The role of infection and vaccination in the genesis of optic neuritis and multiple sclerosis in children

This article describes the association between previous infection and/or vaccination and the development of optic neuritis (ON) in 18 children. Ten of these children subsequently developed clinically definite multiple sclerosis (MS), while in 8 patients a clinically definite etiology could not be confirmed. Vaccination preceded the first ON attack in 6 patients, all but one of whom subsequently developed MS. It also preceded subsequent demyelinating events in 6 patients. Ten of the patients had a bacterial or viral infection within the 2 weeks prior to the first symptoms of ON. Intrathecal antibody synthesis against 2 or more viruses could be shown in 5 out of 8 patients studied; 5 out of 6 patients had oligoclonal antibodies in CSF and 12 out of 16 patients a high IgG index. Neither intrathecal antibody synthesis against 2 or more viruses nor elevated IgG indexes could be found in the control patients. Measles and mumps occurred at a significantly later age in the children who subsequently developed MS than in the control children, and these patients had significantly more events that might have impaired the blood-brain barrier than the controls. These results indicate that immunological events leading to MS may be triggered during childhood. Vaccination and infection often precede ON in childhood. Intrathecal viral antibody production can occur already in childhood at the time of the first symptoms of MS.     

Disposition of a new tetrahydrocarbazole analgesic drug in laboratory animals and man

1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man. 2. Oral doses of the 14C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity. 3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25 mg/kg in rats, 0.1 and 50 mg/kg in dogs, and 1-160 mg in man. In rhesus monkeys given a 0.5 mg/kg oral dose, the Cmax and AUC of I were similar to values obtained following a corresponding dose in dogs. 4. After i.v. administration of a 1.0 mg/kg dose the terminal elimination half-life (t1/2 beta) of I was 4 h in mice and 9-10 h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2 beta of I was decreased to 2.4 h. In rodents the serum clearance and apparent volume of distribution of I were 0.04-0.2 l/kg.h and 0.5-0.8 l/kg, respectively, and 0.6 l/kg.h and 9.8 l/kg in dogs. 5. In rodents and dogs dosed with 14C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug.     

Evaluation of the rat tail model for estimating dermal absorption of lindane

Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.     

Fortschritte bei der operativen Therapie der Divertikelerkrankung des Dickdarms

European Surgery - Es werden in einer retrospektiven Studies die Ergebnisse von 101 Patienten, welche wegen einer komplizierten Kolondivertikulitis in den Jahren 1965 bis 1978 operiert wurden, den...     

Fatal and non-fatal stingray envenomation

A fatality occurred in a previously healthy 12-year-old boy after a penetrating chest injury from a stingray barb. The injury occurred under freak circumstances. Death was a result of cardiac tamponade which was secondary to venom-induced, localized myocardial necrosis and spontaneous perforation, six days after the direct penetration of the right ventricle by the barb. Three other cases of less serious stingray envenomation are described which illustrate the significant localized morbidity that may occur without immediate wound exploration and toilet after adequate anaesthesia. We also report a study of a series of 100 minor stingray envenomations which, when treated, resulted in no morbidity. It is possible that local infiltration with 1% plain lignocaine may have a direct counteraction against stingray venom that remains in the wound area. Stingray venom has insidious, but powerful, localized tissue necrosing properties in humans.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Clinical and therapeutic studies in mesangial immunoglobulin a glomerulonephritis

A long-term clinical and therapeutic study was performed in 47 patients with mesangial IgA glomerulonephritis. The male to female ratio was 2.9∶1. An episode of gross haematuria or the incidental discovery of asymptomatic microscopic haematuria with associated mild proteinuria heralded the apparent onset of renal disease. At the onset of observation 18 patients (38.2%) had high blood pressure. Other 17 patients developed hypertension during observation. Anaemia was uncommon. No essential abnormalities in serum protein and lipid patterns were found. Twenty-nine patients (61.6%) had higher levels of serum immunoglobulins—most frequently of IgA (42.5%). Twenty-two patients had low serum C₃ levels (46.8%). The percentage of patients with renal failure increased from 21.2 to 36.1 during observation. Male sex, hypertension, proteinuria higher than 2 g/24 h, elevated ESR, high serum IgA levels, longer duration of the disease and older age of patients suggest an unfavourable outcome. Long-term treatment with a combination of azathioprine/acenocumarol, or indomethacin, or levamisole has no effect on the clinical manifestation and evolution.