Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics.

Lysis of nucleated cells by complement was studied to determine whether the lytic process by C5b-9 conforms to a one-hit mechanism as in the case of erythrocytes. Two nucleated cell lines, Molt 4 and U937, derived from human T lymphocytes and histiocytes, respectively, were employed as targets. The antibody-sensitized cells were used to develop the titration curves, measuring cell death as a function of limiting quantities of human C6 or C5,6 complex in the presence of an excess of other complement components. The cytolysis curves generated in both experiments were sigmoidal, in sharp contrast to the monotonic curves observed in lysis of erythrocytes treated similarly. The sigmoidal curves of cytolysis indicate a cooperative action of several molecules of C6 or acid-activated C5,6 complex, C(56)a. In contrast to the multi-hit characteristics of cytolysis, dose-response measurements of the release of 86Rb indicated that only one effective molecule of C6 per cell is required for assembly of a 86Rb-releasing channel. This divergence indicates that lysis requires formation of several channels or, alternatively, assembly of large channels that are formed by several molecules of C6. Because prior studies with erythrocyte ghosts have shown that only a single effective molecule of C6 is required for assembly of a transmembrane channel, regardless of size, we prefer to interpret the multi-hit characteristics of nucleated cell lysis as an indication of a multi-channel requirement, rather than channel enlargement.     

Initial and long-term management of autoimmune neuropathies

The inflammatory neuropathies (chronic inflammatory demyelinating polyradiculoneuropathy [CIDP], Guillain-Barré syndrome [GBS] and multifocal motor neuropathy [MMN]) affect only one to two individuals per 100 000 of the population, but result in major disability and impairment. Intravenous immunoglobulin (IVIg) can be used as an initial treatment for CIDP, GBS and MMN. While plasma exchange and corticosteroids can also be used initially, they are not as uniformly effective for each of these disorders as IVIg. Substituting corticosteroids, plasma exchange or immunosuppressants may be appropriate for patients not responding to initial IVIg therapy, and combination therapy may be needed in some patients.There are no data from controlled clinical trials of long-term management strategies for CIDP and MMN; however, empirical evidence suggests that a positive long-term response to IVIg can be achieved by increasing the initial dose or its frequency of administration. Corticosteroids and immunosuppressants may be appropriate in some patients with CIDP. Adverse events with IVIg are usually mild and not treatment limiting; however, patients do need to be monitored for uncommon, but serious, adverse events such as renal insufficiency, stroke and thromboembolic events. Nevertheless, the safety profile of IVIg is exceptional relative to the potential complications of other long-term treatments for CIDP and MMN, especially corticosteroids and immunosuppressants. Predictors of response have been reported for each of the neuropathies, and until controlled clinical trials provide evidence on which to base treatment strategies, effective management will require individualising therapy according to patient response.     

Pharmacokinetics of thiamine in female Baltic salmon (Salmo salar L.) broodfish

A thiamine deficiency disease termed M74 syndrome affects the yolk-sac fry of wild and feral Baltic salmon. However, very little is known about the pharmacokinetics of thiamine in salmon. This study examined the pharmacokinetics of thiamine hydrochloride injected intraperitoneally into feral and farmed Baltic salmon females preparing for spawning. The total thiamine concentrations in the eggs and white muscle of feral females were only half of those in the farmed fish after injection. The relative inefficiency of the incorporation of thiamine into the eggs in feral Baltic salmon may be a predisposition factor for M74 syndrome. The relative bioavailability of intraperitoneally-injected thiamine hydrochloride was shown to be ca. 94% of that administered intra-aortically. A far lower intraperitoneal dose (ca. 20mgkg(-1) fish) than currently used was shown to elevate the total thiamine concentration in the eggs above the critical threshold of M74 syndrome.     

Rhabdomyolysis caused by hot air sauna burn

Sauna-related burns are rare, even in Finland where sauna bathing is a popular leisure pastime. Burns induced by hot air are even more rare and constitute a very small subgroup of all sauna burns. Hot air burns are characterised by a combination of full thickness skin damage with deep tissue destruction. We report here on six consecutive patients suffering from hot air sauna burns with rhabdomyolysis. All six patients were middle-aged, the majority of them men. Acute excessive consumption of alcohol exacerbated by a hot environment resulted in dehydration and loss of consciousness. Immobility and prolonged exposure to hot, dry air resulted in third degree regional burns with 5-32% TBSA. Rhabdomyolysis was evident on admission. The laboratory values of plasma creatine kinase (P-CK), plasma myoglobin (PM), blood pH, and serum potassium (S-K) during the first five days were evaluated. Aggressive fluid management and correction of acidosis and myoglobinuria were started on admission. Surgical management consisted of early, aggressive excision at fascial level, in some patients involving sacrifice of the upper layers of muscle. Even so, mortality in this small series was 50%. The best indicator of poor prognosis was a highly elevated CK value on the second post-injury day.     

THE SMOKING HABITS AND ATTITUDES OF NURSES

The demographic and social characteristics, attitudes to smokers and smoking, and knowledge about smoking were surveyed in 988 (81.3%) of 1,215 trainee and trained nurses in four locations in Perth, Western Australia. Male and female nurses were similar with 51% never having smoked regularly, 17% being ex-smokers and 32% current smokers. In comparison with Australian woman in general, there were less current smokers and more ex-smokers among female nurses. Female nurses smoked substantially more than Australian female doctors. The majority of nurses who had ever smoked (68%) began smoking between ages 15 and 19 years, 26% began in the first year of their nursing training and 26% smoked their first cigarette in the nurses' quarters. The knowledge of nurses about the health effects of smoking was similar to that of Australian doctors as were their opinions regarding their role in setting a non-smoking example to others. A substantial majority supported either a complete ban on smoking, or its restriction to especially segregated areas in aeroplanes, buses, trains, hospitals and cinemas.