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Background: Haemopoietic stem cell treatment has been proposed for severe resistant autoimmune cytopenias. An alternative and safer option may be the monoclonal antibody Campath-1H, which may reset the immune system [...]

As part of the Adventist Ministers' Health Study, a series of cross-sectional surveys conducted in 1992, 1994, and 1997, the serum vitamin B-12 status of 340 Australian Seventh-day Adventist ministers was assessed in 1997. The ministers in the study participated voluntarily. Of this group, 245 were either lactoovovegetarians or vegans who were not taking vitamin B-12 supplements. Their mean vitamin B-12 concentration was 199 pmol/L (range: 58-538 pmol/L), 53% of whom had values below the reference range for the method used (171-850 pmol/L) and 73% of whom had values [is less than] 221 pmol/L, the lower limit recommended by Herbert. Dual-isotope Schillings test results in 36 lactoovovegetarians with abnormally low vitamin B-12 concentrations indicated that dietary deficiency was the cause in 70% of cases. Data from the dietary questionnaires supported dietary deficiency as the cause of low serum vitamin B-12 in this population of lactoovovegetarians and vegans, 56 (23%) of whom consumed sufficient servings of vitamin B-12-containing foods to obtain the minimum daily maintenance allowance of the vitamin (1 [micro]g). Am J Clin Nutr 1999;70(suppl):576S-8S. KEY WORDS Vitamin B-12, cyanocobalamin, lactoovovegetarian, vegan, Schillings test, recommended daily allowance, RDA, Seventh-Day Adventists, ministers

Effective treatment of acute bleeding episodes in patients with hemophilia B relies on factor IX recovery, with higher levels being more desirable, whereas prevention of bleeds with a prophylactic regimen depends on the half‐life of the product. Lower recovery values have been reported following administration of recombinant FIX (rFIX) than following administration of plasma‐derived FIX (pdFIX).

First-feeding Arctic char Salvelinus alpinuswere subjected to two different photoperiods (light conditions at latitude 43°28'N [normal] and 24 h of continuous light) and two different feeding schedules (fed only during the natural photoperiod [normal] and 24-h continuous feeding) for 12 weeks. Arctic char subjected to 24 h of continuous light and continuous feed availability had a significantly lower cumulative mortality (P< 0.05) and higher mean final weights (P< 0.05) without an accompanying increase in within-treatment variability compared with fish raised in either ambient photoperiods or under restricted feeding regimens. These results indicate potential commercial benefits associated with extended photoperiod and feeding regimens for the culture of juvenile Arctic char.

The concept of the coordination defect (CD) was used recently by Bevanand Martin[6] to describe the fluorite‐related superstructures of the intermediate Pr/Tb oxides. The CD is an octahedron of corner‐shared OM4/8tetrahedra enclosing a □M4/8tetrahedron, where □ represents an oxygen vacancy. Various linkages of CDs can define a polyhedral prism with contents appropriate to the phase composition, and this is designated the “structural motif”. The identical, parallel top and bottom planes of this prism are the “motif plane”. This concept is now extended to explore the structures of the ordered phases, delta, gammaand beta, which occur in the zirconia‐scandia system, the respective formulae being Zr3Sc4O12, Zr10Sc4O26and Zr48Sc14O117to Zr50Sc12O118. It is shown that the motif planeis the same in each of the known structures (deltaand gamma), thus defining the close relationship between them. Possible models for the as‐yet unknown structure of the beta phase, in which this same motif planeoccurs, can then be proposed.

We carry out a comparative analysis of performances of a cellular communication system with adaptive modulation and coding (AMC) and a system with power control (PC). It is shown that the performance of an AMC system is higher than the performance of a PC system for an arbitrary probability density function of the signal fading. To achieve identical throughputs of the two systems, the mean transmitted power for PC must be greater than that for AMC. For identical mean transmitted powers, the throughput of an AMC system is always greater than that of a PC system. We consider code division multiple-access (CDMA) systems with arbitrary numbers of fading time-taps (paths), having a statistically independent Rayleigh fading of signals from path to path. The influence of self-interference on AMC and PC performance is studied. This self-interference results from the nonideal path separation in the receiver.

The Thromboelastograph has now been in use for over 50 years and has been largely regarded as a research tool. Increasing automation and refinement of the TEG and standardisation of results has led to decreased speculation regarding its validity as an assay of haemostasis. There are increasing clinical applications including cardiothoracic surgery and liver transplantation. This review discusses the principles and limitations of the TEG. It also focuses on the current clinical applications and potential research interests.

