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Biomedical subjects

J K Miller

Publications and source records attributed to J K Miller.

At least 73 records · Page 4Linked to original sources

The relative antihistaminic and psychomotor effects of hydroxyzine and cetirizine.

Twelve healthy subjects with atopy received single doses of hydroxyzine, 25 mg, its metabolite cetirizine, 10 and 20 mg, and placebo in a four-way crossover study randomized by Latin square design. Skin wheal response to histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. Central nervous system (CNS) effects were measured with critical flicker frequency, Stroop word testing, and visual analog scales. All three active treatments (cetirizine, 10 mg, cetirizine, 20 mg, and hydroxyzine) produced an equivalent suppression of skin wheal response to histamine that was significantly greater than placebo (P less than 0.01). Hydroxyzine produced a significant change compared with placebo in all three CNS parameters. Neither cetirizine, 10 mg, nor cetirizine, 20 mg, produced any significant change in CNS parameters. Both the intensity and time course of CNS effects were related significantly (P less than 0.05) to hydroxyzine concentrations. The CNS changes measured after oral hydroxyzine are the result of the parent drug, whereas its metabolite cetirizine when administered alone produced significant antihistaminic effects without CNS changes.

Adult↗

Lateral and medial epicondylitis of the elbow.

Tennis elbow is a common condition, with the extensor carpi radialis brevis attachment being the usual site of pain. Conservative care including decreased activity, ice, nonsteroidal anti-inflammatory medications, and muscle strengthening will help most people. The small percentage of cases that require surgery usually benefit from debridement of the damaged portion of the extensor carpi radialis brevis attachment. The postoperative course must include muscle strengthening and a gradual return to activity.

Athletic Injuries↗

Ulnar deficiency.

Twenty-nine patients with 34 ulnar deficient limbs were studied; the average follow-up was 7.7 years. To permit early determination of prognosis and decisions regarding treatment, four subtypes of this condition have been identified. Progressive ulnar deviation of the wrist was not observed in any case, and the fibrocartilaginous ulnar anlage was resected only to correct fixed deformities of the wrist. The most useful operation was humeral or radial osteotomy to correct the hand on flank deformity. A group of patients who were optimally treated with prosthetic fitting is discussed.

Elbow↗

Colony probing as an alternative to standard sequencing as a means of direct analysis of chromosomal DNA to determine the spectrum of single-base changes in regions of known sequence.

We demonstrate here the means to directly analyze bacterial chromosomal DNA for all classes of single-base mutations in a specific codon in any region of known sequence through the use of DNA probing as a powerful substitute for standard sequencing techniques. With this method, chromosomal DNA from hundreds of mutants can be examined for single-base changes without any DNA cloning. This method can conveniently provide a large data base for the assessment of all classes of single-base mutations occurring spontaneously or induced by a known or suspected mutagen. The method is demonstrated for the analysis of histidine-independent (His+) revertants of hisG46, a missense mutation of Salmonella typhimurium that can revert in six or seven ways.

Azacitidine↗

President's Page.

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Journal Article↗

President's Page.

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Journal Article↗

President's Page.

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Journal Article↗

Effects of some clinically significant mycotoxins on the incorporation of DNA, RNA and protein precursors in cultured mammalian cells.

The effects of zearalenone (F-2), ochratoxin A and T-2 toxins on the synthesis of DNA, RNA and proteins in mouse L cells were studied. F-2 toxin inhibited protein synthesis to a lesser extent than DNA and RNA synthesis, whereas ochratoxin A inhibited the synthesis of each equally. Exposure to the toxins for 24 hours relatively reduced the synthetic ability of the cells. T-2 toxin inhibited protein and DNA synthesis in parallel but RNA synthesis to a lesser extent. Enhanced incorporation of tritiated thymidine was found when L cells were exposed to 0.4 to 0.016 ng of T-2 toxin ml-1 for 24 hours.

Animals↗

The effects of chronic administration of chlorine dioxide, chlorite and chlorate to normal healthy adult male volunteers.

