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Biomedical subjects

M J James

Publications and source records attributed to M J James.

90 records · Page 5Linked to original sources
PubMed1985

Stability of intravenous admixtures of aztreonam and clindamycin phosphate.

The stability of aztreonam and clindamycin phosphate in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 20 mg/mL and clindamycin phosphate 6 mg/mL; aztreonam 20 mg/mL and clindamycin phosphate 3 mg/mL; aztreonam 10 mg/mL and clindamycin phosphate 6 mg/mL; and aztreonam 10 mg/mL and clindamycin phosphate 3 mg/mL. One of each of these admixtures was stored at 22-23 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 1-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed using high-performance liquid chromatography. No visual changes were observed. The pH of admixtures decreased only slightly during storage. Concentrations of aztreonam and clindamycin phosphate under both storage conditions decreased by less than 10%. Intravenous admixtures of aztreonam and clindamycin phosphate at the concentrations studied are stable for at least 48 hours at 22-23 degrees C and at least seven days at 4 degrees C.

Ampicillin↗
PubMed1984

Congenital diaphragmatic hernia: association between pulmonary vascular resistance and plasma thromboxane concentrations.

After repair of a Bochdalek diaphragmatic hernia, shunting of blood away from the lungs produced progressive hypoxaemia in a neonate. Changes in plasma concentrations of the vasoconstrictor prostanoid thromboxane were associated with changes in pulmonary vascular resistance in this infant. Plasma concentrations of the vasodilator prostanoid prostacyclin were also monitored during acute changes in pulmonary vascular resistance. Tolazoline administration was followed by reductions in pulmonary vascular resistance and in plasma thromboxane and prostacyclin values. Further studies indicated that tolazoline inhibits platelet thromboxane synthesis and vascular prostacyclin synthesis. These data suggest that thromboxane plays a part in the increased pulmonary vascular resistance that occurs after repair of congenital diaphragmatic hernia and that tolazoline may reverse pulmonary hypertension by a mechanism additional to its known action as an alpha adrenergic blocking agent and its effect on histamine release.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Elevated cholesterol and dolichol synthesis in mouse pachytene spermatocytes.

Results are presented here which demonstrate that the rates of [14C]acetate incorporation into cholesterol and dolichol increased 4- to 5-fold as mouse spermatocytes matured from the preleptotene to prepuberal pachytene stages. The rate of acetate incorporation into cholesterol then decreased in late pachynema, remained low at all subsequent stages of meiosis, and was very low in mature sperm. In contrast, the rate of acetate incorporation into dolichol remained elevated in late pachytene spermatocytes and round spermatids, then decreased and remained low in mature sperm. The ratio of the rate of [14C]acetate incorporation into dolichol to the rate of incorporation into cholesterol increased during late meiotic prophase and remained high in round spermatids; this altered ratio is further evidence of independent regulation of dolichol and cholesterol synthesis in testes. It was shown previously that normal adult mouse testes incorporated acetate into dolichol at a much higher rate (1.8 to 2.4% of the rate of incorporation into cholesterol) than did testes from sterile W/Wv mice (0.02%) or X-irradiated mice (0.24%). This high rate of acetate incorporation into dolichol in adult testes is now attributed to differentiating spermatocytes, with particularly high rates being observed during pachynema.

Acetates↗
PubMed1981

Sequential cycles of cholesterol and dolichol synthesis in mouse spleens during phenylhydrazine-induced erythropoiesis.

The results presented demonstrate that erythropoiesis in the mouse spleen was associated with cyclic changes in cholesterol and dolichol synthesis which were independent of each other. Changes in the rate of cholesterol synthesis were correlated with the level of 3-hydroxy-3-methylglutaryl-CoA reductase activity and with the rate of cell division (thymidine incorporation into DNA), but a cycle of dolichol synthesis appeared to be independent of both these parameters. Consequently the incorporation of [14C]acetate into dolichol increased 20- to 30-fold compared to the rate of cholesterol synthesis 5 to 6 days following phenylhydrazine treatment. The pathway for dolichol synthesis branches from that leading to cholesterol at the level of the intermediate farnesyl pyrophosphate, subsequent to the reaction catalyzed by the regulatory enzyme 3-hydroxy-3-methylglutaryl-CoA reductase. Previous studies showed that in several cell culture lines, and in liver, dolichol synthesis and cholesterol synthesis are regulated in a coordinated way by reductase activity. However, during the process of spermatogenesis and in developing mouse brain the regulation of dolichol synthesis appeared to be independent of cholesterol synthesis. Independent regulation of dolichol synthesis is now demonstrated in a third differentiating tissue, the erythropoietic spleen, and the results suggest that a cycle of dolichol synthesis is specifically associated with one or more stages of erythroid differentiation.

Animals↗
PubMed1980

Regulation of hepatic dolichol synthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase.

