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Biomedical subjects

R M Jones

Publications and source records attributed to R M Jones.

At least 55 records · Page 3Linked to original sources
PubMed1999

Tamoxifen metabolism in rat liver microsomes: identification of a dimeric metabolite derived from free radical intermediates by liquid chromatography/mass spectrometry.

Tamoxifen has been shown to be a potent liver carcinogen in rats, and generates covalent DNA adducts. On-line high performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS) has been used to further study the metabolites of tamoxifen formed by rat liver microsomes in the presence of NADPH with a view to identifying potential reactive metabolites which may be responsible for the formation of DNA adducts, and liver carcinogenesis. A metabolite has been detected with a protonated molecule at m/z 773. The mass of this compound is consistent with a dimer of hydroxylated tamoxifen (m/z 388). Analysis of 4-hydroxytamoxifen incubated with a rat liver microsomal preparation showed the formation of a similar metabolite with an apparent MH+ ion at m/z 773, believed to be a dimer of 4-hydroxytamoxifen formed by a free radical reaction. The retention time for this metabolite from 4-hydroxytamoxifen is identical to that of the tamoxifen metabolite, suggesting that these two compounds are the same. The levels of the dimer were higher when 4-hydroxytamoxifen was used as substrate and, in addition, two isomers were detected. It is proposed that tamoxifen was first converted to arene oxides which react with DNA or to 4-hydroxytamoxifen, either directly or via 3,4-epoxytamoxifen, which then undergoes activation via a free radical reaction to give reactive intermediates which can then react with DNA and protein, or with themselves, to give the dimers (m/z 773).

Animals↗
PubMed1999

Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin.

Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure-related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.

Adult↗
PubMed1999

Cell adhesion molecules in normal laryngeal development.

Larynges taken from normally developing rats ranging from embryos starting at embryonic day 10 to adults were harvested. Sections of the larynges were prepared with the use of immunohistochemical techniques with primary antibodies directed to the neural cell adhesion molecule; selected sections were exposed to antibodies directed against the embryonic polysialated form of the neural cell adhesion molecule and against L1. Cell adhesion molecules were present throughout embryonic development associated with the recurrent laryngeal nerve. Downregulation of expression was observed after postnatal day 14. We conclude that cell adhesion molecules may play a role in the normal neural development of the larynx in rats.

Animals↗
PubMed1999

Bone loss at the proximal femur and reduced lean mass following liver transplantation: a longitudinal study.

The longevity of recipients of liver transplant may be compromised by spinal osteoporosis and vertebral fractures. However, femoral neck fractures are associated with a higher morbidity and mortality than spine fractures. As there is little information on bone loss at this clinically important site of fracture, the aim of this study was to determine whether accelerated bone loss occurs at the proximal femur following transplantation. Bone mineral density and body composition were measured at the femoral neck, lumbar spine and total body, using dual x-ray absorptiometry in 22 men and 19 women, age 46 +/- 1.4 y (mean +/- SEM) before and at a mean of 19 mo after surgery (range 3-44). Results were expressed in absolute terms (g/cm2) and as a z score. Before transplantation, z scores for bone mineral density were reduced at the femoral neck (-0.47 +/- 0.21 SD), trochanter (-0.56 +/- 0.19 SD), Ward's triangle (-0.35 +/- 0.14 SD), lumbar spine (-0.76 +/- 0.13 SD), and total body (-0.78 +/- 0.15 SD) (all P < 0.01 to < 0.001). Following transplantation, bone mineral density decreased by 8.0 +/- 1.7% at the femoral neck (P < or = 0.01) and by 2.0 +/- 1.2% at the lumbar spine (P < or = 0.05). Total weight increased by 12.2 +/- 2.3%, lean mass decreased by 5.7 +/- 1.4%, while fat mass increased from 24.1 +/- 2.0% to 35.1 +/- 1.8% (all P < or = 0.001). Patients with end-stage liver disease have reduced bone mineral density. Liver transplantation is associated with a rapid decrease in bone mineral density at the proximal femur, further increasing fracture risk and a reduction in lean (muscle) mass, which may also predispose to falls. Prophylactic therapy to prevent further bone loss should be considered in patients after liver transplantation.

