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J Chambers

Publications and source records attributed to J Chambers.

At least 127 records · Page 7Linked to original sources
PubMed1994

Serial investigation of balloon angioplasty induced changes in the superficial femoral artery using colour duplex ultrasonography.

Percutaneous transluminal balloon angioplasty (PTA) of superficial femoral artery lesions is associated with similar initial success rates in coronary and iliac artery angioplasty but its application is limited by a much higher incidence of restenosis. To improve understanding of the trauma caused to the vessel by balloon angioplasty and the mechanisms contributing to the subsequent processes of healing and restenosis requires serial investigations of the treated arteries in vivo. This paper describes a prospective study using colour duplex ultrasonic imaging to assess arterial changes in 51 patients with atherosclerotic disease undergoing PTA of superficial femoral artery stenoses and occlusions. Each patient was scanned prior to angioplasty and at intervals up to 6 months post-angioplasty. On each scan, measurements were made of the overall vessel and lumen diameters at each site of angioplasty. These measurements indicate that angioplasty improves vessel patency mainly by stretching of the vessel wall, with compression and/or redistribution of the atherosclerotic plaque contributing less than 25% to the improvement of lumen diameter. Serial measurements after angioplasty show complex patterns of change at the angioplasty sites indicating that several mechanisms may be contributing to the processes of vessel healing and subsequent restenosis. Possible mechanisms which could explain the measured changes in overall vessel and lumen diameters are discussed.

Adult↗
PubMed1993

Simple and rapid method for the determination of the diastereomers of difenacoum in blood and liver using high-performance liquid chromatography with fluorescence detection.

A rapid and sensitive high-performance liquid chromatographic method for the analysis of cis and trans diastereomers of the anticoagulant rodenticide difenacoum has been described. The methodology demonstrates potential for the analysis of diastereomers of related 4-hydroxycoumarin anticoagulants. Separations were achieved by reversed-phase chromatography on a Zorbax ODS column with gradient elution using acetonitrile-water, modified with 0.1% acetic acid, as the mobile phase. Detection of the analytes was effected by fluorescence at excitation and emission wavelengths of 310 and 390 nm, respectively. Sample preparation from both plasma and liver has been simplified to reduce preparation time and manipulation. The minimum detectable concentration of each diastereomer was 5 ng/ml. Recoveries of 100% were obtained from plasma and 93% from liver tissue. This method has been used for the investigation of the pharmacokinetics of difenacoum diastereomers in rats, and for investigation of unexplained hypoprothrombinaemic events encountered clinically.

4-Hydroxycoumarins↗
PubMed1993

Hospital mortality in acute myocardial infarction in the era of reperfusion therapy (the Myocardial Infarction Triage and Intervention Project).

This study was conducted in 19 hospitals in the metropolitan Seattle area and included 6,270 unselected patients who had acute myocardial infarction (AMI) between January 1988 and April 1991. Hospital mortality was determined and related to patient demographic and clinical characteristics, the use of reperfusion therapies, and to complications after AMI. Thrombolytic therapy or direct coronary angioplasty < 6 hours from symptom onset was used to treat 1,185 (19%) and 524 (9%) patients, respectively. There were 629 (10%) hospital deaths; most occurred during the first 3 days of hospitalization. Factors affecting mortality after admission included: recurrent chest pain, recurrent AMI, development of heart failure, and the occurrence of stroke. After adjustment for age, treatment with thrombolytic therapy or direct angioplasty had no independent effect on reducing the overall mortality rate. Hospital mortality rates for AMI have improved considerably since 1970, although recurrent myocardial ischemic events continue to have an adverse effect on outcome. The current use of reperfusion treatments has had minimal causal impact on overall mortality rates, principally because less than one third of patients, who are relatively "low risk," are eligible and receive these treatments.

Adult↗
PubMed1993

Last gasp.

Next Monday's World No-Tobacco Day is also the last day on which smoking will be allowed in UK hospitals. Amanda Killoran and colleagues urge local health authorities to seize the initiative.

Humans↗
PubMed1993

Echocardiographic description of the CarboMedics bileaflet prosthetic heart valve.

