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C L Brown

Publications and source records attributed to C L Brown.

At least 55 records · Page 3Linked to original sources
PubMed1994

Synthetic alpha-helical peptides incorporating intercalators for DNA recognition.

The design and synthesis of a water-soluble 14-residue peptide, in which a quinoline intercalator is attached to the peptide backbone via alkylation of a central cysteine residue, is reported. 600 MHz 1H NMR spectroscopy and circular dichroism indicate that the peptide forms a nascent helix in aqueous solution, ie. an ensemble of turn-like structures over several adjacent residues in the peptide. A large number of sequential dNN(i, i+1) connectivities were observed in NOESY spectra, and titration of trifluoroethanol into a solution of the peptide resulted in the characteristic CD spectrum expected for an alpha-helix. At low DNA concentrations, CD spectroscopy indicates that this helical conformation is stabilized, presumably due to folding of the peptide in the major groove of DNA.

Amino Acid Sequence↗
PubMed1994

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Breast↗
PubMed1994

Diagnosis and treatment of patients with gastroesophageal reflux and noncardiac chest pain.

Patients with noncardiac chest pain frequently have some evidence of gastroesophageal reflux. Yet there are few formal studies on the treatment of what appears to be reflux-related chest pain. The purpose of this study was to evaluate the effectiveness of intensive antireflux therapy in patients with noncardiac chest pain and gastroesophageal reflux and to determine whether patients who will respond to this therapy can be identified through routine esophageal testing. Thirteen patients with noncardiac chest pain and evidence of gastroesophageal reflux were treated with intensive antireflux therapy featuring high-dose ranitidine. Chest pain symptoms were scored from 0 (none) to 4 (severe) at entry into the study and at 8 weeks. Mean symptom scores were 2.9 +/- 0.3 at entry and 0.7 +/- 0.3 at 8 weeks. All patients had improvement, including those with a normal endoscopic or barium study (nine patients) and those for whom earlier standard antireflux therapy had failed (seven patients). Only one patient had a positive acid perfusion test, and only seven had any correlation of chest pain and reflux episodes during ambulatory monitoring. We concluded that many patients with noncardiac chest pain have gastroesophageal reflux, including those for whom an empiric trial of standard antireflux therapy fails. More aggressive antireflux therapy often leads to improvement in symptoms. Diagnostic studies requiring strict correlation of chest pain symptoms and reflux episodes are insensitive methods of determining which patients will respond to antireflux therapy.

Adult↗
PubMed1994

Immunocytochemical and serological expression of CA 125: a clinicopathological study of 40 malignant ovarian epithelial tumours.

Elevated serum levels of the tumour-associated antigen CA 125 occur in more than 80% of cases of ovarian carcinoma. The antigen can be demonstrated in formalin-fixed tissue using the monoclonal antibody OC 125, which localizes it to the surface membrane or cytoplasm. This study was performed to determine the relationship between pre-operative serum levels of CA 125 and the subsequent immunocytochemical findings in the surgical specimen. Paraffin-wax embedded sections from 40 consecutive borderline and frankly malignant ovarian epithelial tumours were stained with OC 125. The pattern and distribution of immunostaining were investigated in relation to histological appearances. Serous tumours showed a 100% correlation between immunocytochemical findings and elevated serum levels of CA 125. Amongst the other histological types, correlation was less good; mucinous tumours and undifferentiated carcinomas showed a poor correlation. Immunostaining within tumours was heterogeneous and only loosely related to morphological appearances. Our finding suggests that, with the exception of serous tumours, immunolocalization of CA 125 is insufficiently sensitive to provide reliable clinical guidance to the likely value of serum CA 125 monitoring on follow-up.

Adult↗
PubMed1994

Lung function, surfactant apoprotein content, and level of PEEP in prematurely delivered rabbits.

