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Biomedical subjects

B J Anderson

Publications and source records attributed to B J Anderson.

At least 73 records · Page 4Linked to original sources

RNAs 4A and 5 are present in tomato aspermy virus and both subgroups of cucumber mosaic virus.

Primer extension analysis was used to determine the presence of RNAs 4A and 5 in tomato aspermy virus (TAV) and both subgroups of cucumber mosaic virus (CMV). RNAs 4A and 5 were detected in TAV and all CMV strains (representative of both subgroups) that were analysed, except for one subgroup I CMV strain which lacked detectable RNA 5. In subgroup II CMV strains the RNA 5 population was found to consist of two sequence variants. Comparison of the RNA 5 sequences from TAV and CMV indicated that TAV and subgroup II CMV RNA 5 share a much greater degree of sequence similarity than either has with subgroup I RNA 5. RNA 4A and the encoded 2b protein appear to be unique to the cucumovirus genus of the tripartite viruses, which share an otherwise common genome structure, and may have played a role in the evolutionary origin of this genus.

Cucumis sativus↗

Event status of the Starr-Edwards aortic valve to 20 years: a benchmark for comparison.

BACKGROUND: Considerable effort and expense has been invested in the evolutionary development of cardiac valvular prostheses with the goal of reducing or minimizing specific events related to these prostheses. It is important to measure any improvement achieved with such development by comparison against a historic standard. The Starr-Edwards caged-ball prosthesis model 1260 has been used for 30 years as the predominant or sole model of its kind for aortic valve replacement. This historic opportunity provides a benchmark for subsequent improvement and comparison of current prostheses. METHODS: Between 1969 and 1991, 1,100 patients (median age, 57 years; 838 men and 194 women) underwent aortic valve replacement with or without coronary artery bypass grafting (aortic valve replacement, 964; aortic valve replacement plus coronary artery bypass grafting, 136) with the 1260 Starr-Edwards caged-ball prosthesis. RESULTS: Operative mortality was 6.2% (68 patients). Univariate patient characteristics predictive of early mortality were female sex (p = 0.003), age (> 56 years; p = 0.002), recent operative interval (1985 to 1991 versus 1969 to 1976 or 1977 to 1984; p = 0.002), presence of atrial fibrillation (p = 0.001), and small valve size (7A to 8A = 19 to 21 mm; p < 0.001). Follow-up extended to 11,293 patient-years (mean, 24.8 years) and was 96.9% complete. Survival at 5, 10, 15, and 20 years for all patients including operative mortality was 76.6%, 59.6%, 44.9%, and 31.2%, respectively. Operative variables predictive of poor late survival were advanced New York Heart Association class (III or IV); (p = 0.0001), older age (> 56 years; p = 0.0001), and lower (< 0.56) ejection fraction (p = 0.0001). Freedom from thromboemboli and anticoagulant-related bleeding at 5 years was 90.8% and 98.7%, respectively. Univariate model for greater risk of late thromboemboli identified female sex (p = 0.04), older age (> 56 years; p = 0.0002), and New York Heart Association class III or IV (p = 0.0058), as risk factors. Multivariate analysis for thromboemboli demonstrated older age (p = 0.0007) and New York Heart Association class III or IV (p = 0.0041) as significant. Alternatively, univariate analysis for late bleeding found only the most recent operative interval (p = 0.009) as significant, and the rarity of events prevented a multivariate query. There were no valve failures. CONCLUSIONS: The late results of survival and freedom from late anticoagulant-related bleeding or thromboemboli are excellent, especially in larger (9A and above) sizes, and with the long implant record comparable with more recent prostheses, the Starr-Edwards valve provides an excellent, safe, and durable alternative in the aortic position and provides a benchmark against which to compare other prostheses.

Anticoagulants↗

Single versus bilateral internal mammary artery grafts: 10-year outcome analysis.