Dolichol is an isoprenoid lipid involved in the assembly of many membrane-bound and secreted glycoproteins. Dolichol biosynthesis can be considered as a branch of the cholesterol biosynthetic pathway subsequent to the reaction catalyzed by beta-hydroxy-beta-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl-CoA reductase, EC 1.1.1.34), the major regulatory enzyme of cholesterol biosynthesis. Changes in reductase activity can also affect the rate of dolichol synthesis. Since the majority of plasma glycoproteins are synthesized by the liver, we have measured the rate of dolichol synthesis in mouse-liver slices after various treatments which alter hepatic beta-hydroxy-beta-methyl-glutaryl-CoA reductase activity in vivo. The rate of hepatic dolichol synthesis was decreased by dietary cholesterol and fasting, and increased by feeding cholestyramine. There is also a diurnal variation in the rate of dolichol synthesis. A plot of the rate of dolichol synthesis versus the rate of cholesterol synthesis suggests that, after the formation of isoprene units, the branch of dolichol biosynthesis is saturated at a lower concentration of isoprene intermediates than is required to saturate the branch of cholesterol biosynthesis. After 2 weeks of cholesterol feeding and the consequent depression of hepatic dolichol synthesis, the rate of [3H]mannose incorporation into liver and plasma glycoproteins was unchanged, indicating that the rate of dolichol biosynthesis was not rate-limiting for total glycoprotein synthesis under these conditions.

Animals↗
PubMed1980

Evidence for independent regulation of dolichol and cholesterol synthesis in developing mouse brain.

In order to investigate the regulatory inter-relationships between the branching pathways of dolichol and cholesterol synthesis, we have measured the changing rates of synthesis for these two lipids in developing mouse brains. A sharp peak in the rate of dolichol synthesis occured at 3-7 days after birth which did not coincide with changes in cholesterol synthesis, suggesting independent regulation of dolichol and cholesterol synthesis in developing mouse brains.

Animals↗
PubMed1980

Elevated dolichol synthesis in mouse testes during spermatogenesis.

The synthesis in mouse testes of the isoprenoid lipid dolichol, the phosphate esters of which are involved in glycoprotein assembly, was investigated. Because the pathways for dolichol and cholesterol branch from a common sequence of reactions, comparisons of the rates of synthesis of these two lipids can reveal specific alterations in the flow of metabolites along the branch leading to dolichol. Our results showed that the ratio of dolichol to sterol synthesis in testes was from 20- to 72-fold higher than any ratios we have measured in murine liver or cell cultures. In contrast, testes deficient in spermatogenic cells, from x-irradiated mice, or from mice with mutant W/Wv or at/at genotypes, synthesized normal amounts of cholesterol, but much less dolichol. Thus, the high rate of dolichol synthesis in normal testes appeared to be associated with one or more of the spermatogenic cell types. It was also observed that newly biosynthesized testicular dolichols are slightly more polar than the pig liver dolichols used as standards. Possible modifications of the dolichol structures that might account for the increased polarity are discussed.

Acetates↗
PubMed1976

Port health problems.

As quarantine control of international travellers dies away, health screening of immigrants becomes more important. Port health controls attempt to identify the sick immigrant, thereby limiting disease spread among susceptibles and sparking early treatment. Port health controls also ease the impact of immigrants arriving at destinations by alerting relevant authorities so that they can begin health education procedures early, if they wish. Two problems arise: some destination authorities make little attempt to trace their immigrants and even those that do cannot find more than 70 per cent so notified. For receiving communities the most important disease the immigrant may carry or later develop is tuberculosis. In the indigenous population the incidence of this disease is decaying exponentially but, in communities of recent immigrants, may be stable or even rising. This means that in about ten years the great majority of new tuberculosis cases will be in recent immigrants, unless better preventive techniques are used. The overall trend is likely to be a fall in the number of cases, but the disproportion may provoke problems. What can be done? Assuming incoming immigrants are typical of their country of origin, many must enter Britain mantoux-negative, a fact supported by various destination authorities here which have performed testing. So, the logical solution is to ensure that all receive BCG vaccination, preferably before they migrate or otherwise as they enter Britain, and to ensure their babies born later in Britain also receive the protection of BCG vaccination. Consumption of medical services by the travelling public increases with the number of travellers and, as more people penetrate romantic but unhealthy areas formerly inaccessible, importation of communicable disease also increases. Many of these diseases could be prevented by good advice but, unfortunately, unfamiliarity blunts the edge of prophylaxis and diagnosis. Airport experience indicates that the general practitioner could help his patient more, particularly the overlander, by discussing sanitary precautions and suggesting anti-malarial drugs and immunization against typhoid and infectious hepatitis, when appropriate. Vaccination against smallpox, cholera or yellow fever may be obligatory and a valid certificate required; inoculation against diphtheria, poliomyelitis or tetanus may be sensible, and against rabies if the traveller may come into contact with animals abroad. Although complex queries about health hazards abroad should be addressed to such research centres as the Ross Institute, I suggest much practical advice can be obtained by phoning Heathrow health control 01-759 4361.

Communicable Disease Control↗
PubMedDate not supplied

Cyclooxygenase inhibitors: any reservations?

The discovery of two cyclooxygenase isozymes, constitutive COX-1 and inducible COX-2, has resulted in the rapid development of selective inhibitors of COX-2, such as celecoxib and rofecoxib. Compared with traditional non-steroidal anti-inflammatory drug agents, use of COX-2 selective inhibitors is associated with decreased incidence of adverse gastric events as a result of minimal inhibition of gastroprotective COX-1, but with equivalent anti-inflammatory benefit through inhibition of COX-2. However, there is evidence to suggest that the 'COX-1 = constitutive, COX-2 = inflammatory' paradigm is less distinct than originally proposed. Futhermore, selective COX-2 inhibitors may have other consequences as a result of the change in the eicosanoid profile. Thus, despite the relatively safe gastrointestinal profile, vigilant post-marketing surveillance for other adverse effects is required.

Animals↗