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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 253 records · Page 14Linked to original sources
PubMed1996

Allogeneic blood cell transplants for haematological malignancy: preliminary comparison of outcomes with bone marrow transplantation.

Twenty-six patients with haematological malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from five- or six-antigen matched siblings in whom progenitor cells had been mobilized by G-CSF. Outcomes were compared with a historical control group of 26 BMT patients matched for age and disease status. Granulocyte counts recovered to 0.5 x 10(9)/l in a median of 16 days after BCT compared with 21.5 days after BMT (P = 0.0002). Platelet counts, unsupported for 3 days, reached 20 x 10(9)/l in a median of 14 days vs 20.5 days (P = 0.0003) after BCT compared with BMT in those patients who engrafted. In the BCT and BMT groups, respectively, the risk of grade II-IV acute GVHD was 37 vs 21% (P = 0.16) and of chronic GVHD at 1 year 53 vs 48% (P = 0.9). There was no significant difference in red cell transfusions but BCT patients required fewer platelet transfusions (median 3 vs 5, P = 0.015) and fewer days in hospital (20.5 vs 25, P = 0.02). These results indicate that allogeneic BCT from matched and partially mismatched family donors result in faster engraftment than BMT without a significant increase in GVHD. Allogeneic BCT may prove to be a more tolerable procedure than BMT for both donor and recipient and there are indications of improved cost-effectiveness.

Adolescent↗
PubMed1996

High-dose melphalan +/- total body irradiation and autologous hematopoietic stem cell rescue for adult patients with Ewing's sarcoma or peripheral neuroectodermal tumor.

The role of high-dose therapy and autologous stem cell transplantation (ASCT) in the treatment of patients with Ewing's sarcoma (EWS) remains uncertain. From November 1985 to September 1994, 13 patients aged 16-30 years (median 20.5) received high-dose melphalan (HDM) 140-200 mg/m2 +/- 500 cGy TBI followed by ASCT for relapsed/refractory (n = 4), metastatic (n = 2), or non-metastatic (n = 6) EWS, or for peripheral neuroectodermal tumor (PNET) (n = 1). This regimen was well tolerated with no transplant-related mortality and no toxicity requiring life sustaining measures. Three of the four patients treated for relapsed/refractory EWS had progression-free survivals (PFS) less than 5 months. The only long-term survivor of these four patients received HDM while in complete remission following pulmonary irradiation. Both patients with pulmonary metastases at presentation died just 5 and 6 months post-ASCT. All four patients with non-metastatic, bulky (> 8 cm) osseous EWS progressed at a median of 11 months (range 7-22 months) while the two patients with non-bulky EWS remain progression-free 25+ and 28+ months post-HDM/TBI + ASCT. The 19-year-old patient with a PNET of the thoracoabdominal wall relapsed 4 months post-ASCT. Overall, only three of these 13 patients remain progression-free at 25+, 28+, and 108+ months following HDM +/- TBI and ASCT. In conclusion, HDM +/- TBI did not obviously improve the outcome of these 13 patients relative to that expected following conventional dose therapy alone.

Adolescent↗
PubMed1996

Second allogeneic transplants for leukemia using blood instead of bone marrow as a source of hemopoietic cells.

There is increasing interest in blood cell transplants (BCT) from normal donors as an alternative to BMT. Ten patients with relapsed or persistent leukemia after BMT received intensive cytotoxic conditioning followed by allogeneic BCT. Three BCT were from single-antigen mismatched donors; two of the corresponding recipients had rejected a BMT from the same donor. Two patients received BCT from a different donor (one matched, one single-antigen mismatched). The other six BCT were from the same, fully matched, bone marrow donors. Donors were given G-CSF to mobilize progenitor cells which were collected by a single 2-4 h leukapheresis. Methotrexate, CsA and folinic acid were used for GVHD prophylaxis for all transplants but CsA was discontinued sooner after BCT than after BMT. One patient died without engraftment having rejected a BMT from the same single-antigen mismatched donor 4 years previously. Nine patients had granulocyte recovery at a median of 14 days, up to 6 days faster than with their previous BMT. Platelet recovery was also 2-6 days faster than with BMT in four previously engrafting patients. Four patients died without platelet recovery after BCT within a year of BMT, three of treatment-related toxicity and one of relapse. Two patients developed grade II acute GVHD. Of six patients given BCT more than a year from BMT, four, all with acute leukemia, survive 7, 14, 29 and 29 months after BCT and one relapsed at 7 months. All four survivors developed chronic GVHD. These results indicate that BCT may be useful therapy for relapse occurring more than a year after BMT.

