Search

The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8-fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine. Clinical Pharmacology and Therapeutics (1989) 45, 260–269; doi:10.1038/clpt.1989.26

Heat treatment is employed to diminish the transmission of hepatitis when blood products are administered. It is possible that such a procedure could reduce the biological activity of the proteins and induce changes in structure and aggregation state. We have therefore made in vitro and pharmacokinetic studies of heat treated antithrombin III (AT III) concentrate using both radiolabelled and non-labelled preparations. The purification, heat treatment and the radiolabelling procedures did not induce any changes in the AT III molecules with exception of a decrease in heparin affinity in about 10% of the molecules. The in vivo studies using 125I AT III showed that the fractional catabolic rate was increased and the half-life was shortened by about 20–25% compared to our previous studies on non-heat treated AT III concentrate. Our present findings indicating a mean half-life of 3.0 days are quite comparable to studies by others on non-heat treated AT III, however.

The new substance CGP 4718 A (4-(5-chloro-2-benzofuranyl)-1-methylpiperidine hydrochloride) in animal experiments shows both 5-HT-uptake blocking and (preferentially) MAO-A inhibiting properties. CGP 4718 A was studied in man to evaluate its effects on the noradrenergic, dopaminergic and serotonergic systems by measuring urinary metabolites. In a randomized placebo-controlled cross-over study 6 healthy volunteers (3 males, 3 females) were treated for two weeks with CGP 4718 A (2 × 50 mg/d p.o.) or placebo, respectively. In between was an interval of two weeks without drugs. Daily 24 h urine was collected during and for 2 weeks after treatment. Tryptamine was measured by GC with packed columns, 3-methoxy-4-hydroxyphenyl-ethylene glycol (MHPG), homovanillic acid (HVA), vanillylmandelic acid (VMA) and 5-hydroxyindolacetic acid (HIAA) by capillary GC.

✓ A case is reported of a giant aneurysm of the intracavernous portion of the left internal carotid artery that was treated initially with a left common carotid artery ligation. Six months later the aneurysm was partially removed. During this time the development and evolution of thrombus formation, a serpentine channel, and a hypervascular capsule was easily followed with reeeated computerized tomography and angiography of the aneurysm.

Dogs with an inherited form of ceroid lipofuscinosis are ataxic, blind and demented. During the disease process, they undergo severe cerebrocerebellar atrophy with storage of autofluorescent, lipid peroxide-positive reacting substances whose ultrastructure resembles 'fingerprint' patterns of membranous lamellae. The retina and RPE also undergo pathologic changes. Most important is the inverse relationship between loss of RPE melanin and increased deposition of ceroid. These pathological events in brain and eye lead to altered EEG, ERG and VEP activity. This inbred strain of English setters fulfills essentially all the criteria as a model for the human disease and will prove useful in the future for therapeutic trials.

1. CGS 8216 is metabolised to the hydroxy metabolite CGS 11 361 in rat and in man with a much higher metabolite/parent drug ratio in man (2.5 vs 0.1). 2. The brain/plasma concentration ratio of the parent drug in the rat 30 min after 10 and 25 mg/kg IP is low, suggesting slow penetration of the drug into the brain tissue. 3. No hydroxy metabolite of CGS 8216 was found in the brain of treated rats. 4. The discrepancy between our results and those of Lister et al. i.e. 12–20 times lower drug concentrations in plasma and no detectable drug in brain tissue, are hard to explain. It does not seem likely that it is caused by the use of two different strains of rats with apparently differing age. One explanation might be the better bioavailability of CGS 8216 given in polyethylene glycol/water and the 10-fold lower limit of quantitation of the HPLC method we used. 5. The findings of Lister et al. are not supported by our data.

A severe iron intoxication in a 15-year-old girl resulted in profound damage to vital organs and multiple clotting defects, but no haemorrhagic diathesis. Investigation revealed not only impaired synthesis of coagulation factors but also abnormal proteo-lysis by plasmin as well as by other proteolytic enzymes liberated from leucocytes and damaged tissue cells affecting especially factor VIII and factor XIII.

The force-velocity relationship was determined at the moment of isometric peak twitch force in rabbit papillary muscles using the damped-release technique described previously. The analysis was carried out in each muscle at two or three temperatures within the range 22–338deg; C. The experimental data were fitted with Hill's equation by means of a computer program using the least squares method. Lowering of the temperature caused an increase of the isometric peak twitch force (Po) and also, generaliy, an increase of the extrapolated value of Vmax (the shortening velocity at zero load). The temperature-induced changes of the force-velocity curve were interpreted as being the net result of two opposing effects: I. an altered degree of activation of the contractile system caused by a change in the amount of activator-calcium bound to the contractile proteins (‘inotropic temperature effect’), and 2. a change in the rate of interaction between the A and I filaments independent of the degree of activation (‘specific temperature effect’). The analysis indicated a Q10 of 1.9 for the specific temperature effect. This value accords with the temperature dependence of Vmax that has been observed during tetanic contraction of skeletal muscle.

