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Biomedical subjects

J Chambers

Publications and source records attributed to J Chambers.

At least 145 records · Page 8Linked to original sources

Surgical treatment of sacral fracture in a horse.

An 8-year-old Arabian stallion had signs of severe tailhead pruritus and slowly progressive loss of tail tone for 3 months. Palpation per rectum and radiography of the sacrocaudal region revealed a transverse, ventrally displaced fracture of the caudal portion of the sacrum. Surgical decompression and tail amputation resulted in complete recovery of athletic and reproductive function. Evidence of cauda equina neuritis was not seen on histologic examination of nerve roots obtained at surgery.

Amputation, Surgical↗

The continuity equation tested in a bileaflet aortic prosthesis.

The continuity equation is valid for a population of aortic valves, but its accuracy in individual valves is uncertain. In bileaflet prostheses, obstruction to forward flow is small and individual variability in opening behaviour is minimal. In these valves, the area of the effective orifice should be close to that measured by the manufacturer. A total of 57 patients aged 58 +/- 11 years were studied at a mean of 3.6 months after implantation with a CarboMedics aortic prosthesis. Nine had additional implants in the mitral position and all prostheses were clinically normal. Peak subaortic and transaortic velocities were averaged over 5 beats. The area of the effective orifice was significantly different between the four diameters (P less than 0.00001), and the correlation between the effective and measured area of the orifice was moderate (rs = 0.73, P less than 0.00003). The 95% range for the differences between individual pairs of values, however, was 0.16 +/- 0.61 cm2. Discrepancies probably arose in the estimation of subaortic cross-sectional area and subaortic velocity. Thus, the continuity equation may be inaccurate in an individual prosthetic valve when functioning normally.

Aged↗

Millipore analysis of valvular fluid in sterile valve malfunctions.

Malfunctions of sterile shunts may result from valvular dysfunction. The cerebrospinal fluid shunt valves of 14 patients were excised during surgery for sterile shunt malfunctions. In 6 patients, the malfunction was due specifically to a valve malfunction. Cerebrospinal fluid from each valve was passed through a millipore filter, which was then stained using either hematoxylin and eosin or periodic acid-Schiff. The stained millipore filters were examined by a neuropathologist who was unaware of the cause of the shunt malfunction. Although inflammatory cells were detected in all cases, the patients with valve malfunctions were found to have numerous macrophages and giant multinucleated reactive cells within their valves, while cerebrospinal fluid from valves that had been removed during shunt revisions for reasons other than a malfunctioning valve contained only rare mononuclear cells or macrophages. No valve contained erythrocytes, fibrinous matter, neural or glial tissue, or choroid plexus. The possible causes of valve malfunction, including infection and allergic reactions, are discussed. All patients did well after simple replacement of the valve.

Adolescent↗

Cardiovascular responses to graded reductions in leg perfusion in exercising humans.

Our objective was to determine whether the chemoreflex from human muscle is elicited by small graded reductions in muscle blood flow (MBF) during mild exercise or whether this reflex has an obvious threshold associated with large changes in femoral venous lactate and H+ levels (i.e., as in dogs with high muscle oxidative capacity). Seven subjects exercised supine at 40, 87, and 142 W; lower body positive pressure (LBPP) was applied in 3-min steps at 25, 35, 45, and 50-60 mmHg with the lower body and the cycle ergometer in a sealed box. Estimated MBF (Fick) fell by 5.3 +/- 4.3 to 19.9 +/- 3.8% at four levels of LBPP over three work rates. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) concentration rose with increasing LBPP. MAP was significantly correlated with femoral venous pH, lactate, O2 tension, and O2 content during moderate and heavy exercise, without an apparent threshold. Percentage decreases in muscle vascular conductance exceeded the decreases in MBF twofold, indicating significant opposition to reduction in MBF by the chemoreflex. Approximately 50% of the correction of MBF back toward control (i.e., at 0 LBPP) could be explained by increased cardiac output, calculated from the rise in HR; the remaining correction could be attributed to both sympathetic vasoconstriction (indicated by high NE levels) and to mechanical effects of partial occlusion. Results suggest that in humans stepwise reductions in MBF gradually elicit muscle chemoreflexes with no apparent threshold at these levels of exercise.

