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Biomedical subjects

W Campbell

Publications and source records attributed to W Campbell.

At least 19 recordsLinked to original sources

Crystallization and preliminary crystallographic studies of the FAD domain of corn NADH: nitrate reductase.

Crystals of the flavin domain of corn nitrate reductase expressed in Escherichia coli have been obtained at room temperature, using sodium citrate as precipitant. The crystals diffract to at least 2.5 A resolution at a synchrotron radiation source. Precession photographs show that they belong to the rhombohedral space group R3 with unit cell dimensions a = b = 145.4 A, c = 47.5 A, alpha = beta = 90 degrees and gamma = 120 degrees. There is one subunit per asymmetric unit which gives a packing density of 3.2 A3/Da, indicating a high solvent content in these crystals.

Crystallization

The use of hepatobiliary scintigraphy in patients with acalculous biliary colic.

Twelve patients with biliary colic had no evidence of gallstones but underwent cholecystokinin-augmented hepatobiliary scintigraphy that revealed gallbladder ejection fractions of less than 35%. All 12 patients underwent cholecystectomy. Biliary colic was relieved in all patients at a mean postoperative follow-up of 2.5 years. The biliary colic in these patients was probably caused by abnormal gallbladder emptying, itself apparently produced by either cystic duct obstruction or abnormal motility. Biliary abnormality was seen at operation in most patients, and all patients had abnormalities of the gallbladder or cystic duct seen grossly or histologically. These abnormalities included cystic duct stenosis or adhesions, chronic inflammation, and cholesterolosis.

Adult

Antisense sequences of antigenic peptides are found in MHC class II molecules.

The sequence of the well known antigenic peptide OVA 323-339 as well as other peptides containing reiterative motifs of the core region essential for binding to Class II MHC molecules was compared for homology with the DNA derived antisense peptide sequences corresponding to the alpha chain of the mouse IAd molecule. Homology was obtained within the sequence found in the transmembrane region of the molecule. Increased binding of the peptides containing the reiterative motifs based on the OVA 323-339 sequence may be due to the increased number of contact sites on IAd molecules which were identified as being complementary in a sense-antisense manner.

Amino Acid Sequence

An arginine carboxypeptidase generated during coagulation is diminished or absent in patients with rheumatoid arthritis.

A novel arginine carboxypeptidase that is generated during blood coagulation is diminished in sera obtained from patients with rheumatoid arthritis. The enzyme, which is unrelated to carboxypeptidase N, is more effective than lysine in removing terminal arginine from small synthetic substrates and may function in vivo in the removal of terminal arginine from inflammatory peptides such as C3a and C5a. Either diminished levels of this enzyme or an inability to generate it may be an important consideration in the mechanisms involved in the local inflammation that is observed in patients with rheumatoid arthritis.

Arthritis, Rheumatoid

An arginine specific carboxypeptidase generated in blood during coagulation or inflammation which is unrelated to carboxypeptidase N or its subunits.

An unstable carboxypeptidase N or B like enzyme is generated as a result of coagulation. This enzyme is derived from some plasma component (s) and not from blood cells or platelets. Furthermore, the activity generated is specific for arginine substrates insofar as small synthetic substrates are concerned. The enzyme is unrelated to CPN or any of its subunits or subunit fragments. This transient carboxypeptidase may be involved in the processing and/or scheduling of different functions of bioactive peptides generated during inflammation.

Arginine

120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer.

Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer.

Adult

A randomized clinical trial of haloperidol decanoate and fluphenazine decanoate in the outpatient treatment of schizophrenia.

We carried out an 8-month double-blind clinical trial comparing haloperidol decanoate with fluphenazine decanoate in the maintenance treatment of 72 schizophrenic outpatients. A parallel-groups design was used with stratification by sex and injection interval (2, 3, or 4 weeks). The initial injection interval was based on pretrial maintenance treatment with fluphenazine esters. The dosage equivalency of haloperidol decanoate (1.5 cc or 75 mg) to fluphenazine decanoate (1 cc or 25 mg) used was 3:1. This remained approximately the same throughout a 2-month titration period with a flexible dose regimen, and a further 6-month period with a fixed dose regimen. No statistically significant differences in therapeutic effect were found between the drugs. Both drugs had a similar profile for drug-induced parkinsonism, but there was a trend for differences in masking tardive dyskinesia. Haloperidol and prolactin plasma concentrations were well correlated with dosage, with the exception of haloperidol concentrations in patients receiving injections at 2-week intervals.