OBJECTIVES: The aim of this study was to describe the echocardiographic appearance of the normal CarboMedics prosthesis in the aortic and mitral positions. BACKGROUND: Echocardiography is the standard method of assessing prosthetic valves. However, new valve designs may still be marketed without an accompanying echocardiographic description. The CarboMedics prosthesis is in widespread use, but few noninvasive hemodynamic data have been published. METHODS: Echocardiography was performed in 147 patients with a total of 96 normally functioning CarboMedics prostheses in the aortic position and 75 in the mitral position; in 24 patients, valves were implanted in both positions. The following variables were measured: peak and mean transvalvular velocities, peak and mean instantaneous gradient estimated from the modified Bernoulli equation, aortic acceleration slope, pressure half-time, transvalvular flow and effective orifice area using the continuity equation. Patterns of regurgitation were observed by transthoracic study in all valves and by transesophageal study in selected mitral valve prostheses. RESULTS: For the aortic valve prostheses, estimated mean gradient ranged between 6 and 19 mm Hg. Effective area differed markedly among the anulus diameters (p < 0.001), with a mean value of 1 cm2 for the 19-mm valve and 2.6 cm2 for the 29-mm valve. For the mitral valve prostheses, mean gradient ranged from 3 to 7 mm Hg. There were a total of four washing leaks, one on either side of each pivotal point, and these lasted throughout systole or diastole. One jet was commonly more prominent than the other three. CONCLUSIONS: The CarboMedics prosthesis offered relatively little resistance to forward flow except at small anulus diameters. The washing jets were prominent and would be easy to misdiagnose as a sign of paraprosthetic regurgitation.

Aortic Valve↗
PubMed1993

Pelvic fracture geometry predicts risk of life-threatening hemorrhage in children.

Recent studies have concluded that pelvic fractures in children, unlike those in adults, are not a source of life-threatening hemorrhage. Our study hypothesis was that major bleeding occurs in children with pelvic fractures, and fracture geometry allows early identification of patients at risk for severe hemorrhage. Fifty-seven (5.5%) of 1044 pediatric trauma patients sustained pelvic fractures. The majority of injuries were from motor vehicle crashes (n = 21, 36.8%) and auto-pedestrian collisions (n = 18, 31.6%). Twenty-three children (40.4%) had unilateral anterior fractures (type I), seven (12.2%) had unilateral posterior fractures (type II), 23 (40.4%) had unilateral anterior and posterior fractures (type III), and four (7%) had bilateral anterior and posterior (type IV) fractures. Eighteen children (32.6%) required blood transfusions during the initial 48 hours (mean, 59 mL/kg). Skeletal fixation was applied in ten patients (17.5%), and it controlled bleeding in six (60%). Pelvic angiography identified arterial hemorrhage in three of four patients, and embolization controlled bleeding in all cases. The only death in the series (mortality, 1.7%) was from multisystem trauma. Age, sex, Injury Severity Score, Revised Trauma Score, mechanism of injury, and pelvic fracture geometry were evaluated as risk factors predictive of hemorrhage employing multiple logistic regression. Only pelvic fracture geometry independently identified patients at increased risk of major bleeding. We conclude that pelvic fracture geometry identifies a subset of pediatric trauma patients at high risk for life-threatening hemorrhage and urge a prompt multispecialty approach to these patients.

Accidents, Traffic↗
PubMed1992

Alternative exon usage and processing of the major histocompatibility complex-encoded proteasome subunits.

The finding that two subunits of the proteasome, LMP2 and LMP7, are encoded in the major histocompatibility complex (MHC) has linked the proteasome which represents a major extralysosomal proteolytic system to the processing of intracellular antigens. Here we describe a second form of the human LMP7 cDNA, LMP7-E2, which has been identified during the characterization of novel genes in the MHC. The analysis of the genome organization of LMP7 revealed that LMP7-E1 and LMP7-E2 arise by alternative exon usage. Using specific antibodies against LMP2 and LMP7, we show that they are co-expressed with class I MHC molecules as well as a putative peptide transporter. The polypeptides encoded by LMP7 and LMP2 undergo proteolytic processing when incorporated into proteasomes, and the LMP7 precursor is derived mainly from LMP7-E2. Furthermore, our data suggest that LMP7 and LMP2 are mutually dependent for their incorporation into the proteasomal complex.