The physiological impact of chronic 12 week ingestion of chlorine dioxide and its byproducts, chlorite and chlorate, was compared to the effects of chlorine, chloramine and untreated water. The water disinfectant solutions were administered daily (500 ml, 5 ppm) to normal healthy adult male volunteers. An extensive battery of tests was used to evaluate the physiological impact of the ingested water disinfectants. Upon analysis of both quantitative and qualitative parameters it was concluded that the 12 week chronic administration of chlorine dioxide and its byproducts was accompanied by no clinically important physiological effects.

Adult↗

The effects of chronic administration of chlorite to glucose-6-phosphate dehydrogenase deficient healthy adult male volunteers.

Under controlled laboratory conditions, the safety of daily ingestion of 5 ppm chlorine dioxide, chlorite and chlorate by normal healthy adult males has been established. To determine the effect upon potentially susceptible individuals, a parallel chronic human investigation was undertaken. Study subjects were three healthy adult males deficient in glucose-6-phosphate dehydrogenase. These volunteers received 500 ml of sodium chlorite at a concentration of 5 ppm daily for twelve consecutive weeks; the subsequent observation period extended an additional eight weeks. Upon evaluation of an extensive battery of tests designed to measure the biochemical and physiological response to chlorite ingestion, no clinically significant changes were detected.

Adult↗

Simple technique for the direct isolation of toxoplasma tissue cysts from fetal ovine brain.

A simple technique is described for the isolation of Toxoplasma gondii tissue cysts from fetal ovine brain by centrifugation on a discontinuous density gradient of 30 per cent and 90 per cent Percoll (colloidal silica solution). Brain samples from 51 aborted ovine fetuses were examined by both the Percoll and mouse inoculation techniques; eight infections were detected by the Percoll technique compared to 12 by mouse inoculation. Possible reasons for this discrepancy and the scope for improving the Percoll technique are discussed.

Abortion, Veterinary↗

Salmonella montevideo infection in sheep and cattle in Scotland, 1970-81.

Outbreaks of abortion associated with infection by Salmonella montevideo have affected sheep in the east, especially the south-east, of Scotland each year since 1972. Disease in the north and north-east was usually less severe. Between 1 January 1970 and 31 December 1981, a total of 67 incidents affecting sheep were reported by veterinary laboratories to the Communicable Diseases (Scotland) Unit, 87% of which presented during the main lambing months of February, March and April. Twenty-one episodes of bovine infection were also recorded over the same period, 17 of which involved single animals only, usually an aborted cow or a scouring calf. Despite intensive investigations, neither the origin nor the mode of spread of S. montevideo infection among sheep and cattle in Scotland have been established with any certainty, although there has been considerable evidence indicating the role of scavenging wild birds, particularly seagulls, as vectors transmitting infection to other farms in the same district. Also largely unexplained are the differences in the epidemiology and clinical pattern of disease in the south-east compared to the north and north-east, while sheep in the west of Scotland have remained virtually unaffected throughout.

Abortion, Veterinary↗

Role of mRNA competition in regulating translation: further characterization of mRNA discriminatory initiation factors.

Host and reovirus mRNAs compete with one another for translation in infected cells. Kinetic analysis has suggested that the site of competition is a message discriminatory initiation factor which must bind to the mRNA before it can interact with the 40S ribosomal subunit. The present communication describes an in vitro assay which can detect message discriminatory activities. A competitive situation is established by using reovirus and globin mRNAs, and then the specificity with which this competition is relieved by added components is measured. Among the various initiation factors surveyed with this assay, two have the properties expected of the mRNA discriminatory factor. These are eukaryotic initiation factor 4A and a "cap binding protein" complex. Inasmuch as the cap binding protein complex contains a subunit similar or identical to the initiation factor eIF-4A, it seems likely that only one form of the latter factor may be active in vivo. In vitro, both factors relieve competition among both capped and uncapped reovirus mRNAs according to similar hierarchies. These results suggest that some feature other than the m7G cap, such as nucleotide sequence or secondary structure, is recognized by the discriminatory factor.

