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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 451 records · Page 25Linked to original sources
PubMed1981

Haemophilus influenzae disease in Alaskan Eskimos: characteristics of a population with an unusual incidence of invasive disease.

During 1971-77 the incidence of bacterial meningitis among Alaskan Eskimos was 84.4 cases per 100 000 population per year, which is more than 10 times that for most other U.S. populations. Haemophilus influenzae (HI) accounted for 68% of meningitis cases. The average annual incidence of HI disease per 100 000 children below 5 years of age was 409 for patients with meningitis only and 491 for patients with all systemic HI disease. Children with HI meningitis in Alaska tended to be younger than those in other U.S. populations, 98% of the children affected being less than 18 months of age. The risk for all HI disease was 2.4% during the first year of life. The spectrum of HI disease in Alaska differs from that in other populations in that no patient had epiglottitis and 5% of children had recurrent HI disease. Alaskan newborns and children over 4 years old had HI anticapsular antibody titres that were nearly thrice those for children of similar ages in other U.S. populations (p less than 0.005). The pharyngeal carriage of HI type b (5%) and the rectal carriage of Escherichia coli K100 (2%), an organism with a capsule antigenically similar to HI type b, did not differ from those in other populations. The high incidence of disease almost exclusively in the very young and the early development of antibody in this population suggest that the high rate of disease is due to early exposure to HI type b rather than to an unusual susceptibility to HI type b.

Adolescent↗
PubMed1981

Phosphatidate and oxidized fatty acids are calcium ionophores. Studies employing arsenazo III in liposomes.

Liposomes which have entrapped the metallochromic dye, arsenazo III, constitute a sensitive assay system for ionophoresis of divalent cations. By this means we have compared known calcium ionophores (A23187, ionomycin) with membrane phospholipids, fatty acids, prostanoids, and retinoids. Added at micromolar concentrations to preformed multilamellar liposomes (phosphatidylcholine 7:dicetyl phosphate 2: cholesterol 1) both A23187 and ionomycin, as well as phosphatidic acid and products derived from linoleic acid, linolenic acid, and two eicosatrienoic acids provoked Ca influx (e.g. phosphatidic acid: 0.13 mol of Ca2+/mol of membrane lipid/5 min). A variety of other phospholipids (e.g. phosphatidylinositol), fatty acids (e.g. arachidonic acid), prostanoids (e.g. PGE1) retinoids (e.g. retinoic acid), and glyceryl ether phosphorylcholines ("platelet-activating factors") were without effect. Phosphatidic acid and oxidized fatty acids translocated divalent cations selectively, demonstrating the same rank order as A23187 or ionomycin: Mn greater than Ca greater than Sr much greater than Mg. Membrane lysis did not contribute to the perceived translocation; the liposomes remained impermeable to EDTA, EGTA, arsenazo III, or Mg. Liposomes with phosphatidic acid or oxidized trienoic acids preincorporated at 1-5 mole % of total lipids also permitted translocation of Ca but not Mg. Reduction of ionophoretic fatty acids or ionomycin with stannous chloride abolished their ionophoretic activity. Release of Ca from liposomes which had entrapped arsenazo III-Ca complexes into a medium rich in EGTA permitted calculation of efflux induced by ionophores, whether these were added to the outside of liposomes or preincorporated. Data suggest that phosphatidic acid and oxidized di- and trienoic fatty acids, which act as calcium ionophores in model bilayers, could serve as "endogenous ionophores" in cells.

Arsenazo III↗
PubMed1981

Clinical pharmacokinetics of ketobemidone. Its bioavailability after rectal administration.

The pharmacokinetic constants and rectal bioavailability of the narcotic analgesic ketobemidone were determined in six male patients after surgery. Plasma concentrations were measured following intravenous administration of Ketogin 2 ml, containing ketobemidone chloride 10 mg, and a spasmolytic compound N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and following rectal administration of one suppository of Ketogin, containing ketobemidone chloride 10 mg and the spasmolytic component 50 mg. Following intravenous administration, the disposition of ketobemidone followed a biexponential pattern with a fast distribution phase and a slower elimination phase: the plasma half-life (t1/2) was 2.42 +/- 0.41 h (m +/- SD). After rectal administration, the disposition of ketobemidone fitted a one-compartment model. The elimination half-life was 3.27 +/- 0.32 h. The mean rectal bioavailability for ketobemidone was 44% +/- 9%. The pharmacokinetic constants of the spasmolytic component, N,N-dimethyl-3,3-diphenyl-1-methylallylamine, were also determined in five of the patients, both after intravenous and after rectal administration. The plasma half-life was 3.07 +/- 0.53 h and 3.79 +/- 1.14 h, respectively. The rectal bioavailability was estimated to be 33% +/- 14%.