Amino Acid Sequence↗
PubMed1992

6-substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists.

We have prepared a series of 6-substituted decahydroisoquinoline-3-carboxylic acids, and structurally similar analogs, as potential N-methyl-D-aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate-mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([3H]CGS19755, [3H]AMPA, and [3H]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced lethality in mice. We synthesized many of the possible diastereomers of the decahydroisoquinoline nucleus in order to examine the spatial and steric requirements for affinity at the NMDA receptor and activity as NMDA antagonists. From our structure-activity relationship we identified two potent and selective NMDA receptor antagonists, the phosphonate- and tetrazole-substituted amino acids 31a and 32a, respectively, that show good activity in animals following systemic administration. For example, 31a and 32a selectively displaced [3H]CGS19755 binding with IC50S of 55 +/- 14 and 856 +/- 136 nM, respectively, and selectively antagonized responses due to NMDA in a cortical wedge preparation with IC50S of 0.15 +/- 0.01 and 1.39 +/- 0.29 microM, respectively. And compounds 31a and 32a blocked NMDA-induced lethality in mice with minimum effective doses of 1.25 and 2.5 mg/kg (intraperitoneal), respectively. These novel amino acids are among some of the most potent NMDA antagonists described thus far, and are excellent candidates for development as neuroprotective agents for a number of CNS disorders.

Animals↗
PubMed1992

Major histocompatibility complex (MHC)-encoded HAM2 is necessary for antigenic peptide loading onto class I MHC molecules.

The mutant murine lymphoma cell line RMA-S is unable to present endogenous antigens due to its inability to efficiently assemble class I major histocompatibility complex molecules and antigenic peptides. Therefore, it has been suggested that RMA-S cells are defective either in peptide generation or in peptide transport into the endoplasmic reticulum, where class I major histocompatibility complex molecule assembly is believed to occur. As proteasomes and the putative peptide transporters HAM1 and HAM2 have been implicated in class I antigen processing, we have investigated their expression in RMA-S and its wild-type counterpart RMA. Both proteasomes and HAM1 proteins are expressed at similar levels and show identical subcellular distributions in the two cell lines. However, only one copy of the HAM2 gene is present in RMA-S cells, and it contains a point mutation that leads to a premature stop codon. Thus, the HAM2 protein is absent from RMA-S cells. These data demonstrate that HAM2 is essential for peptide loading onto class I molecules.

Amino Acid Sequence↗
PubMed1992

The Hatle orifice area formula tested in normal bileaflet mechanical mitral prostheses.

The Hatle formula was derived empirically in native mitral stenosis and may not be valid for normal prosthetic valves. Bileaflet mechanical prostheses open fully at low flows and have minimal interindividual variation in orifice area. In these valves effective area and measured manufacturer's area should be similar. We studied 60 patients aged 58 +/- 12 yr at a mean of 5 months after implantation with a CarboMedics prosthesis. There was a coexistent aortic prosthesis in 21. All diastolic measurements were averaged over 5 beats and stroke volume was calculated from the integral of the subaortic velocity trace and the cross-sectional area of the left ventricular outflow tract. For the whole group, area by the Hatle formula was 3.1 +/- 0.7 cm2 and measured area was 2.8 +/- 0.4 cm2. There was no significant correlation between these values (p = 0.329). Pressure half-time was more closely correlated with peak transmitral velocity (p = 0.012), RR interval (p = 0.015), diastolic time interval (p = 0.062) and stroke volume (p = 0.074). We conclude that the Hatle formula should not be applied to normal bileaflet mitral prostheses where pressure half-time reflects nonprosthetic factors more closely than orifice area.

Aged↗
PubMed1992

Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency.

