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Biomedical subjects

B A Erickson

Publications and source records attributed to B A Erickson.

At least 19 recordsLinked to original sources

The effect of selective cyclooxygenase inhibitors on intestinal epithelial cell mitogenesis.

INTRODUCTION: Previous research has demonstrated that nonsteroidal anti-inflammatory agents alter the incidence of colorectal cancer. It has been postulated that the response may be due to the effect of these agents on the activities of the cyclooxygenase (COX) enzymes. The COX enzymes catalyze the conversion of arachidonic acid to biologically active prostanoids. Two forms of COX have been identified. COX-1 is a constitutive enzyme, generally involved in cell functions, while COX-2 is commonly an enzyme which is inducible in response to various stimuli, including mitogens. Recently, specific inhibitors of COX-1 and COX-2 enzymes have been developed. PURPOSE: The present study was undertaken to determine the effects of specific COX-1 and COX-2 inhibitors on the proliferation and the induction of apoptosis of intestinal epithelial cells. METHODS: A continuously proliferating rat small intestinal cell line (IEC-18) and a mouse colon cancer cell line (WB-2054) were utilized for these experiments. The cells were placed in microwells with serum-free or serum-supplemented media. The effects of serum on proliferation were then evaluated in the presence of the COX-1 inhibitor, valerylsalicyclic acid (VSA), the COX-2 inhibitor, SC-58125, or indomethacin. The presence of COX-1 and COX-2 protein was evaluated by Western blotting. Proliferation of intestinal cells was quantitated by incorporation of [3H]thymidine into DNA and cell counting, and apoptosis was determined by evaluating cell attachment. COX activity was evaluated by prostaglandin E2 production measured by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Western blotting of IEC-18 and WB-2054 cell protein demonstrated COX-1 enzyme in cells incubated in serum-free media with increased COX-1 expression produced by incubation in media supplemented with 10% serum. COX-2 enzyme was not demonstrated in serum-free media; however, it was present in cells maintained in 10% serum-supplemented media. Spontaneous DNA synthesis was present in both cell lines and serum increased proliferation. In both cell lines [3H]thymidine incorporation stimulated by serum was inhibited by the COX-2 inhibitor SC-58125, but not by the COX-1 inhibitor VSA. Both indomethacin and SC-58125 produced a dose-dependent increase in apoptotic ratios in both cell lines. PGE2 formation, stimulated by serum, was inhibited by SC-58125, VSA, and indomethacin. CONCLUSION: A differential effect on intestinal cell mitogenesis was seen with different COX inhibitors. The COX-2 inhibitor, but not the COX-1 inhibitor, significantly inhibited [3H]thymidine incorporation in both cell types, suggesting COX-2 inhibitors may be specific inhibitors of normal epithelial cell proliferation and growth of malignant cells. SC-58125, a selective inhibitor of COX-2, has a potent apoptosis inducing effect. The inhibition of PGE2 production did not correlate with the inhibition of proliferation, suggesting the two processes are unrelated.

Animals

Biliary tree malignancies.

Radiation therapy is used as definitive treatment for unresectable bile duct tumors, or as adjuvant therapy after resection. External beam irradiation of 45-50 Gy is generally given whenever feasible. Intraluminal brachy-therapy is a useful technique to deliver higher doses of radiation to the tumor while respecting the tolerance of the surrounding normal tissues. Brachytherapy can be given at a high dose rate or low dose rate via an in-dwelling biliary drainage catheter to boost external beam doses. Brachytherapy alone is reserved for palliative therapy. Techniques should be implemented with care to make them not only effective but safe. The long-term efficacy and morbidity of this mode of radiation should be studied further. Only large prospective trials can lead to resolution of some of the questions yet unsolved in treatment of these challenging malignancies.

Bile Duct Neoplasms

Molecular metastases in stage I pancreatic cancer: improved survival with adjuvant chemoradiation.