Adult↗

Health education in England: a five-year strategy for the Health Education Authority.

The Health Education Authority in England has published its first Strategic Plan, covering the years 1990-1995. The origins and functions of the Authority are described, as are the various factors contributing to the Plan. The strategic objective is defined as being "to ensure that by the year 2,000 the people of England are more knowledgeable, better motivated, and more able to acquire and maintain good health," as suggested by six criteria for program effectiveness. Selected programs include HIV/AIDS, coronary heart disease, cancer, smoking, alcohol, nutrition, and family and child health. Complementary delivery methods are examined, such as use of the mass media, the National Health Service, schools and colleges, and the workplace, utilizing partnerships with health, education, and other agencies, promoting professional development, and dissemination of research and local initiative results.

Aged↗

Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism.

Theoretically, the relationship between plasma aldosterone (PA) and PRA in normal subjects under random conditions should differ from that in patients with primary hyperaldosteronism or primary adrenal failure, but should be similar to that in patients with secondary hyperaldosteronism or hyporeninemic hypoaldosteronism. PA, expressed as a function of PRA, the PA/PRA ratio, provides an index of adrenal sensitivity in normal subjects under routine conditions. The random PA/PRA ratios in patients with primary adrenal disorders did not overlap with those in normal subjects, patients with secondary adrenal disorders, hypertensive subjects, or other patients. A single elevated PA/PRA ratio, i.e. more than 920, associated with elevated PA in 4 patients or normal PA in 6 patients indicated primary hyperaldosteronism in 10 patients. However, 5 of 17 patients with chronic renal failure had elevated PA/PRA ratios, but did not have primary hyperaldosteronism. All 14 patients with secondary hyperaldosteronism had elevated PA associated with normal PA/PRA ratios. A single PA/PRA ratio of less than 28 associated with low PA in 18 patients and a normal PA in 1 patient indicated primary adrenal insufficiency, while a low PA associated with a normal PA/PRA ratio indicated hyporeninemic hypoaldosteronism in 7 patients. Fifty-nine patients with nonadrenal disorders other than renal failure had normal PA and PA/PRA ratios. Therefore, with the exception of patients with advanced renal failure, only a single blood sample is required to establish all diagnoses of disorders of the renin-angiotensin-aldosterone axis under random conditions.

Biomarkers↗

The impact of a music festival on local health services.

A music festival was held in July 1989 near Liskeard in Cornwall. This paper comments on some of the organisational problems, and documents the workload of voluntary workers and professional medical agencies serving the festival. At least 467 of attenders (greater than 1%) sought aid, and 15 patients required hospital admission. There were two deaths and one birth at the site. It is suggested that, in addition to the services provided by voluntary agencies, organisers of mass gatherings should provide suitably qualified medical and nursing personnel on site.

Anniversaries and Special Events↗

Separation of two subpopulations of old human fibroblasts by mitochondria (rhodamine 123) fluorescence.

The mitochondria-binding fluorescent dye rhodamine 123 (R123) was used to sort two subpopulations of cells from mass cultures of old human fibroblasts (HF). Both subpopulations showed unusual dye retention kinetics when compared to young HF. Additionally, electron microscopy revealed differences in numerical density of mitochondria between young and old HF. Moreover, the two subpopulations exhibited differences in radiolabeled thymidine incorporation and proliferative capacity. The results obtained suggest a possible relationship between mitochondria, proliferative potential and cellular aging.

Cell Division↗

Virus-induced autoantibody response to a transgenic viral antigen.

