Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging

Cortical spreading depression (CSD) and peri‐infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3‐dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T₁‐weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T₁‐weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion‐weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.     

Tγδ Cells and their Subsets in Blood and Synovial Tissue from Rheumatoid Arthritis Patients

We have examined the frequencies of T gamma delta cells in blood, synovial fluids, and synovial membranes of patients with rheumatoid arthritis (RA) and in blood from age-matched controls. Immunocytochemical and immunohistochemical techniques were used with monoclonal antibodies BB3 and A13 to define a major and minor blood subset of T gamma delta cells respectively. Together, these antibodies identify the majority (if not all) of the peripheral blood T gamma delta cells. Significantly lower levels of T gamma delta cells were found in the blood of RA patients compared with controls, whilst higher but not significant numbers were found in the synovial fluids of paired samples. Scattered T gamma delta cells were found only in some synovial membranes with a distribution similar to the T alpha beta cells. Analysis of the two different T gamma delta-cell subsets indicated a ratio of BB3 to A13 of about 5:1 in control and RA blood. However, this ratio was less than 1:1 in the RA synovial fluids and membranes. The migratory nature of the A13+ cells could account for their predominance in these sites. The possible pathological significance of these cells in the rheumatoid synovial fluid and synovial membranes is discussed.     

DIFFERING EFFECTS OF CARBOHYDRATE, FAT AND PROTEIN ON THE RATE OF ETHANOL METABOLISM

The rate of metabolism of ethanol in humans has been assessedby intravenous infusion of ethanol/saline under feedback controlto maintain a constant blood alcohol concentration. After equilibration,meals consisting predominantly of carbohydrate, fat or proteinwere eaten and changes in ethanol metabolic rate were found.Carbohydrate caused a significant increase in this rate andfat or protein caused small but non-significant decreases. Infusionof ethanol/saline resulted in a temporary fall in plasma freefatty acid levels and a steady rise in plasma triglycerides.The changes in alcohol metabolism following carbohydrate cannotbe accounted for by changes in insulin, free fatty acid or lactate/pyruvatelevels.     

PHARMACOKINETICS OF SINGLE-DOSE I.V.MORPHINE IN NORMAL VOLUNTEERS AND PATIENTS WITH END-STAGE RENAL FAILURE

Morphine 0.125 mgkg^–1 was administered i.v. to 11 normalsubjects and nine patients with chronic renal failure requiringregular haemodialysis. Plasma morphine concentrations were measuredusing high pressure liquid chromatography (HPLC). Although therewas considerable individual variation in both groups, mean plasmaconcentrations of morphine were significantly higher in thepatients with renal failure for 15 min after administration.The decay of plasma concentration fitted a three-compartmentmamillary pharmacokinetic model in all subjects. Derived values(mean $ SEM) of T^x, volume of distribution of the second compartment(V₂), total volume of distribution at steady state ( V^ss1) andtransfer rate constant from the first to the second compartment(k₁₂) were significantly different between groups. Mean valuesof terminal elimination half-life (T⁷) and total body clearancewere similar in the two groups. It was concluded that eliminationof unchanged morphine is not impaired significantly in patientswith chronic renal failure, although accumulation of morphine-3-glucuronideprobably occurs. Although the pharmacological effect of morphineis not related temporally to plasma morphine concentrations,the higher values in patients with renal failure may be implicatedin their increased sensitivity to the drug     

Effects of cholinesterase inhibitors on the neuromuscular blocking action of suxamethonium

Prolonged neuromuscular block occurs when suxamethonium is givenafter neostigmine or pyridostigmine; however, studies of edrophoniumand suxamethonium have yielded conflicting results. We havestudied, therefore, interactions between suxamethonium and allthree anticholinesterases in rats anaesthetized with pentobarbitone.After recovery from an initial bolus of suxamethonium, saline,edrophonium, pyridostigmine or neostigmine was administeredand a second dose of suxamethonium was then given. All threeanticholinesterases prolonged the duration of neuromuscularblock (90% suppression to 50% twitch recovery) to 127(SEM 9)%,127(10)% and 138 (11)% of baseline for edrophonium, pyridostigmineand neostigmine, respectively. Recovery index (25% to 75% twitchrecovery) was increased also to 125 (9)%; 149 (10%) and 185(15)% of baseline, respectively for the three drugs. Presented in part at the 1992 annual meetings of the AmericanSociety of Anesthesiologists and the California Society of Anesthesiologists.     