Adult↗
PubMed1981

Clinical pharmacokinetics of bezafibrate in patients with impaired renal function.

The pharmacokinetics of the new lipid-lowering drug bezafibrate has been investigated in patients with impaired renal function and hyperlipoproteinaemia. 12 patients received a single oral dose of bezafibrate 300 mg. Plasma and urine samples were collected and bezafibrate was analyzed by gas chromatography. Eight of the patients had moderately impaired renal function, with a creatinine clearance between 20 and 40 ml/min; the mean plasma half-life of bezafibrate in them was 7.8 +3.9 h (SD) and the plasma clearance was 0.03 +0.02 1/kg . h. Three of the patients had a creatinine clearance greater than 40 ml/min; in them the plasma half-life was shorter, 4.6 +1.2 h, and the plasma clearance was higher, 0.06 +0.01 1/kg . h. The slowest elimination of bezafibrate was found in a patient with a creatinine clearance of only 13 ml/min. This patient had a plasma half-life of 20.l h, which is ten times longer than has been reported in healthy volunteers. Thus, when treating hyperlipoproteinaemia in patients with impaired renal function, the dosage of bezafibrate must be individualized because of its reduced renal elimination.

Adult↗
PubMed1981

Spontaneous tandem genetic duplications in Salmonella typhimurium arise by unequal recombination between rRNA (rrn) cistrons.

A method is described to detect and measure the frequency of spontaneous tandem genetic duplications located throughout the Salmonella genome. The method is based on the ability of duplication-containing strains to inherit two selectable alleles of a single gene during generalized transductional crosses. One allele of the gene carries an insertion of the translocatable tetracycline-resistance element Tn10; the other allele is a wild-type copy of that gene. Using this technique, we have measured the frequency of tandem duplications at 38 chromosomal sites and the amount of material included in 199 independent duplications. These results suggest that, in one region of the chromosome, tandem duplications are particularly frequent events. Such duplications have end points within rRNA (rrn) cistrons and probably arise by unequal cross-over between these dispersed repeated sequences. Spontaneously duplications of this type are harbored by as much as 3% of the bacterial population. Preliminary evidence suggests that such duplications may play a significant regulatory role under conditions of rapid growth. Our analysis has suggested the position on the genome of an additional rRNA cistron.

Base Sequence↗
PubMed1981

A polysaccharide-protein complex from Haemophilus influenzae type b. I. Activity in weanling rabbits and human T lymphocytes.

Complexes containing proteins, capsular polysaccharide (polyribosylribitolphosphate [PRP]), and lipopolysaccharide (LPS) had been isolated from the supernatants of cultures of Haemophilus influenzae type b and were found to elicit rabbit antibodies to PRP much more effectively than did purified PRP vaccine. Similar complexes have now been prepared, in which the LPS content and endotoxic activity are greatly reduced. One such preparation, called polysaccharide-protein complex (PC), elicited antibodies to PRP in a "boostable" pattern in weanling rabbits and antibodies to the somatic components of H. influenzae type b, primarily LPS. PC greatly exceeded PRP in the in vitro stimulation of [3H]thymidine incorporation by mononuclear leukocytes from human peripheral blood; the response occurred in T cells rather than in B cells. Lymphocyte stimulation by conventionally purified PRP appeared to be due to a small residuum of material that resembled PC.

Animals↗
PubMed1981

A polysaccharide-protein complex from Haemophilus influenzae type b. II. Human antibodies to its somatic components.

A polysaccharide-protein complex prepared from Haemophilus influenzae type b strain Eagan was used as test antigen in an enzyme-linked immunosorbent assay for human serum antibodies. With washing buffer that did not contain detergent, the assay detected antibody to lipopolysaccharide (LPS) and to non-LPS somatic antigens as well as to polyribosylribitolphosphate (PRP. With buffer that did contain detergent, antibodies to LPS were not detected, whereas detection of antibodies to the non-LPS somatic components and to PRP wa unimpeded. Similarly, purified LPS could be used as test antigen with the former buffer only. IgG, IgA, and IgM antibodies to non-LPS somatic antigens were prevalent in healthy adults and children, and levels increased in 14 of 15 patients recovering from meningitis due to H. influenzae type b; IgG was the predominant class. Antibodies to LPS were prevalent but at lower concentrations, and IgM was the predominant class; levels increased in 12 of the 15 patients.

Adult↗
PubMed1981

A polysaccharide-protein complex from Haemophilus influenzae type b. III. Vaccine trial in human adults.

