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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 199 records · Page 11Linked to original sources
PubMed1997

Prevalence of elevated anticardiolipin antibodies in pregnant women with unexplained elevations of alpha-fetoprotein.

The goal was to determine what proportion of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) have increased levels of anticardiolipin antibodies (ACA), and if this might explain the increased prevalence of adverse pregnancy outcomes. Maternal serum alpha-fetoprotein levels of 12,295 pregnant women were evaluated at 15-19.5 gestational weeks. Elevated readings (> 2.5 MOM) were identified in 190 women (1.5%) and 86 (0.7%) of these had unexplained causes. Specimens (80) were recovered and ACA levels for cardiolipin were determined using enzyme-linked immunosorbant assay. Positive IgG ACA were identified in 10 out of 80 cases (12.5%) of elevated MSAFP; 3 out of 80 cases (3.8%) had positive IgM ACA. The control women with normal MSAFP levels had positive IgG ACA in 3 of 86 cases (3.5%) and 1 of 86 cases (1.2%) for IgM. Women with increased MSAFP and positive ACA had infants with an average birth weight of 2684 +/- 889 g compared to 2793 +/- 847 g in women with increased MSAFP and normal ACA. No significant differences in IgG ACA were found in pregnant women with unexplained elevated MSAFP (10/80, 12.5%) compared to women with normal MSAFP (3/86, 3.5%). As expected, lower birth weight was identified in women who had elevated MSAFP (2738 +/- 868 g) vs. women with normal MSAFP 3181 +/- 1082 g (P = 0.004), independent of ACA positivity.

Adolescent↗
PubMed1997

Mohs micrographic surgery for the treatment of primary cutaneous melanoma.

BACKGROUND: Mohs micrographic surgery is thought to be a useful therapy for cutaneous melanoma. Controversy persists, however, because there are few published reports that document its safety and efficacy. OBJECTIVE: Our purpose was to determine the safety and efficacy of Mohs micrographic surgery for the treatment of cutaneous melanoma. METHODS: A consecutive sample of 535 patients referred for treatment of 553 primary cutaneous melanomas was entered into the study. Of this sample, 99.5% of patients completed their first 5 years of follow-up. All melanomas were excised by means of fresh-tissue Mohs micrographic surgery with frozen-section examination of the margin. The 5-year Kaplan-Meier melanoma mortality, metastasis, and local recurrence rates were compared with historical control cases. RESULTS: Mohs micrographic surgery provided 5-year survival and metastatic rates equivalent to or better than historical controls that were treated by standard wide-margin surgery. Satellite metastases were not more common with the narrow margins used with Mohs micrographic surgery. Local recurrences from inadequate excision of the primary tumor were infrequent (0.5%). The majority of melanomas were successfully excised with a narrow margin (83% were excised with a 6 mm margin). CONCLUSION: Mohs micrographic surgery is an effective therapy for primary cutaneous melanoma. It may be particularly useful to conserve tissue for melanomas on the head, neck, hands, or feet or for melanomas with indistinct clinical margins.

Female↗
PubMed1997

Partially mismatched blood cell transplants for high-risk hematologic malignancy.

Eleven patients with high-risk hematologic malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from partially mismatched family members in whom progenitor cells had been mobilized by G-CSF. Donors were mismatched by up to one antigen in the GVH direction and up to three antigens in the rejection direction. Outcomes were compared with those of 22 patients receiving BCT from fully matched donors. Two mismatched patients died without engraftment on day 21 and 32. One had rejected bone marrow from the same donor, the other was mismatched by two antigens in the rejection direction and received the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5 (range 16-33) days for the mismatched group compared with 16 (11-28) days for the matched group (P = 0.01). No correlation was found between CD34+ cell dose and time to granulocyte or platelet recovery. In the mismatched and matched BCT groups respectively, the risk of grade II-IV acute graft-versus-host disease (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in the matched group and no correlation was found. One of 11 mismatched patients and eight of 22 matched patients had relapse or persistent disease. Disease-free survival at 1 year was similar at 55% for mismatched and 50% for matched BCT. These results indicate that allogeneic BCT from partially mismatched family members is accompanied by a high incidence of GVHD but may result in comparable survival to BCT from fully matched donors.