BACKGROUND: The superior long-term patency of the internal mammary artery (IMA) confers important short-term and late survival advantages when grafted to the left anterior descending coronary artery. However, it remains uncertain whether patients derive additional survival benefit when both IMAs are used in coronary revascularization. METHODS: Between June 1983 and May 1986, 160 patients (mean age 60 years) received bilateral IMA grafts for coronary artery bypass procedures, and in 93% of patients, the right IMA was used to bypass the left coronary system. During a similar interval, a group of 161 patients matched for symptomatic status and extent of disease (mean age, 62 years) received a single left IMA and saphenous vein grafts. RESULTS: The two groups were similar with respect to gender, preoperative angina class, priority status, extent of coronary artery disease, left ventricular function, and number of distal anastomoses. Diabetes was more prevalent in the patient group receiving a single IMA graft (27% versus 17.5%; p = 0.05). Early outcome was similar in the two groups; operative mortality was 0.6% for the patient group receiving single IMA grafts and 0% for those with bilateral IMA grafts. The mean follow-up of 320 hospital survivors was 10 years. Univariate analysis revealed significantly fewer overall deaths in the patients receiving bilateral IMA grafts (n = 30; p = 0.05), and less late cardiac mortality (n = 12; p = 0.016). Ten-year actuarial survival for patients dismissed from the hospital was 76% for those receiving single IMA graft versus 85% for those receiving bilateral IMA grafts. Multivariate analysis revealed diabetes (risk ratio = 1.73), advancing age (risk ratio = 1.08), and lower ejection fraction (risk ratio = 1.01) to be the only significant predictors of late cardiac death. Use of a single IMA graft was not significant (p = 0.138) despite a risk ratio of 1.78. Use of only a single IMA graft correlated with an increased risk of angina recurrence (p < 0.001), late myocardial infarction (p = 0.019), and risk of any cardiac event (p < 0.001). CONCLUSIONS: Independent risk factors for late death were diabetes mellitus, older age, and reduced ejection fraction. Patients receiving bilateral IMA grafts had better long-term survival than those with a single IMA graft, but this was not independent of diabetes. Multivariate analysis, however, did confirm that compared with single arterial grafts, bilateral IMA grafting was an independent predictor of lower rates of angina recurrence, late myocardial infarction, and the composite end point of any cardiac event.

Actuarial Analysis↗

Results of allograft aortic valve replacement for complex endocarditis.

METHODS: Between November 1985 and July 1995, 36 patients underwent allograft aortic valve replacement for endocarditis. The mean age of the 29 men and seven women was 53 years (range 25 to 79 years). Previous procedures included mechanical (n = 9), bioprosthetic (n = 5), and allograft (n = 2) aortic valve replacement, aortic valvotomy (n = 1), and orthotopic heart transplantation (n = 1). Infecting organisms were Staphylococcus and Streptococcus species in 69% of patients and fungi in 6%. Intraoperative findings demonstrated valvular vegetations (n = 25), annular abscesses (n = 25), and cusp destruction (n = 13). Complex reconstruction of the aortic anulus was required in 25 patients, and associated procedures included mitral valve repair (n = 2), mitral valve replacement (n = 3), coronary artery bypass grafting (n = 8), repair of ventricular septal defect (n = 4), left ventricular aneurysmectomy (n = 1), and repair of atrial septal defect (n = 1). Allograft valve insertion was performed by the scalloped technique in seven, intraaortic cylinder technique in 19, and allograft aortic root replacement in 10. RESULTS: Follow-up was 100% complete at a mean of 2.6 +/- 2.8 years after valve replacement. Operative mortality was 13.8%. Complications included low cardiac output (n = 10), bleeding (n = 2), myocardial infarction (n = 1), stroke (n = 1), renal insufficiency (n = 2), respiratory insufficiency (n = 3), and heart block (n = 8). Late echocardiogram (mean 2.6 +/- 1.8 years) demonstrated grade III/IV aortic regurgitation in five patients. There were seven late deaths (five cardiac, not valve-related; two noncardiac). No patient has had recurrence of endocarditis. Actuarial survival at 5 years was 53.1% +/- 11.5%. Univariate analysis demonstrated prosthetic valve endocarditis to adversely affect late survival (p = 0.04). Cumulative risk of reoperation at 5 years was 8.0% +/- 5.6%. CONCLUSION: Allograft aortic valve replacement facilitated reconstruction of complex aortic valve endocarditis with a low reoperation rate and no recurrent endocarditis in this series.