ObjectiveTo evaluate hereditary and acquired hemostatic abnormalities associated with recurrent spontaneous early (first-trimester) abortions.MethodA group of 56 Greek women with two or more unexplained primary spontaneous abortions, and a reference group of 148 women without a history of recurrent abortions, were screened for hypercoagulability. A randomly selected population of first-trimester pregnant women was also chosen for factor V Leiden genetic screening.ResultsA total of 21 of the women with recurrent abortions, compared with 12 of the reference group, showed increased activated protein C resistance. Fourteen per cent had positive lupus anticoagulant, compared with 11.5 of the reference group. For the rest of the parameters, there was no difference between the two groups. Of 22 women studied for factor V Leiden, one was homozygous and one was heterozygous. Results were compared using Fisher' exact test and two-tailed Student' ttests.ConclusionsIncreased activated protein C resistance appears to be an important factor in women with recurrent abortions. These data indicate the need for routine investigation of activated protein C resistance in women with recurrent abortions.

Hypercoagulable states are found in up to 10 per cent of patients with a history of unexplained venous thrombosis. To investigate the prevalence in arterial thrombosis, thrombophilia screening was performed on 124 patients who had previously undergone lower-limb revascularization, 45 claudicants and 27 controls. Of the patients who had undergone revascularization 40 per cent had a hyper-coagulation abnormality (low levels of protein C, protein S and antithrombin III or presence of the lupus anti-coagulant) in comparison with 27 per cent of claudicants and 11 per cent of controls (P< 0·01). Furthermore, patients who had suffered reocclusion after revascularization were significantly more likely to have a hypercoagulation abnormality than those who had not (P< 0·05), even if the occlusion had occurred more than 6 months previously. Lupus anticoagulant was the abnormality most frequently detected and, like low protein C levels, was found only in patients with peripheral vascular disease. It appears that hypercoagulable states are common in patients with arterial disease and may predispose to failure of revascularization.

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph- negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl- related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

DISCUSSION The waterproof ness of structural diaphragm walls M. Puller water bar shownin Fig. 4 has much to There is a tendency for all diaphragm wall commend it. panel joints to leak below the water-table due to 49. An excess of shear transfer steel at the shrinkage of the concretein a panel as it sets slab level in the wall also causes mixing and and hardens. Unless special measures are taken pollution of the concrete just where perfect conto place water bars in the panel joints, leakage crete is required watertightness. Bent-in for is inevitable...

The profile and integrated intensity of the calcium 422.67 nm resonance line from a commercially available demountable hollow cathode lamp have been examined using several filler gases at pressures between 1 and 7 Torr and operating currents in the range of 6 to 30 mA. The results are interpreted in terms of the reduced Doppler and self-absorption broadening obtained in this source compared to these effects in a commercially available, sealed, neon-filled hollow cathode lamp source.

The synergistic effect of pancuronium bromide (PCB) and d-tubocurarine (DTC) on the onset time of neuromuscular blockade was tested in 108 ASA physical status I and II adults anaesthetized with thiopentone, nitrous oxide and halothane. Either saline or a small (priming) dose (DTC, 0.04mg·kg-1or PCB, 0.007 mg·kg-1) was administered 3 min before a paralyzing dose of either DTC or PCB. The total dose of relaxant was equivalent to DTC, O.4mg·kg-1, or PCB, 0.07mg·kg-1. Neuromuscular activity was measured using train-of-four stimulation applied every 12 s. Time to 50 per cent first twitch blockade was 63 ± 4.6 s (mean ± SEM) with DTC and 88 ± 5.2 s with PCB (p < 0.002). Times to 90 per cent blockade were not different between the two drugs (161 ±20 s and 141 ±21 s respectively). Priming a DTC blockade with either DTC or PCB or priming a PCB blockade with PCB produced an acceleration of less than 10 s at all levels of blockade. Compared with PCB alone, priming PCB blockade with DTC reduced the time to 50 per cent blockade to 71 ±4.5 s (p< 0.02) and to 90 per cent blockade to 111 ±8 s(p< 0.05). Priming did not affect the duration of action significantly, except in the case of PCB priming of DTC, where duration was increased from 39 ± 4.4 to 57 ±4 min (p < 0.02). It is concluded that priming with a synergistic relaxant might increase speed of onset without prolonging the duration of neuromuscular blockade. However, the effect of DTC priming of PCB onset is too small to be clinically significant.

