Biomedical subjects

D Roe

Publications and source records attributed to D Roe.

At least 37 records · Page 2Linked to original sources

PubMed1999

Trichotillomania and the mourning process: a case report and review of the psychodynamics.

We present our theory of trichotillomania (hair pulling) as a manic phenomenon, complementary to its classic comprehension as a mourning response. Under certain conditions, separation or threat of separation can generate sadness or grief, while in pathological cases, when the loss is experienced as unbearable, the response might be depressive or manic. We suggest that in trichotillomania (TR), like in mania, manic defenses are used to cope with separation. We believe hair pulling is an expression of primary magical thinking, offering the subject an illusion of control and victory over the object. A representative case of a young woman suffering from bipolar disorder with TR is described. Based on our case analysis, we argue that TR may not necessarily be a variant of OCD, but rather classified among the affective disorders.

Adult↗

PubMed1998

Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines.

Selenium supplementation has been shown for many years to work as an anticarcinogenic agent both in epidemiology and in in vitro studies. Selenium supplementation has recently been shown to decrease total cancer incidence. However, the mechanism of action of selenium as an anticarcinogenic agent has yet to be elucidated. Selenomethionine was the predominant form of selenium in the dietary supplement in the study by Clark et al. (Clark, L.C., Combs, G.F., Turnbull, W.B., Slate, E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A., Graham, G.F., Gross, E.G., Krongrad, A., Lesher, J.L., Park, H.K., Sanders, B.B., Smith, C.L., Taylor, J.R. and The Nutritional Prevention of Cancer Study Group (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. J. Am. Med. Assoc., 276 (24), 1957-1963) and therefore we evaluated the growth inhibitory effects of selenomethionine against human tumor cells. Selenomethionine was tested against each of three human tumor cell lines (MCF-7/S breast carcinoma, DU-145 prostate cancer cells and UACC-375 melanoma) and against normal human diploid fibroblasts. All cell lines demonstrated a dose-dependent manner of growth inhibition by selenomethionine. Selenomethionine inhibited the growth of all of the human tumor cell lines in the micromolar (microM) range (ranging from 45 to 130 microM) while growth inhibition of normal diploid fibroblasts required 1 mM selenomethionine, approximately 1000-fold higher than for the cancer cell lines. In short, normal diploid fibroblasts were less sensitive than the cancer cell lines to the growth inhibitory effects of selenomethionine. Furthermore, we show that selenomethionine administration to these cancer cell lines results in apoptotic cell death and aberrant mitoses. These results demonstrate the differential sensitivity of tumor cells and normal cells to selenomethionine.

Antineoplastic Agents↗

PubMed1998

A novel mutation identified in carnitine palmitoyltransferase II deficiency.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of mitochondrial fatty-acid oxidation which presents as three distinct phenotypes (neonatal, infantile, and adult onset). CPT II exons from an adult-onset CPT II-deficient patient were amplified and directly sequenced to further investigate the molecular basis of this disorder. A novel mutation, C471T, in exon 4 of the carnitine palmitoyltransferase II gene was found which created a stop codon, TGA, at residue 124 of the protein (R124Stop). This mutation would result in severe protein truncation. This unique mutation was found on one allele while the S113L mutation, previously reported, was present on the other allele.

Adult↗

PubMed1998

Identification of four novel mutations in patients with carnitine palmitoyltransferase II (CPT II) deficiency.

Carnitine palmitoyltransferase II (CPT II) deficiency, an autosomal recessive disorder of fatty-acid oxidation, presents as three distinct phenotypes (neonatal, infantile, and adult onset). In order to investigate the molecular basis of these three phenotypes, six patients with CPT II deficiency have been studied. All six unrelated patients in this study experienced the clinical symptoms of CPT II deficiency. Three patients had the neonatal form, one had the milder infantile form, and the remaining two had the adult-onset form with "muscular" symptoms only. Their diagnoses were based upon in vitro analysis of the mitochondrial beta-oxidation pathway in fibroblasts and standard enzyme assays. We devised a method to screen the entire coding sequence and flanking splice junction of the CPT II gene. A total of six different mutations have been identified, including four novel mutations. Among them, the previously reported common mutation, S113L, was only found in 3 of 12 variant alleles. Three of the six mutations have been identified in a few unrelated patients, while the remaining three have been found in single families. This study, as well as those by others, indicates genetic heterogeneity in this disease. In addition to tabulating the mutations, the correlation of mutant genotype to clinical phenotype is briefly discussed.

