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Biomedical subjects

I James

Publications and source records attributed to I James.

At least 55 records · Page 3Linked to original sources

["Cyrano" angiomas].

Hemangioma of the nasal tip (Cyrano nose) is a cavernous or capillary cavernous form. Its development is related to immaturity. It occurs in infants a few days after birth, and increases with regularity. The natural outcome is favorable, and the angioma decreases in most cases after 5 or 6 years of age. Due to the location and the aesthetic prejudice involved, the parents often ask for early surgical treatment. A study of 4 cases and a literature review indicate the surgical intervention should take place later, ie one should wait and only operate on the sequelae resulting from the development of the hemangioma. Late surgical treatment led to resection of the remaining lesion and to repair of the nasal tip.

Age Factors↗

Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states.

The pharmacokinetics of ximoprofen, a potent new non-steroidal anti-inflammatory agent, has been investigated in normal healthy subjects and in patients with hepatic or renal disease. After intravenous infusion of 22.8 mg to healthy subjects, plasma ximoprofen concentrations declined in a polyexponential manner with a terminal phase half-life of 1.9 h. The systemic clearance of ximoprofen was 115 ml.min-1 and the volumes of distribution were 18.01 Vz and 13.81 Vss. Ximoprofen was 80-90% bound to plasma proteins. The systemic availabilities (f) of orally and rectally administered doses of 30 mg of ximoprofen were 98% and 56% respectively and, in the case of the rectal dose, absorption appeared to be prolonged leading to "flip-flop" kinetics. After single oral doses of 30 mg of ximoprofen to patients with hepatic disease, half-life (2.2 h), peak plasma concentrations (1.55 micrograms.ml-1 cf 1.04 micrograms.ml-1 in healthy subjects) and areas under the curve (6.12 micrograms.h.ml-1 cf 3.54 micrograms.h.ml-1 in healthy subjects) were significantly different from those in healthy subjects. After single oral doses of 30 mg of ximoprofen to patients with renal disease, pharmacokinetic parameters of half-life (4.0 h), mean residence time (6.0 h) and area under the curve (9.2 micrograms.h.ml-1) were significantly different from those in healthy subjects. There were no significant differences in pharmacokinetic parameters between patients having differing degrees of renal disease. These data nevertheless suggest that accumulation of ximoprofen in hepatic or renal disease would be of slight or negligible clinical relevance and that no alteration of the dose regimen (up to 15 mg twice daily) may be required when ximoprofen is administered in these disease states.

Adult↗

Pneumotropic revertants derived from a pantropic mutant, F1-R, of Sendai virus.

Revertants were isolated from the protease activation mutant of Sendai virus, F1-R, which causes a systemic infection in mice. The fusion (F) glycoprotein of F1-R is susceptible to activation cleavage by ubiquitous cellular proteases and is thus responsible for pantropism in mice (Tashiro et al., 1988. Virology 165, 577-583). The revertants regained several phenotypes of wild-type virus; they required exogenous trypsin for activation of the F protein in cell cultures and in nonpulmonary mouse tissues and they were exclusively pneumotropic in mice. On the other hand, phenotypes of F1-R that remained unchanged by the revertants were bipolar budding in polarized epithelial cells, enhanced electrophoretic migration of the matrix protein, and the lack of a glycosylation site in the F2 subunit of the F protein. Comparative RNA sequence analysis of the F gene of the revertants revealed that the reduced cleavability of the F protein of the revertants was the result of the predicted single amino acid reversion (Pro to Ser) at residue 115 adjacent to the cleavage site. Thus the sequence at the cleavage site of the revertants was Ser-Lys compared with Pro-Lys for F1-R and Ser-Arg for wild-type virus. The results indicate that enhanced cleavability of the glycoprotein, a feature often associated with multiple basic residues within the cleavage site of paramyxovirus F proteins and influenza virus hemagglutinins, can also be determined by a single basic amino acid following proline. Additionally, the revertants were less susceptible to the activator for wild-type virus present in mouse lungs and less pathogenic for this organ than wild-type virus. These results provide further evidence that proteolytic activation of the F protein by host proteases is the primary determinant for organ tropism and pathogenicity of Sendai virus in mice. One of the revertants was also temperature sensitive (ts); the ts lesion in the nucleoprotein gene was identical to that found in ts-f1, the ts host range mutant from which F1-R was derived.

Amino Acid Sequence↗

Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy young and elderly subjects: comparison with elderly rheumatic patients.