Adolescent↗
PubMed1996

Sertraline in the treatment of premenstrual dysphoric disorder.

It is estimated that 2 to 9 percent of women suffer from premenstrual dysphoric disorder (PMDD). Despite decades of research, effective treatments for the condition have eluded investigators. Research criteria for (PMDD) were established to promote investigation into the treatment and psychobiology of severe, dysphoric premenstrual symptomatology. Application of these new criteria to clinical trials adds needed rigor to research in this area and justifies the identification of effective treatments. In this study, rigorous criteria were utilized in a 12-center trial investigating the efficacy of the serotonin reuptake inhibitor sertraline in the treatment of PMDD. The study was completed and data was available for 162 women. A preliminary analysis demonstrated a positive response (very much improved or much improved) in 68 percent of patients treated with sertraline, compared with only 40 percent of patients treated with placebo (p < .01). This preliminary analysis provides strong support for the efficacy of sertraline as a treatment of severe premenstrual dysphoria.

1-Naphthylamine↗
PubMed1995

The cDNA sequence of human endothelial cell multimerin. A unique protein with RGDS, coiled-coil, and epidermal growth factor-like domains and a carboxyl terminus similar to the globular domain of complement C1q and collagens type VIII and X.

Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. Multimerin is composed of varying sized, disulfide-linked multimers, the smallest of which is a homotrimer. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. The cDNA for human multimerin was isolated from lambda gt11 endothelial cell libraries using antibodies, and the isolated cDNA clones were used to obtain the full sequence. The full-length multimerin cDNA was 4.2 kilobase pairs. Northern analyses identified a 4.7-kilobase transcript in cultured endothelial cells, a megakaryocytic cell line, platelets, and highly vascular tissues. The multimerin cDNA can encode a protein of 1228 amino acids with the probable signal peptide cleavage site between amino acids 19 and 20. The protein is predicted to be hydrophilic and to contain 23 N-glycosylation sites. The adhesive motif RGDS (Arg-Gly-Asp-Ser) and an epidermal growth factor-like domain were identified. Sequence searches indicated that multimerin is a unique protein. Analyses identified probable coiled-coil structures in the central portion of the multimerin sequence. Additionally, the carboxyl-terminal region of multimerin resembles the globular, non-collagen-like, carboxyl-terminal domains of several other trimeric proteins, including complement C1q and collagens type VIII and X.

Amino Acid Sequence↗
PubMed1995

Human T-cell lymphotropic virus type I and severe neoplasia of the cervix in Jamaica.

Human T-cell lymphotropic virus type I (HTLV-I) was associated with carcinoma of the cervix in Japan in a recent study that compared hospital cases with healthy population-based controls. To test this relationship in women more alike for cervical neoplasia risk factors (including sexual behavior and human papilloma virus; HPV), we enrolled consecutive patients from a colposcopy clinic in Kingston, Jamaica (an HTLV-I endemic area). Patients underwent Pap smear, colposcopy, biopsy and cervical swab for detection of HPV by polymerase chain reaction. Cases were defined as women with CIN-3 or invasive cancer (CIN-3/CA). Controls included all patients with either CIN-I or koilocytotic atypia, atypical squamous cells of undetermined significance or benign cervical pathology (all but one had at least inflammatory changes). Patients with CIN-2 were excluded to minimize risk of case-control misclassification. Cases were much more likely to be HTLV-I seropositive than controls. Although mean age differed significantly between cases (mean age = 39 years) and controls (mean age = 33 years), control for age did not explain the relation of CIN-3/CA with HTLV-I. Among HPV DNA positive subjects the age-adjusted association was not diminished but lost statistical significance. HTLV-I seroprevalence may be independently associated with progression to severe neoplasia of the cervix.

