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Biomedical subjects

R K Brown

Publications and source records attributed to R K Brown.

At least 19 recordsLinked to original sources

Oxidative damage to DNA in patients with cystic fibrosis.

Patients with cystic fibrosis (CF) may be more susceptible to oxidative-cell injury due to impaired absorption of dietary-antioxidants. In addition, recurring pulmonary infections regularly subject them to oxidative stress. Our objective was to determine whether the concentration of urinary 8-hydroxydeoxyguanosine (oh8dG), a marker of free radical-induced DNA damage, is elevated in CF patients and to correlate its excretion with clinical status. The first morning void of urine was collected from 13 CF patients and 10 control children of similar age. To determine clinical status, forced expiratory volume (FEV1) and forced ventilatory capacity (FVC) and a Taussing-Schwachman score were obtained for each patient. Urinary oh8dG was measured by high performance liquid chromatography (HPLC) with electrochemical detection and the concentration normalized against creatinine concentration. The mean concentration (+/- SD) of urinary oh8dG was significantly higher in the CF group (2.78 +/- 1.21 vs. 1.51 +/- 0.38 nmol/mmol creatinine). A significant positive correlation was found between urinary oh8dG concentration and plasma alpha-tocopherol concentration in the CF patients (r = 0.947, p = 0.0001), suggesting that vitamin E might be involved in the excretion of oh8dG. However, no correlation was found between urinary oh8dG in CF and markers of lung function or the qualitative index of clinical status. These results confirm that patients with CF are susceptible to oxidative-induced DNA damage, although this appears to be independent of clinical status. Increased DNA damage may explain, in part, why CF patients have a higher incidence of malignancy compared to normal healthy age-matched controls.

Adolescent

Evidence for increased oxidative damage in patients with cystic fibrosis.

Patients with cystic fibrosis (CF) may be more susceptible to oxidative cell injury than normal healthy children due to both the impaired absorption of antioxidant nutrients and the increased oxidative stress caused by chronic pulmonary infections. The purpose of this study was to examine whether markers of oxidative damage to lipids (malondialdehyde-like substances and lipid hydroperoxides) and proteins (protein carbonyls) were present in the plasma of CF patients. Mean values (+/- SD) of thiobarbituric acid-reactive substances were significantly higher in patients (6.93 +/- 1.47 mumol/L; n = 25) than in controls (5.84 +/- 0.59 mumol/L; n = 10). FFA hydroperoxides were not detected in control subjects (the detection limit of the assay was 0.02 mumol/L), but in 11 of the 33 CF patients studied they were found in a range of 0.03-0.34 mumol/L. Plasma protein carbonyl concentrations did not differ significantly between the two groups (p = 0.076), although a much wider distribution was observed in the CF patients (range 0.17-5.64 nmol/mg protein) than in the control group (range 0.24-1.55 nmol/mg protein). No correlation was found between thiobarbituric acid-reactive substances and FFA hydroperoxides or between either of these markers and protein carbonyl content. Concentrations of plasma vitamin E, vitamin C, and protein sulfhydryls were within the normal ranges in both control subjects and CF patients. The concentration of uric acid was significantly reduced (p < 0.01) in the CF group (204 +/- 96.99 mumol/L) compared with that in control subjects (352 +/- 81.11 mumol/L), but reduction in plasma levels of this antioxidant did not correlate with increased markers of free radical damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Postfracture irradiation effects on the biomechanical and histologic parameters of fracture healing.

The effects of single-dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague-Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10-day delay group, fractures showed greater strength than did those in the 3-day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short-term deleterious effects on fracture repair, but that long-term results may be similar to those associated with expeditious irradiation.

Animals

Detection of toxic viral-associated double-stranded RNA (dsRNA) in influenza-infected lung.

While many of the molecular events in viral replication are well studied, the molecular mechanisms by which viral infections trigger such constitutional symptoms as fever and 'malaise' are unknown. The hypothesis that these viral constitutional symptoms can be triggered by the toxic action of dsRNA associated with viral replication was investigated. Total lung RNA from mice acutely infected with PR8 influenza virus, but not from sham-infected mice, was shown to induce fever and altered sleep (excess slow-wave sleep, enhanced amplitudes of electroencephalographic slow waves, and reduced rapid eye movement sleep) when injected into the rabbit brain. Viral-associated dsRNA was shown to be responsible for the rabbit responses by differential nuclease digestion. Influenza viral dsRNA was directly demonstrated in the active lung RNA preparations by reverse transcriptase-polymerase chain reaction techniques. The time course of the responses paralleled those seen in the same model inoculated with nanogram quantities of the synthetic dsRNA polyriboinosinic-polyribocytidylic acid and suggested that they were mediated by induced cytokines. A model for the role of viral-associated dsRNA in eliciting both local cytotoxicity and viral constitutional symptoms is presented.

Animals

Nuclear scintigraphy in the evaluation of renal colic.

Forty patients with acute onset renal colic were studied using technetium-99m DTPA renal scintigraphy. Thirty-two were found to have varying degrees of obstruction. In the obstructed group the level was determined by the scan alone in 24 of 32 cases (75%). When the analysis included an abdominal radiograph, the level of obstruction was ascertained in 29 of 32 cases (91%). A delayed nephrogram, as evidenced by an "empty renal pelvis sign" at 5 minutes, was observed in all but one of the cases of obstruction (97%). Delayed clearance of activity from the pyelocalyceal system or ureter was also seen in 97%. In all cases of obstruction either one or both of these signs were observed. However, delayed clearance was found to be a nonspecific finding and was noted in 25% of nonobstructed cases. The finding of the "empty renal pelvis sign" at 5 minutes was found to be specific and was not seen in the nonobstructed group. The authors conclude that radionuclide renal scanning is an effective method for evaluating selected patients with suspected renal colic.

