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Biomedical subjects

J M Robertson

Publications and source records attributed to J M Robertson.

At least 19 recordsLinked to original sources

The reinforcing and discriminative stimulus properties of para-ethoxy- and para-methoxyamphetamine.

The purpose of this study was two-fold: 1) to assess the degree to which para-methoxyamphetamine and para-ethoxyamphetamine maintain self-administration behavior, and 2) to determine the similarity or difference between these drugs and amphetamine in drug discrimination tests. Animals were trained to self-administer 0.3 mg/kg/infusion cocaine on a fixed-ratio 5 (FR5) schedule of reinforcement. Substitution of para-ethoxyamphetamine (PEA), para-methoxyamphetamine (PMA), or saline produced similar results; in all cases responding decreased substantially. A separate group of animals was trained to discriminate amphetamine (1 mg/kg) from saline in a fixed-ratio (FR10), food-reinforced paradigm. PEA and PMA produced only limited responding on the amphetamine-appropriate lever (maximum of approximately 30%). Both PMA and PEA had effects on response rate which were similar to those of amphetamine, although PMA had slightly greater rate-decreasing effects than the other two compounds. These data suggest that neither PMA nor PEA are reinforcing in rats, and do not possess amphetamine-like discriminative properties.

Amphetamines

Discriminative stimulus properties of substituted amphetamine derivatives.

Animals were trained to discriminate amphetamine (1 mg/kg) from saline in a fixed-ratio (FR 10), food-reinforced paradigm. Amphetamine-appropriate responding was engendered by the training dose, and by 3 mg/kg, while at lower doses there was a progressive decrease in the extent of responding on the drug-appropriate lever. The following three novel amphetamine derivatives were tested for their ability to produce amphetamine-appropriate responding: 2,5-dimethoxy-4-ethoxy-amphetamine (DMEA); 2,5-dimethoxy-4-methylthio-amphetamine (DMMTA), and 2,4,5-trimethoxy-amphetamine (TMA). DMEA produced only minimal (< 20%) amphetamine-appropriate responding over a dose range of 0.1-10 mg/kg. Substantial decreases in response rate limited testing of the other amphetamines to a dose maximum of 3 mg/kg, but over the range of 0.1-3.0 mg/kg there was little evidence for generalization. At 3 mg/kg of either DMMTA or TMA, only 2 of 10 animals completed at least one uninterrupted FR 10 on either lever, and with either compound only 1 of these 2 animals responded more than 50% on the drug-appropriate lever. Of the three compounds tested, DMMTA had the greatest response rate-decreasing effect.

Amphetamines

The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.

Aged

The use of 3-D dose volume analysis to predict radiation hepatitis.

Although it is well known that the tolerance of the liver to external beam irradiation depends on the volume of liver irradiated, few data exist which quantify this dependence. Therefore, a review was carried out of our clinical trial for the treatment of intrahepatic malignancies in which the dose of radiation delivered depended on the volume of normal liver treated. Three dimensional treatment planning using dose-volume histogram analysis of the normal liver was used for all patients. Nine of the 79 patients treated developed clinical radiation hepatitis. None of the patient related variables assessed were associated with radiation hepatitis. All patients who developed radiation hepatitis received whole liver irradiation, as all or part of their treatment, which produced a mean dose greater than or equal to 37 Gy. Dose volume histograms were used to calculate normal tissue complication probabilities based on parameters derived from the literature. The risk of complication was greatly overestimated among patients receiving a high dose of radiation to part of the liver without whole liver treatment. An estimation of model parameters based on the clinical results indicated a larger magnitude for the "volume effect parameter" than the literature estimate (n = 0.69 +/- 0.05 vs 0.32; p less than 0.001). Computation of the normal tissue complication probabilities using the larger value of n produced a good description of the observed risk of radiation hepatitis. These findings suggest that dose volume histogram analysis can be used to quantify the tolerance of the liver to radiation. The predictive value of this parameterization of the normal tissue complication probability model will need to be tested with liver tolerance and dose volume histogram data from an independent clinical trial.

Adult

Fluorescence-based, multiplex allele-specific PCR (MASPCR) detection of the delta F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Cystic fibrosis (CF) is a common genetic disorder in Caucasians, and in some populations 70% of cases are associated with a 3 base pair (bp) deletion (delta F508) in the CFTR gene. We have implemented a fluorescence-based, multiplex allele-specific polymerase chain reaction (MASPCR) assay for deletion of the delta F508 mutation. Different allele-specific fluorescently-tagged primers are used in the PCR reaction to distinguish between normal and delta F508 alleles. Fluorescent PCR products are then visualized in a single lane on an agarose gel following electrophoresis combined with real-time multicolour fluorescence detection. The approach simplifies diagnosis of the most common mutation in the CFTR gene, and holds promise for a multiplex allele-specific, fluorescence-tagged gene amplification strategy for detection of additional CF mutations which may result in more cost-effective testing without increasing the risk of missed or erroneous diagnoses.

