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Biomedical subjects

B Paton

Publications and source records attributed to B Paton.

At least 19 recordsLinked to original sources

Number of repetitions to maximum in hop tests in patients with anterior cruciate ligament injury.

The unilateral horizontal, triple cross-over and vertical hops are commonly used as outcome measures after knee injury but there is little knowledge of the number of repetitions needed to reach maximum performance. Seventy subjects who had either an anterior cruciate ligament deficient or reconstructed knee participated in this study. Unilateral vertical, horizontal, and triple cross-over hop testing was applied to each leg until two consecutive decrements in performance occurred. The number of repetitions to reach maximum during these tests were calculated. Fifteen repetitions of the horizontal and vertical hops, and 10 repetitions of the triple-crossover hop enable distances to be achieved that are acceptably close to maximal levels in these knee-injured patients. In order to increase the likelihood of finding a patient's maximum hop performance after knee injury, more repetitions are suggested than has been reported in the literature.

Adult↗

Skeletal muscle strength and endurance in patients with mild COPD and the effects of weight training.

This study poses two questions: 1) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease (COPD)? and 2) what is the effect of a randomized, controlled, 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients (age 49+/-11 yrs), mean forced expiratory volume in one second (FEV1) 77+/-23% pred and 52 healthy, sedentary subjects (age 51 (10) yrs), mean FEV1 109+/-16% pred. The 43 COPD patients were randomly allocated into training (n=26) and control (n=17) groups. Isokinetic and isotonic muscle function, whole body endurance, maximal exercise capacity and lung function were measured. The COPD patients had reduced isokinetic muscle function (with the exception of sustained upper limb strength) as compared with healthy sedentary subjects. Muscle function improved after weight training in the COPD patients. Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption. A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which cannot be explained by factors such as hypoxaemia and malnutrition. Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning.

Adult↗

Infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a monocular patient with Stevens-Johnson syndrome.

PURPOSE: To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome. METHOD: Case report. A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates. RESULTS: Anterior chamber aspirate disclosed acid-fast bacilli. A repeat corneal transplant was performed and antibiotic therapy begun. Histopathology showed focal acute inflammation surrounding collections of acid-fast bacilli, which were speciated as M. abscessus. CONCLUSIONS: M. abscessus is a cause of infectious crystalline keratopathy and endophthalmitis. Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy.

Adult↗

Red cell flux during the cardiac cycle in the rabbit myocardial microcirculation.

OBJECTIVE: (1) To measure regional phasic myocardial red cell flux during a cardiac cycle using a laser Doppler velocimeter. (2) To test the responses of regional red cell flux to a vasodilator (adenosine), a vasoconstrictor (angiotensin II), and an inotrope (isoproterenol). METHODS: Using an anaesthetised open-chest rabbit with the pericardium intact a 140-micron-tip fibre optic probe was placed in the left ventricular myocardium in various locations. With the fibre in place drugs were given to alter myocardial loading conditions while red cell flux was registered. RESULTS: Phasic red cell flux was similar in the epicardium to endocardium giving an average endo/epi ratio of 1.14 in the rabbit heart. At least two peaks of increased red cell flux within a single cardiac cycle were observed. Some unique patterns for red cell flux were observed in specialised myocardial structures. Adenosine increased red cell flux but minimally changed the pattern of phasic flux throughout the cycle. CONCLUSIONS: Laser Doppler velocimetry permits the recording of phasic red cell flux during the cardiac cycle in the myocardial microcirculation. Its pattern is determined by both coronary arterial inflow and venous outflow. The pattern of red cell flux may be characteristic for a region-probably determined by difference in tissue pressure (attributable to the pattern of muscle fibre shortening and collagen tethering) and changes in capillary length and density.

Adenosine↗

Body position, age and mass effect of adiposity on adipose tissue red cell flux in morbid obesity.

OBJECTIVE: To measure red cell flux of adipose tissue in morbidly obese patients' pannus in the upright and supine position to determine factors which would render the lower pannus susceptible to ischemic necrosis. DESIGN: A cohort study of morbidly obese subjects without ischemic necrosis. SETTING: University teaching hospital. PATIENTS: Twenty-three consecutive morbidly obese patients referred for gastroplasty. MEASUREMENTS: Red cell flux, measured as RMS voltage by a laser Doppler velocimeter. An optical fiber with a tip diameter of 250 mu was inserted into the upper and lower pannus and output recorded in the upright and supine positions. Other variables recorded were age, BMI, blood pressure and serum lipids. RESULTS: Adipose tissue red cell flux demonstrates considerable spatial and temporal heterogeneity from subject to subject and in various locations in the pannus. No differences in red cell flux were detected in response to change in position. However, regression analysis demonstrated that the gradient between the upper and lower abdomen in the supine position was increasingly positive with age and in the upright position it was increasingly positive with increasing weight or BMI. CONCLUSIONS: These data suggest that red cell flux is heterogeneously distributed in the abdominal pannus and is not greatly influenced by body position. However, with increasing age and adiposity there is a gradient for decreased red cell flux to the lower portion of the pannus. This may be a factor in rendering this part of the pannus prone to ischemic fat necrosis.