The pharmacokinetics of ximoprofen were studied in young and elderly subjects after single and repeated doses up to 30 mg. In healthy elderly subjects (30 mg dose), a mean peak plasma drug concentration of 1.78 micrograms ml-1 +/- 0.83 s.d. occurred at a mean time of 1.95 h +/- 1.40 s.d. and, thereafter, concentrations declined monoexponentially with a mean half-life of 3.8 h +/- 1.4 s.d. Comparison of these data with those from younger healthy subjects showed that peak drug concentrations, areas under the curve and half-lives were about two-fold greater in the elderly, these differences probably reflecting a lower systemic drug clearance. Similar results were obtained on comparing data from young healthy subjects and elderly rheumatic patients receiving single and repeated doses of ximoprofen (15 mg twice daily). In patients, the half-life of ximoprofen was 2.5 h +/- 0.7 s.d. Within either group, pharmacokinetic parameters after single or repeated doses were similar: ximoprofen did not accumulate in the plasma of the young or elderly.

Adult↗

The role of histamine in the acute inflammatory responses to intradermal platelet activating factor.

1. The role of histamine in PAF-induced acute inflammatory responses (flare and weal) in the skin has been evaluated in a series of three separate studies. 2. Terfenadine, a potent H1-selective histamine antagonist virtually abolished the flare response and significantly inhibited the weal response. 3. Histamine depletion in the skin using compound 48/80 resulted in similar effects on the flare and weal response. Two consecutive daily injections of compound 48/80 were found to deplete comprehensively skin sites of histamine and the ability of skin to respond to PAF was completely restored within 2 weeks of compound 48/80 treatment. 4. Intradermally injected PAF was associated with acute rises in plasma histamine in blood drawn from a draining vein with peak concentrations occurring within 5 min of injection. 5. No difference in PAF-induced flare and weal response was found between atopic and non-atopic subjects and this was reflected in the peak plasma histamine results. A significantly higher baseline plasma histamine was found in the atopic group, however, when compared with the non atopic group. 6. It is concluded that histamine has an important role in the acute inflammatory responses to intradermally injected PAF, although there does appear to be a significant direct vascular component in the PAF-induced weal response.

Benzhydryl Compounds↗

Moderate hypothermia in the management of resistant automatic tachycardias in children.

BACKGROUND: Automatic focus tachycardias are often resistant to electrical and pharmacological treatment. Moderate systemic hypothermia (32-34 degrees C) may reduce the tachycardia rate in children with His bundle tachycardia after cardiac surgery. METHODS: The case notes of seven children with automatic focus tachycardias treated with hypothermia were reviewed. Six had His bundle tachycardia after cardiac surgery and one had ectopic atrial tachycardia; all had signs of low cardiac output. RESULTS: Hypothermia led to a reduction in heart rate in all patients (from 211 (28) (mean (SD] to 146 (5) beats/minute, p less than 0.001), with rises in systolic blood pressure (from 74 (14) mm Hg to 97 (10) mm Hg, p less than 0.01) and hourly urine output (from 0.5 (0.4) ml/kg to 4.6 (2.8) ml/kg, p less than 0.02). No direct adverse effects were noted. The arrhythmia did not resolve in three children, who died (two with His bundle tachycardia after Fontan procedures and one with ectopic atrial tachycardia); the other four regained sinus rhythm which was maintained at follow up of 3-13 (mean 9) months. CONCLUSIONS: Moderate systemic hypothermia led to slowing of the arrhythmia rate and an improvement in cardiac output in patients with resistant automatic focus tachycardias. It can be used to improve the haemodynamic condition while other measures of arrhythmia control are being pursued or until spontaneous recovery of normal rhythm.

Anti-Arrhythmia Agents↗

The influence of maternal undernutrition in ovine twin pregnancy on fetal growth and Doppler flow-velocity waveforms.

The effects on placental blood flow velocity of maternal undernutrition during mid pregnancy were investigated in 38 twin bearing pregnant sheep by Doppler analysis of umbilical and uteroplacental arterial waveforms. Mid pregnancy undernutrition resulted in fetal growth restriction manifest at term gestation by reduced mean birth weight. Arterial waveform systolic/diastolic ratios from the umbilical and uteroplacental arterial circulations were not influenced by maternal nutrition either during the dietary deprivation or during a subsequent period of dietary supplementation. An effect of heart rate on systolic/diastolic ratios could not be demonstrated. The results indicate that the fetus responds to mid pregnancy maternal undernutrition with restricted growth but without alterations in systolic/diastolic ratios in umbilical or uteroplacental arterial waveforms.

Animals↗

Longitudinal assessment of changes in reproductive hormones during normal pregnancy.