The induction of autoantibodies and their possible role in the pathogenesis of autoimmune disease are poorly understood. Involvement of infectious agents has been suspected, but direct evidence is sparse. Whether immunological unresponsiveness to self by antibody-forming B cells is maintained by clonal abortion, clonal anergy or suppression, or how the scenario of interactions between helper T cells, B cells and antigen-presenting cells is distorted in autoantibody responses, is being analysed and widely debated. To evaluate tolerance of neutralizing B-cell responses we used transgenic mice expressing the cell membrane associated glycoprotein (G) of vesicular stomatitis virus (VSV) as self-antigen. We show that autoantibodies to VSV-G cannot be induced by VSV-G in adjuvant or by recombinant vaccinia virus expressing VSV-G, but are triggered by infection with wild-type VSV. The data show that helper T-cell tolerance is crucial in maintenance of B-cell non-reactivity and that cognate T-B recognition is necessary to break tolerance of self-reactive B cells. These results may help to understand mechanisms of virus-induced autoimmunity.

Animals↗

Splice junction mutations in a yeast tRNA gene which alter the rate and precision of processing.

We have introduced mutations into a tRNALeu3 gene which alter the intron boundaries and examined their effects on RNA splicing. Our results show that the 5'-proximal splice junction is not specified by the position of an adjacent base-paired stem present in all naturally occurring tRNA precursors. Also, efficient cleavage of 5'-splice junctions unique to these mutants, -CpU-, -UpA- and -UpG-, indicates the purine found at the 5'-side of this site in all natural precursors is dispensable. Some alterations of the sequence and structure at the 5'-proximal splice site reduce the rate of cleavage therein and result in accumulation of molecules composed of the 5'-half of the tRNA plus the intron. The precise position of the 5'-proximal cleavage site can vary +/- 1 base in these mutants. The 3'-proximal splice junction is rendered inactive by changing the prospective splice junction sequence from -ApC- to -CpC- and reducing the size of an unpaired loop at this site from six to two bases. Very small amounts of RNA composed of the 3'-half of the tRNA plus the intron accumulate from this precursor. We conclude that splice junction sequence and structure affect both the rate and precision of intervening sequence removal.

Base Sequence↗

Purification and N-terminal characterization of Chinchilla villidera alpha-1-antitrypsin.

1. Chinchilla, Chinchilla villidera, alpha-1-antitrypsin has been purified to homogeneity and partially characterized according to mol. wt, amino acid and carbohydrate composition and N-terminal amino acid sequence (30 residues). 2. The mol. wt is between 52,000 and 55,000 as determined by PAGE or sedimentation equilibrium. 3. The best alignment between chinchilla, human and baboon alpha-1-antitrypsin amino acid sequences offsets the chinchilla sequence 6 positions vs the primate structures. 4. This alignment suggests potential importance of the sequence His-Glu-Gln-Glu-His at positions 11-15. 5. Additionally, the segment Leu-Ala-Glu-Phe-Ala, positions 25-29, is strictly conserved. 6. Shorter N-terminal sequences available for rat and rabbit alpha-1-antitrypsin appear to follow the offset alignment vs the primate structures.

Amino Acid Sequence↗

Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.

Amino Acid Sequence↗

Intraventricular septal hypertrophy in type 1 diabetic patients with microalbuminuria or early proteinuria.

To investigate whether the slightly increased blood pressure that occurs in early diabetic renal disease is associated with hypertensive left ventricular hypertrophy, M-mode echocardiograms were recorded in 11 non-diabetic control subjects and four groups of Type 1 diabetic patients. These were 15 patients without microvascular complications, 10 with microalbuminuria, 12 with early persistent proteinuria, and 8 with established renal impairment. Mean blood pressure was 133/80 mmHg (uncomplicated patients), 143/85 mmHg (microalbuminuria), 147/92 mmHg (early proteinuria) and 158/85 mmHg (renal impairment). Mean intraventricular septal width in the uncomplicated diabetic patients was 9.8 (SE 1.2) mm which did not differ from non-diabetic control subjects. Mean septal width was significantly greater in the other groups (microalbuminuria, 12.7 (1.1) mm, p less than 0.02; proteinuria, 12.0 (0.7) mm, p less than 0.05; renal impairment, 15.5 (1.8) mm, p less than 0.001). Left ventricular mass increased progressively between groups and was significantly increased in those with renal impairment (140 (21) vs 103 (5) g m-2 in uncomplicated patients, p less than 0.05). Septal width in the diabetic population not receiving antihypertensives (n = 37) was significantly correlated with systolic blood pressure (r = 0.45, p less than 0.005) which was the only variable independently related to septal width and ventricular mass. It appears that the slight increase in blood pressure that occurs in microalbuminuria and early proteinuria is frequently associated with hypertensive left ventricular hypertrophy.

