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Biomedical subjects

C Doré

Publications and source records attributed to C Doré.

At least 19 recordsLinked to original sources

Effects of four common anticonvulsants on the high pressure nervous syndrome in the rat.

This study reports results from experiments designed to test common, clinically useful anti-convulsants for their effectiveness, if any, against the high pressure nervous syndrome (HPNS) in rats. Phenytoin, carbamazepine, phenobarbitone, or diazepam were administered orally to rats before compression. Endpoints used to assess the progression of the HPNS were T1, T3, and T5 (onset of, continuous, and severe tremor), myoclonus, and seizures. Of the four drugs tested, only phenobarbitone increased the onset pressure for tremor and seizures by: T1 33%; T3 11%; T5 14%; seizures 10%. Neither phenytoin, carbamazepine, nor diazepam had any significant effect on any of the endpoints studied. High dose chronic pretreatment with phenytoin also had no effect on the HPNS. These data suggest that conventional anticonvulsant treatment would be of limited value for HPNS in man, and the lack of effect also suggests that HPNS seizures are of an unusual type.

Animals

Aortic compliance measured by non-invasive Doppler ultrasound: description of a method and its reproducibility.

1. Aortic compliance (expressed as percentage increase in lumen diameter for a pulse pressure of 10 mmHg) was calculated from the characteristic pulse wave velocity deduced from 'foot to foot' transit times of the blood flow pulse over a measured length of aorta. Two continuous wave Doppler ultrasound transducers were used: one insonating the root of the left subclavian artery, the other the abdominal aorta proximal to its bifurcation. Measurements were made after the subject had been supine for 5 min to achieve stable conditions. 2. Transit times were calculated on-line in real-time from the delay between the start of the systolic upstroke in the flow velocity sonograms recorded by the two transducers. 3. Within-visit variation was minimized by measuring over 45 cardiac cycles repeated three separate times and calculating an overall mean value for aortic compliance. A full measurement took 5-10 min. 4. Reproducibility of this overall mean value of aortic compliance was assessed at 1 month in 30 subjects (aged 60 +/- 7 years, mean +/- SD) and at 3 months in 23 different subjects (59 +/- 8 years). Aortic compliance values ranged from 0.1 to 2.0%/10 mmHg. 5. The mean paired difference between aortic compliance values was -0.02 between 0 and 1 months, and 0.03 between 0 and 3 months, with respective 95% confidence limits of -0.06 to 0.03 and -0.03 to 0.09 embracing zero, thus not differing significantly from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta

Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo.

Rat lung isografts were preserved for 48 hr at 0 degrees C using a simple organ flush technique. After storage alone, isotonic saline flush resulted in significantly raised indices of lipid peroxidation in vitro (Schiff bases and thiobarbituric-acid-reactive material [TBAR]). Lungs flushed with hypertonic citrate (HCA) had significantly less oxidative damage than saline-flushed lungs. The addition to the HCA flush of verapamil, a calcium channel blocker, or desferrioxamine, an iron chelator, significantly reduced TBA reactivity in stored lungs compared with HCA alone. After 1-hr reperfusion in vivo, lipid peroxidation was reduced in HCA-flushed lungs compared with saline flush (TBAR alone), but no additional protection from the use of desferrioxamine or verapamil was demonstrated. Electron microscopy after saline flush and storage alone showed gross endothelial swelling and fragmentation. Reperfusion with blood for 1 hr resolved cell swelling, but alveolar/capillary wall rupture occurred. HCA protected against cell swelling, but endothelial vesiculation and widening of the basement membrane were observed. After reperfusion, HCA-flushed lungs developed much endothelial loss that was considerably reduced by the use of desferrioxamine and verapamil. The lipid peroxidation results suggest that iron- and calcium-mediated free radical production may be important mechanisms in oxidative damage to stored rat lungs. Electron microscopy findings correlated with biochemical evidence of free-radical-mediated injury. Reduction of endothelial loss on reperfusion by the use of verapamil and desferrioxamine provides circumstantial evidence that ischemia and reperfusion damage of organs stored for transplantation is partly due to Fe++(+)- and Ca+(+)-dependent mechanisms that probably involve increased free radical production.