The concentrations of hormones measured in serum from maternal blood change dramatically during pregnancy. While the relative contributions of sex steroids shift from maternal ovaries and adrenals to the fetoplacental unit, other maternal tissues such as pituitary and liver respond to increasing concentrations of estrogen and secrete increasing amounts of prolactin and sex-hormone-binding globulin. To determine longitudinal changes in circulating maternal hormones, we collected blood from 60 women on three occasions during their pregnancies. We observed a 1.7-fold increase in testosterone concentration in serum; concentrations of sex-hormone-binding globulin in serum rose 5.6-fold. The major increase (6.8-fold) in estradiol in serum occurred within the first 16 weeks, followed by a further 4.8-fold increase by term. Mean concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione in serum increased 11.9-, 3-, and 1.3-fold, respectively, whereas concentrations of dehydroepiandrosterone sulfate (DHEAS) fell by 50%. Mean serum prolactin concentrations increased 3.8-fold during the first trimester and by a similar amount during the final 24 weeks of pregnancy. We used these data, obtained from a cohort of women with uncomplicated pregnancies, to construct reference intervals for hormones in maternal serum.

Androgens↗

Antinociception produced by capsaicin: spinal or peripheral mechanism?

We have studied the effects of capsaicin, administered at concentrations found to be antinociceptive in behavioural tests, on nociceptive responses evoked both in spinal dorsal horn neurons in vivo and in spinal ventral roots in vitro. In halothane anesthetized rats, C-fibre evoked input produced by transcutaneous electrical stimulation in the peripheral receptive field was recorded from single wide dynamic range neurons located in superficial and deep dorsal horn of the lumbar spinal cord. This input was reduced by systemic administration of capsaicin at an antinociceptive dose (20 mumol/kg s.c.). Intradermal injections of capsaicin localized to the peripheral receptive field produced a transient increase in C-fibre evoked activity followed by a prolonged period of localized insensitivity to C-fibre stimulation. Spinal i.t. administered capsaicin also produced a rapid but reversible attenuation of peripherally evoked C-fibre input. In a neonatal rat spinal cord-tail preparation maintained in vitro, superfusion of the spinal cord with capsaicin (100-500 nM) produced a transient depolarization which was followed by an attenuation of responses to peripheral noxious heat and to spinal administration of substance P. Similar activity was produced by a prolonged superfusion of the spinal cord with substance P (50-200 nM). An HPLC method was used to estimate the concentration of capsaicin in a number of tissues following s.c. administration at an antinociceptive dose. In addition capsaicin concentrations were determined in the spinal cord following an i.t. administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Intensive care management of children following heart and heart-lung transplantation.

We report the intensive care management of 23 children (age 3-15 years) following orthotopic heart (HT) and combined heart and lung transplantation (HLT) performed at our 2 institutes between February 1985 and August 1989. Cyclosporin A, azathioprine and steroids were given as routine immunosuppression, whilst anti-thymocyte globulin (ATG) was used for the first 3 post-operative days. Mean ventilation time was 24.6 h (range 4-74 h). Cardiovascular support comprised isoprenaline infusions in all patients (mean period 65.7 h) whilst dopamine and other inotropic agents were used less frequently. Sequential atrioventricular pacing was required more often in the HT patients (n = 9) than in the HLT patients (n = 4). Fluid input was restricted to maintain a plasma osmolality of 290-300 mosm/kg. There were 2 perioperative deaths both due to acute right heart failure. Other post-operative complications included: bleeding (n = 3); acute graft rejection (n = 4); infection (n = 3); systemic hypertension (n = 6); neurological abnormalities (n = 2); renal dysfunction (n = 6) and hyperglycaemia (n = 6).

Adolescent↗

Effects of maternal cigarette smoking on ultrasonic measurements of fetal growth and on Doppler flow velocity waveforms.

Serial ultrasound biometry and Doppler flow velocity waveform analysis were used to measure the effects of maternal smoking in a prospective study of 535 pregnancies. Smoking was associated with significant reductions in maternal weight gain, birthweights and placental weights. Decreased fetal biparietal diameter measurements were observed in pregnancies of smoking women; this effect was maximal at 24 weeks' gestation, was restricted to male fetuses and was not associated with altered head circumferences after birth. Umbilical artery and uteroplacental systolic/diastolic ratios were similar in pregnancies of smoking and non-smoking women, indicating that the effects of smoking on placental vascular resistance are periodic rather than continuous. The findings of this study confirm the need for studies of fetal growth to include prenatal measurements obtained by high resolution ultrasound imaging, rather than relying on findings obtainable by examination of the infant after birth.

Adult↗

The effect of heart rate on Doppler flow velocity systolic-diastolic ratios in umbilical and uteroplacental arterial waveforms.