To study the in vivo activity of the surfactant apoproteins (SP-A, SP-B, SP-C), we administered surfactants with defined apoprotein compositions to prematurely delivered rabbit pups. Rabbits given simple phospholipid mixtures containing dipalmitoylphosphatidylcholine and phosphatidylglycerol supplemented with both SP-B and SP-C or either protein alone had significantly greater lung compliance during ventilation and lung expansion during a quasi-static pressure-volume maneuver than did saline-or lipid-treated controls. The response to the surfactants containing SP-B/C was markedly dependent on the level of end-expiratory pressure used during ventilation. When the rabbits were ventilated with a positive end-expiratory pressure (PEEP) of 4 cmH2O, lung function in the pups treated with SP-B/C was not significantly different from rabbit surfactant-treated controls. Addition of SP-A to the surfactants containing SP-B/C did not significantly further improve lung function if the pups were ventilated with a PEEP of 4 cmH2O. With a lower PEEP of 1 cmH2O, lung function in the pups given surfactants containing SP-B/C was no longer equivalent to the lung function of the rabbit surfactant-treated controls. At the lower PEEP, SP-A significantly improved lung function when it was added to surfactants containing SP-B and SP-C. No beneficial effect of SP-A was seen when the surfactant contained either SP-B or SP-C alone. We conclude that with assisted ventilation that includes a moderate level of PEEP, SP-B and SP-C significantly enhance the effect of a simple phospholipid mixture on the lung function of prematurely delivered rabbits. At lower levels of PEEP the effects of SP-B and SP-C on lung function are markedly reduced but can be restored by the addition of SP-A. Our results are consistent with the existence of cooperative protein-protein interactions in surfactant function in vivo and suggest that the response to a surfactant will be determined by both the ventilation strategy and the surfactant composition. composition.

Animals↗
PubMed1994

HIV/AIDS policies and sports: the National Football League.

With the assistance of highly respected experts in the field of HIV/AIDS, the NFL has developed a comprehensive policy that should decrease the spread of HIV and any other blood-borne pathogens among its players and medical staff. Transmission of HIV infection is likely to be rare in the NFL. This is supported by the fact that in over 10 yr of the AIDS epidemic, the CDC has not attributed one AIDS case to athletic competition. Whatever the rate of HIV infection, on-the-field transmission is certainly less frequent than hepatitis B, which is manyfold more transmissible than HIV. Based on these facts, a player with HIV infection poses virtually no threat to others or himself by further athletic participation in the NFL. In addition, the relatively short average playing career of an NFL player and the extended period between HIV contraction and development of AIDS symptoms decrease the prospect that a player's HIV-positive status would affect his athletic performance. Consequently, HIV testing should remain voluntary, and continued participation in the NFL of HIV-infected players should remain a private decision between the player and his physician.

AIDS Serodiagnosis↗
PubMed1993

Effect of restenosis at one previously dilated coronary site on the probability of restenosis at another previously dilated coronary site.

The purpose of this study was to determine whether in patients with 2 sites dilated by percutaneous transluminal coronary angioplasty (PTCA), the sites undergo restenosis independently. Although restenosis remains a critical limitation after PTCA, there is little information separating site- and patient-dependent determinants of restenosis. In particular, if patients with 2 sites dilated have restenosis at 0 or 2 sites more frequently and at 1 site less frequently than expected by random chance, then patient-related factors may be important in the restenosis process. The source of data was the clinical data base at Emory University. Patients who had previously coronary surgery or PTCA, and those who underwent PTCA in the setting of acute myocardial infarction were excluded. In all, 515 patients with 2 sites dilated undergoing angiographic restudy at 4 months to 1 year after PTCA formed the study population. Site 1 was the first site dilated. At site 1, 224 of 515 sites (45%) were restenotic, and at site 2, 193 (33%) were restenotic. Multiple clinical and angiographic variables were analyzed as possible correlates of restenosis. The most powerful univariate and multivariate correlate of restenosis at either site 1 or 2 was the behavior of the other site. If site 2 was patent, then site 1 was restenotic 28% of the time compared with 69% if site 2 was restenotic. If site 1 was patent, site 2 was restenotic 20% of the time compared with 60% if site 1 was restenotic. This relation was stronger if the 2 sites were in the same coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Solution conformation of the antitumor drug streptonigrin.