Adult↗

Rectal paracetamol dosing regimens: determination by computer simulation.

A pharmacokinetic dynamic simulation model was used to predict rectal paracetamol dosing schedules which would maintain steady state plasma concentrations of 10-20 mg.l-1. These plasma concentrations of paracetamol are known to reduce fever. The conventional dosing schedule of 15 mg.kg-1 four hourly was unsatisfactory. Steady state concentrations of 8-12 mg.l-1 were only reached after 16 h. A loading dose of 50 mg.kg-1 followed by 30 mg.kg-1 six hourly achieved plasma concentrations of 9-18 mg.l-1. Paracetamol is a mild analgesic. A higher plasma paracetamol concentration of 25 mg.l-1 is known to give satisfactory analgesia to 60% of children after tonsillectomy. This concentration can be reached after a loading dose of 70 mg.kg-1 and a maintenance dose of 50 mg.kg-1 8 hourly. Doses above 150 mg.kg-1.day-1 have been reported to cause reversible liver toxicity after 2-8 days and should not be sustained.

Acetaminophen↗

Aspects of theophylline clearance in children.

Michaelis-Menten pharmacokinetic parameters for theophylline were estimated in a three-month infant following an accidental overdose of intravenous aminophylline. Fitting of time-concentration data was performed using nonlinear regression with MKMODEL. A mixed order elimination model was superior to a first order model. Parameter estimates were standardized to a 70 kg human using an allometric power model. Parameter estimates (SE) were: maximum rate of metabolism (Vmax) 71 (42) mg.h-1, Michaelis-Menten constant (Km) 32.3 (33.5) mg.l-1, volume of distribution (Vd) 46.9 (2.6)l. This Michaelis-Menten constant is lower than that reported for adults and consequently non-linear elimination will occur at lower plasma concentrations in infants than in adults. Theophylline clearance has traditionally been reported as directly proportional to body weight. This per kilogram model gives an erroneous impression that clearance is greatest in early childhood and then decreases with age until adult rates are reached in late adolescence. Age-related clearance values reported in the literature were reviewed using an allometric 3/4 power model. This size model demonstrates that clearance increases in infancy and reaches adult rates in the first one to two years of life.

Accidents↗

Relationship of muscle strength to potassium concentration in a hypokalaemic infant.

A nine-month infant, weighing 9.8 kg, presented with hypotonia secondary to acute hypokalaemia (1.0 mmol/l). Muscle strength improved as the serum potassium was increased. Muscle strength was assessed by the pressure generated inside a saline-filled endotracheal tube cuff during a grasp reflex. Potassium concentration and hand grip strength were related using a sigmoidal Emax model. Zero effect was assumed when the potassium concentration was zero. The Emax, EC50 and Hill coefficient values were determined by non-linear regression using the MKMODEL program. Parameter estimates (SE) were EC50 1.79 (0.15) mmol/l, Hill coefficient 3.79 (0.92), Emax 114.4 (8.9) mmHg.

Acute Disease↗

Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients.