BACKGROUND: Reports of improved survival rates for patients with resected adenocarcinoma of the pancreas coincide with the adoption of adjuvant chemoradiation protocols. The impact of nodal micrometastases demonstrated by molecular assays and adjuvant therapy on survival of patients with stage I pancreatic cancer has not been adequately assessed. METHODS: A retrospective analysis of postoperative chemoradiation on survival in 61 patients undergoing resection of pancreatic adenocarcinomas from 1984 to 1997 was performed. Archival tumors and regional nodes from 25 patients with stage I cancers were tested for a Kiras oncogene mutation using polymerase chain reaction and analysis for restriction fragment length polymorphisms (PCR/RFLP). RESULTS: Adjuvant chemoradiation was associated with improved survival for stage I (P < .01), but not stage III, disease. Seventeen (68%) of 25 patients with stage I disease tested had evidence of mutant Kiras in one or more regional nodes. Survival did not differ for patients with molecular micrometastases. Six of 17 (35%) patients with micrometastases received adjuvant chemoradiation and had improved survival (P < .05). CONCLUSIONS: The majority of patients with stage I pancreatic cancer have PCR/RFLP evidence of lymph node micrometastases. Adjuvant chemoradiation improves survival in these patients by treating micrometastases not detected by histology. Adjuvant chemoradiation should be used for patients with stage I pancreatic cancers.

Adenocarcinoma

Urea reduction ratio and urea kinetic modeling: a mathematical analysis of changing dialysis parameters.

Based mainly on the simplicity of its calculation, the urea reduction ratio (URR) has been suggested as an alternative to urea kinetic modeling (Kt/V) as a measure of hemodialysis adequacy. However, recent studies have raised questions concerning the accuracy of URR, particularly in the presence of residual kidney function (KrU). This study was initiated to evaluate the relationship between URR and Kt/V under a variety of dialysis conditions. Equations based on the variable-volume, single-pool model described by Gotch were used to construct a model incorporating the variables used in the estimation of URR and Kt/V. The model's prediction of URR correlated closely with measured URR in 30 patients (r = 0.9987, p < 0.000001). This analytic approach showed that changes in each of several dialysis parameters caused divergence in the values of URR and Kt/V. The model showed that URR could be less than 0.65, while total Kt/V was greater than 1.2, whether or not KrU was present. In fact, when KrU was greater than 1. 0, URR could be less than 0.65, while Kt/V might be 2.0 or higher. On the other hand, the model showed instances where URR could be greater than 0.65, when Kt/V was less than 1.2. This occurred only when KrU was less than 1.0. To determine the prevalence of these anomalies in clinical practice, 767 kinetic modeling determinations were evaluated in 207 patients. One of the above discrepancies was observed at least once in 30.9% of the patients, representing 12.1% of all determinations. In addition, it was found that omitting KrU from the calculation of Kt/V generally leads to a Kt/V <1.2. This, when associated with a URR <0.65, could erroneously imply inadequate dialysis. The patient data are consistent with the view that URR and Kt/V are the net result of several variables that may act together or even in opposing directions. Based on this mathematical model and the observed clinical data, the use of URR alone to assess dialysis adequacy, or neglecting the contribution of KrU to Kt/V, may lead to changes in the dialysis prescription that are neither correct nor necessary.

Aged

Lipophorin levels in the yellow fever mosquito, Aedes aegypti, and the effect of feeding.

High density lipophorin (HDLp) is the major lipid transport vehicle in insect hemolymph. Using an indirect ELISA, levels of HDLp were measured in the yellow fever mosquito, Aedes aegypti. The level of lipophorin, when normalized to the total weight of the insect, was similar in the different developmental stages. Starvation (access to water only) of adult females did not affect the level of HDLp nor its density when compared to sugar-fed females. On the other hand, blood feeding (of normally sugar-fed females) resulted in a three-fold increase of the HDLp level at 40 h after feeding. This increase was accompanied by a slight but significant increase in the density of HDLp at 24 h after feeding. Ingestion of a lipid-free protein meal or a lipid-supplemented protein meal induced changes in HDLp level and density that were comparable to those induced by ingestion of a blood meal. Ingestion of a blood meal, following starvation (access to water only) from the moment of adult emergence, did not induce an increase in HDLp level. The results presented indicate that, in contrast to other insect species, A. aegypti responds to an increased need for lipid transport in the hemolymph by increasing the amount of HDLp. Arch. Insect Biochem.

Aedes

Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992.