The Lesch-Nyhan disease is caused by an almost complete lack of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Partial HPRT-deficiency, associated with less severe phenotype, has also been identified. We have characterized mutations occurring in HPRT cDNA isolated from patients with HPRT-deficiency with an emphasis on examining the more unusual partial variants of HPRT-deficiency. HPRT cDNA was amplified by PCR, cloned and analyzed by automated DNA sequence analysis. Twenty-two, unrelated individuals with HPRT deficiency were studied including eight classic Lesch-Nyhan patients and fourteen patients representing the different groups of partial HPRT deficiency. We found a diverse pattern of mutations with point mutations accounting for the majority of abnormal HPRT genes. Nonsense mutations and exon deletions were only found in HPRT cDNA isolated from classic Lesch-Nyhan patients. Mutations associated with partial HPRT-deficiency were frequently located in the amino terminal part of the molecule. A CpG mutational hot spot was identified at the position for Arg-51 in the HPRT protein. Two hyperuricemic patients exhibited unusual splice site mutations: in one this led to the creation of an additional exon in the HPRT gene and in the other part of exon 6 was missing in a subpopulation of the transcripts, producing the effect of a dominant, negative mutation.

Amino Acid Sequence↗
PubMed1992

Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients.

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Limitations and pitfalls in the assessment of prosthetic valves with Doppler ultrasonography.

Normal Doppler-derived data for new prosthetic designs are currently gathered after marketing. Therefore the cardiologist needing to assess a new valve may need to equate Doppler results with data gathered invasively during premarket testing. This invites error because catheterization and Doppler ultrasonography are not always directly comparable. This review discusses difficulties in defining normal prosthetic function and problems arising from the comparison of catheter and Doppler data. It concludes that (1) the hemodynamic formulas in current use have limitations when applied to normally functioning prosthetic valves, (2) patterns of normal regurgitation differ widely between different valve designs and may occasionally resemble paraprosthetic leaks, (3) there is a good case for reporting only raw Doppler data rather than derived pressure drop or effective orifice area, (4) a new prosthetic design should be tested in vivo with Doppler ultrasonography before marketing, and (5) nonprosthetic factors affecting Doppler data and flow information should always be given.

Cardiac Catheterization↗
PubMed1991

Smoking.

Explore the source record for details and available documents.

Advertising↗
PubMed1991

A randomized double-blind crossover comparison of four rate-responsive pacing modes.

The aim of this study was to compare, both subjectively and objectively, four modern rate-responsive pacing modes in a double-blind crossover design. Twenty-two patients, aged 18 to 81 years, had an activity-sensing dual chamber universal rate-responsive (DDDR) pacemaker implanted for treatment of high grade atrioventricular block and chronotropic incompetence. They were randomly programmed to VVIR (ventricular demand rate-responsive), DDIR (dual chamber demand rate-responsive), DDD (dual chamber universal) or DDDR (dual chamber universal rate-responsive) mode and assessed after 4 weeks of out-of-hospital activity. Five patients, all with VVIR pacing, requested early reprogramming. The DDDR mode was preferred by 59% of patients; the VVIR mode was the least acceptable mode in 73%. Perceived "general well-being," exercise capacity, functional status and symptoms were significantly worse in the VVIR than in dual rate-responsive modes. Exercise treadmill time was longer in DDDR mode (p less than 0.01), but similar in all other modes. During standardized daily activities, heart rate in VVIR and DDIR modes underresponded to mental stress. All rate-augmented modes overresponded to staircase descent, whereas the DDD mode significantly underresponded to staircase ascent. Echocardiography revealed no difference in chamber dimensions, left ventricular fractional shortening or pulmonary artery pressure in any mode. Cardiac output was greater at rest in the dual modes than in the VVIR mode (p = 0.006) but was similar at 120 beats/min. Beat to beat variability of cardiac output was greatest in VVIR mode (p less than 0.0001), with DDIR showing greater variability than DDD or DDDR modes (p less than 0.05). Mitral regurgitation estimated by Doppler color flow imaging was similar in all modes, but tricuspid regurgitation was significantly greater in VVIR than in dual modes (p less than 0.03). Subjects who preferred the DDDR mode and those who found the VVIR mode least acceptable had significantly greater increases in stroke volume when paced in the DDD mode than in the ventricular-inhibited (VVI) mode at rest (22%) when compared with subjects who preferred other modes (2%, p = 0.03). No other objective variable was predictive of subjective benefit from any rate-responsive pacing mode. Thus, dual sensor rate-responsive pacing (DDDR) is superior objectively and subjectively to single sensor (VVIR, DDIR and DDD) pacing and subjective benefit from dual chamber rate-augmented pacing is predictable echocardiographically.

Adult↗