Retinae of Abyssinian cats homozygous for a retinal degeneration gene, and normal controls, have been investigated using antibodies directed against opsin, transducin alpha (TD-alpha), S-antigen (48K protein), interphotoreceptor retinoid-binding protein (IRBP), and cone outer segments. IRBP-immunoreactivity (IR) is much reduced at stage 2 of the disease in affected retinae; later massive photoreceptor cell death occurs. In cats, at a late stage of the disease, the retina exhibits few S-antigen-IR cells in the peripheral part of the retina whereas, in the central part, some patches of cells exhibiting opsin-IR, TD-alpha-IR, and S-antigen-IR are present in remnants of the outer nuclear layer (ONL). No IRBP-IR is detectable at this stage. The form and size of the majority of these remaining cells, however, does not resemble that of normal photoreceptors. No, or only rudimentary, inner and outer segments are present; long bifurcating basal protrusions often occur. These cells, which could be remains of cone elements, are S-antigen immunoreactive. Double labelling for different retina-specific proteins reveals a co-localization of opsin, TD-alpha and S-antigen in some, but not all, remaining photoreceptor elements. Cells exhibiting opsin-IR also show TD-alpha-IR and S-antigen-IR located within the entire cell and its protrusions. In control retinae and retinae at early stages of the disease, immunoreactions are comparable with all antibodies used. However, TD-alpha-IR is less intensive in the photoreceptor terminals. S-antigen-IR cones are most frequently present in the peripheral retina. Reduction of IRBP at an early stage of the disease could be one of the factors leading to photoreceptor cell death at later stages.

In 6 healthy, young volunteers the kinetics of L-tryptophan (TRP) following 3 different single oral doses (1.5, 3, 6 g) simultaneously with urinary tryptamine (TA) excretion were examined. Blood and urine samples were collected hourly before and for 14 h after TRP. TRP in plasma and TA in urine were analysed by specific and sensitive HPLC methods using UV and fluorometric detection, respectively. The measurements were repeated in one volunteer after pretreatment with the decarboxylase inhibitor benserazide (3 × 125 mg/d for 15 days), and in 2 volunteers after pretreatment with the selective and reversible inhibitor of MAO-A, brofaremine (150 mg/d for 10 days).

In the studies presented, the relative extent of tyramine (TYR) deamination to p-hydroxyphenylacidic acid (HPAA) and of TYR conjugation was determined before and during treatment with 5 different MAO inhibitor (MAOI) drugs. Healthy ambulatory subjects were treated p.o. for 2 – 4 weeks. Data were evaluated from (n) subjects. MAOI drugs were: Brofaromine (Brof): 100 – 150 mg/d (9); clorgyline (Clor): 5, 10, 15 mg/d (3); selegiline (Sel): 5, 20 mg/d (6); tranylcypromine (TCP): 20 mg/d (4) and phenelzine (Phen): 30, 45 mg/d (l). After oral doses of TYR causing systolic blood pressure (BP) increases of 30 mm Hg, plasma concentrations of HPAA, conjugated (conj) TYR (after enzymatic deconjugation) and of unconjugated (unc) TYR were determined by HPLC. The area under the plasma level-time curve (AUC) was calculated considering the different TYR doses given (AUCspec). The following results were obtained: 1. In l6 untreated subjects une TYR and conj TYR in plasma amount to 0.4 ± 0.2% and 12.5 ± k4.3% of the sum of total TYR + HPAA. 2. During subchronic MAO inhibition, the AUCspec of conj TYR after oral TYR administration increases in varying degrees from 12.5% to 92% of the total AUCspec (total TYR + HPAA). This is accompanied by a maximal decrease of AUCspec of HPAA from 87.1% to 8%. 3. The following order of increasing potency for inhibiting gastrointestinal MAO could be established: Sel (MAO-B, irreversible), Brof (MAO-A, reversible), Phen (MAO-A+B, irreversible), Clor (MAO-A, irreversible) and TCP (MAO-A+B, partially irreversible).