Adult↗

PubMed1997

Predictive value of skull radiography for intracranial injury in children with blunt head injury.

BACKGROUND: The value of routine skull radiography as a method of predicting intracranial injury is controversial. We aimed to assess the effectiveness of skull radiography by prospectively studying head-injured children admitted to a children's hospital that serves an urban population. METHODS: Over a 2-year period, 9269 children attended our accident and emergency department with head injury, and 6011 were referred for skull radiography. All children who were admitted to hospital or had a skull fracture (n = 883) were included in the study. Computed tomography (CT) was done in children with skull fractures on radiography and in those without fractures if there were neurological indications. FINDINGS: Radiographs showed 162 fractures (2.7% of all radiographs and 18% of study group radiographs). Staff in the accident and emergency department missed 37 (23%) fractures. CT scan was done on 156 children, of whom 107 had a skull fracture. 23 children were found to have intracranial injuries on CT. The presence of neurological abnormalities had a sensitivity for identification of intracranial injury of 91% (21 of 23) and a negative predictive value of 97%. The corresponding values for skull fracture on radiography were 65% (15 of 23) and 83%. Four children died, of whom only one had a skull fracture. INTERPRETATION: In children, severe intracranial injury can occur in the absence of skull fracture. Skull radiography is not a reliable predictor of intracranial injury and is indicated only to confirm or exclude a suspected depressed fracture or penetrating injury, and when non-accidental injury is suspected, including in all infants younger than 2 years. Clinical neurological abnormalities are a reliable predictor of intracranial injury. If imaging is required, it should be with CT and not skull radiography.

Brain Injuries↗

PubMed1997

Long-term precision of glomerular filtration rate measurements using 51Cr-EDTA plasma clearance.

The long-term precision of chromium-51 ethylenediamine tetraacetic acid (51Cr-EDTA) measurements of glomerular filtration rate (GFR) was evaluated in a retrospective study of data obtained over a 12 year period. Each GFR measurement was derived from plasma samples taken at 2, 3 and 4 h following injection of 3 MBq 51Cr-EDTA. The records of 7507 patients were reviewed, from which 55 subjects were identified as having had studies on 10 or more occasions. The mean number of studies per patient was 12.9 (range 10-23) over a mean period of 9.4 years (range 4.3-11.8 years). Plots of GFR, clearance half-life, (T1/2) and volume of distribution (VD) were drawn for each patient and used to identify subjects showing linear changes with time that could be fitted using linear regression. Each residual was expressed as a percentage of the expected value calculated from the regression line and all the residuals combined to give histograms for GFR, T1/2 and VD. Each histogram was fitted with a normal distribution between the -3 S.D. and +3 S.D. limits using weighted least squares. Final results for the coefficient of variation were: GFR 9.8%, T1/2 6.7%, VD 9.4%. The precision errors were used to calculate the smallest statistically significant change measurable by the 51Cr-EDTA technique. With 10% significance and 80% power, the smallest measureable change was 30% for GFR and 20% for T1/2. Unless there are clinical grounds for thinking that a patient's volume of distribution has changed, T1/2 is the optimal parameter for identifying real changes in renal function.

Chromium Radioisotopes↗

PubMed1997

Catamenial pneumothorax heralding menarche in a 15-year-old adolescent.