ORG NC45 was compared with succinylcholine to produce muscle relaxation for short, intra-abdominal operations in 40 patients during nitrous oxide-oxygenenflurane anaesthesia. Intubating conditions after ORG NC45, 100 μg/kg, were similar to those after succinylcholine 1 mg/kg, although this was achieved at amean time of 229.9 10.8 sec compared with 129.8 ± 14.2 sec after succinylcholine. Muscle relaxation during surgery, mean duration 32.5 minutes, was provided in the succinylcholine group with an infusion and in the ORG NC45 group by repeated boluses, 10 μg/kg, which were required in four patients. At the end of surgery ORG NC45 was antagonized with atropine, 17 μg/kg, and neostigmine, 36 μg/kg, which were repeated in two patients. Postoperative recovery of neuromuscular function was indistinguishable between the two groups. We conclude that ORG NC45 is asuitable relaxant for short, intra-abdominal operations if sufficient time, three to four minutes, is allowed to produce good intubating conditions.

Measurements of total electrical conductivity on fluorite-type U3O8-Y2O3(Sc2O3) solid solutions have been made as a function of temperature and U/Y(Sc) ratio. The following compositions were studied: (U0.7Y0.3)O2+x, (U0.6Y0.4)O2+x, (U0.5Y0.5)O2+x, (U0.45Y0.55)O2+x, (U0.4Y0.6)O2+x, (U0.35Y0.65)O2+x, (U0.3Y0.7)O2−x, (U0.5Sc0.5)O2+xand (U0.38Sc0.62)O2+x. Preliminary measurements on the latter two compositions were carried out for comparison purposes. The maximum conductivity value occurred for the U3O8-Sc2O3solid solutions, and for (U0.7Y0.3)O2+xin the U3O8-Y2O3system. The conductivity in these fluorite-type solid solutions is mainly electronic, the conduction mechanism being hopping-type. The energy of activation lay between 25 and 40 kJ mol−1. The (U0.3Y0.7)O2−xcomposition appeared to be an ionic conductor with an activation energy of ∼110 kJ mol−1below 800 to 850° C. The diffusion of cations of U3O8-Y2O3into ZrO2-Y2O3was studied during passage of current: no observable diffusion occurred over the period of current passage (384 h). Attempts were made to determine the anionic contribution to the total conductivity in U3O8-Y2O3solid solutions using the blocking electrode technique. Results indicated that complete isolation of the specimen-blocking electrode (YSZ) interface from the ambient gases is necessary if such measurements are to be reliable. The diffusion coefficients calculated from the conductivity data using the Nernst-Einstein relation were two orders of magnitude higher than those obtained by a direct method.

The distribution of biomass encapsulated within alginate beads can be examined using a Scanning Electron Microscope (SEM). Existing methods for the preparation of suitable specimens are extremely time consuming, involving fixing of samples with glutaraldehyde, dehydrating with successive acetone washings and final drying using a critical point technique. These preparations are necessary to avoid significant specimen shrinkage, however, the resultant specimens are sometimes difficult to analyse using an SEM or light microscope. A reliable quick method has been developed where alginate specimens are directly mounted using a water based adhesive, then dried under controlled conditions. These specimens were found to be robust enough for SEM processing and gave true measurements of the original alginate beads including microorganism orientation.

The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals. Selective changes in B cell and T cell responses to CII in animals treated this way are interpreted to indicate a state of tolerance or hyporesponsiveness to CII. Tolerant animals made less serum antibody, to bovine and rat CII, of the IgG2b isotype and more of the IgG1 isotype.Phenotypic and functional analysis of peripheral lymph node cells showed that those from tolerized animals expressed less MHC Class II, proliferated less and secreted less IgG2b anti-CII antibody in response to stimulation in vitro with CII when compared with cells from non-tolerant animals. However, this depression of the immune responses to CII seen in vitro was overcome when the cells were incubated with increasing amounts of CII. Tolerance could be transferred to normal animals. Spleen cells, and nylon wool-filtered splenic T cells (but not mesenteric lymph node cells) adoptively transferred hyporesponsiveness to normal recipients which were then less susceptible to collagen-induced arthritis. Transfer of serum from gavaged animals did not modify the susceptibility of normal recipients to arthritis. Spleen cells from gavaged animals suppressed proliferative and antibody responses in co-cultures in vitro with lymph node cells from animals immunized with CII in FIA. The suppressive spleen cell population contained more cells expressing MHC Class II, in both the CD8+ and CD4+ populations. These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism that affects both T cells and B cells, most likely through the action of regulatory cytokines IL-4, IL-10 and TGFβ.

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.

Micro lipid droplets fuse with each other in vivo to form larger precursors of milk lipid globules. The extent of fusion dictates the size range of lipid globules in milk. A cell-free system in which micro lipid droplet fusion can be induced has been developed. Fusion was promoted by calcium and a protein complex from cytosol. Exogenously supplied gangliosides were potent fusion-promoting agents. Endogenous gangliosides were detected on micro lipid droplet surfaces by immunocytochemical localization. Monoclonal antibody to disialyllactosylceramide (GD3) inhibited micro lipid droplet fusion. These observations are suggestive of a role for gangliosides in micro lipid droplet fusion in situ.

