Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans

Following induction of the microsomal liver enzymes, lower total prednisolone concentrations in plasma and an altered pattern of the prednisolone metabolites generated were observed. The purpose of the present study was to establish whether--as a consequence of an enhanced clearance--lower unbound concentrations of prednisolone in plasma are detectable after enzyme induction and to determine if the altered prednisolone metabolism modulates the biological effect. Before and during phenytoin dosage in ten volunteers, the mean (+/-SD) total body clearance (ml min-1 kg-1) of both total and unbound prednisolone increased from 2.74 +/- 0.47 to 3.94 +/- 0.66 (P less than 0.001) and from 10.76 +/- 2.68 to 16.00 +/- 3.17 (P less than 0.001), respectively. These increments were due to increased non-renal clearances. The immunosuppressive activity as a function of time in plasma determined as the percent inhibition of the mixed lymphocyte reaction decreased by one third after phenytoin dosing, while the EC50 values of unbound prednisolone were unaffected. Thus enzyme induction decreases both the unbound prednisolone concentration and the steroid efficacy.     

Cerebral vasculitis in severe Kawasaki disease: early detection by magnetic resonance imaging and good outcome after intensive treatment

Kawasaki disease is an acute vasculitis, that has a classic complication of acquired coronary artery aneurysm. Severe forms with multi‐organ involvement or neurological dysfunction are rare. Cerebral vascular involvement has been related to large‐vessel injury or cardioembolism, leading to focal brain infarction. A 4‐year‐old female presented with unusual, rapidly catastrophic Kawasaki disease with refractory shock, acute renal failure, and coma, requiring intensive haemodynamic management. The observation of diffuse micro‐haemorrhages (T2*‐weighted sequence) associated with white matter injury on brain magnetic resonance imaging (MRI) pointed towards lesions of the medium/small blood vessels. Cerebral vasculitis was suspected and the immunosuppressive treatment was increased Subsequently, the patient’s recovery was rapid. On follow‐up severe, bilateral vitritis was evident and surgery improved visual outcome. Early recognition of severe or unusual forms of Kawasaki disease could lead to more favourable outcome using appropriate treatment strategies. Diffuse cerebral micro‐haemorrhages on T2* brain MRI sequences might be a key sign for the diagnosis of medium or small cerebral vessel involvement.     

Case Report: Secondary biliary cirrhosis possibly related to congenital hepatic fibrosis. Evidence for decreased number of portal branch veins and hypertrophic peribiliary vascular plexus

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.     

Different cortical activation patterns in blind and sighted humans during encoding and transformation of haptic images

In this study, we investigated whether the occipital cortex of blind humans is activated during haptic perception and/or transformation of a haptic image. Slow event-related brain potentials were monitored from 18 electrodes in 12 sighted and 15 congenitally blind participants while they were engaged in a haptic mental rotation task. In both groups, slow negative shifts appeared over (a) the frontal cortex at the beginning of each processing episode, (b) the left-central to parietal cortex during encoding and maintaining of a haptic image, and (c) the central to parietal cortex during image transformation. A pronounced slow negative potential over the occipital cortex emerged only in the blind individuals and was time-locked to the processing epochs. Its amplitude increased with the amount of processing load. The slow wave effects observed in the blind individuals could indicate that occipital areas participate in specific, nonvisual functions or they could reflect a coactivation of these areas whenever the activation level of task-specific processing modules located elsewhere in the cortex is raised by nonspecific thalamocortical input.     

ALCOHOL DEPENDENCE: IS CARBOHYDRATE-DEFICIENT TRANSFERRIN A MARKER FOR ALCOHOL INTAKE?