In the paediatric population, developmental changes can be predicted by age and are independent of size, which is predicted by bodyweight. Size is commonly standardised using either the per kilogram or the body surface area models. A great many physiological-, structural- and time-related variables scale predictably within and between species with weight exponents of 0.75, 1 and 0.25, respectively. Use of the per kilogram size model has led to the misconception that children have an enhanced capacity to metabolise drugs because of their relatively large liver size or increased hepatic blood flow. This is not necessarily the case. For example, the clearance of opioids often approaches adult rates within the first few months of life when an allometric 3/4 power model is used to scale for size. Age-related changes in physiological processes, such as respiration and cardiac output, disappear with appropriate size models. Size is an important, but little recognised, component in the speed of onset of drugs effects and uptake of inhalational anaesthetic agents. Size models cannot be reliably used to predict dose regimens for children from schedules established for adult patients. Dosage regimens are dependent on clearance and volume of distribution as well as pharmacodynamic factors, which change with age. The age-dependent pharmacodynamic changes described for some opioids in the very young have not yet been completely disentangled from age-related pharmacokinetic changes. When bodyweight is standardised and disentangled from age, developmental changes can be understood more clearly. The future investigation of drugs used in paediatric practice must also include an appropriate size model in order to differentiate age-related factors from size-related factors.

Adult↗

Cucumber mosaic virus RNA 5 is a mixed population derived from the conserved 3'-terminal regions of genomic RNAs 2 and 3.

Analysis of encapsidated RNA from the Q strain of CMV (Q-CMV) has indicated the presence of a discreet population of molecules of approximately 300 nt termed RNA 5 (Peden, K.W.C., and Symons, R.H., Virology 53,487-492, 1973.). Q-CMV RNA 5 was isolated and the 5'-end sequence was determined by direct RNA sequencing. This sequence corresponded to the exact beginning of the imperfectly conserved 3'-terminal region of genomic RNAs 1, 2, and 3. A probe generated from RNA 3 consisting of the last 130 nt of this region hybridised to RNA 5. Oligonucleotides containing sequences from the 5'- and 3'-ends of the conserved region were used to generate RNA 5 cDNA clones by RT-PCR on gel-purified RNA 5. Sequencing of these clones and primer extension analysis of transcripts (derived from the cDNA clones) and purified RNA 5 indicated that RNA 5 consists of the conserved 3'-terminal region of genomic RNAs 2 and 3.

Base Sequence↗

Motor-skill learning: changes in synaptic organization of the rat cerebellar cortex.

Rats trained on motor-skill learning tasks for 30 days were previously found to have more synapses in the volume of tissue proportional to a Purkinje cell than rats that exercised or were inactive. In the motor learning tasks, hooded rats were required to traverse an obstacle course requiring balance and coordination. Rats in two exercise groups were required to walk rapidly or allowed to run in activity wheels. Controls were relatively inactive in standard housing and handled once daily. Synapses were classified to determine which synaptic types changed in number across levels of the molecular layer in the paramedian lobule. The motor learning group had significantly more parallel fiber synapses and climbing fiber synapses per unit Purkinje cell reference volume than all other groups. There were also more synapses and more parallel fiber synapses per reference volume in the outermost than in the innermost molecular layer. The plasticity reported here occurs in vivo under normal physiological conditions. Excitatory synapses account for at least 80% of the synapses in the molecular layer. The results support prior predictions that parallel fiber synapses are modifiable during conditions of learning.

Animals↗

A retrospective comparison of treatment outcome in the posterior and anterior tongue.

BACKGROUND: The perceived poor survival for tongue base cancer compared with the anterior tongue influences selection of treatment. METHODS: Treatment outcome is compared in patients with epidermoid carcinoma of the tongue base (n = 112) and anterior tongue (n = 188). A multivariate Cox's proportional hazard model is used to assess the independent effect of tumor location on survival. RESULTS: Seventy-one percent of patients with tongue base tumors had advanced stages of disease (Stages III & IV) at presentation compared with 32% for the anterior tongue (P = .000). Disease-specific survival at 5 years for the tongue base was 26%, and for the anterior tongue was 64%. Significant risk factors for disease relapse included age > 50 years, advanced stages of disease, and radiotherapy as a single treatment modality. The adjusted hazard ratio for disease relapse for the tongue base compared with the oral tongue was 1.2 (95% CI = 0.83, 1.74; P = .332). CONCLUSIONS: Treatment response for tongue base and anterior tongue tumors is similar. The pessimism that besets the management of cancer of the tongue base may not be justified in all patients.