Adult↗

Is accurate rate response programming necessary?

Exercise capacity and general well-being are improved by appropriately programmed rate responsive pacemakers when compared to fixed rate units. Ten patients had activity sensing DDDR units implanted for combined AV block and sinus node incompetence. Ten patients had Sensolog activity sensing VVIR units implanted for complete heart block. The effects of over and under programming of rate response in both dual and single chamber activity sensor rate adaptive pacemakers has been assessed subjectively by visual analog scales and specific activity questionnaires and objectively by graded treadmill testing and the performance of standardized daily activities. Patients were randomly programmed to absent rate response (VVI in the Sensolog group), hyporesponsive (DDD in the dual chamber group), appropriate response (VVIR, DDDR according to Manufacturer's instructions) and over responsive (VVIR+, DDDR+) in a double-blind crossover design. Thirty percent of patients demanded early crossover from VVI, 30% from DDDR+ and 50% from VVIR+. Perception of Exercise Capability was similar to objective exercise treadmill times which were shorter in VVI than in VVIR or VVIR+ (P less than 0.05) or control subjects (P less than 0.001). There was no difference between any dual chamber mode or control subjects. General well-being was poorest in DDDR+ and VVIR+ modes despite objective improvement in exercise capacity. Symptoms were least in VVIR and DDDR and all but one patient chose appropriate programming as their overall preferred mode. Thus, even inaccurate rate response programming results in similar and improved exercise capacity compared to absent rate response but overprogramming is unacceptable to most patients, confirming that appropriate programming and sensor specificity is critical in rate responsive pacing.

Arrhythmia, Sinus↗

Limitations of Doppler ultrasound in the assessment of the function of prosthetic mitral valves.

Pressure half time has been assumed to be a relatively flow-independent measure of orifice area, but it may also be influenced by atrial and ventricular factors. Pressure half time and peak left ventricular inflow velocity were measured by continuous wave Doppler ultrasound in 164 patients with normally functioning Carpentier-Edwards, Björk-Shiley, and Starr-Edwards mitral prostheses. Pressure half time was shorter in the Björk-Shiley than in the other value types and peak transmitral velocity was highest in the Starr-Edwards prostheses. These differences, however, were partly explained by coexistent differences in transmitral flow. Filling time accounted for 19% and stroke volume for 15% of the variance in pressure half time compared with only 5.6% for prosthetic design and 0.4% for annulus diameter when each of these variables was considered alone. The design of the prosthesis explained 18% of the variance in peak transmitral velocity, while cardiac output and annulus diameter did not contribute significantly. With Doppler ultrasound it is impossible to define reliable normal ranges for prosthetic function independently of atrial and ventricular function. Formulas for orifice area based on peak transmitral velocity and flow seem more likely to reflect the behaviour of normally functioning prostheses than those based on pressure half time.

Blood Flow Velocity↗

Crystal structure and stability of a DNA duplex containing A(anti).G(syn) base-pairs.

The synthetic dodecanucleotide d(CGCAAATTGGCG) has been analysed by single-crystal X-ray diffraction techniques and the structure refined to R = 0.16 and 2.25 A resolution, with the location of 94 solvent molecules. The sequence crystallizes as a full turn of a B-DNA helix with ten Watson-Crick base-pairs and two adenine-guanine mispairs. The analysis clearly shows that the mismatches are of the form A(anti).G(syn). Thermal denaturation studies indicate that the stability of the duplex is strongly pH dependent, with a maximum at pH 5.0, suggesting that the base-pair is stabilized by protonation. Three different arrangements have been observed for base-pairs between guanine and adenine and it is likely that A.G mismatch conformation is strongly influenced by dipole-dipole interactions with adjacent base-pairs.

Adenine↗