhaled breath condensate (EBC) of the study cohort. EBC was collected immediately before and after the HD session and also at 20 and 60 min of HD treatment (n = 14) and once in controls. Peak expiratory flow (PEF), white blood cell (WBC) count, PaO(2) and circulatory cyclic guanosine monophosphate (cGMP), Il-6 and Il-8 concentrations were measured concomitantly. Finally, H2O2 diffusion through the dialyser cuprophane membrane was determined in an in vitro experiment. RESULTS: At baseline, EBC H2O2 concentration was 22 times higher in HD patients than in controls (2.92 +/- 4.64 vs 0.16 +/- 0.13 microM, P < 0.001). Although the maximum decrease in PEF (431 +/- 52 vs 398 +/- 56 l/min, P < 0.01) and WBC count (6.72 +/- 1.02 vs 3.82 +/- 1.51 x 10(3)/ microl, P < 0.01) occurred at 20 min after the start of HD, no significant changes in breath H2O2 levels were noted throughout the session. Plasma IL-6 and IL-8 levels remained unchanged whereas cGMP rose 1.3 times at 60 min (P < 0.01). In vitro, H2O2 rapidly diffused through the cuprophane membrane. CONCLUSION: Chronic HD patients exhale more H2O2 than healthy subjects. Although no change of breath H2O2 concentration was observed during HD, as H2O2 easily diffuses through the dialyser membrane, it is not possible to rule out that HD stimulates H2O2 generation.