Autotransfusion has been included in the routine protocol in some units as an effort towards blood conservation. In this study we aimed to measure the efficacy and limitations of autotransfusion and whether a heparin-bonded circuit had any advantage. One hundred five patients were randomised to one of three post-operative treatments. Group 1 (n = 34) was not autotransfused whereas groups 2 (n = 36) and 3 (n = 35) received autotransfusion with the circuit of group 3 coated with heparin. Homologous blood and blood products were given according to strict protocols identical for all groups. Transfused and circulating blood was analysed for haemostatic variables and the requirement for homologous blood was recorded. Autotransfused blood contained no intact platelets and very high levels of D-Dimers (a peptide fragment released when fibrin is lysed) which resulted in high levels of systemic D-Dimers in patients receiving autotransfusion. Flow cytometric analysis revealed that whilst platelet glycoprotein 1 b receptors were severely reduced immediately following surgery, there was no additional damage caused by autotransfusion. Furthermore, there was no difference in platelet aggregation, von Willebrand factor (vWF) multimetric analysis or clotting profiles between the groups. Median (interquartile range) blood loss was 898 ml (638-1195) in group 1, 853 ml (595-1348) in group 2 and 770 ml (615-1000) in group 3 (Kruskal-Wallis P = 0.46). Median transfusion requirements were 2 units in each group. Whilst auto-transfusion does not appear to compromise haemostasis, it does not reduce the requirement for homologous blood and heparin-bonding of the circuit has no impact.

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg · kg−1, during halothane anaesthesia were measured in eight children, 3–10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 ±23.2 g, mean ±SD, at the jaw and 11.3 ±5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 ±33.4 g and 7.9 ±4.2 g, respectively. The duration of the phenomenon was 1–2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 ±6 sec —control groups; 39 ±11 sec —strabismus group, than at adductor pollicis, 61 ±34 sec —control groups; 75 ±28 sec —strabismus group (P < 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children. L’augmentation de la tension du masséter et de l’adducteur du pouce aprés succinylcholine 1 mg · kg−1durant une anesthésie à l’halothane fut mesurée chez huit enfants âgés de 3 à 10 ans lors d’une correction de strabisme. Les résultats furent comparés avec ceux obtenus dans un groupe contrôle de patients. La stimulation avec l’ ondée-de-quatre (TOF) fut appliquee au nerf cubital et au nerf stimulant le masséter simultanément. La fermeture de la mâchoire fut mesurée par un système de transduceur de force. Chez tous les patients, la succinylcholine a amené une augmentation du tonus de base de la mâchoire et du pouce. Dans le groupe strabisme. l’étendue de cette augmentation était (moyenne ±SD) 55,7 ±23,2 g à la mâchoire et 11,3 ±5,6 g au pouce. Ceci n’était pas significativement différent des valeurs obtenues chez les contrôles (45,3 ±33,4 g et 7,9 ±4,2 g, respectivement). La durée de ce phénoméne était de 1–2 minutes pour les deux muscles étudiés et n’était pas statistiquement différente dans le groupe strabisme. Le temps pour l’acquisition d’un blocage neuromusculaire complet était significativement plus rapide au niveau des masséters (31 ±6 sec-groupe contrôle vs 39 ±11 sec —groupe strabisme), que l’adducteur du pouce (61 ±34 sec —groupe contrôle vs 75 ±28 sec —groupe strabisme) (P < 0.05 et 0.01 respectivement). On conclut que la succinylcholine amène une augmentation similaire dans la tension des mâchoires et des degrés comparables de blocage neuromusculaire chez les patients devant subir une chirurgie pour correction de strabisme comme chez tous les enfants.