Animals

Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine.

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.

Analysis of Variance

Oxylog studies of energy expenditure and schistosomiasis in the Sudan.

The effects of varying intensities of S. mansoni infection on physical work performance in agricultural tasks were studied in 269 male farmers living in the highly endemic Gezira area of the Sudan. The subjects were in the age range 18-50 years, and they were subdivided into four infection groups: non-infected (passing no S. mansoni eggs in their faeces), lightly infected (egg excretion 1-499), moderately infected (egg excretion 500-999), and heavily infected (egg excretion 1000+ eggs g-1 faeces). The Oxylog, a portable oxygen analyser, was used to measure energy expenditure throughout the field studies. The investigations showed that heavy S. mansoni infection significantly lowered oxygen intake by 20-30% during agricultural work tasks. There was a clear relationship between the intensity of S. mansoni infection and both the aerobic power output and morbidity in those populations. Anti-schistosomal treatment (praziquantel) given over a period of 1 year produced a marked improvement in working capacity and reduced morbidity.

Adult

Criteria for estimating likelihood of difficulty of endotracheal intubation with the Macintosh laryngoscope.

Many anatomical factors in difficult intubation at direct laryngoscopy have been evaluated. Lateral radiographs were taken of nineteen patients in whom tracheal intubation proved particularly difficult, and fourteen patients whose intubation was reasonably straightforward. Stepwise discriminant analysis was used to select the best measurements for distinguishing between the difficult and straightforward groups. The variables which together are most reliable in predicting likely difficulty in intubation are reduced atlanto-occipital extension, reduced mandibular space, and lastly, increased antero-posterior thickness of the tongue. A formula and graph have been derived to relate these variables with likelihood of difficulty, and a method has been described of applying this information at the bedside, without using X-ray examination, to estimate the likelihood of difficulty in intubating a new patient. Eighteen months' experience of the application of this clinical evaluation have so far found it reliable.

Adolescent

Effect of exposing mice to 50 ATA helium pressure at different stages of pregnancy.

Pregnant T-O mice were exposed to 50 ATA He-O2 pressure for 4 days at different stages of gestation: 4-7, 6-9, and 9-12 days gestation. Controls were exposed to 1 atmosphere absolute (ATA) air. After the exposure period, pregnancy continued until 18 days gestation when the mice were killed and autopsied. Data were collected relating to the litters and placentas (Litter size, percent resorptions, placental weight, fetal-to-placental ratio) and fetuses (weight, crown-rump length, sex, skeletal abnormalities) and analyzed using analysis of variance. Results showed a small but significant increase in the percent resorptions in the pressure group and also a decrease in crown-rump length and placental weight. None of these changes were related to the stage of gestation in which the mice were exposed. No teratogenic effects of pressure were seen. We conclude that exposure to 50 ATA He-O2 during pregnancy in mice produces a small nonselective effect on fetal growth and development but does not affect any specific event taking place during these stages of embryogenesis.

Animals

T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin 2.

Highly purified human recombinant interleukin 2 (IL-2) markedly accelerated lethal GVHD in the H-2-identical B10.BR----CBA combination, but had no effect when the donor cells were depleted of mature (Thy-1.2-positive) T lymphocytes, indicating a strong immunopotentiating effect of IL-2 on mature T cells causing GVHD. In the same donor-host combination, IL-2 did not influence the recovery from the post-transplantation bone marrow aplasia. The results suggest that IL-2 could be considered for adjuvant hormonal therapy to enhance immune recovery in recipients of T-cell-depleted allogeneic marrow.

Animals

The single-passage extraction of 18F in rabbit bone.