Alleles

Automated DNA profiling by fluorescent labeling of PCR products.

DNA profiling has been automated by the fluorescent tagging of amplified variable number tandem repeat (VNTR) loci. This was achieved by the use of fluorescently labeled primers in the amplification of 10 ng of genomic DNA, coupled with laser detection of the products during electrophoresis. The PCR products are sized by co-electrophoresing a standard size ladder mixed with every sample, thereby eliminating errors in size estimation caused by lane-to-lane differences in migration rate. This increases the precision of VNTR characterization and enables alleles that differ by a single 15-bp repeat to be resolved. The system is capable of high throughput: Twenty-four samples are electrophoresed and analyzed within 6 hr. Also, because four different dyes are available, three different loci can be simultaneously characterized with the fourth dye used for the internal standard. Approximately 100 unrelated British caucasians were analyzed at the loci D1S80, D17S5, and ApoB. The probabilities of two unrelated individuals matching by chance (pM) at these three loci were determined to be 0.065, 0.040, and 0.069, respectively, with a combined pM of 1.8 x 10(-4).

DNA

The use of fluorescence detection and internal lane standards to size PCR products automatically.

We have developed chemical procedures, optical and electrophoretic instrumentation and computer software automate the analysis of polymerase chain reaction (PCR) products. DNA molecules labeled with up to four different fluorescent dyes are analyzed within a single electrophoresis gel lane. A size calibration curve is created for each electrophoresis lane from the electrophoretogram of uniquely labeled DNA fragments belonging to an internal lane standard that co-electrophoreses with the PCR products. The unknown molecular lengths of PCR products are automatically calculated from the calibration curve. Data from control experiments with DNA segments of known molecular length demonstrate the accuracy and precision of such sizing. This system has been applied to the analysis of PCR products for research in the areas of human identification, genetic mapping and genetic disease.

Base Sequence

Breast conservation therapy. Severe breast fibrosis after radiation therapy in patients with collagen vascular disease.

Two patients with collagen vascular disease (rheumatoid arthritis and scleroderma) had extremely poor cosmetic results after breast radiation therapy (RT). The patient with rheumatoid arthritis received 5251 cGy at 210 cGy per day, followed by a 1600 cGy iridium-192 implant boost. Between 8 and 11 months post-RT she had severe breast fibrosis, retraction, and pain that required a mastectomy for relief. The patient with scleroderma received 5040 cGy at 180 cGy per day without a boost. Between 1 and 4 months post-RT the systemic symptoms of scleroderma progressed and the breast became hard and retracted. Both rheumatoid arthritis and scleroderma are chronic systemic diseases characterized by severe inflammation and an autoimmune component. The presence of scleroderma at or before treatment should be considered a contraindication to breast RT, whereas the presence of active rheumatoid arthritis should be considered a relative contraindication. An autoimmune mechanism will be presented to explain both the fibrosis and the systemic progression of collagen vascular disease that was observed.

Adenocarcinoma

Ultrasonic decalcification of the aortic annulus during aortic valve replacement.

Aortic valve replacement for calcifica aortic stenosis requires meticulous debridement of the aortic annulus to effect optimal valve seating. Since 1987, we have used ultrasonic energy to debride the aortic annulus during aortic valve replacement in 56 patients. In our experience, ultrasonic debridement of the annulus is superior to traditional methods of debridement, affords improved seating of the valve, and may allow placement of a larger valve. Our follow-up ranges from 2 to 32 months (mean follow-up, 13 +/- 9 months) with 0% incidence of paravalvular leak or valve failure. We advocate the use of ultrasonic debridement as an adjunctive tool in aortic valve replacement.

Adult

A possible role for vitamins C and E in cataract prevention.

Biochemical evidence suggests that oxidative stress caused by accumulation of free radicals is involved in the pathogenesis of senile cataracts. If so, appropriate amounts of the antioxidant vitamins C and E might be expected to prevent or retard the process. Such activity has been observed in several in vitro and in vivo studies of experimentally-induced cataracts. A recent epidemiologic study found that cataract patients tended to have lower serum levels of vitamins C, E, or carotenoids than did control subjects. The present investigation, which compared the self-reported consumption of supplementary vitamins by 175 cataract patients with that of 175 individually matched, cataract-free subjects, revealed that the latter group used significantly more supplementary vitamins C and E (P = 0.01 and 0.004, respectively). Because the results suggested a reduction in the risk of cataracts of at least 50%, a randomized, controlled trial of vitamin supplementation in cataract prevention may be warranted.

Aged

Effect of right atrial appendectomy on the release of atrial natriuretic hormone.