RESPONSIVENESS OF KEITEL FUNCTIONAL INDEX COMPARED WITH LABORATORY MEASURES OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS

This study compares functional changes to change in measuresof disease activity following the introduction of slow-actinganti-rheumatic drugs (SAARD) in patients with active rheumatoidarthritis (RA). Clinical and laboratory variables were simultaneouslymonitored at 6-monthly intervals, over approximately 18 months.Function was measured by a performance testing, the Keitel functionindex (KFI), which was divided into sections representing smalland large joints [and (HFI); wrist (WFI) and limb function index(LFI)]. One-hundred-and-fifteen patients were studied, of whom21 were male. The mean age of the subjects was 49 yr (s.D. ±12) and mean duration of disease 7 yr (S.D. ± 7). Themean KFI at entry was 38 (S.D. ± 18) while at the endof the study it was 31 (s.D. ± 17) (P < 0.0001). Thechange in KFI following therapy correlated with the change inRitchie articular index (RAI) (r = 0.4; P < 0.0001), earlymorning stiffness (EMS) (r = 0.3; P = 0.004), swollen jointcount (JC) (r = 0.4; P = 0.0005). C-reactive protein (CRP) (r= 0.2; P < 0.05) and Lansbury systemic index (LSI) (r = 0.35;P = 0.002), but not with change in Westergren erythrocyte sedimentationrate (ESR) or change in time to onset of fatigue. Multiple regressionanalysis showed that 32% of the variation in KFI at the endof the study could be predicted by a combination of ESR, sulphasalazinetherapy, RAI, disease duration and chloroquine treatment atonset (P < 0.05). When HFI at end of study was the dependentvariable, 21 % of the variation could be predicted by a combinationof ESR, CRP, Lansbury systemic index and JC at onset (P <0.05). The duration of disease did not significantly influencethe potential for change in functional status. This study showedthat detailed measurement of function is important in assessingRA activity. Functional impairment in RA is a dynamic processinfluenced by changes in clinical disease activity with treatment. KEY WORDS: Keitel function index, Disease activity, Outcom, Hand function index     

SUSPECTED CUTANEOUS DRUG TOXICITY IN RHEUMATOID ARTHRITIS--AN EVALUATION

Cutaneous toxicity from drugs used to treat RA is a major perceivedproblem. Over a 2-yr period we have prospectively reviewed 114patients with a suspected adverse cutaneous reaction to anti-rheumaticdrugs. In 71 (62%), the rash was thought to be unrelated todrug therapy. This group included 10 in whom the rash had resolvedbefore review (usually < 1 week), 38 with a rash relatedto their rheumatoid disease and 23 with eruptions unrelatedto either drugs or arthritis. Fortythree (38%) patients hadrashes thought to be related to their drug therapy. Gold therapy(both oral and intramuscular) was implicated most frequently(31 patients). However, the majority of these (23) had a pityriasiform/discoideczematous eruption that responded to potent topical steroidsoccasionally with a reduction in gold dosage. In this sample it was possible to continue drug therapy in 82%of patients with what were initially thought to be cutane ousadverse drug reactions. Careful evaluation should allow a majorityof patients to continue drug therapy from which they are oftengaining benefit. KEY WORDS: Rheumatoid arthritis, Cutaneous drug toxicity, Vasculitis, Capillaritis, Pruritus, Asteatotic eczema, Pityriasis rosea, Discoid eczema, Pemphigus, Alopecia     

A DOUBLE-BLIND STUDY OF THE EFFECTIVENESS OF LOW LEVEL LASER TREATMENT OF ROTATOR CUFF TENDINITIS

Thirty-five patients with rotator cuff tendinitis were randomlyallocated to active (CB Medico Master III 830 nm Ga As AL diode)laser or dummy laser treatment twice weekly for 8 weeks. Movementrange, painful are score, resisted movement score and responsesto visual analogue scales for night pain, rest pain, movementpain and functional limitation were measured second weekly.All responses improved from baseline but there was no differencebetween the two groups. These results fail to demonstrate theeffectiveness of laser therapy in rotator cuff tendinitis. KEY WORDS: Rotator cuff tendinitis, Laser, Treatment