Adolescent

The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide.

BRL 34778, exo-4-amino-5-chloro-2-methoxy-N-[9-(4-fluorophenylmethyl)-9-azabi cyclo(3.3.1) non-3-yl]-benzamide, is a very potent and specific dopamine D2-receptor antagonist. It exhibits a Ki value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(Ki 5700 nM) and for many other receptor types. Its action is potent and of long duration in models for antipsychotic activity (4 h ED50s PO are 0.017 mg/kg for antagonism of apomorphine-induced climbing in mice and 0.028 mg/kg for antagonism of amphetamine-induced locomotion in rats). In contrast to its high potency in models for antipsychotic activity, BRL 34778 is much weaker in models for extrapyramidal effects and sedation (4 h ED50s PO are 2.4 mg/kg for inducing catalepsy in rats and 1.14 mg/kg for inhibition of rearing behaviour in rats). These data indicate potent activity of BRL 34778 in models for antipsychotic activity but low activity in models for extrapyramidal effects and sedation.

Adenylyl Cyclase Inhibitors

Diclofenac sodium for post-tonsillectomy pain in children.

Diclofenac sodium was assessed as an analgesic for postoperative pain following paediatric tonsillectomy in a randomised double blind trial. In a comparison made with both a pethidine and a control group diclofenac was shown to be an effective analgesic. No significant difference in analgesic efficacy was demonstrated between the two drugs, although patients who received diclofenac tended to be less drowsy postoperatively than those who received pethidine. There were no significant differences between the two drugs in respect of time to awaken from anaesthesia or incidence of postoperative vomiting.

Anesthesia Recovery Period

Risk versus motivation: the emergency room treatment of attempted suicide.

This paper deals with patients who attempt suicide, focusing on their evaluation in the emergency room. It is suggested that as the actual risk of completed suicide in suicide attempters is low, the evaluating psychiatrist might preferentially focus on assessing the patient's motivation for self-destructive behaviour. Recent studies are reviewed which demonstrate a linkage between self-destructive acts and the status of relationships with significant others. An illustrative case history is presented.

Adult

BRL 20596, a novel anilide with central dopamine antagonist activity.

BRL 20596 (N-(4-amino-5-chloro-2-methoxyphenyl)-1-phenylmethyl-4-piperidine-carbox amide) is a novel anilide related to clebopride (a gastric prokinetic benzamide) in which the sole change is reversal of the amide bond. Previous studies have shown conformational and electronic differences between these molecules which result in the anilide losing its gastric prokinetic activity, whilst retaining its central nervous system activity. Pharmacological and biochemical properties of BRL 20596 are compared here in animals with chlorpromazine, clebopride, haloperidol and sulpiride. BRL 20596 potently inhibited a number of behaviours, such as conditioned avoidance, amphetamine-induced stereotypy and turning, and apomorphine-induced climbing. Homovanillic acid (HVA) levels in the striatum and nucleus accumbens were raised at similar dose levels to those which inhibited these behaviours, whilst sedative activity was only exhibited at much higher dose levels. Haemodynamic changes were only observed with high IV doses of BRL 20596. Much lower doses of sulpiride were needed to raise prolactin levels than to raise HVA levels. This was not the case with BRL 20596 and the other drugs, where the doses needed for the two effects were similar. The results suggest that BRL 20596 is a central dopamine antagonist, with low sedative and haemodynamic activity.

Animals

Cervical motion assessment: a new, simple and accurate method.