This study was performed to détérmine the effects of various doses of succinylcholine on resting tension and evoked twitch height at the masséter and adductor pollicis muscles in children. Twenty patients, aged 3–10yr, ASA physical status I or II, were randomly assigned to receive succinylcholine 0.15, 0.25, 0.50 or 1.00 mg · kg−1, during halothane-nitrous oxide anaesthesia. Supramaximal train-of-four stimulation was applied simultaneously to the ulnar nerve and the nerve to the masséter. Transducers recorded force at the jaw and the thumb. Maximum blockade of the first twitch (T1) and maximum resting tension change were measured. Potency of succinylcholine at the two muscles was estimated by linear regression of the logit transformation of T1versus log dose. The relationship between resting tension change and log dose was established by linear regression. The masséter muscle was more sensitive to succinylcholine than the adductor pollicis with an ED95of 0.28 ± 0.02 (mean ±SEM) vs 0.44 ± 0.05 mg · kg−1(P < 0.05). Onset of neuromuscular blockade was faster at the masséter, and recovery occurred simultaneously in both muscles. A dose-related increase in resting tension was observed in both muscles, but its magnitude was five times greater at the masséter. With succinylcholine, 1 mg · kg−1, this increase was 51.6 ± 16.8 g at the masséter and 9.1 ± 2.3 g at the adductor pollicis. Tension returned to baseline within 1–2 min. It is concluded that in children (1) succinylcholine produces dose-related changes in resting tension; (2) this effect, although quantitatively important at the masséter, is not restricted to that muscle; and (3) relatively small doses of succinylcholine are required to block neuromuscular transmission at the jaw. Cette etude fut congue afin de d’étérminer les effets de différentes doses de succinylcholine sur la tension de repos et la hauteur du twitch évoqué pour le muscle du mass’étér et l’adducteur du pouce chez les enfants. Vingt patients ages de 3–10 ans, état physique ASA I ou II, ont été randomises afin de recevoir la succinylcholine 0,15, 0,25, 0,50 ou 1.00 mg · kg−1, lors d’une anesthésie l’halothane-protoxyde d’azote. Une stimulation d’une ondée-de-quatre (TOF) a été appliquee simultanément au nerf cubital et au nerf du masséter. Des transduceurs ont enregistré des forces au niveau de la mâchoire et du pouce. Le blocage maximal du premier twitch (T1) et les changements de la tension de repos maximal ont été mesurés. Le muscle masséter était plus sensible a la succinylcholine que l’adducteur du pouce avec un ED95de 0,28 ± 0,02 (moyenne ± SEM) vs0,44 ± 0,05 mg · kg−1(P < 0.05). Le débit du blocage neuromusculaire était plus rapide pour le masséter et la recuperation est survenue simultanément dans les deux muscles. Une augmentation dépendamment de la dose dans la tension de repos a été observée dans les deux muscles et son amplitude était cinq fois plus élevée au niveau du masséter. Avec du succinylcholine, 1 mg · kg−1cette augmentation était de 51,6 ± 16,8 g au masséter et 9,1 ± t2,3 gà l’adducteur du pouce. Cette augmentation de la tension diminua au niveau contrôle a l’interieur de 1–2 min. On conclut que chez les enfants 1) la succinylcholine produit des changements dépendants de la dose dans la tension de repos; 2) cet effet, quoique quantativement supérieur au niveau du masséter, n’est pas limité à ce muscle; et 3) relativement des petites doses de succinylcholine sont nécessaires afin d’acquérir un blocage neuromusculaire au niveau de la mâchoire.

The pharmacokinetic behaviour and neuromuscular blockade produced by the administration of fazadinium bromide at a dose of 1 mg/kg have been studied in seven patients with end-stage renal failure. No significant differences were found in the pharmacokinetic or pharmacodynamic properties when compared with patients with normal renal function. It is suggested that fazadinium may be superior to either d-tubocurarine or pancuronium in providing muscle relaxation for patients with renal failure.

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I– II patients (60, âgéd 65–80 yr, and 40, âgéd 20–45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N2O/O2and fentanyl, rocuronium 120,160, 200, or 240 μg · kg−1was administered to determine dose-response curves. When maximum block had been obtained,further rocuronium to a total of 300 μg · kg−1was given. Additional doses of 100 μg · kg−1were administered when the first twitch height (T1) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T1was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED50was 196 ±8 (SEE for the mean) in elderly,vs 215±17 iμg · kg− 1in young patients (NS). When individual cumulative dose-response curves were constructed, the ED50was 203 ± 7(SEM) and 201 ± 10 μg · kg− 1in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 ±1.1 (SD) vs 3.1 ± 0.9 min, P < 0.05). The time to 25% T1recovery was longer in the elderly (11.8 ± 8.1 vs 8.0 ± 6.5 min,P<0.05) as was the recovery index, time from 25 to 75% T1recovery (15.5 ± 6.2 vs 11.2 ± 4.9 min, P< 0.05). The duration of neuromuscular block after each maintenance dose was longer in the elderly (P<0.01) and increased gradually with time. It is concluded that rocuronium is an intermediate-acting neuromuscular blocking drug with a similar potency in elderly and young patients, but the onset and recovery of neuromuscular blockade are slower in the elderly.