Adult↗
PubMed1995

Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months.

BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.

AIDS-Related Opportunistic Infections↗
PubMed1995

Sodium pentobarbital versus alpha-chloralose anesthesia. Experimental production of substantially different slopes in the transmural CP/ATP ratios within the left ventricle of the canine myocardium.

BACKGROUND: Transmural analyses of the creatine phosphate (CP)/ATP ratio in various lamina of the canine myocardium have previously revealed significant variations in the CP/ATP ratio, with the subendocardial layer displaying a decreased ratio relative to the subepicardial layer. Without exception, these results were obtained under sodium pentobarbital anesthesia. These findings have been interpreted to imply that the normal endocardium may be operating in the oxygen-limited domain or that there are transmurally varying set points for the regulation of oxidative phosphorylation. METHODS AND RESULTS: In this work, we examine the effect of the anesthetic regimen on the transmural CP/ATP ratio within the left ventricular wall of the canine myocardium using spatially localized 31P-nuclear magnetic resonance (NMR) and an open-chest model. Two anesthetics were compared, alpha-chloralose and sodium pentobarbital. Under sodium pentobarbital, the CP/ATP ratio ranged from 1.92 +/- 0.06 to 2.51 +/- 0.08 from endocardium to epicardium, resulting in a transmural slope in the CP/ATP ratio of 0.149 +/- 0.047 (n = 22). Under alpha-chloralose, CP/ATP ratios ranged from 2.18 +/- 0.05 to 2.32 +/- 0.06, with a transmural slope of 0.035 +/- 0.018 (n = 38). Thus, the transmural slope in CP/ATP ratio was nearly four times greater with sodium pentobarbital than with alpha-chloralose, and the difference in these slopes was statistically significant (P = .029). No difference was observed in average CP/ATP obtained from the entire wall with either anesthetic. CONCLUSIONS: These results demonstrate that the transmural trend in CP/ATP ratio previously reported in the myocardium is likely to be a direct reflection of the sodium pentobarbital anesthetic regimen, not truly reflecting the trend in the normal unanesthetized animal. Moreover, since the transmural variation in CP/ATP ratio was greatly reduced with alpha-chloralose, it appears unlikely that the endocardium in the normal unanesthetized heart is operating in the oxygen-limited domain. These results also point to the importance of the anesthetic regimen in biochemical analysis, indicate the necessity of increased caution in directly translating results obtained under anesthesia, and demonstrate the unique power of in vivo NMR to extract such subtle biochemical information.

Adenosine Triphosphate↗
PubMed1995

Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings.

OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. RESULTS: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia.

Adolescent↗
PubMed1995

The relation of body size to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States).

We analyzed data from a cross-sectional study of 107 premenopausal women to evaluate the relations of height, weight, and body mass index (BMI) with plasma hormone levels. Participants were 20- to 40-year old women residing in Maryland (United States), whose reported menstrual cycle lengths were not more than 35 days and whose measured weights for height were 85 to 130 percent of 'desirable' based on 1983 Metropolitan Life Insurance tables. Fasting blood specimens were collected on each of days 5-7, 12-15, and 21-23 of every participant's menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Adjusted for age, taller women had significantly higher follicular-phase plasma-estradiol levels (percent difference/cm = 1.5, 95 percent confidence interval [CI] = 0.3-2.7, and heavier women had significantly lower plasma sex-hormone binding globulin (SHBG) levels averaged across the menstrual cycle phases (percent difference/kg = -1.2; CI = -1.9-(-0.6). Body weight within the range studied, however, was not related significantly to the concentration of SHBG-bound estradiol during any phase of the menstrual cycle. The results of this cross-sectional study suggest a possible mechanism by which height may influence breast cancer risk.

Adult↗
PubMed1995

Nicotine self-administration in rats.

Considering the importance of self-administration models in determining mechanisms of drug maintained behavior, we attempted to replicate the findings of nicotine self-administration by Corrigall and Coen. Male, Sprague-Dawley rats, trained on food reinforcement, acquired relatively high and stable rates of self-administration of IV nicotine bitartrate (0.03 mg/kg, free base). Extinction and reacquisition followed substituting saline and then nicotine, respectively. Responses, infusions and intake decreased at 0.003 mg/kg, while intake increased at 0.06 mg/kg. This model of nicotine self-administration provides a reliable alternative to experimenter-administration models for examining the effects of nicotine.