Adolescent

Radionuclide evaluation of liver transplants.

Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.

Bile Duct Diseases

Computerized chest tomography in asbestos workers suspected of having pleural disease.

Forty-five computerized tomographic (CT) chest studies were performed on workers suspected of having pleural disease after being exposed to asbestos material. Ten of the 45 reviewed were court cases, and 32 workers acutely exposed at University of California-Los Angeles (UCLA) were studied with routine four views of the chest. CT confirmed the initial interpretation of chest films obtained at UCLA.

Asbestosis

Hepatic hemangiomas: evaluation by magnetic resonance imaging and technetium-99m red blood cell scintigraphy.

A study was performed to evaluate and compare the sensitivity of magnetic resonance imaging (MRI) and radionuclide blood-pool scanning in the detection of hepatic hemangiomas. All patients had known hemangiomas which were first detected on either ultrasound or computed tomography. Sixteen patients with a total of 23 lesions were investigated. Eleven patients had both MRI and blood-pool scans performed. In the group studied by both modalities, 18 lesions were detected ranging in size from 1 to 11 cm. All lesions were detected by both techniques. However, two of the 18 lesions had an atypical appearance on MRI. Our experience to date indicates that the anatomic location and specific diagnosis of hemangiomas can be made with a high degree of certainty when both MRI and blood-pool scanning techniques are utilized.

Adult

Hepatic abscess in liver transplantation. Accurate diagnosis and treatment.

Serial HIDA scanning was performed on a patient following liver transplantation. During the patient's course he developed biliary obstruction that manifested as a photopenic region in the liver, on the HIDA scan which filled in on the delayed views. The patient subsequently developed a region in the superior portion of the right lobe of the liver that did not fill in with activity on delayed views. The patient was experiencing low-grade fevers and was clinically believed to have either an abscess or an episode of rejection. A gallium scan was performed revealing a photopenic defect in the same region as the HIDA. Because of the clinical suspicion of abscess, a percutaneous transhepatic drainage study was performed, revealing a large abscess cavity in the suspect area within the liver. Following the drainage the patient did well. This case illustrates the usefulness of serial HIDA scanning in patients who have received liver transplants. It also is important to note that the gallium scan was negative in this hepatic abscess. In the authors' opinions, the finding of an intrahepatic fluid collection in a septic patient that does not fill with activity on the HIDA study, should be considered the source of the infection, until proven otherwise, and should be drained regardless of the findings of other studies.

Child, Preschool

Magnetic resonance imaging artifacts: mechanism and clinical significance.

Many types of artifacts may occur in magnetic resonance imaging. These artifacts may be related to extrinsic factors such as patient motion or metallic artifacts; they may be due specifically to the MR system such as power gradient drop off and chemical shift artifacts; they may occur as a consequence of general image processing techniques, as in the case of truncation artifacts and aliasing. Change in patient position, pulse sequence, or other imaging variables may improve some artifacts. Although reduction of some artifacts may require a service engineer, the radiologist has the responsibility to recognize MR imaging problems. The radiologist's knowledge of MR imaging artifacts is important to the continued maintenance of high image quality and is essential if one is to avoid confusing artifactual appearances with pathology.

Diagnostic Errors

Accurate demonstration of hepatic infarction in liver transplant recipients.

Serial HIDA scanning has proven to be a valuable tool in the postoperative management of liver transplant patients. Previous reports have documented its efficacy in detecting biliary leakage, abscess, and rejection. We have also found HIDA scanning to be a sensitive method for detecting early hepatic infarction before ultrasonographic changes occur. Two cases are presented to demonstrate the characteristic findings seen with hepatic infarctions.

Child

The interaction of platelet proteins with three fibroblast-derived collagenases.

Three collagenases were purified from the culture medium of human skin fibroblasts using ammonium sulfate fractionation, ion-exchange chromatography and gel filtration. The cationic collagenase had a molecular weight of 42,000; two anionic collagenases had molecular weights of 63,000 and 115,000. Preincubation of the individual collagenases with purified human and bovine platelet heparin binding proteins resulted in the inhibition of the two anionic activities, but only by bovine low heparin affinity platelet protein (beta-TG). Such inhibition was dose-dependent at the microgram level, was not antagonized by heparin, and persisted even when the collagenases had been transformed into their 53,000 and 105,000 forms through treatment with p-aminophenylmercuric acetate. Neither human nor bovine high heparin affinity platelet factors (PF-4) nor human low heparin affinity platelet protein (beta-TG) were inhibitory to any of the three collagenases studied. This suggests that the ability of platelet proteins to inhibit collagenase is specifically influenced by the ionic nature of the enzyme and this inhibition is specifically dependent upon the species and type of platelet protein.

Animals

Asbestosis and the serratus anterior muscle.

Twenty-seven patients with a history of asbestos exposure were reviewed at the UCLA Medical Center in December 1981. All patients were referred by the United States Department of Labor. The patients were told they had asbestosis on the basis of their history of exposure and chest radiographs taken at a local asbestos screening program and initially interpreted by a "B" reader. None of the 27 patients reviewed were found to have evidence of asbestosis either clinically or radiographically. The false-positive radiographic interpretations were due to the extrathoracic musculature (serratus anterior) mimicking intrathoracic disease. Since the study described here was done, an additional 330 patients have had their radiographs reviewed.

Adult