The molecular genetic analysis of protein S deficiency has been hampered by the complexity of the protein S (PROS) gene and by the existence of a homologous pseudogene. In an attempt to overcome these problems, a reverse transcript-polymerase chain reaction (RT-PCR) mutation screening procedure was developed. However, the application of this mRNA-based strategy to the detection of gene lesions causing heterozygous type I protein S deficiency appears limited owing to the high proportion of patients exhibiting absence of mRNA derived from the mutation-bearing allele (“allelic exclusion”). Nevertheless, this strategy remains extremely effective for rapid mutation detection in type II/III protein S deficiency. Using the RT-PCR technique, a G-to-A transition was detected at position +1 of the exon IV donor splice site, which was associated with type I deficiency and resulted in both exon skipping and cryptic splice site utilization. No abnormal protein S was detected in plasma from this patient. A missense mutation (Asn 217 to Ser), which may interfere with calcium binding, was also detected in exon VIII in a patient with type III protein S deficiency. A further three PROS gene lesions were detected in three patients with type I deficiency by direct sequencing of exon-containing genomic PCR fragments: a single base-pair (bp) deletion in exon XIV, a 2-bp deletion in exon VIII, and a G0to-A transition at position-1 of the exon X donor splice site all resulted in the absence of mRNA expressed from the disease allele. Thus, the RT-PCR methodology proved effective for further analysis of the resulting protein S-deficient phenotypes. A missense mutation (Met570 to Thr) in exon XIV of a further type III-deficient proband was subsequently detected in this patient's cDNA. No PROS gene abnormalities were found in the remaining four subjects, three of whom exhibited allelic exclusion. However, the father of one such patient exhibiting allelic exclusion was subsequently shown to carry a nonsense mutation (Gly448 to Term) within exon XII.

This study was undertaken to compare the potency of vecuronium in patients anaesthetized in Montreal or Paris. Anaesthesia was induced with thiopentone and maintained with N2O, and intermittent boluses of thiopentone andfentanyl in 18 patients in Paris and 19 in Montreal. Neuromuscular blockade was measured using train-offour stimulation of the ulnar nerve. The force of contraction of the adductor pollicis muscle was measured. Single doses of vecuronium, 20, 30, or 40 μg · kg−1were given by random allocation. Dose response curves were constructed by obtaining the linear regression of the logit of the first response (T1) neuromuscular blockade versus log dose. The patients in Paris required 27% more vecuronium (95% confidence limits 5–53%; P = 0.01) for the same intensity of blockade. In Montreal, the ED50and ED90(±SEE for the mean) values were 26.0 ±1.4 and 44.2 ±2.5 μg · kg−1compared with 33.0 ±3.3 and 71.9 ±7.2 μg · kg−1in Paris respectively. The patients were comparable with respect to age, sex, height and weight. These results confirm, for vecuronium, the transatlantic difference in potency of neuromuscular blocking drugs which was previously observed with d-tubocurarine between London and New York.

Postoperative analgesia was provided to nine grossly obese patients with a continuous intravenous meperidine infusion. The narcotic was infused at an initial rate of 1.3 mg.min-1for 45 minutes, then 0.7 mgmin-1for 30 minutes followed by 0.5 mgmin-1for the next 24 hours. Pain was assessed at hourly intervals, serial blood samples were taken for measurement of plasma meperidine concentrations, and respiratory function was assessed by serial measurement of vital capacity and arterial blood gas analysis.

This study was designed to measure the potency of vecuronium with and without nitrous oxide. Anaesthesia was induced with thiopentone and fentanyl in 56 adult patients. The subjects were randomly assigned to receive nitrous oxide, 70%, or intermittent boluses of thiopentone and fentanyl for maintenance of anaesthesia. Train-of-four stimulation was applied to the ulnar nerve every 20 sec, and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 20, 30 or 40 μg·kg−1was given by random allocation five minutes after induction of anaesthesia. Maximum depression of the first response (T1) in the train-of-four was measured, and dose— response curves were constructed. In the absence of nitrous oxide, the ED50and ED95were mean ± standard error of the mean (SEM), 29.2±1.8 and 59.3±3.6 μg·kg−, respectively. In the group receiving nitrous oxide, these values were 25.3 ±1.2 and 42.3±2.0 μg· kg−1respectively. By analysis of covariance, the dose-response curves were shown to be shifted with respect to one another (P<0.05). Administration of nitrous oxide was associated with a 19.5% increase in potency (95% confidence limits: 1.7 to 40.4%). It is concluded that nitrous oxide has a slight potentiating effect on neuromuscular blockade, and that this effect occurs within five to ten minutes after the beginning of its administration.

The paper considers the closed-cycle gas turbine plant from the educational aspect of knowledge and understanding. The special qualitative features of the T-s diagram are discussed and a quantitative treatment of a simple model presented. A new expression for the maximum efficiency is given and interesting aspects of the results discussed. Technical and educational conclusions are drawn from the work.

