Search PubMed⌕ Search

Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 397 records · Page 22Linked to original sources
PubMed1986

Pathophysiology of hemolysis in infections with Hemophilus influenzae type b.

The capsular polysaccharide of Hemophilus influenzae type b, polyribosyl ribitol phosphate (PRP), is released from growing organisms during human infection and can be found in body fluids. It binds to untreated erythrocytes. Many patients with invasive infections with this organism develop significant hemolysis, but the mechanism has been unclear. We have found that PRP binds to human erythrocytes in vivo. PRP-coated erythrocytes have a shortened circulation time in mice, but do not lyse spontaneously or fix complement. PRP-coated erythrocytes exposed to antiserum to H. influenzae type b are undamaged in the absence of complement, but are rapidly and effectively lysed in the presence of an intact complement system both in vitro and in vivo in mice. PRP-coated red cells are taken up by liver and spleen. Antiserum to PRP increases hepatic uptake of PRP-coated red cells more than splenic, and appears to induce intravascular, complement-mediated hemolysis, as well as extravascular hemolysis. Patients with invasive infection develop hemolysis when circulating PRP and antibody to PRP are present simultaneously. PRP can sometimes be detected on patient erythrocytes when free PRP is present in serum, but this is an inconsistent finding. The hemolytic anemia that occurs during human infection with H. influenzae type b may be due to absorption of PRP to red cells and immune destruction of sensitized erythrocytes. The process requires an intact complement system; both complement-mediated cell lysis and extravascular hemolysis contribute to red cell destruction.

Anemia, Hemolytic↗
PubMed1985

Community general practitioner.

The attainment of quality in general practice entails explicit recognition of the public-health content of primary care. General practitioners should accept responsibility for auditing the state of the practice health, monitoring and controlling environmental disease, planning local services, auditing the effectiveness of preventive programmes, and evaluating the population effects of medical intervention. This requires specific training in the skills of population medicine, reallocation of scarce resources, and cooperation with existing public-health doctors. Eventual integration of community medicine and general practice is desirable.

Community Medicine↗
PubMed1985

Managing alcohol problems in general practice.

A questionnaire on the management of alcohol problems was sent to 467 general practitioners. Of the 312 who replied, nine tenths thought that they had a legitimate role in working with patients with drinking problems, but less than a half thought that they were adequately equipped to perform this role. Only two fifths felt motivated to work with drinkers, less than a third were satisfied with the way in which they worked with drinkers, and fewer than one in 10 obtained work satisfaction from working with drinkers. Only 29% of doctors regularly gave advice to patients to reduce alcohol consumption, but 56% believed that their advice was effective. Doctors who had positive attitudes to working with drinkers undertook more work related to alcohol problems in their practice. There is a need to provide further education for general practitioners about alcohol related matters, and this education should include advice on intervention with heavy drinkers.

Alcoholism↗
PubMed1985

Safe limits of drinking: general practitioners' views.

A survey was carried out by questionnaire of general practitioners' views on what the safe upper limits of alcohol consumption are for health education for men and women. The results showed lower limits than those suggested by "alcohol experts" in a previous survey.

Alcohol Drinking↗
PubMed1985

Pharmacokinetics and distribution of flucloxacillin in pacemaker patients.

The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t 1/2 alpha = 0.13 h). The plasma half-life of elimination (t 1/2 beta) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the beta-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 1/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the beta-phase (Vd beta free) was 2.18 1/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 micrograms/ml and 9.5 micrograms/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b.

We studied an immunogen consisting of oligosaccharides derived from Haemophilus influenzae type b capsular polysaccharide (PRP) coupled to CRM197, a nontoxic relative of diphtheria toxin. Subcutaneous injections were given to eight subjects at ages 2, 4, and 6 months, simultaneously with conventional diphtheria-tetanus-pertussis (DTP) vaccine. After the first immunization, total serum anti-PRP antibodies declined in all subjects, but increased in most after the second immunization and after the third in seven of seven subjects analyzed. In these seven infants, the geometric mean level at age 9 months (0.73 micrograms/ml) exceeded by at least 40 times the means of historical control groups given DTP only or DTP plus (uncoupled) PRP vaccine. An isotype-specific assay showed that IgM antibodies increased after the first immunization with the coupled vaccine in all eight infants. Against the background of declining maternal IgG antibody, elevations in IgG antibody were detected after the second or third immunization in six of the eight. These six at age 9 to 11 months were immunized with (uncoupled) PRP vaccine, and a "boost" in anti-PRP antibody, including an IgG component, was found.

Antibodies, Bacterial↗
PubMed1985

Transposition of Tc1 in the nematode Caenorhabditis elegans.

We have identified a strain of Caenorhabditis elegans in which the transposable element Tc1 is genetically active. Most spontaneous mutations affecting the unc-54 myosin heavy chain gene of C. elegans variety Bergerac are due to insertions of Tc1 within unc-54. The Bergerac genome contains an unusually high number of Tc1 elements, but this is not responsible for transpositional activity. Another variety of C. elegans, strain DH424, contains an equally high number of Tc1 elements, but transpositions are not detected. Tc1 insertion mutations are genetically unstable. They revert to unc-54+ in both germ-line and somatic cells. Germ-line revertants are wild type and contain precise or nearly precise excisions of Tc1. Somatic revertants are genetic mosaics; they contain small patches of revertant muscle tissue in otherwise mutant animals. The pattern of mosaicism often allows us to know when and where during muscle development the excisions occur. Somatic reversion can be over 1000-fold more frequent than germ-line reversion.

Animals↗
PubMed1985

The gene structures of spontaneous mutations affecting a Caenorhabditis elegans myosin heavy chain gene.

