Biomedical subjects
Publications and source records attributed to A Webster.
Light and electron microscopic studies of a patient with sickle cell trait who had an episode of sickling during coronary artery surgery, from which he died, showed fibrin thrombi, focal alveolar wall necrosis, and epithelial cell damage. It is suggested that in cases of sickle trait full precautionary measures should be taken to prevent sickling in these circumstances.
We report a fatal case of hepatitis B reactivation following autologous bone marrow transplantation for acute lymphocytic leukaemia. The presence of antibodies to HBs and HBc at presentation indicated previous infection with hepatitis B; these antibodies disappeared during the course of treatment for leukaemia. HBsAg was first detected in serum 5 weeks post-transplant; liver function tests began to deteriorate 8 weeks later, when HBeAg was first detected. The hepatitis followed a fulminant course, and the patient died 10 days later, in the 15th week following transplant.
A monoclonal antibody method was used as a primary O serotyping method for 1084 isolates of Pseudomonas aeruginosa, using commercially available antibody reagents in slide agglutination tests with whole-cell antigen. Differences in distribution of serogroups were found between various hospitals in the district. Serotyping provided useful information in the investigation of suspected incidents of cross-infection. Colonization at multiple sites, or over periods of time, in a single patient usually involved only a single serogroup.
Teicoplanin, a recently introduced glycopeptide antibiotic, has been used, in combination with other antibiotics, to treat 31 episodes of septicaemia caused by Gram-positive organisms. Teicoplanin has double the activity of vancomycin against many Gram-positive bacteria, but allergic reactions and toxicity appear to be infrequent. A single daily dose is sufficient to maintain therapeutic levels, which is an advantage in conditions requiring long-term treatment. Of the 31 episodes treated, 16 were associated with infective endocarditis, 11 with Hickman catheter infection, two with bone and joint infection, and two with infection of other indwelling prosthetic devices. Staphylococcus epidermidis was isolated in 18 infections, of which seven treatment courses were unsuccessful. One death occurred from an uncontrolled infection, three deaths from underlying disease (one of which had relapsed twice), and one after withdrawal of treatment following febrile reaction. Eleven episodes were cured. Six episodes of Staphylococcus aureus septicaemia were treated, of which two failed to respond, two relapsed, one improved and one was cured. The remaining seven episodes were caused by streptococci (including Streptococcus faecalis), and in all of them cure was achieved despite the lack of consistent serum bactericidal activity in vitro.
Antibiotic-resistant coagulase-negative staphylococci are a frequent cause of infection in indwelling central venous (Hickman) catheters. Teicoplanin has been evaluated in the treatment of 19 immunosuppressed patients with staphylococcal Hickman catheter infections, nine of whom were septicaemic. All infections were eradicated, with minimal side effects. In 16 cases, the catheter was retained until no longer required. Two recurrent infections were eradicated by a second course of teicoplanin. We conclude that teicoplanin is an effective and well-tolerated antibiotic in the treatment of Hickman catheter infections in immunosuppressed patients.
Teicoplanin, a new glycopeptide antibiotic, has been used to treat twelve patients with bacterial endocarditis due to Gram-positive organisms. Teicoplanin has activity against Gram-positive bacteria similar to vancomycin but therapeutic levels are maintained by a single daily dose, given as an intravenous bolus. Of six patients with native valve infections, two cases, due to viridans streptococci, were successfully treated with teicoplanin alone and two others, caused by Streptococcus faecalis, were cured by combinations including teicoplanin. One of these patients sustained high tone hearing loss during treatment. The remaining two patients were drug addicts with endocarditis due to Staphylococcus aureus which recurred despite repeated multiple therapy. Of six prosthetic valve infections, antibiotic combinations including teicoplanin cured three cases, caused by streptococci. Infection persisted or treatment was curtailed in three cases of Staphylococcus epidermidis endocarditis. In this small open study, teicoplanin appeared as effective as vancomycin in the treatment of endocarditis but had the considerable advantage of ease of administration.
Streptococcus pyogenes is a potential cause of serious infections in plastic surgery and burns units. We report an outbreak of this organism in one such unit, which was successfully managed by closing the ward, and treating infected patients with a new antibiotic, teicoplanin.
Explore the source record for details and available documents.