AbstractThe crystal structure of mawbyite, PbFe2(AsO4)2(OH)2has been refined. The mineral is monoclinic, C2/mwith a= 9.066(4), b= 6.286(3) c= 7.564(3) Å, ß = 114.857(5)°, Z = 2; the structure has been refined to a conventional R = 4.3% using 361 observed reflections [I> 3s(I)]. The structure contains chains of edgesharing Fe(O,OH)6octahedra which are linked by AsO4tetrahedra and Pb atoms in distorted square antiprismatic co-ordination. The hydrogen bonding network in the structure has been modelled using bond valence calculations. Mawbyite is confirmed to be isostructural with tsumcorite and dimorphous with carminite and the relationship between these two structures is discussed.

AbstractThe crystal structure of kintoreite, PbFe3(PO4)2(OH,H2O)6, has been refined. The mineral is rhombohedral, Rmwith a= 7.3310(7), c= 16.885(2) Å, Z = 3; the structure has been refined to R = 3.0% and Rw= 3.0% using 183 observed reflections [I > 2s(I)]. Kintoreite has the alunite-type structure which consists of sheets of corner-sharing Fe(O,OH)6octahedra parallel to (001). The sheets are composed of clusters of three corner-linked octahedra which are tilted so that the three apical O atoms form the base of the XO4tetrahedra. The clusters of octahedra are linked to similar groups by corner-sharing to form six membered rings. The Pb cations occupy the cavities between pairs of octahedral sheets and are surrounded by six oxygen atoms from the tetrahedra and six oxygen atoms from the octahedra to form a very distorted icosahedron. The mean bond lengths for the various coordination polyhedra are X–O 1.55 Å, (X= P, As, S); Fe–(O, OH) 2.01 Å; Pb–O 2.84 Å. The composition of the crystal used in the refinement was PbFe3(PO4)1.3(AsO4)0.4(SO4)0.3(OH,H2O)6. The XO4anions are disordered, as in beudantite, rather than being ordered, as they are claimed to be in corkite.

AbstractA study of the composition and unit cell data of a suite of lead-rich minerals of the alunite-jarosite group from the oxidized zone of the ore body at Broken Hill, New South Wales, Australia, has revealed almost complete XO4(X= As, P, S) solid solution in these minerals at this deposit. The species in the group noted are hidalgoite, hinsdalite, beudantite, segnitite and plumbogummite. These minerals at Broken Hill exhibit a number of growth textures, including oscillatory zoning, colloform banding and replacements. Zoning in these minerals is due to the segregation of Al- and Fe-rich members, and compositions indicate a strong coupling of Fe3+with and Al with

AbstractThe crystal structure of carminite, PbFe2(AsO4)2(OH)2has been refined. The mineral is orthorhombic, Cccmwith a= 16.591(2), b= 7.580(1), c= 12.285(1) Å, Z = 8; the structure has been refined to a conventional R = 3.3% using 913 observed reflections [I>2s(I)]. The structure contains stepped chains of edge-sharing pairs of Fe(O,OH)6octahedra; these chains are linked by AsO4tetrahedra and Pb atoms in distorted square antiprismatic co-ordination. The hydrogen bonding network in the structure has been modelled using bond valence calculations.

AbstractWycheproofite is a new hydrated sodium aluminium zirconium phosphate from a pegmatite vein in granite at Wycheproof, in northwestern Victoria, Australia. The mineral occurs as compact, finely fibrous masses in small cavities in the quartz/feldspar/muscovite/schorl-bearing pegmatite. The fibrous crystals are between 5 and 10 µm wide and up to several mm long. Accompanying minerals include two other zirconium phosphates — kosnarite and a new species, selwynite, the K-analogue of gainesite — as well as wardite, eosphorite, cyrilovite, leucophosphitc, rockbridgeite, a kidwellite-like mineral and saleeite. The wycheproofite aggregates are pale pinkish to brownish orange, with a vitreous to pearly lustre. The streak is colourless, fracture rough, cleavage not observed and the Mohs hardness is between 4 and 5. Optical data are incomplete due to the fibrous nature of the mineral; the indices of refraction are in the range 1.62–1.64. The measured density is 2.83 g cm-3. Chemical analysis gave (wt.%) Na2O 6.36, K2O 0.44, CaO 0.66, FeO 0.36, MnO 0.21, Al2O312.03, Cs2O 0.03, ZrO232.43, HfO21.24, P2O535.85, SiO20.23, F 0.34, H2O 9.0, less 0=F 0.14, Total 99.04. The simplified formula is NaAlZr(PO4)2(OH)2·H2O. Wycheproofite is triclinic with unit cell parameters a=10.926(5) Å, b= 10.986(5) Å, c= 12.479(9) Å, a= 71.37(4)°, ß= 77.39(4)°, ?= 87.54(3)° V= 1375.9 Å3. For Z= 6, the calculated density is 2.81 g cm-3. The strongest lines in the X-ray powder diffraction pattern are [dobs(Å), Iobs,hkl] 2.603 (100) 040; 4.128 (80) 121; 3.711 (65) 023; 3.465 (60) 030; 8.865 (40) 101; 3.243 (35) 132. The crystal structure has not been solved due to the finely fibrous nature of the material available. The name is for the locality, which in the local Australian Aboriginal language means ‘witchie bushes growing on a hilltop’.Data on the third occurrence of kosnarite, KZr2(PO4)3, at Wycheproof are also given.