We have isolated spontaneous mutations affecting the unc-54 major myosin heavy chain gene of Caenorhabditis elegans (variety Bristol). Spontaneous unc-54 mutants occur in C. elegans populations at a frequency of approximately 3 X 10(-7). We have studied the gene structure of 65 independent unc-54 mutations using filter-transfer hybridization techniques. Most unc-54 mutations (50 of 65) exhibit no abnormalities detected with these techniques; these mutations are small lesions affecting less than 100 base pairs. Approximately 17% of the mutations (11 of 65) are simple deletions, ranging in size from less than 100 base pairs to greater than 17 kilobases. One isolate contains two separate deletions, each of which affects unc-54. Two mutants contain tandem genetic duplications that include a portion of unc-54 and extend 8-10 kilobases beyond the 5' terminus of the mRNA. Conspicuously absent from our collection of spontaneous unc-54 mutations are any resulting from insertion of transposable genetic elements. Such mutants, if they occur, must arise at a frequency of less than 5 X 10(-9).

Animals↗
PubMed1985

Serum factor-dependent resistance of Haemophilus influenzae type b to antibody to lipopolysaccharide.

Haemophilus influenzae type b (Hib) grown in broth is much more sensitive to killing by antibody to lipopolysaccharide (LPS) and complement than is Hib in bacteremic rats; upon brief incubation with low-molecular-weight components of plasma or serum, however, broth-grown cells are phenotypically converted to a resistance resembling that in vivo. This conversion was found to consume a limiting factor in serum filtrate, to require protein synthesis, and to occur independently of the presence of capsule. Less antibody to LPS bound to cells of the resistant (Res) phenotype than to cells of the sensitive (Sen) phenotype. In electrophoretic analysis the mobility of LPS bands was identical, but the staining density of the LPS bands extracted from Res cells (with phenol-water) was two-to fourfold greater than from an equal number of Sen cells. A similar differential was found in an immunologic assay of LPS in the extracts. Thus, Hib in the Res phenotype (and perhaps Hib in vivo) contains more LPS than Hib in the Sen phenotype, but its LPS appears less accessible to antibody.

Animals↗
PubMed1985

Single-dose kinetics and bioavailability of sodium-hydrogen divalproate.

Sodium-hydrogen divalproate (SHD) is a new chemical entity that quickly dissociates into valproic acid (VPA) and sodium valproate in water and is absorbed as VPA from the gastrointestinal tract. SHD is formulated as an enteric-coated tablet and may also result in less gastrointestinal irritation than other preparations of VPA. The bioavailability of valproate from SHD enteric-coated tablets (Epival, Abbott-50711) and from sodium valproate enteric-coated tablets (Ergenyl) was compared in a single-dose, double-blind, crossover study. Fourteen healthy volunteers (mean age 28.7 years) participated. A single oral dose of 250 mg SHD (assayed potency 249.3 mg VPA) or 300 mg sodium valproate (assayed potency 251.1 mg VPA) was given to each volunteer. Blood samples were collected intermittently up to 48 h and VPA in serum was assayed by gas chromatography. The areas under the serum concentration-time curves (AUC0----infinity) did not show any statistically significant difference (2,925.0 +/- 189.1 versus 2,816.2 +/- 162.2 h X mumol/L) between SHD and sodium valproate. The elimination parameters for SHD were t1/2 = 12.6 +/- 0.7 h and CLs = 0.008 +/- 0.0005 L/kg/h. Vd,area was 0.146 +/- 0.004 L/kg. Data for sodium valproate were not significantly different. Thus, the extent of bioavailability and the single-dose kinetics of SHD and sodium valproate are similar with the exception of a more rapid absorption (Tmax 2.37 versus 3.23 h) and a higher concentration (Cmax 192 versus 176 mumol/L) for SHD. Both of these differences were statistically significant (p less than 0.01).

Adult↗
PubMed1985

Left ventricular diastolic function in a population of healthy elderly subjects. An echocardiographic study.

Diastolic left ventricular function was comparatively assessed in 19 healthy elderly individuals (mean age 71 years) and in 20 young normal subjects (mean age 26 years), using digitized echocardiograms. Peak and average filling rates were slower in the group of elderly subjects than in the younger population (128 +/- 26 and 75 +/- 11 v 182 +/- 37 and 92 +/- 17 mm per second, respectively, P less than .001). The duration of the rapid filling phase and the time to peak filling rate were significantly longer in the older than in the younger population (207 +/- 39 and 125 +/- 21 v 174 +/- 38 and 90 +/- 26 ms, respectively, P less than .01). The atrial contribution to total ventricular filling was 18 +/- 6% in the elderly and 10 +/- 3% in the young (P less than .001). The group differences of most of these measurements of diastolic function retained statistical significance after correction for heart rate. Measurements of left ventricular systolic function were similar in both age groups. The authors conclude that aging is associated with a decline of left ventricular compliance, unrelated to heart rate or systolic performance. The contribution of atrial contraction to ventricular filling is quantitatively larger in elderly individuals.

Adult↗
PubMed1985

Novel insertion mutation in Caenorhabditis elegans.

The mutation e1662 is an allele of the Caenorhabditis elegans unc-54 gene induced with the difunctional alkylating agent 1,2,7,8-diepoxyoctane. unc-54 encodes the major myosin heavy chain isozyme of body wall muscle cells. Filter-transfer hybridization and DNA sequence analysis show that e1662 is an insertion of 288 base pairs of DNA within unc-54. The inserted DNA is identical to a 288-base pair region of unc-54 located ca. 600 base pairs from the insertion site. Thus, e1662 is a displaced duplication. A 14-base pair sequence located at one end of the duplicated segment is found adjacent to the site of insertion. These homologous sequences are juxtaposed head-to-tail by the insertion event. e1662 thus contains a tandem direct repeat extending across one of its junctions.

Alkylating Agents↗