We investigated %CDT (carbohydrate-deficient transferrin) in92 ethanol-intoxicated alcohol-dependent patients after consecutiveadmission to hospital and followed them for 28 days under controlledconditions. At admission, 63% (58 patients) showed elevatedCDT (>2.5%) and 34 patients (37%) had normal CDT levels (<2.5%).No correlation of the %CDT values to alcohol-related disabilities,severity of the withdrawal syndrome, alcohol-drinking patternbefore admission, or several other factors was found. The sensitivityof GGT (     

Problems of Sensing Tachyarrhythmias by an Antitachycardia Pacemaker (Symbios 7008)

Atrial burst pacing is an effective method of terminating supraventricular tachycardia. In the patient presented in this report, a Symbios 7008 pacemaker (Medtronic Inc., Minneapolis, MN, USA) was implanted for two reasons: (1) severe AV conduction defect (AH, 230 msec; HV, 150 msec) and bifascicular block following anterior myocardial infarction; and (2) paroxysmal atrial flutter. The conduction defect ruled out programming other than atrial burst in DDD mode. Activation of burst pacing required appropriate programming of the "tachycardia detection window" on the basis of the cycle length of the flutter waves. In the case reviewed, episodes of atrial flutter with variable cycle lengths of 230 to 280 msec necessitated reprogramming of the AV interval, the refractory period, and the upper rate interval. The use of an antitachycardia device in automatic mode may be limited by variations in tachycardia cycle length.     

Trypanosoma brucei infection in nude mice: B lymphocyte function is suppressed in the absence of T lymphocytes

B lymphocyte function was assessed in outbred nude mice and nu/+controls infected with Trypanosoma brucei brucei. On day 10 of the infection in outbred nu/nu mice in which the initial wave of parasites was strongly controlled, B cell function was unaltered on enhanced compared with uninfected animals or infected nu/+. In other nu/nu mice unable to control the initial parasitaemia, thymidine incorporation and Ig secretion by spleen cells were increased on day 10 and their response to lipopolysaccharide in vitro negated. By day 15 however, even the spleen cells of infected nu/nu which controlled the initial wave of parasites were proliferating and secreting Ig on removal from the mice and they were unable to respond to LPS in vitro. These experiments confirm results of a previous study of B cell function in T cell-depleted mice (Askonas et al. 1979). T. b. brucei infection of mice causes both enhanced Ig production and suppression of the ability of B cells to respond to mitogen even in the absence of T cells, but the presence of T cells may accelerate the changes which occur in B lymphocytes following this infection.     

Project Megapoles: Promoting better health for socially disadvantaged groups across Europe

A new public health network is looking at ways of achievingbetter health and reducing differences in health between Europe'scapital cities. A report from the Socially Disadvantaged Groupssub-network of Megapoles.     

Hand function in relation to brain lesions and corticomotor‐projection pattern in children with unilateral cerebral palsy

Aim To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). Method The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7–16y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability Classification System level I or II. Hand function was assessed with the Box and Blocks test and Assisting Hand Assessment (AHA). Conventional structural magnetic resonance images were assessed visually for type, location, and extent of brain lesions. Single‐pulse transcranial magnetic stimulation (TMS) provided information on organization of corticomotor projections. Results The most favourable hand function was seen in children who had white‐matter damage of immaturity with mild white‐matter loss and contralateral motor projections. Children with ipsilateral projections had the most impaired function. Nevertheless, in this subgroup a range of ability was seen (AHA 29–59%). Motor‐projection patterns appeared to be influenced by lesion extent and location, but not by lesion type. Interpretation Combining information from structural magnetic resonance images and TMS can improve prediction of hand function. A wide variation in hand function was seen within all motor‐projection patterns. Although the most impaired hand function was seen in the ipsilateral motor‐projection group, some children in this group had fairly good ability. Such information is important for treatment planning.     

Computerised version of the Chou and Fasman protein secondary structure predictive method

A DEC-SYSTEM 10 FORTRAN computer program to carry out secondary structure prediction of proteins, according to the algorithm of Chou & Fasman (1, 2), is described. Program results are compared with predictions made by Chou & Fasman.