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Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 73 records · Page 4Linked to original sources
PubMed1999

Adaptation of human fibroblasts to radiation alters biases in DNA repair at the chromosomal level.

PURPOSE: To determine whether adaptation to ionizing radiation biases repair of radiation-induced chromosomal breaks. MATERIALS AND METHODS: Normal human fibroblasts were radiation-adapted by exposure to 10 cGy of gamma-radiation. FISH probes for chromosomes 2, 4, 7, 18 and 19 were used to determine the chromosomal origin of the DNA in micronuclei resulting from a subsequent 4Gy exposure of these cells, and corresponding non-adapted cells. RESULTS: Compared with 4 Gy exposed but non-adapted cells, the radiation-adapted cells subsequently exposed to 4 Gy showed an overall decrease in the frequency of micronuclei. However, the micronuclei that did form in the adapted cells had a decreased frequency of DNA originating from chromosomes 2 and 18, an increased frequency of DNA from chromosome 19 and no change in frequency of DNA from chromosomes 4 and 7. CONCLUSIONS: Adaptation to radiation increased the overall cellular repair of radiation-induced chromosomal breaks, but also created a repair bias such that some chromosomes were preferentially repaired or discriminated against, while the repair of others was unbiased.

Adaptation, Physiological↗
PubMed1999

Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

BACKGROUND: Patients with cirrhosis have a reduced life expectancy. Anesthesia and surgery have been associated with clinical decompensation in patients with cirrhosis. METHODS: The authors retrospectively reviewed the records of all patients with the diagnosis of cirrhosis who underwent any surgical procedure under anesthesia at their institution between January 1980 and January 1991 (n = 733). Univariate and multivariate analyses were used to identify the variables associated with perioperative complications and short- and long-term survival. RESULTS: The perioperative mortality rate (within 30 days of surgery) was 11.6%. The perioperative complication rate was 30.1%. Postoperative pneumonia was the most frequent complication. Multivariate factors that were associated with perioperative complications and mortality included male gender, a high Child-Pugh score, the presence of ascites, a diagnosis of cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine concentration, the diagnosis of chronic obstructive pulmonary disease, preoperative infection, preoperative upper gastrointestinal bleeding, a high American Society of Anesthesiologists physical status rating, a high surgical severity score, surgery on the respiratory system, and the presence of intraoperative hypotension. CONCLUSION: Risk factors have been identified for patients with cirrhosis who undergo anesthesia and surgery.

Adolescent↗
PubMed1999

Diagnosis and staging of ovarian cancer: comparative values of Doppler and conventional US, CT, and MR imaging correlated with surgery and histopathologic analysis--report of the Radiology Diagnostic Oncology Group.

PURPOSE: To determine the optimal imaging modality for diagnosis and staging of ovarian cancer. MATERIALS AND METHODS: Two hundred eighty women suspected to have ovarian cancer were enrolled in a prospective study before surgery. Doppler ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging were used to evaluate the mass; conventional US, CT, and MR imaging were used to stage spread. RESULTS: All three modalities had high accuracy (0.91) for the overall diagnosis of malignancy. In the ovaries, the accuracy of MR imaging (0.91) was higher than that of CT and significantly higher than that of Doppler US (0.78). In the extraovarian pelvis and in the abdomen, conventional US, CT, and MR imaging had similar accuracies (0.87-0.95). In differentiation of disease confined to the pelvis from abdominal spread, the specificity of conventional US (96%) was higher than that of CT and significantly higher than that of MR imaging (88%), whereas the sensitivities of MR imaging (98%) and CT (92%) were significantly higher than that of conventional US (75%). CONCLUSION: MR imaging is superior to Doppler US and CT in diagnosis of malignant ovarian masses. There is little variation among conventional US, CT, and MR imaging as regards staging.

Adult↗
PubMed1999

Developments in the therapeutic applications of bisphosphonates.

The authors review the structural, pharmacologic, and clinical aspects of bisphosphonates, a class of drugs currently used to treat several disorders of bone and calcium metabolism. Pertinent literature on the bisphosphonates was reviewed with the help of a MEDLINE search and several bibliographies, including published clinical trials, monographs, and review articles. The bisphosphonates are analogs of pyrophosphate that, when given orally or intravenously, bind avidly to exposed bone mineral and disrupt bone turnover. These agents comprise three groups or generations, based on their potency and chemical structures. All three generations are effective in treating hypercalcemia, Paget's disease of bone, osteoporosis, and other disorders of accelerated bone turnover. The third-generation agents have the greatest potency and offer the promise of a convenient way to suppress or prevent osseous metastasis in patients with certain malignancies. As a group, these agents are well tolerated and, when administered correctly, rarely cause toxicity. The bisphosphonates are safe and effective agents for the treatment of disorders of accelerated bone turnover.

Animals↗
PubMed1999

Bacterial colonization/infection and the surgical management of pressure ulcers.