Adult↗

Hypertrophic obstructive cardiomyopathy in pediatric patients: results of surgical treatment.

Between April 1975 and May 1995, 25 pediatric patients on one hospital service underwent extended left ventricular septal myectomy because of hypertrophic obstructive cardiomyopathy. Ages ranged from 2 months to 20 years (mean, 11.2 years). Seventeen patients had moderate to severe mitral valve insufficiency. Medical therapy had failed in all patients and one patient had undergone dual-chamber pacemaker implantation without improvement. Left ventricular outflow tract gradients ranged from 50 to 154 mm Hg (mean, 99.9 +/- 25.2). Concomitant cardiac procedures included mitral valve repair (n = 2), automatic implantable cardioverter defibrillator implantation (n = 1), and closure of atrial septal defect (n = 1). Intraoperative premyectomy left ventricular outflow tract gradients ranged from 20 to 117 mm Hg (mean, 60.4 + 26.2) and postmyectomy gradients ranged from 0 to 20 mm Hg (mean, 6.6 +/- 5.9). Postmyectomy mitral insufficiency was reduced to a regurgitant fraction of 0% to 12%, and no patient required mitral valve replacement. One patient required a pacemaker because of complete heart block; on subsequent follow-up, normal sinus rhythm had returned. There was no early mortality and no instance of aortic or mitral valve injury or ventricular septal defect. Follow-up ranged from 10 months to 20 years (mean, 6.4 years). There were no late deaths. Left ventricular outflow tract gradients by echocardiography were a mean of 14.2 mm Hg with a median of 5.0 mm Hg. All patients had normal sinus rhythm. Reoperation because of recurrent left ventricular outflow tract obstruction was necessary in two patients at 3.2 years and 12.4 years after initial myectomy, respectively. All patients but one have New York Heart Association class I or II function. We conclude that extended septal myectomy is a safe and effective means of relieving cardiac symptoms and left ventricular outflow tract obstruction in pediatric patients with severe hypertrophic obstructive cardiomyopathy unresponsive to medical management, and late survivorship compares favorably with the natural history of the disease.

Adolescent↗

RNA 4 sequences from cucumber mosaic virus subgroups I and II.

The complete sequences of RNA 4 from cucumber mosaic virus (CMV) strains Ny (subgroup I) and Sn (subgroup II) have been determined and compared to all other known complete CMV RNA 4 sequences. The identification of a unique EcoRI site, present only in subgroup-II RNA 4 sequences, provides the basis for a simple method of classifying CMV isolates.

Base Sequence↗

Risk of thromboembolism with the aortic Carpentier-Edwards bioprosthesis.

Porcine bioprostheses provide an excellent alternative to mechanical prostheses for heart valve replacement in patients unable to comply with systemic anticoagulation and in the elderly. Long-term results of this prosthesis, however, demonstrated identical survival and parallel event-free status, albeit at a lower rate than the mechanical valves. Some discrepancy exists as to the need for and duration of systemic anticoagulation in the bioprosthesis, and some evidence exists to contraindicate anticoagulation due to a higher late mortality rate in patients with an aortic bioprosthesis. The records of 561 patients having the Carpentier-Edwards bioprosthesis in the aortic position as an isolated valve procedure were reviewed. The overall rate of bioprosthetic failure events was low (0.23%/patient year) and the survival (5 year, 74.8 +/- 2.4%; 10 year, 52.9 +/- 4.9%) and event-free statistics (5 year, 67.9 +/- 2.6%; 10 year, 42.4 +/- 5.1%) were excellent. No gender difference was present. A vulnerable period for neurologic events was identified by hazard function whereby the incidence of stroke was high; these were increased in the patient variables of compromised ejection fraction (0.54; p < or = 0.003), older age (< or = 73 years; p < or = 0.02), and preoperative atrial fibrillation or paced rhythm (p < or = 0.01). This pattern was similar for both transient ischemic events and strokes and rapidly decreased over the first few months of the first year and the first few years of the 12-year follow-up. These patients were not routinely anticoagulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Results of an autologous tissue reconstruction for replacement of obstructed extracardiac conduits.