Accurate assessment of head motion can be a useful tool in clinical studies. Since the head moves on a combination of axes in the cervical spine, evaluation of neck motion is difficult. Assessment of cervical mobility is further complicated because of inadequate reference points on the head from which to measure. Hence, numerous methods for approximating cervical range have been devised. These methods include visual estimation, radiographic analysis, schematography, photography, and a variety of goniometer devices. Disadvantages of these techniques are lack of accuracy and objectivity, radiation exposure, expense, time consumption, and equipment availability. To measure cervical mobility, a standard gravity goniometer with spirit level and head adapter was used, which allowed stabilization. The gravity goniometer can be obtained in a variety of sizes at most hardware stores. The head adapter consists of a wood block into which an arc is carved and elastic straps suspended for securing on the head. The reliability of this instrument was tested and compared to the universal goniometer, and correlation coefficients were determined. When two experienced examiners used the universal goniometer to assess cervical motion, significant intraclass correlation coefficients (ICC) were found with three of the six criteria measures (p less than 0.05). When one experienced and one novice examiner used the gravity goniometer with head adapter, highly significant ICC values were found for all six criteria measures (p less than 0.01). A single experienced examiner comparing both instruments on the same subjects produced significant ICC values in four of the six criterion measures (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cervical Vertebrae

Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt (-5 degrees) in middle-aged healthy men.

Cardiovascular deconditioning after prolonged bedrest has been attributed to inactivity. To examine the role of the altered distribution of body fluids, 5 healthy men, aged 41 to 48 years, were studied before, during and after a 20-hour period of bedrest with head-down tilt (-5 degrees). This intervention produces a marked central shift of intravascular and interstitial fluid, but the short duration minimizes the effects of inactivity. Central venous pressure, cardiac output and stroke volume all increased significantly (p less than 0.05) from supine baseline mean values; central venous pressure from 8.6 to 12.6 cm H2O, cardiac output from 6.9 to 7.9 liters/min, and stroke volume from 104 to 113 ml after 15 minutes of tilt, but all values returned to baseline within 20 hours. Supine central venous pressure after tilt was 7.4 cm H2O, cardiac output 5.7 liters/min and stroke volume 84 ml. Blood volume decreased 0.51 liters. After tilt, orthostatic stress produced a higher heart rate (90 +/- 18 vs 68 +/- 12 beats/min). Maximal oxygen consumption decreased (2.36 +/- 0.41 vs 2.62 +/- 0.48 liters/min), mainly owing to reduced stroke volume (87 +/- 22 vs 107 +/- 18 ml, p less than 0.05). Thus, tilt produced a transient increase in central venous pressure, stroke volume and cardiac output, but supine mean values were below baseline levels after 20 hours. The post-tilt state was qualitatively and quantitatively similar to that seen after 2 to 3 weeks of bedrest or several days of spaceflight. These results are also similar to those from a previously studied group of ten 20- to 30-year-old normal men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Dopamine autoreceptors and the effects of drugs on locomotion and dopamine synthesis.

Criteria for distinguishing dopamine autoreceptor agonism from other mechanisms of inhibiting locomotion were examined, together with the relationship between inhibition of locomotion and dopamine synthesis. ED50 potencies to inhibit locomotion of mice were established for drugs from a number of categories. Spiperone 0.02 mg kg-1 significantly (P less than 0.05) reversed inhibition of locomotion by known dopamine agonists but not that by the other types of drug. Idazoxan antagonized inhibition of locomotion due to alpha 2-agonists but not dopamine agonists. RU 24926 (N-propyl-N,N-di[2-(3-hydroxyphenyl)ethyl]amine) was antagonized by both spiperone and idazoxan. Only for dopamine agonists was there good correlation (r = 0.97) between potencies to inhibit locomotion in mice and L-dihydroxyphenylalanine (L-DOPA) accumulation in the nucleus accumbens of rats treated with gamma-butyrolactone and 3-hydroxybenzylhydrazine. The specific dopamine D1-agonist, SK&F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine), was inactive in both tests at doses up to 10 mg kg-1. The mixed dopamine agonist/antagonist, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine, commonly known as (-)-3-PPP, acted as a dopamine agonist in both tests but inhibited locomotion more potently than L-DOPA accumulation. The inhibitory effects of dopamine agonists on locomotion were not prevented by alpha-methyl-p-tyrosine pretreatment. The data suggest that spiperone-reversible inhibition of locomotion in mice is a good criterion for dopamine autoreceptor agonists. The receptors involved are affected by low doses of both dopamine agonists and antagonists and seem similar to those involved in the autoreceptor mediated inhibition of dopamine synthesis. However, inhibition of locomotion is not due simply to suppression of dopamine release brought about as a secondary consequence of effects on synthesis; a separate mechanism for inhibiting dopamine release is probably involved.

Animals