The purpose of this paper is to review the current recommendations and guidelines for the care and treatment of pressure ulcers with specific reference to the control of infection within these wounds and surgical management. After reviewing the literature published between May 1993 and April 1998, it is our contention that no significant changes in the clinical management of this problem are warranted. This may signal the need for further study in this area. Recommendations for the optimal care of clean and infected pressure ulcers are included.

Bacterial Infections↗
PubMed1999

AR-R15896AR blocks the early NMDA-induced loss of MAP2 in primary cortical cultures.

The low-affinity use-dependent N-methyl-D-aspartate (NMDA) receptor antagonist AR-R15896AR is neuroprotective in primary rat cortical cultures exposed to toxic concentrations of NMDA and reduces the magnitude of NMDA-triggered increases in [Ca2+]i. Here we show using fluorescence staining and measurements of microtubule-associated protein-2 (MAP2) levels, that AR-R15896AR inhibits the NMDA-induced loss of MAP2 that occurs within 2 min following NMDA exposure. Understanding the multiple, Ca(2+)-triggered intracellular events that occur following NMDA receptor stimulation is important to the development of safe and effective neuroprotective agents.

Animals↗
PubMed1999

Quadrangular space syndrome associated with superficial radial sensory neuropathy.

Compression of the axillary nerve in the quadrangular space is an unusual cause of pain and paresthesia of the upper extremity. In this report, the authors present a patient with a 1-year history of an undiagnosed axillary nerve compression associated with radial sensory neuropathy who improved after surgical decompression of the quadrangular space.

Adult↗
PubMed1999

New directions in type 2 diabetes mellitus: an update of current oral antidiabetic therapy.

This article reviewed the relevant literature including published clinical trials and reviews on currently available oral hypoglycemic agents. Results showed that the benefits of glycemic control have been established through multiple clinical trials. Long-term control of blood glucose levels in type 1 and type 2 diabetic patients will decrease the incidence and prolong the time until progression of diabetic retinopathy, nephropathy, and neuropathy. Our increased understanding of the pathophysiology behind type 2 diabetes has led to the development of many new agents that are aimed at treating the underlying insulin resistance and relative insulinopenia. The sulfonylureas as a group have been used for many years and act by stimulating insulin secretion. They are useful alone or as combination therapy with insulin or another oral hypoglycemic agent. The biguanides act by decreasing hepatic glucose production and by increasing peripheral insulin sensitivity. The alpha-glucosidase inhibitors act nonsystemically by blocking the metabolism of digested polysaccharides and therefore lowering the amount of carbohydrate absorbed in a meal. Benzoic acid derivatives act in a manner similar to that of sulfonylureas by enhancing pancreatic insulin production. They offer a shorter duration of action, lowering the risk of hypoglycemia. The thiazolidinediones increase peripheral insulin sensitivity and are effective as both monotherapy and combination therapy. Oral hypoglycemic agents, when properly administered, are very effective in controlling type 2 diabetes and preventing long-term complications.

Carbamates↗
PubMed1998

Characterization of the microtubule-binding domain of microtubule-associated protein 1A and its effects on microtubule dynamics.

To determine how MAP1a interacts with microtubules we expressed several 6myc-tagged MAP1a fragments in P19 EC and HeLa cells. Confocal immunofluorescence microscopy showed that the fragment consisting of amino acids (aa) 1-281 of MAP1a did not bind while the fragment consisting of aa 1-630 did, indicating that the region of MAP1a between aa 281 and 630 contains a microtubule-binding domain. Deletion of the basic repeats from aa 336-540 did not result in loss of microtubule binding, suggesting that the regions flanking the basic repeats can bind MAP1a to microtubules. These observations were confirmed using an in vitro microtubule binding assay. The levels of acetylation and detyrosination of polymerized microtubules were assessed by quantitative dot blotting in cells expressing MAP1a fragments or MAP2c. Compared with untransfected cells, the polymerized tubulin in cells expressing full-length MAP1a was more acetylated and detyrosinated, but these increases were smaller than those seen in cells expressing MAP2c. Consistent with this, the microtubules in MAP2c expressing cells were more resistant to colchicine than those in cells overexpressing MAP1a. These data implicate aa 281-336 and/or 540-630 of MAP1a in microtubule binding and suggest that MAP1a is less able to stabilize microtubules than MAP2c.

Antibodies, Monoclonal↗
PubMed1998

Risk of patients with severe aortic stenosis undergoing noncardiac surgery.