A case of spontaneous recurrent pneumothoraces (PTX) that has compelling features of a catamenial (CTM) origin is presented. A 15-year-old adolescent presented with a spontaneous PTX within 24 hours of menarche. A second PTX occurred one month later. While most cases of spontaneous PTX occur in male patients and are idiopathic, CTM PTX occur solely in menstruating female patients, have different treatment options, and recur with menses in the absence of appropriate therapy. Emergency practitioners should have a high clinical suspicion for CTM PTX in all female patients with spontaneous PTX, especially those which are recurrent or are associated with menstruation or menarche, in order to provide the patient with a complete spectrum of treatment plans.

Adolescent↗

PubMed1996

Gustave Dax and the early history of cerebral dominance.

In 1863, 2 years before Paul Broca published his heralded paper on the special role of the left hemisphere in speech, Gustave Dax sent a paper to the Académie de Médecine in Paris, France. His lengthy submission included an insightful memoir presumably written by his father Marc in 1836 and supportive material that he had collected himself. The present article examines the events leading to Gustave's 1863 submission to the Académie. It also presents an English translation of the negative response that this paper received and a translation of the short article that Gustave published in 1865. These materials help to show how cerebral dominance was first discovered, how it was made public, and how the first advocates of the concept were judged by their contemporaries.

Dominance, Cerebral↗

PubMed1996

Acute and chronic effects of morphine in pigeons responding under a progressive-ratio schedule of food delivery.

Although progressive-ratio schedules have often been used by behavioral pharmacologists to index the relative reinforcing effects of drugs of abuse, they have been ignored in the study of tolerance to opioids. The present study examined tolerance to morphine in pigeons responding under a progressive-ratio 5 schedule of food delivery. Acute administrations of morphine produced general dose-dependent reductions in response rates and breaking points. Dose-response curves for both measures shifted rightward substantially (roughly fivefold) following chronic (daily) exposure to morphine, indicating that tolerance developed to the drug's effects.

Animals↗

PubMed1996

Gustave Dax and his fight for recognition: an overlooked chapter in the early history of cerebral dominance.

The year 1865 was revolutionary in neuroscience. In this year, three papers were published on the topic of cerebral dominance for speech. These papers were authored by Paul Broca, Marc Dax, and Gustave Dax, and they contributed to a priority debate that cannot be easily resolved. Gustave Dax claimed that his long dead father had written a memoir and presented it orally in Montpellier in 1836, thus making him the first person to write about cerebral dominance. He also claimed that he was the second person to write on the subject, the first to support his father's claims, and the first to try to localize the center for speech in just one part the left hemisphere, the middle (temporal) lobe. Paul Broca, however, was now getting much of the credit for these discoveries. To set the record straight, Gustave published several letters. This paper presents translations of Gustave's letters of 1866, 1875, and 1877, as well as the historical note written by Raymond Caizergues in 1879, and recreates the events that triggered the younger Dax's anger.

France↗

PubMed1995

Comparison of proliferating cell nuclear antigen versus the more standard measures of rectal mucosal proliferation rates in subjects with a history of colorectal cancer and normal age-matched controls.

Measurement of proliferation rates by the more standard in vitro uptake techniques of [3H]thymidine and 5'-bromo-2'-deoxyuridine (BrdUrd) labeling indices (LIs) were compared to proliferating cell nuclear antigen (PCNA) in rectal mucosal biopsies from 16 subjects with resected colorectal cancer and 14 normal age-matched controls. Correlation coefficients for BrdUrd versus PCNA, [3H]thymidine versus PCNA, and BrdUrd versus [3H]thymidine were 0.691, 0.876, and 0.770, respectively. No significant differences (P > 0.05) were detected in total mean LIs between the LI methods for the normal group. In contrast, total PCNA LIs were found to be significantly different in the resected cancer patients when compared to either BrdUrd (P = 0.005) or [3H]thymidine (P < 0.001). A significant difference (P = 0.010) in total PCNA LI but not in total [3H]thymidine or BrdUrd LIs was also observed between normal controls and resected colorectal cancer subjects. Compartmental analysis of the cancer group versus the normals showed a significant difference in compartments 1 and 3 for PCNA LIs only. The reproducibility of two PCNA LI counts was excellent (r = 0.9). In addition, the reliability of mean LIs were > 0.8 with the exception of [3H]thymidine in the normal group (0.7). These study results demonstrate that PCNA LIs in human rectal mucosal biopsies are correlated highly with other more commonly used cellular proliferation measurements; however, PCNA LIs were found to be significantly higher than the other two methods in the resected colorectal cancer subjects.