Absorptiometry, Photon↗
PubMed1999

Histopathologic evaluation of an expanded polytetrafluoroethylene-nitinol stent endoprosthesis in canine iliofemoral arteries.

PURPOSE: The authors assess a new ePTFE-nitinol stent for its long-term patency, healing, and properties of endothelialization. MATERIALS AND METHODS: Adult greyhounds (n = 18) underwent bilateral iliofemoral placement of an endoprosthesis (Hemobahn) consisting of a nitinol stent lined with an ultrathin expanded polytetrafluoroethylene (ePTFE) material. Histologic and quantitative morphometric analyses were performed on devices explanted at 2 weeks and 1, 3, 6, and 12 months. The source of endothelialization was examined in four additional devices modified by sealing either the proximal and distal ends or the entire graft with poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP), a nonporous laminate to prevent potential transgraft endothelial cell migration. RESULTS: Device patency assessed with both intravascular ultrasound and histologic study showed minimal arterial stenosis, irrespective of implant duration. The neointima at less than 3 months consisted of fibrin and inflammatory infiltrate; at later time points, it was composed of mostly smooth muscle cells. Flow surfaces were more than 75% endothelialized by 3 months, which was nearly complete by 6 months. Modified endoprostheses entirely enveloped with FEP resulted in endothelialization of only the proximal and distal ends; the middle regions showed nonocclusive thrombi. Conversely, devices wrapped proximally and distally showed nearly complete endothelialization. CONCLUSIONS: This ePTFE-nitinol endoprosthesis demonstrated long-term patency at up to 1 year after implantation and showed early and nearly complete endothelialization by 6 months. The design promoted rapid endothelialization of flow surfaces, particularly in the midregion of the device possibly by transgraft migration.

Alloys↗
PubMed1999

alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role.

Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review. The alpha-2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.

Adjuvants, Anesthesia↗
PubMed1999

Acute epiglottitis despite vaccination with haemophilus influenzae type B vaccine.

We present the case of a 20-month-old child who required admission to the intensive care with a presumptive diagnosis of acute laryngo-tracheo-bronchitis, for the management of acute upper airway obstruction. This child had received a complete course of Haemophilus influenzae type B (Hib) vaccine. Subsequent events showed that the diagnosis was not laryngo-tracheo-bronchitis but acute epiglottitis. We propose that a full course of vaccination is no guarantee against a subsequent illness with Hib and may actually lead to the wrong diagnosis and possibly life-threatening consequences.

Acute Disease↗
PubMed1999

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1999

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 2: Auditory and somatosensory evoked responses.

The anaesthetic-sparing activity of dexmedetomidine during isoflurane anaesthesia was examined, using the end-point of lack of response to tetanic nerve stimulation. Nine subjects were given two doses of dexmedetomidine (target plasma concentrations of 0.3 ng ml-1 and 0.6 ng ml-1, respectively) and saline on separate occasions. We measured auditory (AER) and somatosensory (SER) evoked responses at end-tidal isoflurane concentrations of 0.2-1.4%. Pa and P25-N35 amplitudes increased as isoflurane concentration was reduced (P < 0.001). Dexmedetomidine had no significant effect on this relationship. In contrast, P15-N20 (SER) amplitude increased (P < 0.001) as isoflurane concentration was reduced. The dose of dexmedetomidine had a significant interaction with this trend (P < 0.002). Decreasing the concentration of isoflurane at the high dose of dexmedetomidine had less impact on P15-N20 amplitude than decreasing isoflurane at the low dose or with saline. The mechanism by which dexmedetomidine spares isoflurane is discussed in the light of these evoked response changes.