Aortic stenosis (AS) is a major risk factor for perioperative cardiac events in patients undergoing noncardiac surgery. We previously showed that selected patients with AS who were not candidates for, or refused, aortic valve replacement could undergo noncardiac surgery with acceptable risk. We extended our previous experience over a subsequent 5-year period by retrospectively analyzing the perioperative course of all patients with severe AS (aortic valve area index < 0.5 cm2/m2 or mean gradient > 50 mm Hg), determined with Doppler echocardiography or cardiac catheterization, who underwent noncardiac surgery. Nineteen patients underwent 28 surgical procedures: 22 elective and 6 emergency. The types of these procedures were 12 orthopedic, 6 intraabdominal, 4 vascular, 4 urologic, 1 otolaryngologic, and 1 thoracic. Mean age was 75 +/- 8 years. Of the 19 patients, 16 (84%) had > or = 1 symptom: dyspnea, angina, syncope, or presyncope. Mean left ventricular ejection fraction was 61 +/- 11%. The type of anesthesia was general in 26 procedures and continuous spinal in 2. Intraarterial monitoring of blood pressure was used in 20 of the 28 surgical procedures. Intraoperative hypotensive events were treated promptly, primarily with phenylephrine. In all cases the anesthesia team was aware of the severity of the AS and integrated this into the anesthetic plan. Two patients (elective operation in 1 and emergency in 1) had complicated postoperative courses and died. There were no other intraoperative or postoperative events in any of the other patients. Although aortic valve replacement remains the primary treatment for patients with severe AS, selected patients with severe AS, who are otherwise not candidates for aortic valve replacement, can undergo noncardiac surgery with acceptable risk when appropriate intraoperative and postoperative management is used.

Aged↗
PubMed1998

Borderline findings in fetal cardiac sonography.

Borderline or equivocal sonographic findings in the fetal heart are occasionally encountered. Echogenic foci in the ventricles, small pericardial effusions, and mild discrepancy in ventricular size are three such problematic findings. The significance of each of these findings, as currently understood, will be discussed in this article.

Down Syndrome↗
PubMed1998

The frequency and clinical significance of specific IgE to both wasp (Vespula) and honey-bee (Apis) venoms in the same patient.

BACKGROUND: Changeover from Phadebas RAST to Pharmacia AutoCAP increased double-positivity to both honey-bee and common wasp (vespula) venom in our patients. OBJECTIVE: We examined the frequency of IgE double-positivity, its clinical relevance and utility in investigating potentially allergic patients. METHODS: One hundred and eighty-two patients with hymenoptera allergy were tested using RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history of reactions to vespulae (22), honey-bee (10) and unidentified hymenoptera (vespinae) (7). RESULTS: After changing from RAST to AutoCAP double-positivity increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave similar median class results (vespula = 3, honey-bee = 2). Thirty-six CAP patients had systemic reactions of Mueller grade II and above. In vespula-allergic double-positive subjects, high CAP classes (> or = class 3) to honey-bee were common (30%). In 25% the CAP classes were equal. In honey-bee-allergic subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were equal for both venoms. In 43% of vespinae-allergic patients the CAP class was equal to both (class 2 and 3). In contrast, intradermal skin test double-positivity was uncommon. Double-negative skin test results were common in the CAP double-positive population (22% of honey-bee-allergic, 13% of vespula-allergic and 43% of vespinae-allergic patients). Vespula allergic patients have higher bee-venom IgE than vice versa. Twenty-seven per cent of CAP double-positive patients (representing 8% of all venom allergic patients tested over this period) had equal class IgE to both venoms which was not helpful in diagnosis. Combination of skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double-positive serology. CONCLUSION: If used in isolation CAP may be misleading, especially if only one venom is tested. Identification of the causative venom must utilize both clinical history and skin testing in these double-positive patients, and challenge testing if indicated.

Adolescent↗
PubMed1998

Modulation of radiation-induced strand break repair by cisplatin in mammalian cells.

PURPOSE: To investigate the repair of ionizing radiation-induced DNA lesions in human skin fibroblasts in the presence of cisplatin-DNA adducts and to determine the persistence of DNA repair inhibition by cisplatin. MATERIALS AND METHODS: Normal human fibroblasts (AG 1522) treated with cisplatin were exposed to 4 Gy 60Co gamma-radiation and assayed for repair of radiation-induced damage under growth-permissive conditions. DNA damage was measured by the fluorescence analysis of DNA unwinding (FADU) and cytokinesis-blocked micronucleus assays. RESULTS: Rejoining of strand breaks caused by 4 Gy radiation in cells without cisplatin pre-treatment appeared to be biphasic with an initial fast component (up to 15 min of repair time) followed by a slower component, and was completed by 90 min. Cisplatin treatment (10 microg/ml, 30 min) immediately before irradiation had no effect on the fast rejoining component, but inhibited the slow component (p<0.01). The same cisplatin treatment 24 h prior to irradiation inhibited both slow and fast components (p<0.01). In contrast, decreasing the cisplatin exposure to 1.0 microg/ml for 30 min, 24h prior to irradiation, resulted in an increased amount of strand break repair at each time point measured compared with irradiated control cells. This mild cisplatin treatment (95% survival) also resulted in a reduction of radiation-generated micronuclei indicating an adaptive response. CONCLUSIONS: Cisplatin used in combination with ionizing radiation can produce differential cellular responses depending upon the severity of the cisplatin treatment and the time interval between cisplatin and radiation exposures.

Cell Nucleus↗