Adult↗

PubMed1994

Validation of proliferation indices as surrogate endpoint biomarkers.

During the 1990s, research interest in the use of chemopreventive agents to reverse human colon carcinogenesis increased exponentially. In parallel, there has been an increase in the need for putative surrogate endpoint biomarkers (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra et al., among others, the rate and patterns of rectal mucosal proliferation have been established as intermediate biomarker endpoints for colon cancer risk, modulated by potential chemopreventive agents including calcium, wheat bran fiber, and nutritional stress diets. Researchers rely heavily on these rectal mucosal proliferation indices as surrogate endpoints to evaluate the relative efficacy of various chemopreventive intervention strategies. Standardization through quality control/quality assurance (QC/QA) programs which continuously validate the accuracy, reproducibility, and variability of these indices is increasingly needed. Along with many others, we have attempted to validate 3H-thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be followed in the validation process for new as well as "old" biomarkers prior to their use as primary efficacy surrogate endpoints for chemopreventive agent intervention trials.

Adenoma↗

PubMed1991

Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in a human myeloma cell line model.

In an effort to develop a clinically useful approach to overcoming P-glycoprotein-mediated multidrug resistance (MDR1), we evaluated combined chemosensitization with verapamil and quinine in a multidrug-resistant (MDR) human myeloma cell line model. In clonogenic assay, verapamil was used at concentrations from 0.1 to 1.0 micrograms/mL, bracketing the plasma levels achieved by oral administration and high-dose intravenous (IV) infusion, respectively. The dose of quinine was held constant at 1.0 micrograms/mL, a plasma concentration readily achieved by oral administration. At each dose level of verapamil tested, the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed. Verapamil at 0.1 microgram/mL combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1.0 micrograms/mL. Furthermore, the combination of 1.0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually (P less than .001) and inhibited drug efflux as effectively as verapamil alone at 10 mumols. Our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming MDR1 in patients with drug-refractory B-cell neoplasms such as multiple myeloma or non-Hodgkin's lymphomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Embryofetal effects of pentamidine isethionate administered to pregnant Sprague-Dawley rats.

The effects of pentamidine isethionate on the developing embryo and fetus have not been previously published. Pregnant Sprague-Dawley rats were given various doses of pentamidine during the period of embryogenesis. Animals were killed on days 18 to 20 of pregnancy and their fetuses were removed by hysterectomy. Autopsies were performed on all fetuses. There were significant differences among groups with regard to maternal weight gain and pregnancy resorption. More pregnancy resorptions were noted in the group that received normal human doses (4 mg/kg/day) of pentamidine than in the control group (p less than 0.05). One structural anomaly consisting of unilateral renal agenesis was noted in the 711 fetuses examined. Skeletal survey of fetal rats was unremarkable. Pentamidine was without teratogenic effects in rats when administered in doses similar to those recommended for adult humans; however, it appears to have an embryocidal effect when given in those same doses during embryogenesis.

Abnormalities, Drug-Induced↗

PubMed1990

Comparison of Biello, McNeil, and PIOPED criteria for the diagnosis of pulmonary emboli on lung scans.

The McNeil, Biello, and newly proposed PIOPED (from the National Institutes of Health-sponsored study, Prospective Investigation of Pulmonary Embolism Detection) interpretive methods for detection of pulmonary embolism on lung scans were compared in 96 patients who also underwent pulmonary angiography. Segmental findings on 99mTc perfusion and aerosol ventilation scans, chest radiographs, and pulmonary angiograms obtained within 48 hr of each other were encoded along with other information into a data base to facilitate analysis. The McNeil, Biello, and PIOPED criteria were applied to the encoded data. Although the PIOPED set of criteria yielded the most favorable likelihood ratio for predicting an angiogram showing pulmonary emboli and a favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli, it had the highest number of indeterminate studies. The McNeil criteria demonstrated the least favorable likelihood for predicting pulmonary emboli on an angiogram. The Biello and McNeil criteria showed the most favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli. Analysis of receiver-operating-characteristic (ROC) curves yielded the greatest area under the ROC curve for the Biello criteria, but there were no statistically significant differences among the three sets of criteria. This study suggests that the Biello scheme represents the best compromise of the sets of criteria studied.