OBJECTIVES: This study sought to describe prevalence rates of chronic gynecological conditions and correlates of these conditions in a representative sample of US women. METHODS: National Health Interview Survey data from 1984 through 1992 for women aged 18 to 50 were used. RESULTS: The estimated annual prevalence rate for the reported presence of one or more gynecological conditions was 97.1 per 1,000 women. Menstrual disorders were most common, with an annual prevalence rate of 53.0 per 1,000 women. Adnexal conditions and fibroids were the next most common conditions, with rates per 1,000 women of 16.6 and 9.2, respectively. Prolapse, endometriosis, and fibroids were the conditions most likely to lead to hysterectomy within the year prior to the interview. More than three quarters (77.1%) of women with gynecological conditions had talked with a doctor in the previous year concerning their condition, and 28.8% reported spending 1 or more days in bed in the previous year because of their condition. CONCLUSIONS: Nearly a tenth of American women aged 18 to 50 report having one or more chronic gynecological conditions annually, the most common being disorders of menstruation.

Adolescent

Echographic monitoring of response of extraocular muscles to irradiation in Graves' ophthalmopathy.

PURPOSE: Confirmation of the efficacy of orbital irradiation in Graves' ophthalmopathy is needed due to the unpredictable natural history of the disease, the variation in individual clinical presentations, the contribution of other simultaneous treatments, and the lack of controlled studies using objective criteria to classify and assess response over time. Orbital echography before and at select intervals following orbital irradiation is proposed as an objective parameter of tissue response to orbital irradiation over time. METHODS AND MATERIALS: From January, 1983 to September, 1993, 55 patients with progressive Graves' ophthalmopathy underwent 20 Gy retrobulbar irradiation. On retrospective review, standardized orbital echography was performed randomly prior to irradiation in 37 of the 55 patients to assess the acoustic characteristics of the extraocular muscles and to quantitate their individual and summed diameters. Twenty-one patients had at least one follow-up echographic evaluation at random intervals of 0 to 27.5 months following completion of irradiation. Twelve patients received steroids before or during irradiation, which were tapered in proximity to completion of radiation. Follow-up ranged from 2 to 65 months with the majority followed at least 6 months (18 patients). RESULTS: Of the 21 patients with serial studies, 18 showed an interval decrease in individual and summed muscle size over time and return of symmetry. Interval improvement was documented as early as the 1 month follow-up study, with continued improvement seen during the 3-9-month studies, with stability typically achieved within 12 months. One patient had further changes between the 21 and 27.5 month follow-up studies. Exacerbation of disease was, however, echographically demonstrated in three patients at 6.5, 8.5, and 13 months. Follow-up studies in two of these patients again revealed improvement, one following tapered steroids. The third patient required orbital decompression. CONCLUSION: Objective parameters of response are needed to document both the immediate and long-term outcome of orbital irradiation on the course of Graves' ophthalmopathy and confirm its efficacy. Serial echography is proposed as a new technique for providing parameters to judge response.

Follow-Up Studies

Lacrimal collecting system lymphomas: integration of magnetic resonance imaging and therapeutic irradiation.

Lymphomas arising within the lacrimal collecting system are rare tumours and unusual causes of lacrimal obstructive symptoms. The presentation, diagnosis, and treatment of this disease in five patients are described, as well as a review of the existing literature. Emphasized in this series is the efficacy of magnetic resonance imaging of these presentations and the importance of irradiation in their treatment.

Adult

Altered motility causes the early gastrointestinal toxicity of irradiation.

PURPOSE: Total abdominal radiation produces symptoms of nausea, vomiting abdominal cramping and diarrhea. Each of these symptoms is associated with disordered intestinal motility. This article reviews studies of large and small intestinal contractile activity following radiation exposure. METHODS AND MATERIALS: Studies of motility utilize strain gauge transducers surgically implanted on the seromuscular layer of the small intestine. All studies were performed in mixed breed dogs to record the occurrence of normal contractions, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) before, during and after irradiation (22.5 Gy in 9 fractions at 3 fractions/week). Giant migrating contractions and retrograde giant contractions are infrequent in the healthy state. However, in diseased states, GMCs are associated with abdominal cramps and diarrhea, and RGCs precede vomiting. RESULTS: In fasted animals, fractionated abdominal irradiation dramatically increased the frequency of GMCs, with the incidence peaking after the second dose. The increased frequency of GMCS occurred as early as a few hours after the first radiation fraction, and returned to normal within days of cessation of radiation. RGCs were also significantly increased after abdominal irradiation. The frequency of RGCs was greatest on the first and sixth dose of radiation. Clinically, the dogs developed nausea, vomiting and diarrhea as early as the first day of irradiation. In dogs studied in the fed state, decreased amplitude, duration, and frequency of postprandial contractions occurred. These changes may slow intestinal transit during irradiation. Radiation also produced a striking increase in the frequency of colonic GMCs; these changes in colonic motor activity were associated with diarrhea as early as the second irradiation. CONCLUSION: Changes in GI motility during fractionated irradiation precede the appearance of histopathological lesions in the GI tract. Thus, the symptoms of nausea, vomiting, and diarrhea experienced during radiotherapy (particularly those within the first week) are directly related to changes in bowel motility. It is hoped that further understanding of the etiology of these distressing symptoms will help to guide their treatment.