Between May 1983 and March 1, 1995, 50 patients had replacement of an obstructed pulmonary ventricle-pulmonary artery conduit with an autologous tissue reconstruction in which a prosthetic roof was placed over the fibrous tissue bed of the explanted conduit. The roof was constructed with xenograft pericardium (most recently) (n = 42), homograft dura mater (n = 5), or Dacron fabric (n = 3). Patient ages ranged from 5 to 34 years (median 16 years). The explanted conduits were Hancock conduits (n = 33), Tascon conduits (n = 6), homograft (n = 4), Dacron tube (n = 3), and others (n = 4). Preoperative maximum systolic gradients ranged from 44 to 144 mm Hg (median 78 mm Hg). Thirty-seven concomitant cardiac procedures were done in 29 patients. When a valve was necessary (n = 15), it was possible to place a large-sized valve in the autologous tissue reconstructions (range 22 to 29 mm, median 26 mm). Cardiopulmonary bypass times ranged from 34 to 223 minutes (median 84 minutes), and aortic crossclamp times ranged from 0 (in 32 patients) to 109 minutes (median 0 minutes). Intraoperative postrepair peak systolic gradients from pulmonary ventricle to pulmonary artery ranged from 0 to 33 mm Hg (median 13 mm Hg). There was one early death (2%) in a patient who had additional cardiac procedures. Follow-up was complete in all patients and ranged from 1 month to 11.8 years (median 7.5 years). There were two sudden late deaths: conduits in both were known to be free from obstruction. Forty-four of the 47 surviving patients had evaluation of the gradient by echocardiography or cardiac catheterization 1 month to 11 years (median 7 years) after operation. The gradients ranged from 5 to 45 mm Hg (median 20 mm Hg). None of the conduits developed an obstructive peel, valve obstruction, or valve incompetence. At 10 years, the freedom from reoperation for conduit obstruction was 100%, and freedom from reoperation for any cause was 81%. This technique simplifies conduit replacement, allows for a generous-sized outflow tract, has a low risk, and yields late results that appear superior to those of cryopreserved homografts or other types of extracardiac conduits.

Adolescent↗

The risk of stroke in the early postoperative period following mitral valve replacement.

All patients (285) undergoing mitral valve replacement (MVR) with a Carpentier-Edwards (C-E) bioprosthesis +/- coronary bypass grafts (CABG) were reviewed (109 men and 176 women with a median age of 70 years). Overall, the 5-year survival rate was 58.9%, 62.7% for MVR (199 patients) and 50.1% for MVR+CABG (86 patients). Late survival was adversely affected by the operative time variables of NYHA class IV, older (> or = 70 years) age, low (> or = 56%) ejection fraction (EF), and the additional performance of associated procedures+CABG with MVR (P < or = 0.001). The 5-year freedom from stroke rate was 89.2%, 89.1% for MVR and 90.2% for MVR +/- CABG. Advanced heart class was the only significant variable associated with a greater risk of late stroke (P < or = 0.01). Neither chronic preoperative atrial fibrillation nor operative obliteration of the left atrial appendage increased or decreased the late risk of stroke in patients following MVR. Hazard function for stroke occurring in the first postoperative year (first 48 h excluded to discount intraoperative events) demonstrated the highest rate within the first month (40%), rapidly diminishing thereafter. This pattern was reproduced in the 12-year hazard function in that the rate of stroke occurrence was greatest in the first year (6.7%) following implantation. The mean stroke rate over 12 years was 2.5%. Strokes following MVR +/- CABG are more likely to occur in older and more compromised patients, and the higher early rate is not reflected in the mean rate. A more aggressive approach to early anticoagulation with IV heparin, Coumadin, and possibly antiplatelet therapy is advocated to reduce this complication rate.

Adolescent↗