Angiography↗

PubMed1988

Phase I clinical and pharmacokinetic study of mitoxantrone given to patients by intraperitoneal administration.

On the basis of its high degree of cytotoxicity against fresh human ovarian cancers and its relative lack of vesicant activity, mitoxantrone administered by the i.p. route was studied in a Phase I and pharmacokinetic trial. Thirty-three patients with good performance status and diagnoses of metastatic or recurrent ovarian (31 patients) and colon (two patients) cancers were treated with 12- to 38-mg/m2 doses, administered by the i.p. route every 4 wk for up to ten treatment courses. Mitoxantrone doses were escalated at 2- to 3-mg/m2 increments in groups of three to 11 patients. Thirty-eight mg/m2 (by i.p. dwell without removal) were considered the maximally tolerated dose in that, of eight treated patients, four experienced severe leukopenia and six experienced severe abdominal pain. Response to i.p. mitoxantrone was evaluable in 17 patients. None of seven patients with clinically measurable intraabdominal or pelvic tumor masses responded; however, in three (50%) of six patients with nonmeasurable disease, there was normalization of previously elevated serum CA-125 concentrations for 3, 17, and 24 mo. Additionally, two (50%) of four patients who underwent third-look laparotomies were found to have greater than 75% reductions in i.p. tumor masses with response lasting 24 and 25 mo. At 38 mg/m2, mitoxantrone was associated with a mean concentration.time product of 100 micrograms.h/ml in the i.p. space and of 0.071 micrograms.h/ml in plasma, yielding an i.p./plasma area under the curve ratio of 1408. We conclude that chemical peritonitis is the dose-limiting toxicity of i.p. administered mitoxantrone and that a dose of 23 mg/m2 every 3 to 4 wk should be used in future Phase II trials in ovarian cancer patients with minimal residual intraabdominal and pelvic disease following second-look laparotomy.

Adult↗

PubMed1988

Ornithine decarboxylase and polyamine levels in columnar upper gastrointestinal mucosae in patients with Barrett's esophagus.

Ornithine decarboxylase (ODC) activity was elevated in the premalignant metaplastic columnar epithelium (mean activity, 0.13 unit/mg protein, N = 18 individual samples from 18 patients), compared to either adjacent gastric (mean activity, 0.02 unit/mg protein, N = 9) or small intestinal (mean activity, 0.02 unit/mg protein, N = 9) epithelium in patients with Barrett's esophagus. Enzyme activity ranged from 0 (less than detectable) to more than 0.5 unit/mg protein in the metaplastic tissue. However, neither putrescine, spermidine, spermine (as individual parameters), nor total polyamine contents were related to ODC activity in the individual patient biopsies. Spermidine/spermine ratios ranged from 0.38 to 2.18 and were also not related to enzyme activity in any apparent manner. Nevertheless, cell strains derived from the metaplastic tissue were growth inhibited by alpha-difluoromethylornithine, an enzyme-activated, suicide inhibitor of ODC. In two different cell strains derived from Barrett's epithelium, growth was affected with drug concentrations as low as 0.05 mM. While the mechanism responsible for the elevation in enzyme activity is unknown, the regulation of polyamine metabolism appears to be altered in this premalignant tissue. The growth inhibition of Barrett's epithelium-derived cell lines by ODC inhibitors suggests a potential role for these compounds in the treatment of this disease.

Barrett Esophagus↗

PubMed1988

Thermal dose-response of magnetic-induction thermoradiotherapy.

Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.

Combined Modality Therapy↗