AbstractDuftite, PbCu(AsO4)(OH) is orthorhombic, space group P212121with a= 7.768(1), b= 9. 211(1), c= 5.999(1) Å, Z = 4; the structure has been refined to R = 4.6% and Rw = 6.5% using 640 observed reflections [F> 2s(F)]. The structure consists of chains of edge-sharing CuO6‘octahedra’, parallel to c; which are linked via AsO4tetrahedra and Pb atoms in distorted square antiprismatic co-ordination to form a three dimensional network. The CuO6‘octahedra’ show Jahn-Teller distortion with the elongation running approximately along <627>. The hydrogen bonding network in the structure was characterized using bond valence calculations. ‘ß-duftite’ is an intermediate in the duftite-conichalcite series, which has a modulated structure based on the intergrowth of the two structures in domains of approximately 50 Å. The origin of the modulation is thought to be associated with displacements in the oxygen lattice and is related to the orientation of the Jahn-Teller distortion of CuO6‘octahedra’. Approximately half of the strips show an elongation parallel to <627> while the other strips are elongated parallel to [010]. This ordering results in an increase in the bcell repeat compared to duftite and conichalcite.

A retrospective study of postoperative respiratory morbidity in 247 patients requiring renal transplantation between 1955 and 1973 showed that 7 patients required postoperative controlled ventilation for up to 6 days. The non‐depolarising relaxants tubocurarine and pancuronium were used in only 65 patients, but all 7 cases of respiratory failure occurred in this group. This suggests that the use of these drugs in anephric patients is potentially hazardous so far as postoperative respiratory insufficiency is concerned.

The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. The onset and recovery time constants of inhibition of brief acetylcholine pulses, caused by long pulses of relaxants for all of the muscle relaxants, were inversely related to apparent dissociation constants (KD values), that ranged from 4.56 microM (gallamine) to 0.11 microM (doxacurium). The kinetics showed only modest temperature dependence (Q10 values of 1/time constant of offset were typically < 1.4). Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

Doxacurium (30 µg/kg) pharmacokinetics and pharmacodynamics were evaluated in nine elderly (age range, 70 to 83 years) and nine young (age range, 19 to 39 years) patients under nitrous oxide–isoflurane anesthesia. The force of contraction of the adductor pollicis was monitored and plasma samples were collected for an 8-hour period. In the elderly group, doxacurium elimination half-life was prolonged (119.7 versus 75.9 minutes) and plasma clearance was significantly reduced (1.75 versus 2.54 ml/min/kg) without any change in volume of distribution. Onset (12.9 versus 8.9 minutes) and recovery times (113.4 versus 48.1 minutes) were longer in the elderly group. The equilibrium rate constant to the effect compartment (keo) was decreased in the elderly (0.039 versus 0.051 min-1), whereas the effect compartment concentration at 50% block was similar in both groups (44.7 versus 54.1 ng/ml). An age-related reduction in muscle blood flow may be responsible for the decrease in keo. The pharmacokinetic changes observed in the elderly are consistent with a decreased function in the organs of elimination.

An attack by Bupalus piniariusL., the Pine looper, at Cannock Chase in 1953 (Forestry, xxxii. 166) led to an annual routine survey of pupal populations by the Forestry Commission. This survey revealed a gradual rise to epidemic levels at Tentsmuir by 1957 and to control by fogging. The paper describes the precautions taken before control to make sure that losses occurring between pupal and larval stage had not removed the threat. These precautions included sampling on a sufficient scale but the author shows how this last minute sampling could be much reduced by the assumption of a pupal count/egg density relationship. He describes the fogging technique and the climatic conditions needed for success and gives results in larval drop counts.

Mechanical heart valves are associated with a risk of thromboembolism and anticoagulation is generally recommended. However, this is inevitably associated with a risk of intracranial bleeding. The case of a patient who sustained an intracranial bleed while taking warfarin for a prosthetic aortic valve and a further two intracranial bleeds while on heparin as an inpatient is discussed and the literature on the management of intracranial haemorrhage in patients on warfarin with prosthetic valves is reviewed.