Hyperventilation provokes symptoms of carpal tunnel syndrome.

Hyperventilation causes respiratory alkalosis. The nervous system is more excitable in alkalosis. This phenomenon can be observed as paraesthesia in fingers and toes as well as around the lips in anxious patients breathing rapidly. We wanted to test this phenomenon on already irritable nerves like the median nerve in carpal tunnel syndrome (CTS). We deployed 50 patients who came in to the day case unit for carpal tunnel decompression with electro-physiologically proven diagnosis. We devised a test whereby patients were made to hyperventilate under prescribed conditions and repeated Phalen's test and Tinel's sign for comparison. These were compared with a control group chosen randomly among hospital staff. 86% patients had a positive result which was just behind Phalen's test in sensitivity. It was also 100% specific as there were no false positives. Hyperventilation is a phenomenon which provokes carpal tunnel syndrome. Its clinical value remains to be seen due to cumbersome method and probable patient non-compliance but it is a new discovery. It may be useful in other irritable-nerve-syndromes as a test to add to our available armament. It may be an additional factor or a primary reason for nocturnal paraesthesias in CTS patients.

Perforin-positive cytotoxic lymphocytes in pregnancy.

OBJECTIVE: To investigate whether perforin-positive, cytotoxic lymphocytes are present in the first and second trimester as well as at term during normal gestation. STUDY DESIGN: A monoclonal antibody raised against human perforin was used to detect perforin expression in mononuclear cells in first-trimester abortion, second-trimester preterm labor due to cervical incompetence and term placentas obtained after normal delivery. Fresh frozen tissue sections containing first- and second-trimester decidua and placental tissues as well as decidua of maternal and fetal surfaces of term placenta were stained using an immunoperoxidase method. RESULTS: Occasional perforin-positive lymphocytes were present in stroma of chorionic villi of term placenta, while most were found in decidua and coagulated blood in maternal vessels and intervillous spaces. The majority of these lymphocytes were CD3-, CD2+ and CD56+. Quantitative comparison of decidual perforin-positive lymphocytes demonstrated a relative increase in these lymphocytes in decidua of second-trimester and term placentas. CONCLUSION: The presence of perforin-positive cytotoxic lymphocytes in maternal blood and decidua during gestation suggests their roles in pregnancy.

3,4-Dichloroisocoumarin serine protease inhibitor induces DNA fragmentation and apoptosis in susceptible target cells.

3,4-Dichloroisocoumarin (DCI) inhibition of serine proteases generates reactive intermediates that have been theorized to affect apoptosis. To examine this possibility various target cells were treated with different concentrations of DCI and assessed for intracellular nuclear DNA fragmentation and apoptosis. DCI treatment caused oligonucleosomal DNA fragmentation in cell lines expressing high levels of protease activity (LAK cells, NK-92, CTLL-2, L929, 3T3). This DNA breakdown characteristic of apoptosis occurred in a dose-dependent fashion within 4-6 hr of treatment and was confirmed by electron microscopy. In cell lines expressing low levels of protease activity (unstimulated human peripheral blood mononuclear (PBMN) cells, YAC-1 cells), DCI effectively inhibited protease activity without inducing oligonucleosomal DNA fragmentation. ZN2+ ions significantly inhibited DCI-induced DNA degradation. The mixture of DCI and BLT esterase active NK cell lysate triggered DNA fragmentation in isolated YAC-1 nuclei. Degree of DNA fragmentation in YAC-1 nuclei was proportional to the level of BLT esterase activity. Cell lysate protease activity, initially inhibited by DCI acylation, was restored by hydroxylamine deacylation, thus preventing DCI-mediated DNA fragmentation. Our results suggest that DCI treatment of cells expressing high levels of protease activity generates toxic levels of acyl-enzyme intermediates. These intermediates may trigger nuclear DNA breakdown and apoptosis by activating endogenous endonucleases. This effect may compromise the analysis of apoptosis in experimental systems using high concentrations of DCI for extended periods.