Behavioral depression produced by exposing animals to a stressor that they cannot control (uncontrollable shock) was reversed by infusion of the monoamine oxidase (MAO) inhibitor pargyline into the locus coeruleus (LC) region of the brain stem. Following exposure to uncontrollable shock, rats were infused through bilateral cannulas implanted in the LC region with either pargyline or vehicle. At 110 min after infusion, animals were tested for behavioral activity in a swim tank. Immediately following the behavioral test, animals were sacrificed for determination of the monoamines [norepinephrine (NE), dopamine (DA), serotonin (5-HT)], as well as 5-hydroxy-indoleacetic acid (5-HIAA) in various brain regions. The results showed that animals exposed to uncontrollable shock and then infused with vehicle exhibited significantly less activity in the swim test than animals not exposed to shock and similarly infused with vehicle; thus, the usual behavioral depression following exposure to uncontrollable shock was observed. On the other hand, shocked animals infused with pargyline did not show reduced activity in the swim test. Unshocked animals infused with pargyline showed no more activity than did shocked animals infused with pargyline or unshocked animals infused with vehicle, which demonstrated that the infusion of pargyline into shocked animals did not eliminate the shock-induced depression of activity simply by generally stimulating motor activity. Measurement of the concentration of NE, DA, 5-HT, and 5-HIAA present in seven brain regions at the conclusion of the swim test showed that pargyline infusion into the LC eliminated the large depletion of NE in the LC that is normally observed after exposure to uncontrollable shock while having no effect on NE levels in the other brain regions examined. The level of 5-HT in the LC was also raised by infusion of pargyline into the LC, but again, there was no effect of pargyline infusion on 5-HT levels in any of the other brain regions. In conclusion, infusion of pargyline into the LC region of the brain eliminated both the large depletion of NE in the LC region and the behavioral depression that otherwise results from exposure of animals to uncontrollable shock.
These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.
Teicoplanin was used to treat 94 hospital in-patients of confirmed or presumed Gram-positive infections over a period of 12 months. Eighty-five patients were subsequently found to be evaluable; 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections, 12 septicaemias, 2 chest infections, 7 osteomyelitis or septic arthritis, and 15 were immunosuppressed patients with infected Hickman line site infections. The cure rate of the 85 evaluable episodes was 90% (76 cured). Teicoplanin was well tolerated intravenously and intramuscularly. Adverse reactions occurred in five patients. One patient suffered high tone hearing loss, two patients suffered transient rash, one developed a drug fever and one patient who had concomitant gentamicin developed vestibular damage. It is concluded that teicoplanin is a relatively safe and effacacious treatment for Gram-positive infection.
A simple and rapid method is described for the preparation of a marine oil fraction highly enriched in (n - 3) polyunsaturated fatty acids. Cod roe, containing lipid up to 15% of its dry weight, approximately 70% of which is phospholipid, was the starting material. Incubation of a concentrated aqueous extract of the roe with porcine pancreatic phospholipase A2 (EC 3.1.1.4) was the key step in the procedure. Extraction of the freeze-dried reaction product with diethyl ether containing formic acid produced an oil in a yield of 1.0 g/100 g wet wt of starting roe. The oil contained over 95% as free fatty acids, with 20:5 (n - 3) and 22:6 (n - 3) accounting for up to 24 and 40%, respectively, of the total free fatty acids. The therapeutic use of the oil is mentioned.
The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomised and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/ml and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 l/kg, 68 ml/min and 12 h respectively. Autonomic effects were maximal within 0.5 h of intravenous administration and at about 1-2 h after oral dosing. Significant effects on pupil diameter, visual near point, salivary secretion and heart rate occurred after intravenous treatment and similar but less marked effects occurred after the oral dose. Significant autonomic effects were still detectable 12 h after both forms of treatment.
Explore the source record for details and available documents.
Following an open pilot study, BW 245C , a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms BW 245C produced significant (p less than 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C . Platelet aggregation responses to ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms BW 245C . Aggregation responses to collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms BW 245C and also at 120 minutes after 50 micrograms BW 245C . Bleeding time was unchanged in response to either dose of BW 245C . There was no change in headache or abdominal discomfort scores following either dose of BW 245C . Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.
Nematodes of the genus Onchocerca were found in mineralized foci in subcutaneous tissues near the stifle joint in several animals and in the gastrosplenic ligament in one case. These tissues were submitted to this laboratory by veterinary meat inspectors suspecting lesions of bovine tuberculosis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.