Adrenergic alpha-Agonists↗
PubMed1999

areABC genes determine the catabolism of aryl esters in Acinetobacter sp. Strain ADP1.

Acinetobacter sp. strain ADP1 is able to grow on a range of esters of aromatic alcohols, converting them to the corresponding aromatic carboxylic acids by the sequential action of three inducible enzymes: an areA-encoded esterase, an areB-encoded benzyl alcohol dehydrogenase, and an areC-encoded benzaldehyde dehydrogenase. The are genes, adjacent to each other on the chromosome and transcribed in the order areCBA, were located 3.5 kbp upstream of benK. benK, encoding a permease implicated in benzoate uptake, is at one end of the ben-cat supraoperonic cluster for benzoate catabolism by the beta-ketoadipate pathway. Two open reading frames which may encode a transcriptional regulator, areR, and a porin, benP, separate benK from areC. Each are gene was individually expressed to high specific activity in Escherichia coli. The relative activities against different substrates of the cloned enzymes were, within experimental error, identical to that of wild-type Acinetobacter sp. strain ADP1 grown on either benzyl acetate, benzyl alcohol, or 4-hydroxybenzyl alcohol as the carbon source. The substrate preferences of all three enzymes were broad, encompassing a range of substituted aromatic compounds and in the case of the AreA esterase, different carboxylic acids. The areA, areB, and areC genes were individually disrupted on the chromosome by insertion of a kanamycin resistance cassette, and the rates at which the resultant strains utilized substrates of the aryl ester catabolic pathway were severely reduced as determined by growth competitions between the mutant and wild-type strains.

Acinetobacter↗
PubMed1999

Postnatal development of myosin heavy chain isoforms in rat laryngeal muscles.

The developmental transitions of myosin heavy chain (MHC) isoforms of rat posterior cricoarytenoid (PCA), thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid (LCA) muscles were examined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot techniques. The muscles were microscopically dissected from animals on postnatal days 0, 3, 7, 10, 14, 21, 28, 35, 45, and 55 and from adult animals. Silver-stained SDS-PAGE gels of each muscle were analyzed densitometrically to measure the composition of MHC isoforms, and Western blot was carried out to identify specific bands. Characterizations of the internal laryngeal muscles determined by the composition of MHCs were correlated with their function in the adult. Temporally, differentiation reflects onset of function. Differentiation of isoforms and transition to adult forms occur first in the TA muscle, followed by the PCA, LCA, and CT muscles. Expression of type IIL was observed only in muscles innervated by the recurrent laryngeal nerve. Postnatally observed developmental differences of myosin phenotypes suggest that regulation of MHC expression is influenced by neural activity or other environmental factors.

Aging↗
PubMed1999

Comparing periodontal disease in identical twins: a case report.

Previous investigators have shown that numerous environmental and genetic variables may contribute to the pathogenesis of periodontal disease. This case report presents clinical and laboratory findings of a set of Caucasian female identical twins. One patient presented clinically with mild gingivitis and no clinical or radiographic signs of periodontitis. The other exhibited gingivitis with localized, moderate-to-severe periodontitis. Neither patient reported a history of systemic conditions that might influence their periodontal health, and neither presented other known risk factors, such as tobacco use. The only apparent variable was related to their oral hygiene. The periodontally involved patient exhibited higher plaque scores than her twin in all clinical visits. Subgingival plaque cultures revealed the presence of Porphyromonas gingivalis and Bacteroides forsythus only in the diseased twin. Both patients had low colony counts of Prevotella intermedia and Eikenella corrodens, but only the healthy twin harbored small quantities of Fusobacterium nucleatum. This case report offers an opportunity to assess etiology of periodontitis in two genetically identical patients whose only obvious difference was their oral hygiene.

Adult↗
PubMed1998

Thiol-disulfide redox buffers maintain a structure of immunoglobulin A that is essential for optimal in vitro binding to secretory component.