Polysaccharide-protein complex prepared from Haemophilus influenzae type b strain Eagan was evaluated for toxicity and immunogenicity in adult volunteers given intramuscular injection. Most subjects had moderate local inflammation that was maximal the day after vaccination. No lot of vaccine significantly exceeded a saline placebo in production of systemic symptoms. Neither the local nor the systemic reactions of individual subjects appeared to be related to prevaccination serum antibody titers. Serum antibody responses to the capsular polysaccharide (polyribosylribitolphosphate [PRP]) component were detected in approximately 80% of the subjects. The PRP content of the vaccine antigens varied, and the rate and extent of responses were as expected for an equivalent dose of purified PRP vaccine. Antibody responses were not enhanced by aluminum phosphate. There was no booster response to a second injection given after six months. Responses to the residual lipopolysaccharide component occurred in 80% of the subjects, primarily in the IgG class. Responses to the nonlipopolysaccharide somatic components were detected less frequently.

Adult↗
PubMed1981

Entrapment of human leukocyte interferon in the aqueous interstices of liposomes.

Human leukocyte interferon has been trapped in the aqueous interstices of multilamellar liposomes (phosphatidylcholine, dicetyl phosphate, and cholesterol [7:2:1]). Such liposomes trapped [3H]inulin (aqueous space marker) and interferon to the extent of 0.22 +/- 0.01 mg (n = 8) and 350 +/- 54 U (n = 4) per mumol of liquid, respectively, as judged by molecular sieve chromatography. Interferon trapped within liposomes was resistant to tryptic digestion under conditions which completely inactivated free interferon. Studies in which interferon was added to preformed liposomes excluded the possibility that interferon bound nonspecifically to the outer layer of the multilamellar liposomes. When interferon was added to the aqueous medium in which liposomes of various net surface charges were permitted to form, trapping of interferon varied directly with the interlamellar aqueous compartments of the liposomes. The demonstration that stable liposomes can entrap interferon suggests that these may constitute suitable vectors for the delivery of interferon to cells.

Humans↗
PubMed1981

Radiation myelopathy in patients treated for carcinoma of bronchus using a six fraction regime of radiotherapy.

The adoption of a six-fraction regime of radiotherapy for patients with locally advanced carcinoma of the bronchus was followed by the appearance of radiation myelitis in eight cases. These were among a group of 130 patients given radiotherapy with anterior and posterior treatment fields, without shielding of the spinal cord. Radiation myelitis was found only in those where the calculated spinal-cord dose exceeded 3350 cGy (rad). The possible precipitating factors in the eight patients who suffered myelopathy were compared with those in the remaining 62 patients who also received spinal-cord doses calculated to be greater than 3350 cGy (rad). Only one difference was found--the haemoglobin concentration was significantly higher in those who suffered neuropathy compared with those who did not (P = 0.05).

Aged↗
PubMed1980

Clinical pharmacokinetics and oral bioavailability of ketobemidone.

The basic pharmacokinetics and oral bioavailability of ketobenmidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemiodone was 34% +/- 16% (SD, n = 6). The mean plasma half-life of elimination (t1/2 beta) was about the same following oral (2.45 +/- 0.73 h; SD, n = 5) as after intravenous administration (2.25 +/- 0.35 h; SD, n = 6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin (ketobemidone 5--10 mg every 6--7 h) in patients with severe pain is too low.

Administration, Oral↗
PubMed1980

A general method, employing arsenazo III in liposomes, for study of calcium ionophores: results with A23187 and prostaglandins.

Multilamellar (MLV) and large unilamellar (LUV) lipid vesicles (liposomes) trap the metallochromic dye arsenazo III [2,7-bis(arsonophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid ] in their aqueous compartments. When ionophore A23187 was preincorporated into either MLV or LUV above 0.001 mol%, addition of Ca to the outside of liposomes produced spectral shifts characteristic of the Ca . AIII2 complex. The method permitted detection of two molecules of A23187 per liposome. Liposomes with A23187 were permselective: divalent cations were translocated in the order Mn greater than Ca greater than Sr greater than Mg congruent to Ba. Because prostaglandins (PGs) may act as Ca ionophores, we have incorporated into MLVs and LUVs stable prostaglandins (PGE2, PGI2, PGB1), endoperoxide analogs, and a water-soluble, polymeric derivative of PGB1:PGBx. None acted as ionophore. In contrast, when added to the outside of preformed MLV or LUV, PGBx, at concentrations above 1 micro M, provoked permselective uptake of Ca equivalent to that induced by 10 nM A23187. These studies demonstrate not only that liposomes containing arsenazo III may be employed in a sensitive asssay for agents that translocate divalent cations, but that a water-soluble derivative of a naturally occurring fatty acid, PGBx, is a potent ionophore.

Arsenazo III↗