Animals↗
PubMed1995

The efficacy of psychosocial treatments in primary care. A review of randomized clinical trials.

Depression and anxiety are the most common psychiatric disorders among ambulatory medical patients and are associated with significant functional disability. However, they remain underrecognized and/or inadequately treated. The AHCPR Depression Guideline Panel recently reviewed the efficacy of pharmacologic interventions for mood disorders in the primary care section, but there are as yet no comparable analyses of the efficacy of psychosocial interventions for primary care patients experiencing depression or anxiety. This review of randomized, controlled trials conducted in primary care settings generally supports the efficacy of psychosocial treatments (PSTs) provided to ambulatory medical patients with psychiatric disorders. However, methodologic deficiencies in these trials (i.e., diagnostic classification of study subjects, attrition patterns, and criteria for assessing treatment response) limit the generalizability of their findings to routine practice. Studies evaluating the effect of PSTs on health care cost and utilization found changes in physicians' prescribing practices, patients' use of psychotropic medication, and number of patient visits to primary care physicians. However, results varied across studies because of methodologic deficiencies similar to those noted previously. Suggestions are offered for improving the internal and external validity of randomized PST trials in primary care settings.

Anxiety Disorders↗
PubMed1995

Knee joint effusion and proprioception.

The purpose of this study was to examine the effects of excessive fluid in the knee joint on proprioception. Twenty healthy subjects with no knee pathology participated in this study. Subjects were randomly assigned to control and experimental groups. Baseline measurements of subjects performing a tracking task were then recorded. Specifically, one knee joint was moved passively by a dynamometer through a range of motion from approximately 90 degrees flexion to 10 degrees from full extension at a joint angular velocity of 60 degrees/sec. Subjects were blindfolded and required to track the passively moving joint as accurately as possible for a period of 1.25 minutes with the opposite limb. An electrogoniometer was used to monitor the motion of the active tracking limb. Ninety mL of a solution of saline and dextrose were injected into the knee joint cavity of the experimental subjects, and they repeated the tracking task. After a 5-minute rest, the control group subjects also repeated the task. The results indicated that the injection of fluid did not change the subjects' error in tracking the passively moving limb (p > 0.05). No change in the error associated with tracking was observed for the control group (p > 0.05). It is suggested that the effects of long-term effusions and the nature of the inflammatory fluid might be more responsible for the loss of proprioception observed in some clinical conditions.

Adult↗
PubMed1995

The construction and characterization of colanic acid deficient mutants in an extraintestinal isolate of Escherichia coli (O4/K54/H5).

Extraintestinal strains of Escherichia coli possess a variety of virulence factors that enable them to cause disease. These strains express a group 2 capsular polysaccharide which is important in the pathogenic process. Extraintestinal strains evaluated to date are also capable of producing the group 1 capsular polysaccharide colanic acid. The blood isolate CP9 (O4/K54/H5) constitutively produces the group 2, K54 capsule but can be induced to produce colanic acid. In this report we assess whether colanic acid contributes to the pathogenesis of this extraintestinal pathogen. CP9 and its derivatives that are deficient in their ability to produce colanic acid (TR94), the K54 group 2 capsule +/- colanic acid (CP9.137, TR1374) and the O4 specific antigen +/- colanic acid (CP921,CP925) were used to test whether the group 1 capsule colanic acid conferred protection against the bactericidal effects of serum and recombinant bactericidal/permeability-increasing protein (rBPI-23) in vitro. Additionally, CP9, CP9.137 and TR94 were evaluated in the rat granuloma pouch, an in vivo model for localized infection, and by intraperitoneal inoculation into mice, a systemic infection model. In summary, the inability of CP9 to produce colanic acid in the presence or absence of its K54 and O4 antigens had no effect on its ability to survive these host defenses in vitro and did not affect its virulence in these two in vivo models of infection.

Animals↗