Abdomen↗

Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole.

We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be > 10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a > 90% reduction in fungal load (P < 0.05) and 33% were sterile. After 4 weeks, all had a > 99% reduction in fungal load (P < 0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a > 90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model.

Administration, Oral↗

Bacillus-induced endophthalmitis: new series of 10 cases and review of the literature.

We reviewed the charts of 10 patients who were admitted to the Massachusetts Eye and Ear Infirmary over a 10-year period with the diagnosis of Bacillus species endophthalmitis. To our knowledge this is the largest single series in the literature and includes the first two reported cases of Bacillus endophthalmitis following glaucoma filtering procedures. Seven cases developed following penetrating ocular trauma. One occurred in an intravenous drug abuser. Five eyes ultimately underwent enucleation; only the two eyes that developed endophthalmitis after elective surgery retained useful vision. Review of the literature indicates that parenteral and intravitreal antibiotic prophylaxis against endophthalmitis after penetrating ocular trauma should include gentamicin, in combination with vancomycin or clindamycin, to provide adequate coverage against infection with Bacillus spp., as prognosis is poor once infection is established. Bacillus spp. cultured from ocular tissues or fluids should not be dismissed as contaminants.

Adult↗

Preliminary evidence for a processing error in the biosynthesis of Gaucher activator in mucolipidosis disease types II and III.

Activator protein (AP), which stimulated fibroblast sphingomyelinase activity, was isolated from the spleen of a patient with Gaucher's disease type I by the combined techniques of heat and alcohol denaturation, DEAE-cellulose column chromatography, gel filtration, preparative polyacrylamide-gel electrophoresis and decyl-agarose chromatography. Urea/sodium dodecyl sulphate (SDS)/polyacrylamide-gel electrophoresis showed two bands, one with an Mr of approx. 3,000 and the other with an Mr of 5,000-6,500. Similarly, SDS/polyacrylamide-gel electrophoresis performed in the absence of urea revealed the presence of two components, one of which adsorbed to a concanavalin A (Con A) column. Both components stimulated sphingomyelinase activity. On a non-denaturing polyacrylamide gel containing Triton X-100, four major components, two of which bound to Con A, were detected with the dye Stains-All. Cross-reacting material (CRM) to polyclonal Gaucher spleen AP antibodies was detected in normal fibroblasts and in fibroblasts from patients with sphingomyelinase and beta-glucocerebrosidase deficiency states (Niemann-Pick and Gaucher's diseases respectively). CRM in normal fibroblasts adsorbed to Con A columns and had the same mobility on SDS/polyacrylamide-gel electrophoresis as Con A-adsorbing Gaucher spleen AP. Normal AP was not observed in mucolipidosis type II (I-cell disease) fibroblasts; instead, extracts from these cells revealed the presence of two closely migrating bands with higher Mr values than normal fibroblast CRM. Furthermore, extracts of media from I-cell fibroblast cultures, but not from control or Gaucher fibroblast cultures, contained AP activity towards sphingomyelinase and beta-glucocerebrosidase. Fibroblasts from a patient with mucolipidosis type III (pseudo-Hurler polydystrophy) showed an intermediate pattern consisting of normal as well as the higher-Mr CRM. Our data provide evidence for the existence of AP in cultured skin fibroblasts and suggest that these proteins may be targetted to the lysosome by post-translational modification in a similar manner to that reported for lysosomal enzymes.

Cells, Cultured↗

Partial deficiency of dihydroxyacetone phosphate acyltransferase activity in both classical and infantile Refsum's diseases.

We measured the activity of dihydroxyacetone phosphate acyltransferase (DHAP-AT) in fibroblasts of controls and patients with classical Refsum's disease (RD), infantile Refsum's disease (IRD) and Zellweger's syndrome (ZS). We confirmed that DHAP-AT activity is severely reduced in ZS fibroblasts and amniocytes. We also demonstrated a partial deficiency of DHAP-AT activity in RD and IRD fibroblast cultures. These diseases are probably distinct but related entities in which peroxisomal biogenesis is affected to varying degrees.

Acyltransferases↗

Accumulation and defective beta-oxidation of very long chain fatty acids in Zellweger's syndrome, adrenoleukodystrophy and Refsum's disease variants.