Animals↗

Studies of antibody titres in experimentally induced ovine toxoplasmosis.

Analysis of serological data from 63 experimentally infected sheep showed an inverse relationship between rise in toxoplasma indirect haemagglutination (IHA) titre after infection and titre at the time of infection. It was observed that, on average, sheep with a preinfection IHA titre of 1:200 or higher did not exhibit a significant rise in titre after infection. The ratio of toxoplasma antibody titres measured by the IHA and dye tests and the ratio of IHA titres in the IgM and IgG antibody fractions were shown to vary according to the duration of infection indicating that serological techniques could be developed to distinguish between latent and acute ovine toxoplasmosis.

Animals↗

Life span and tissue distribution of 111indium-labeled blood platelets in hypomagnesemic lambs.

Circulating platelets may be activated by exposed triple-helical collagen in atherosclerotic lesions in Mg-deficient ruminants. Autologous platelets, labeled in vitro with 111In and determined to be active, were injected into 5 hypomagnesemic and 3 control lambs fed semipurified diets with 100 or 2,000 mg of Mg/kg of feed for 3 months. During the first 68 hours, 111In concentrations were 11 times higher in packed cells than in plasma. Packed-cell 111In increased 60% during the first 2 hours, probably due to initial tissue sequestration and later release of labeled platelets. Thereafter, platelet half-life span averaged 60 and 63 hours for hypomagnesemic and control lambs. After 68 hours, lambs were injected with native vascular collagen fibrils at 500 micrograms/kg of body weight to initiate reversible platelet aggregation. Within 1 minute, 83% of packed-cell 111In disappeared from circulation. Thirty minutes later, the lambs were euthanatized and necropsied and in the lungs, liver, and spleen, 111In averaged 24%, 19%, and 9%, respectively, of 111In injected 68 hours earlier. Organ deposits were not affected by Mg intake, but 111In in the lungs was somewhat lower in 2 lambs injected with inactivated collagen. Pathologic changes induced by reversible platelet aggregation were compatible with right ventricular failure complicated by pulmonary edema, similar to changes in hypomagnesemic lambs that died spontaneously. Platelets in blood exposed to vascular lesions in hypomagnesemic ruminants could be a major mortality risk factor in grass tetany disease.

Animals↗

Ovine enzootic abortion: the acquisition of infection and consequent abortion within a single lambing season.

The spread of enzootic abortion was observed in a flock of 37 unvaccinated Scottish blackface ewes, in mid-pregnancy at the start of the trial. Eight ewes were infected with the ZC 26 strain of chlamydia and allowed to run with 29 untreated controls until lambing was completed. All eight inoculated ewes aborted between 26 and 51 days after infection and chlamydial infection was demonstrated in seven of the abortions. Complement fixing antibodies were not detected in the controls until nine days after the first infected abortion, but within four weeks 69 per cent of the control ewes had developed significant complement fixation titres. Ten of the control ewes lost lambs, chlamydial infection was demonstrated in seven cases, two were undiagnosed and one was attributed to dystocia. The seven infected cases occurred between 69 and 87 days after the start of the trial and coincided with a further rise in the percentage of seropositive controls to a maximum of 90 per cent by the end of lambing.

Abortion, Veterinary↗

Response of immune and susceptible ewes to infection with Toxoplasma gondii.

Inocula containing 75, 250 or 1000 Toxoplasma gondii tissue cysts were used to infect seronegative gimmers and seropositive ewes in the fourth month of pregnancy. The seronegative gimmers developed typical toxoplasma infections at all dose levels. Four of them aborted and the surviving lambs showed rising indirect haemagglutination titres in the first two to three months of life indicating congenital infection. The seropositive ewes showed no response to challenge, all their lambs survived and there was no serological evidence of congenital infection. Indirect haemagglutination titres in the seropositive ewes remained unchanged throughout the experiment, titres in the gimmers rose sharply from the 10th day after infection and by three months were the same as those in the ewes.

Animals↗