We have shown that human secretory component (SC) binds in vitro to different samples of human and murine dimeric immunoglobulin A (IgA). The binding ratio in the IgA/SC complex is 1:1. IgA which is stably bound to SC is separated from unreacted IgA by anion exchange chromatography. A part of IgA/SC complexes formed in vitro is unstable to this elution; the proportion varies between different samples of IgA; it increases following prolonged incubation of IgA at 37 degrees C. Incubation of IgA with glutathione/glutathione disulfide (GSH/GSSG) redox buffers increases the proportion able to form a stable complex with SC to approximately 90%. The presence of bound SC is not essential for this process but does allow it to occur at a lower GSH/GSSG concentration. The stable IgA/SC complex consists of a structure with a disulfide bond between IgA and SC apparently in equilibrium with a structure in which this bond is absent. The proportion bound covalently is similar for different samples of IgA and is insensitive to incubation with GSH/GSSG. It is significantly greater for secretory IgA (sIgA) and for IgA and SC incubated together with a starting mixture of cysteine/cystine. Monoclonal, antigen-specific IgA, all of which is optimally bound to SC in essentially the same way as in native sIgA, can be isolated in high yield. Our results support a mechanism for optimal binding of IgA to SC, that can occur both in vitro and in vivo, in which a thiol disulfide interchange occurs between a free IgA thiol and a sensitive SC disulfide following the initial non-covalent interaction.

Anion Exchange Resins↗
PubMed1998

The cuffed oropharyngeal airway. Its clinical use in 100 patients.

We studied the efficacy of the cuffed oropharyngeal airway in 100 patients. Insertion of the airway after induction of anaesthesia with propofol was easy in 95 of 100 patients, moderately difficult in four patients and failed in one patient. Complications, such as coughing, gagging or body movement, occurred during induction and insertion in 15 patients. Insertion of the airway was not associated with tachycardia or hypertension. Manual ventilation through the airway was easy in less than 30% of patients immediately after insertion. Manual ventilation became easier after adjusting the position of the patient's head, neck or jaw. During spontaneous breathing, adjustment of the head, neck or jaw was required in 30% of patients. Complete airway obstruction occurred in one patient after insertion of the device and in two patients during maintenance of anaesthesia. The airway was left in place during emergence from anaesthesia in the remaining 97 patients. No complications occurred in 91 patients and coughing occurred in the remaining six patients before or during removal of the airway. No regurgitation, vomiting or laryngospasm occurred in any patient at any time. Therefore, the cuffed oropharyngeal airway has a potential use in anaesthetised patients who are breathing spontaneously.

Adolescent↗
PubMed1998

Central venous pressure and its effect on blood loss during liver resection.

BACKGROUND: Any strategy to reduce blood loss in liver resection and decrease blood transfusion would be of benefit to the patient and surgeon. This study evaluates the association of central venous pressure (CVP) with blood loss and blood transfusion during liver resection. METHODS: One hundred consecutive hepatic resections in the period 1986-1996 were studied prospectively concerning CVP, volume of blood lost, and volume of blood transfused. Blood loss volume and blood transfusion were analysed for those with a CVP less than or equal to 5 cmH2O, and greater than 5 cmH2O. A multivariate analysis assessed potential confounding factors in the comparison. RESULTS: The median blood loss in patients with a CVP of 5 cmH2O or less was 200 ml (n=40) and that in those with a CVP above 5 cmH2O was 1000 ml (n=52) (P=0.0001). Only two of 40 patients with a CVP of 5 cmH2O or less had a blood transfusion whereas 25 of 52 patients with a CVP greater than 5 cmH2O required a transfusion (P=0.0008). A multivariate analysis did not show confounding factors. CONCLUSION: The volume of blood lost during liver resection correlates with the CVP. Lowering the CVP to less than 5 cmH2O is a simple and effective way to reduce blood loss during liver surgery.

Aged↗
PubMed1998

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures.

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).

Adolescent↗