The accumulation of very long chain fatty acids in plasma and skin fibroblasts was measured in at least four separate inherited disease states. Both the magnitude and the nature of the fatty acid changes reflected the clinical status of individual patients. In Zellweger's syndrome, and to a lesser extent in infantile Refsum's disease, there was an increase in 24:0, 26:0, 26:1, and a number of even longer chain fatty acids, while in the X-linked form of adrenoleukodystrophy these changes were less pronounced. Zellweger fibroblasts in culture took up lignoceric, phytanic and stearic acids and incorporated them into a variety of lipids in a manner comparable to control fibroblasts. However, these cells were unable to convert phytanic or lignoceric acid to CO2. Infantile Refsum's and X-linked adrenoleukodystrophy fibroblasts showed normal conversion of these acids to CO2. Normal fibroblast homogenates produced radioactive acetate from [1-14C] stearic and [1-14C] lignoceric acids indicating that both substrates were beta-oxidised under these conditions. Homogenates of fibroblasts from all patients patients with biochemical evidence of accumulation of very long chain fatty acids showed normal or near-normal stearic acid beta-oxidation, but were deficient in lignoceric acid beta-oxidation. Residual lignoceric acid beta-oxidation activity varied from approximately 15% in Zellweger syndrome up to 50% in X-linked adrenoleukodystrophy. It is postulated that the accumulation of very long chain fatty acids results from defects in peroxisomal beta-oxidation. In Zellweger's syndrome, and possibly in infantile Refsum's disease, it is probable that this defect is secondary to a primary abnormality affecting the structure and/or function of peroxisomes, while the primary defect in X-linked adrenoleukodystrophy may be confined to a pathway specific for the oxidation of very long chain fatty acids.

Adrenoleukodystrophy↗

Autonomic nervous system regulation of epicardial coronary vein systolic and diastolic blood velocity as measured by a laser Doppler velocimeter.

The velocity of blood in a major epicardial coronary vein accompanying the left anterior descending coronary artery of dogs was measured by means of a 140-micron fiber optic probe connected to a laser Doppler velocimeter. Right atrial pressure, left ventricular intramyocardial and cavity pressures, aortic pressure, as well as peripheral and central coronary venous pressures were compared with the velocity of blood measured in the epicardial coronary vein midway between the sites of the catheters measuring proximal and distal coronary vein pressures. During control conditions, coronary vein velocity was 14-18 cm/s during systole and 1.0-2.1 cm/s during diastole. Right stellate ganglion stimulation, norepinephrine or isoproterenol increased diastolic coronary vein velocity significantly, whereas left stellate ganglion stimulation did not. Average peak systolic velocity was not affected by these interventions. During these positive inotropic interventions, the peak coronary vein velocity usually occurred later in the cardiac cycle than during control conditions. Positive inotropic interventions appeared to decrease coronary vein velocity during systole and increase it during diastole. Left vagosympathetic trunk stimulation decreased diastolic but not systolic coronary vein velocity and usually caused peak coronary vein velocity to occur earlier in the cardiac cycle than during control states. Changes induced by vagosympathetic trunk stimulation usually occurred within one cardiac cycle. It is concluded that coronary vein blood velocity can be influenced by the autonomic nervous system.

Animals↗

Operation for discrete subvalvular aortic stenosis.

Over the past 20 years, 37 patients (31 children and six adults) have undergone operations for discrete subvalvular aortic stenosis. Prior to 1975, resection of the subvalvular membrane alone was the procedure of choice. However, the recurrence rate was high (36%). Since 1975, resection of the membrane plus left ventricular myectomy has been routine. The recurrence rate in this group has been lower (20%) but is still high. Overall, 11 patients (30%) have had significant recurrence (average gradient 63 mm Hg). Eight of these 11 have undergone a second operation with re-resection of a membrane and left ventricular myectomy. One patient died and in three others (42%) significant symptoms and gradients remained. One of these three has undergone a successful aortoventriculoplasty, and two patients are awaiting a similar operation. Lessons learned from this experience include the following: (1) Regardless of the type of initial operation, a significant rate of recurrence can be anticipated. (2) Progressive aortic insufficiency and fibromuscular tunnel stenosis occur commonly unless adequate relief of the obstruction is achieved by the first operation. (3) Because repeat resection with left ventricular myectomy is unlikely to be effective when aortic insufficiency and/or tunnel stenosis are present, aortoventriculoplasty should be employed as the definitive reoperative procedure.

Adolescent↗

Homograft and prosthetic aortic valve replacement: a comparative study.

Homograft aortic valve replacement was done in 103 patients and prosthetic aortic valve replacement in 106 between January 1962 and December 1973. Patients who received homograft and prosthetic valves were compared with respect to age, sex, preoperative functional impairment, infection, dyspnea, angina, hemodynamics, chest X-ray, electrocardiogram, associated operations, early and late mortality, and valve failure. Combined total mortality was 28% (12% operative, 8% first postoperative year, 8% late). Ten percent of valve required replacement. One year after operation, 70% of survivors were asymptomatic, 27% were improved, and 3% were unchanged or between homograft and prosthetic valve replacement. Valve-related failure and infections were more common after homograft aortic valve replacement. Emboli, hemorrhage, and hemolysis were commoner after prosthetic valve replacement. Fungal infections occurred in five homograft patients but in no patient with a prosthetic aortic valve. Severe properative symptoms or recent endocarditis was associated with greater mortality and valve failure in both the homograft and the prosthetic series. Increased mortality and failure was also seen in patients with either preoperative aortic regurgitation with high left ventricular end-diastolic pressure and low cardiac index, or aortic stenosis with cardiomegaly or roentgenographic evidence of congestive heart failure. Therefore, in two series of patients at equal risk, mortality and valve failure were similar for homograft and prosthetic aortic valve replacement.

Adolescent↗