In an analysis of the influence of heart rate on Doppler flow velocity waveform-systolic/diastolic ratios from 1555 umbilical artery waveform studies and from 1497 uteroplacental waveform studies, a negative correlation was observed between the ratio and the corresponding heart rate. This relationship was not influenced by gestational age and was similar in pregnancies with normal outcomes when compared with all pregnancies. The magnitude of this inverse relationship is such that the effect of heart rate on systolic/diastolic ratios must be considered when Doppler flow velocity waveform analyses are used as experimental tools to assess placental vascular resistance but it does not appear to be an important factor in general clinical practice when measurements are made during fetal inactivity and when heart rates are within normal ranges.

Blood Pressure↗

A systematic comparison of feedback and staff discussion in changing the ward atmosphere.

The efficacy of therapeutic programmes depends on several characteristics of the treatment environment. For this reason therapists are increasingly directing their efforts towards changing the social characteristics of treatment units. This study aimed to promote change in social climate by providing nursing staff with structured information about their unit. The 'real' and 'ideal' social climate of the unit was defined and assessed using the Ward Atmosphere Scale. All staff were asked to complete it during an assessment period. Feedback about their perception of the unit was provided to staff in two ways. One group of staff received written feedback only; a second group received in addition the opportunity to discuss the feedback and strategies for reducing the real-ideal discrepancies in four once-monthly meetings. The effect of the feedback on the social climate of the unit was ascertained by further assessment using the WAS and from interviews with all staff. The evaluation suggested that the feedback had contributed to changes in several procedures in the unit and to a reduction in the real-ideal discrepancies for the systems maintenance elements. The effect was greater for the group of staff who had the opportunity to discuss the feedback in a formal setting.

Communication↗

Surgery of 346 patients with unoperated cleft lip and palate in Sri Lanka.

By means of a surgical expedition involving an independently financed team of surgeons, anesthetists and nurses, 410 operations were performed on 346 patients in the course of 52 operating days. This paper describes the preoperative, operative, and postoperative scenarios and how clinical practice was tailored to adapt to a new environment without compromising standards. The differences between operating on the lip and palate in the adult compared to younger children are highlighted. The clinical research implications are more evident from other papers on this topic published in this journal, but the enlightenment of working and teaching in a third world country cannot be underestimated.

Adolescent↗

Clinical significance of antibodies to a 68 kDa U1RNP polypeptide in connective tissue disease.

In a series of 163 patients with systemic lupus erythematosus (SLE) and/or systemic sclerosis and/or mixed connective tissue disease (MCTD), the presence of antibodies to a 68 kDa U1RNP associated polypeptide was more predictive for SLE (88%) than for MCTD (38-68%) using 3 different sets of proposed criteria for the latter condition. In all but one case studied serially the immunoblotting profile remained constant. In SLE recognition of the 68 kDa polypeptide identified a subset with increased vasoreactivity with Raynaud's phenomenon (96%, p less than 0.001) and swollen fingers (68%, p less than 0.001) whereas recognition of a 47 kDa La (SSB) polypeptide was associated with photosensitivity (72%, p less than 0.02), less renal involvement (p less than 0.05) and an older age of disease onset (46.6 years +/- 18.3 SD, p less than 0.002).

Antibodies↗

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations.

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.

Adult↗

[Value of the use of a vicryl-collagen tape for the treatment of cleft palate. Experimental study in dogs].

The purpose of this study was to evaluate the bone forming capacity of a Vicryl/collagene tape, placed in a defect of the palatal bone. In order to decrease the rate of bucco-nasal fistulaes after primary closure of a cleft palate, the authors carried out an experiment on dogs. First of all, we had to demonstrate the good tolerance of the tape in the buccal cavity. The first group of 5 dogs redieved the tape between buccal mucosae and palatal bone. The tolerance was excellent concerning the 12 biopsies on the mucosae after 1 month; 10 were totally normal and 2 revealed signs of inflammation on the medial incision. Concerning the second group, we needed to know the delay of bone formation of a "neo-palatal" defect; for that reason a 2 cm2 bone resection and a histological observation after 1 month and 1,5 months, in the right palatal bone was performed. Then we performed the same resection in 5 other dogs, and let the vicryl tape in the defect before closing the mucosae. The histological results of the second group showed that the ossification began after 1 month, and after 1.5 months the defect was totally covered by bone. The good results we obtained led us to go on with this experiment even if the low number of dogs included in this series does not allow us to a statistical evaluation. Exact responsibility of both, vicryl and collagene, has to be determined by a longer experiment, before realising the device in child's cleft palate.

Animals↗