The solution conformation of the antitumor drug streptonigrin in THF-d8 has been determined by dynamic 1H NMR spectroscopy (400 MHz). The major solution conformation agrees with the structure observed in the solid state [Chiu, Y.-Y.; Lipscomb, W. N. J. Am. Chem. Soc. 1975, 97, 2525-30]. Rings A, B, and C are coplanar, with ring C held in place by a hydrogen bond from the amino group on ring C and the pyridyl nitrogen in ring B. This conformation is stable in the range pH 3.9-8.9. At lower pH, the hydrogen bond is disrupted due to protonation of the pyridyl nitrogen in ring B. The major species present at pH 3.9-8.9 and 180 K is the zwitterion 1b (80%). Below 190 K, slow proton transfer between the free acid 1a and the zwitterion 1b is observed on the NMR time scale. Addition of a catalytic amount of base to the solution increases the rate of exchange 1a<-->1b, and only one set of resonances is observed. In CD2Cl2 this proton transfer is not observed. Implications for the structure(s) of metal complexes formed by streptonigrin are discussed.

Hydrogen-Ion Concentration↗
PubMed1993

Can restenosis after coronary angioplasty be predicted from clinical variables?

OBJECTIVES: The purpose of this study was to determine whether variables shown to correlate with restenosis in one group (learning group) could be shown to predict recurrent stenosis in a second group (validation group). BACKGROUND: Restenosis remains a critical limitation after percutaneous transluminal coronary angioplasty. Although several clinical variables have been shown to correlate with restenosis, there are few data concerning attempts to predict recurrent stenosis. METHODS: The source of data was the clinical data base at Emory University. Patients who had had previous coronary surgery and patients who underwent coronary angioplasty in the setting of acute myocardial infarction were excluded. A total of 4,006 patients with angiographic restudy after successful angioplasty were identified. They were classified into a learning group of 2,500 patients and a validation group of 1,506 patients. The correlates of restenosis in the learning group were determined by stepwise logistic regression, and a model was developed to predict the probability of restenosis and was tested in the validation group. By using various cut points for the predicted probability of restenosis, a receiver operating characteristic curve was created. Goodness of fit of the model was evaluated by comparing average predicted probabilities with average observed probabilities within subgroups on the basis of risk level determined by linear regression analysis. RESULTS: In the learning group 1,145 patients had restenosis and 1,355 did not. Correlates of restenosis were severe angina, severe diameter stenosis before angioplasty, left anterior descending coronary artery dilation, diabetes, greater diameter stenosis after angioplasty, hypertension, absence of an intimal tear, eccentric morphology and older patient age. The model derived from the learning group was used to predict restenosis in the validation group. By varying the cut point for the predicted probability of restenosis above which restenosis is diagnosed and below which it is not, a receiver operating characteristic curve was created. The curve was close to the line of identity, reflecting a poor predictive ability. However, the model was shown to fit well with the predicted probability of restenosis correlating well with the observed probability (r = 0.98, p = 0.0001). CONCLUSIONS: Clinical variables provide limited ability to predict definitively whether a particular patient will have restenosis. However, the current model may be used to predict the probability of restenosis, with some uncertainty, at least in well characterized patients who have already had angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1993

Colorectal metastases to the liver: selective chemoembolization.

PURPOSE: To evaluate the efficacy and safety of selective chemoembolization in patients with colorectal metastases to the liver. MATERIALS AND METHODS: Forty-six patients underwent the regimen, which involved use of doxorubicin and ethiodized oil, with 75% selectively administered to different subsegments and 25% into the respective main hepatic artery. RESULTS: In eight patients, the lesions disappeared and carcinoembryonic antigen levels returned to normal. Eleven patients showed no disease progression for 12 months; two others, for 24 months. Thirteen patients died; three were lost to follow-up in the 1st year. Six patients were followed up for 5 years, seven for 3 years, 16 for 2 years, and 30 for 1 year. Five of seven patients who survived 3 years or more exhibited homogeneous distribution of the chemoembolic agent throughout the metastatic tumor. CONCLUSION: Selective chemoembolization is recommended for treatment of patients with colorectal metastases to the liver, a resectable primary tumor, and no evidence of other metastatic disease.