Atrial natriuretic hormone is released from the right atrial appendage in response to atrial distention. During cardiac operations the right atrial appendage is usually partially removed or ligated for venous cannulation. To evaluate the effect of right atrial appendectomy on the release of atrial natriuretic hormone and its natriuretic and diuretic responses, we prospectively randomized into two groups 23 patients undergoing elective coronary artery bypass operations. There were 16 male and 7 female patients with a mean age of 62 +/- 7 years. Group A (n = 11) had the right atrial appendage removed, and group B (n = 12) had the right atrial appendage preserved and venous cannulation done lateral to the appendage. The two groups were comparable for sexual distribution, age, number of grafts, and extracorporeal bypass time. All patients had normal left ventricular and renal functions, and they did not receive any diuretics during the study period. The patients were studied both preoperatively and postoperatively whereby the atrial natriuretic hormone serum levels, urine volume per minute, fractional excretion of sodium, amount of sodium excreted, and central venous pressure were measured before and after volume expansion with 5% albumin, 7.5 ml/kg. There was no statistical difference in these parameters preoperatively. In the postoperative period, however, group B patients had higher atrial natriuretic hormone levels after volume expansion than group A patients (376 +/- 84 versus 184 +/- 31 pg/ml; p less than 0.05), higher urine volume per minute (4.4 +/- 1.0 versus 2.0 +/- 0.4 ml/min; p less than 0.05), higher fractional excretion of sodium (2.30 +/- 0.66 versus 0.64 +/- 0.19; p less than 0.02), and higher amount of sodium excreted (511.1 +/- 150.9 versus 83.9 +/- 22.8 mmol/min; p less than 0.02). The central venous pressure was similar both before (9 +/- 1 versus 9 +/- 1 mm Hg) and after (16 +/- 1 versus 15 +/- 1 mm Hg) volume expansion in both groups. We conclude that preserving the right atrial appendage during cardiac operations significantly increased the release of atrial natriuretic hormone, resulting in increased urinary sodium excretion and better diuresis in the postoperative period.

Aged

Fibrin glue inhibits intra-abdominal adhesion formation.

To determine the effect of fibrin glue on intra-abdominal adhesion formation, 45 rats were randomized to three groups. Each animal received two adhesion models. Group 1 received no further treatment. Groups 2 and 3 had the adhesion models covered with fibrinogen from fresh frozen plasma (1.77 g/L) and cryoprecipitate (23.6 g/L), respectively. In group 1, 13 of 15 rats had high-grade adhesions in both models. In group 2, high-grade adhesions were noted in nine of 15 rats in model 1 and in 12 of 15 rats in model 2. In group 3, however, high-grade adhesions were seen in only three of 15 rats in model 1, with 11 rats having no adhesions, and in only two of 15 rats in model 2. Histologic analysis suggested accelerated healing in group 3. We conclude that (1) fibrin glue inhibits intra-abdominal adhesion formation in rats, (2) the inhibitory action is dependent on the fibrinogen concentration of the fibrin glue, and (3) adhesions are reduced by fibrin glue regardless of whether the peritoneal defect is closed.

Abdominal Muscles

Fatal left ventricular perforation during mitral balloon valvoplasty.

Percutaneous balloon dilation of left-sided cardiac valves is being performed with increasing frequency. We describe and document the mechanism of injury of left ventricular perforation during mitral balloon valvoplasty. Despite a technically successful surgical repair with hemodynamic restoration, the patient was brain dead. We emphasize (1) the risk and the potentially catastrophic nature of left ventricular perforation during mitral balloon valvoplasty and (2) the need for surgical standby and rapid operative decompression for this complication.

Aged

Tracheal and main bronchial disruptions after blunt chest trauma: presentation and management.

Tracheobronchial disruption is one of the less common injuries associated with blunt thoracic trauma. This injury can be life threatening, however, and failure to diagnose it early can lead to disastrous acute or delayed complications. Nine cases of tracheobronchial disruption in the setting of nonpenetrating thoracic trauma were seen at four Los Angeles trauma centers between 1980 and 1987. Mechanism of injury, presentation, diagnosis, and management of these patients were reviewed. Disruptions involved the trachea in 3 patients, the right bronchus in 5 patients, and the left bronchus in 2 patients. Tracheobronchial disruptions occurred in settings of high-energy impact-type injuries and were more likely to have associated injuries than they were to occur alone. Common presenting signs included subcutaneous emphysema, dyspnea, sternal tenderness, and hemoptysis. Radiographic findings were most commonly pneumothorax, pneumomediastinum, and clavicle or rib fractures. Rigid bronchoscopy and fiberoptic bronchoscopy were both highly accurate methods for diagnosis but only in the hands of trained cardiothoracic surgeons. Delay in diagnosis increased the likelihood of postoperative complications.

Accidents, Traffic

Ascending aortic dissection in weight lifters with cystic medial degeneration.

We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection.

Adult