Pairs of rabbit papillary muscles were mounted in series to make it possible to study the effects of asynchronous activation on myocardial contraction. The two muscles were connected together via platinum loops hooked to a lever (displacement transducer), the other end of each muscle being fixed to a force transducer. The force of each muscle was measured at various contraction frequencies with the lever fixed (isometric contractions) or freely movable (auxotonic contractions). With auxotonic contractions, asynchronous activation (25 or 50 ms interval between stimulation of the two muscles) increased the movements of the muscles, decreased their force, and prolonged the duration of the contraction at 37°C. These effects were greater, the higher the contraction frequency within the range 30–150 beats/min. On the basis of these results, it is suggested that the physiological asynchrony of the myocardial contraction in vivo tends to offset frequency-induced changes at the cellular lever (enhanced intensity of active state, shortening of active state duration).

The relation between contraction frequency and mechanical performance was investigated in isolated perfused heart preparations and in papillary muscles from human fetuses at mid-gestation. The influence of mepivacaine on the isometric force and the action potential of the papillary muscles and on the contractility of the whole hearts was also studied. Under the experimental conditions used, the isometric force of the papillary muscles increased with frequency within the range 60 to 180 contractions per min. The right intraventricular pressure of the isovolumetrically contracting hearts was influenced only to a minor degree by changes in contraction rate between 60 and 150 contractions per min and decreased at higher frequencies. Mepivacaine (0.625–10 μg/ml) caused a dose-dependent decrease of the active force and a slight reduction of the duration of the action potential in the papillary muscle. The effects of contraction frequency and of mepivacaine are discussed in relation to the asynchrony of the ventricular contraction.

Background Epidemiological data on characteristics of patients undergoing open or laparoscopic cholecystectomy are limited. In this register study we examined characteristics and mortality of patients who underwent cholecystectomy during hospital stay in Sweden 2000 – 2003. Methods Hospital discharge and death certificate data were linked for all patients undergoing cholecystectomy in Sweden from January 1st 2000 through December 31st 2003. Mortality risk was calculated as standardised mortality ratio (SMR) i.e. observed over expected deaths considering age and gender of the background population. Results During the four years of the study 43072 patients underwent cholecystectomy for benign biliary disease, 31144 (72%) using a laparoscopic technique and 11928 patients (28%) an open procedure (including conversion from laparoscopy). Patients with open cholecystectomy were older than patients with laparoscopic cholecystectomy (59 vs 49 years, p < 0.001), they were more likely to have been admitted to hospital during the year preceding cholecystectomy, and they had more frequently been admitted acutely for cholecystectomy (57% Vs 21%, p < 0.001). The proportion of women was lower in the open cholecystectomy group compared to the laparoscopic group (57% vs 73%, p < 0.001). Hospital stay was 7.9 (8.9) days, mean (SD), for patients with open cholecystectomy and 2.6 (3.3) days for patients with laparoscopic cholecystectomy, p < 0.001. SMR within 90 days of index admission was 3.89 (3.41–4.41) (mean and 95% CI), for patients with open cholecystectomy and 0.73 (0.52–1.01) for patients with laparoscopic cholecystectomy. During this period biliary disease accounted for one third of all deaths in both groups. From 91 to 365 days after index admission, SMR for patients in the open group was 1.01 (0.87–1.16) and for patients in the laparoscopic group 0.56 (0.44–0.69). Conclusion Laparoscopic cholecystectomy is performed on patients having a lower mortality risk than the general Swedish population. Patients with open cholecystectomy are more sick than patients with laparoscopic cholecystectomy, and they have a mortality risk within 90 days of admission for cholecystectomy, which is four times that of the general population. Further efforts to reduce surgical trauma in open biliary surgery are motivated.

SummaryBackground We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. Objective The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. Methods Pregnant women from eastern Denmark were invited during 2008–2010 to a novel unselected ‘COPSAC2010’ cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. Results Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. Conclusions The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

The work presented here addresses the outer electroding of a fully textile piezoelectric strain sensor, consisting of bi-component fibre yarns of β-crystalline poly(vinylidene fluoride) (PVDF) sheath and conductive high density polyethylene (HDPE)/carbon black (CB) core as insertions in a woven textile, with conductive poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) coatings developed for textile applications. Two coatings, one with a polyurethane binder and one without, were compared for the application and evaluated as electrode material in piezoelectric testing, as well as tested for surface resistivity, tear strength, abrasion resistance and shear flexing. Both coatings served their function as the outer electrodes in the system and no difference in this regard was detected between them. Omission of the binder resulted in a surface resistivity one order of magnitude less, of 12.3 Ω/square, but the surface resistivity of these samples increased more upon abrasion than the samples coated with binder. The tear strength of the textile coated with binder decreased with one third compared to the uncoated substrate, whereas the tear strength of the coated textile without binder increased with the same amount. Surface resistivity measurements and scanning electron microscopy (SEM) images of the samples subjected to shear flexing showed that the coatings without the binder did not withstand this treatment, and that the samples with the binder managed this to a greater extent. In summary, both of the PEDOT:PSS coatings could be used as outer electrodes of the piezoelectric fibres, but inclusion of binder was found necessary for the durability of the coating.