Animals

Nasopharyngeal brachytherapy.

There has been a recent resurgence of interest in implementing brachytherapy in the management of nasopharyngeal carcinoma, not only as treatment for recurrent disease, where it has secured a notable role, but also as an elective boost following external beam irradiation in an attempt to improve local control. Examination of the use of nasopharyngeal brachytherapy over nearly the last century may provide guidance for such endeavors and encourage further evolution of these techniques. Throughout this interval, ingenuity has prevailed in attempts to treat a secluded anatomical site which has been difficult to access, explore, and implant in an acceptable manner.

Brachytherapy

Periocular lymphoproliferative diseases: natural history, prognostic factors, and treatment.

A study was undertaken to assess the natural history of periocular lymphoproliferative diseases, identify key prognostic factors, and clarify the role of orbital irradiation. Thirty-four patients with periocular lymphoproliferative disease were treated with orbital irradiation between 1975 and 1990. Eight patients had atypical lymphoid infiltrate, and 26 had malignant lymphoma. Forty-three eyes were irradiated with en-face electrons or 6-MV photons. Five-year disease-free survival for all stages was 65%; it was not significantly affected by bilaterality or site. Stage, distinction between atypical lymphoid infiltrate and malignant lymphoma, and working formulation grade were important prognostic indicators. A complete response during irradiation was achieved in 24 of 43 (56%) eyes at a median dose of 2,400 cGy, and a partial response was achieved in 19 (44%), with resolution at a median of 2.8 months. Patients with periocular reactive lymphoid hyperplasia or atypical lymphoid infiltrate may have or are at significant risk of developing lymphoma and dissemination. Local treatment remains important; orbital irradiation achieves prompt local control with acceptable morbidity.

Adult

Characterization of secretion pattern of human prostatic acid phosphatase: a reassessment.

The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma.

Acid Phosphatase

Strategies for reducing i.v. drug waste and coping with increased workload.

The amount of i.v. drugs wasted in our centralized i.v. admixture program was initially identified as a problem in 1982. The i.v. drug waste in 1982 was approximately $72,000, which represented 8.8% of the total i.v. drug budget. The i.v. admixture workload had also increased 35% from 1980 to 1982. The pharmacy department decided to approach the i.v. drug waste and increased workload problem by purchasing premixed i.v. solutions. The objective of this study was to evaluate whether premixed i.v. solutions are cost effective by decreasing both drug waste and i.v. preparation time. In addition, pharmacy standardized the doses of various i.v. drugs and instituted an on-call card system for the ordering of selected drug by nursing. By using the above methods, the pharmacy department was able to absorb an additional 37% increase in workload from 196,418 units in 1982 to 269,176 units in 1985. Also, pharmacy was able to reduce the i.v. drug waste from 8.8% of the i.v. budget in 1982, to 2.35% of the 1985 i.v. budget. Both of these goals was achieved without additional staff.

Cost-Benefit Analysis

Seizures induced by the cocaine metabolite benzoylecgonine in rats.

The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.

Animals

Quality assurance in anatomic pathology: automated SNOMED coding.

This case study details the set-up and implementation of the PathNet autocoder (Cerner Corporation) in a busy anatomic pathology laboratory. After initial start-up, procedures were developed to improve the system's performance. Four classes of software coding errors were identified, and an index was developed to measure the number of cases between errors (CBE). Through modifications in the program, the CBE increased sharply by the end of the six-month study period. During the last three months of the study, the efficiency of case retrieval was tested by comparing manual and electronic methods on the same reference cases. This demonstrated significant time saving and removed the variability of manual coding. The technique employed in this study may assist other institutions seeking to implement such a coding system within their respective environments.

Clinical Laboratory Information Systems