Adult↗
PubMed1993

Cervical dilation: accuracy of visual and digital examinations.

OBJECTIVE: To determine the accuracy of visually versus digitally determined cervical dilation. METHODS: We studied 64 pregnant women with rupture of the amniotic membranes. One of two residents performed a speculum examination, estimated the dilation and effacement visually, and noted whether fetal parts or amniotic membranes were present. The same examiner then determined digitally the cervical dilation and effacement and station of the presenting part. RESULTS: There was a statistically significant correlation between visually and digitally determined cervical dilation (r = 0.78, P < .001). CONCLUSION: Visual estimation of cervical dilation correlates well with digital examination.

Adult↗
PubMed1992

Background and methods for the lovastatin restenosis trial after percutaneous transluminal coronary angioplasty. The Lovastatin Restenosis Trial Study Group.

Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double-blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2-tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

Asynchrony of changes in tissue and plasma thyroid hormones during the parr-smolt transformation of coho salmon.

The relationship between plasma thyroid hormone concentrations and the thyroid hormone concentrations in selected tissues was examined throughout the spring during the typical course of parr-smolt transformation in coho salmon (Oncorhynchus kisutch) in fresh water and also in coho salmon moved prematurely to seawater. The thyroid hormones thyroxine (T4) and triiodothyronine (T3) were extracted from brain, liver, and muscle tissue. The T4 and T3 concentrations in the extracts and plasma were measured by radioimmunoassay. The peak in plasma T4 occurred in late April; however, the concentration of T4 in the brain and liver increased before levels of T4 in plasma increased. During the rise in plasma T4, the T4 content in muscle decreased. Plasma T3 concentrations were unchanged in March and April, but decreased in May. Transfer to seawater eliminated the late April peak in plasma T4 levels, indicating suppressed thyroid activity; however, the tissues of salmon in seawater contained more T3 than tissues of salmon in fresh water at this time. These findings indicate complex peripheral regulation of thyroidal status in this teleost and represent the first bridge between compartmental models of thyroid hormone kinetics and actual measurement of tissue pools of thyroid hormones in an ectothermic vertebrate. In summary, tissue concentrations of thyroid hormones did not echo plasma concentrations, indicating that thyroidal status cannot be inferred from plasma data alone.

Aging↗
PubMed1992

Coxsackievirus B4 infection of the mouse pancreas: acute and persistent infection.

The course of infection of a pancreas-adapted isolate of coxsackievirus B4 was followed over a 10 month period in a murine model. Following intraperitoneal inoculation a typical acute infection was seen in nine of 10 inbred mouse strains. Virus rapidly infected the exocrine pancreas, titres peaking 3 to 4 days post-infection (p.i.). Lesions were almost exclusively confined to pancreatic acinar cells and varied in severity among the inbred strains. Virus shed into the blood-stream was not cell-associated. Evidence of persistent infection was found in nine mouse strains and infective virus was recovered from the pancreas of seven strains for up to 10 months p.i. Approximately 28% of pancreases examined beyond the acute phase showed focal inflammation and 22% showed focal necrosis (cell death). Virus was occasionally recovered from other organs (heart, liver and spleen), but lesions were rarely seen. Virus-specific antigen was localized to small groups of pancreatic acinar cells using an indirect immunogold silver staining technique. These observations suggested that the virus persists in pancreatic tissues because it seems unlikely that virus disseminated from distant sites would cause such localized infection. In three of these strains, the course of infection may have been influenced by superinfection with mouse hepatitis virus.

Acute Disease↗