The only clinically applicable method for the quantitative measurement of blood flow to the skeleton which has so far been developed rests on the assumption that the initial extraction of the bone-seeking isotope 18F from blood by bone is known and constant. Previous work to measure the single-passage extraction ratio of this isotope in rabbit bone has been criticised, so a novel technique has been developed in which isotope recirculation cannot occur. In addition, the post mortem uptake of isotope from surrounding tissues and the vascular tracer content of the bone can be monitored. The apparent extraction ratios of two bone-seeking isotopes, 85Sr and 18F, were measured in nine animals, and extrapolated to the time of death from both the time at which dissection of the bones began (giving a maximum value) and the time at which it ended (giving a minimum). Mean blood flow to the femur was 0.562 ml min-1 (SD = 0.170, n = 15) and mean blood flow to the tibia was 0.290 ml min-1 (SD = 0.140, n = 12). Statistical analysis of the results showed that there were significant differences in the extrapolated ratio between animals and significantly higher extraction of isotope in the tibia than in the femur. There was no significant difference between the extraction of 85Sr and that of 18F. The best estimate of the single-passage extraction ratio of 85Sr and 18F which can be made, therefore, is that in rabbit femur it is 0.88 (SE 0.04) and in the rabbit tibia it is 1.08 (SE 0.04). Post mortem uptake of isotope increases the apparent extraction ratio by about 1% per minute.

Animals

Tolerance of one-month intranasal interferon.

Under double-blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between "colds" on placebo and low-dose interferon and "reactions to treatment" on high-dose interferon. The features of the reactions to treatment were a protracted build-up of local symptoms and minor epistaxis. None of the volunteers on the high-dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low-dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge. The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long-term prophylactic against the common cold.

Administration, Intranasal

Acquired immunological tolerance of foreign cells is impaired by recombinant interleukin 2 or vitamin A acetate.

The susceptibility of newborn mice to the inception of tolerance after exposure to antigen is associated with their deficiency in the production of endogenous interleukin 2 (IL-2). As further evidence of the complicity of IL-2 in the inception and maintenance of tolerance, it is shown here that a solid and long-lasting state of tolerance induced by the intravenous injection into newborn CBA mice of lymphoid cells from (CBA X C57BL/10ScSn)F1 hybrids can be brought to an end by the administration of exogenous IL-2 or by supplementing an otherwise normal diet with vitamin A acetate, the effect of which is to increase the proportion of the moiety of the T-cell population that produces IL-2. These results indicate that certain nonspecific stimuli can influence whether immunological tolerance is maintained.

Animals

Normal values for trabecular and cortical bone in the radius measured by computed tomography.

Quantities related to the amount of trabecular bone in the distal radius and cortical bone in the radius mid-shaft have been measured in 262 normal adults of both sexes aged 21-89 years by computed tomography (CT). A special-purpose CT system (ISOTOM) which incorporated a source of 125I (29 keV) was used to make the measurements. The relationships between these quantities and age, weight, height and surface area have been evaluated, and the results have been used to draw conclusions on the significance of values measured in female patients with osteoporosis, Colles' fracture of the wrist and generalised osteoarthritis.

Absorption

A diet enriched in vitamin A acetate or in vivo administration of interleukin-2 can counteract a tolerogenic stimulus.

A conventional diet enriched in retinyl acetate (vitamin A acetate; VAA) or in vivo administration of exogenous interleukin-2 (IL-2) can effectively annul the otherwise tolerogenic stimulus represented by (CBA X C57BL/10ScSn) F1 cells injected intraperitoneally into newborn CBA mice. On the basis of these data and results of others, we postulate that an antigenic stimulus associated with a relative lack of IL-2 (or generally the lack of a 'secondary stimulus') can be tolerogenic rather than immunogenic. However, the tolerogenicity of the antigenic stimulus can be substantially reduced or even converted to sensitization (R. P. Cleveland & H. N. Claman, J. Immun. 124, 474-480, 1980), when the antigenic signal is appropriately associated with a concomitant or additional stimulus possibly mediated through IL-2.

Animals

Sperm size in patients with inflammatory bowel disease on sulfasalazine therapy.

The size of the heads of spermatozoa from eight men with chronic inflammatory bowel disease (IBD) treated with sulfasalazine (SS) were measured by image analysis. These were compared with the size of sperm heads from noncolitic men with normal semen indices and with the sperm head size of noncolitic oligospermic men. The patients on SS therapy had a significantly larger sperm head size for the 99th percentile than the noncolitic oligospermic men. After withdrawal of the drug, sperm head size increased further before becoming smaller. The size did not return to that of the sperm of men with normal semen indices during the period studied. Possible mechanisms for the increase in sperm size are discussed and its association with the reversible infertility caused by SS medication.

Adult