Recent advances in ubiquitous low-power electronics call for the development of light-weight and flexible energy sources. The textile format is highly attractive for unobtrusive harvesting of energy from e.g., biomechanical movements. Here, we report the manufacture and characterisation of fully textile piezoelectric generators that can operate under wet conditions. We use a weaving loom to realise textile bands with yarns of melt-spun piezoelectric microfibres, that consist of a conducting core surrounded by β-phase poly(vinylidene fluoride) (PVDF), in the warp direction. The core-sheath constitution of the piezoelectric microfibres results in a—for electronic textiles—unique architecture. The inner electrode is fully shielded from the outer electrode (made up of conducting yarns that are integrated in the weft direction) which prevents shorting under wet conditions. As a result, and in contrast to other energy harvesting textiles, we are able to demonstrate piezoelectric fabrics that do not only continue to function when in contact with water, but show enhanced performance. The piezoelectric bands generate an output of several volts at strains below one percent. We show that integration into the shoulder strap of a laptop case permits the continuous generation of four microwatts of power during a brisk walk. This promising performance, combined with the fact that our solution uses scalable materials and well-established industrial manufacturing methods, opens up the possibility to develop wearable electronics that are powered by piezoelectric textiles.

Groin hernia repair can be performed under general (GA), regional (RA), or local (LA) anaesthesia. This multicentre randomised trial evaluates patient acceptance, satisfaction, and quality of life with these three anaesthetic alternatives in hernia surgery.One hundred and thirty-eight patients at three hospitals were randomised to one of three groups, GA, RA, or LA. Upon discharge, they were asked to complete a specially designed questionnaire with items focusing on pain, discomfort, recovery, and overall satisfaction with the anaesthetic method used. The global quality-of-life instrument EuroQol was used for estimation of health perceived.Significantly more patients in the LA group than in the RA group felt pain during surgery ( P0.001). This pain was characterised as light or moderate and for the majority of LA patients was felt during infiltration of the anaesthetic agent. Postoperatively, patients in the LA group first felt pain significantly later than patients in the other two groups ( P=0.012) and significantly fewer LA patients consumed analgesics more than three times during the first postoperative day ( P=0.002). The results concerning nausea, vomiting, and time to first meal all favour LA. No difference was found among the three groups concerning overall satisfaction and quality of life.In a general surgical setting, we found LA to be well tolerated and associated with significant advantages compared to GA and RA.

The note contains corrected figures for shore displacement in the Degerfors area, Middle Sweden, in comparison with Hyyppas figures from Finland.

T he investigation of the traces of ancient changes of climate which the present writer started in British East Africa in 1927-1928 was partly carried out on high mountains there, partly in the eastern branch of the Great Rift Valley in the neighbourhood of the Equator (NILSSON, 1932). Traces of former pluvial periods in British East Africa (abbreviated B. E. A. below) are abundant. The heavier precipitation of these periods gave rise to large glaciers, the extension of which are marked by huge moraines far down the slopes of the highest mountains, and in the areas between the mountains we find almost everywhere evidence of such periods in the numerous river beds and ancient lake basins, now wholly or partly dried up. Especially in the basins of the Rift Valley, the series of ancient lake sediments and beaches give a very good idea of the sequence of pluvial and interpluvial periods and their subepochs which have followed each other up to the present time. During my work in B. E. A. it gradually became clear to me that traces of pluvial and interpluvial periods must no doubt occur also in adjacent parts of Africa where the conditions for their development were favourable. It seemed to me that Abyssinia must be, from my point of wiew, a very promising country, though HUME and CRAIG (1911) and other geologists consider that Abyssinia, even during the pluvial periods, had a drier climate than it has to-day. .In July 1932 I went to Kenya Colony in order to complete my former observations in the Nakuru-Naivasha Basin and on Mount Kenya, but the main object of my expedition was to extend the field of investigation to Abyssinia. During the first half of 1933 I travelled by caravan from Addis-Abbaba to the Blue Nile, Lake Tana and the high mountains of Semien in the northernmost part of the Abyssinian Plateau. Afterwards I visited the Zwai-Shalla Basin in the Rift Valley and also Mount Kaka, the highest point of the Somaliland Plateau, situated at the NW. corner of the plateau. In Fig. I Mount Kaka lies just N. of A in the word Alutu, E. of Lake Zwai.