Adolescent↗
PubMed1997

Factors influencing yields of progenitor cells for allogeneic transplantation: optimization of G-CSF dose, day of collection, and duration of leukapheresis.

Mobilization of hematopoietic progenitor cells by G-CSF was attempted on 89 occasions in 85 healthy donors. Three dose ranges of G-CSF were chosen for analysis: low (4-7.4 micrograms/kg), intermediate (7.5-10 micrograms/kg) and high (> 10 micrograms/kg). A target blood level for apheresis of 20 x 10(6)/L CD34+ cells was reached by day 3 in 75 patients (84%) and by day 4 in all but 1 (99%). Target yields above 2.5 x 10(6)/kg for 75 unmanipulated transplants were exceeded in a single collection in 73 donors (97%). Correlation of CD34+ cell yields to blood CD34+ cell level before leukapheresis was moderate only (r2 = 0.32). There was close linear correlation between processed volume and cumulative CD34+ cell yield, with a median r2 value of 0.98 (range 0.74-1.00). Yields of CD34+ cells achieved on day 3 were significantly lower after the high dose than after the intermediate G-CSF dose (21 +/- 3 versus 29 +/- 6 x 10(6)/L blood processed, p = 0.03). After the low dose of G-CSF, yields on day 4 were higher than on day 3 (48 +/- 10 versus 22 +/- 4 x 10(6)/L blood processed, p = 0.01). There was no difference between day 3 and day 4 yields with the intermediate G-CSF dose. In 73 of 93 (78%) leukaphereses, the CD34+ cell yield was more than 100% of the estimated intravascular CD34+ cells at the beginning of collection and ranged up to 342%. These data indicate that a daily dose of 7.5-10 micrograms/kg G-CSF, given as a multiple of 300 and 480 micrograms ampoules, is a convenient regimen giving adequate yields from a single collection on day 3 or 4 in most donors. Measuring blood CD34+ cell levels is of limited value in predicting yields, but monitoring CD34+ cell yields during leukapheresis may help to minimize unnecessary or inefficient collection.

Antigens, CD34↗
PubMed1997

Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections.

Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration. These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.

Acute Disease↗
PubMed1997

A controlled trial of light therapy for the treatment of pediatric seasonal affective disorder.

OBJECTIVE: To evaluate the efficacy of light therapy for the treatment of pediatric seasonal affective disorder (SAD). METHOD: 28 children (aged 7 to 17 years) at two geographically distinct sites were enrolled in a double-blind, placebo-controlled, crossover trial of bright-light treatment. Subjects initially entered a week-long baseline period during which they wore dark glasses for an hour a day. They were then randomly assigned to receive either active treatment (1 hour of bright-light therapy plus 2 hours of dawn simulation) or placebo (1 hour of clear goggles plus 5 minutes of low-intensity dawn simulation) for 1 week. The treatment phase was followed by a second dark-glasses phase lasting 1 to 2 weeks. After this phase, the children received the alternate treatment. Response was measured using the parent and child versions of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version (SIGH-SAD). RESULTS: Data were analyzed as change from baseline. SIGH-SAD-P total depression scores were significantly decreased from baseline during light therapy compared with placebo (one-way analysis of variance, rho = .009), and no differences were found between the placebo and control phases. Subscores of atypical and typical depression were also significantly decreased during the active treatment (rho = .004 and .028, respectively). A similar trend was noted with the SIGH-SAD-C, but this did not reach significance. At the end of the study, 78% of the parents questioned and 80% of the children questioned rated light therapy as the phase during which the child "felt best." CONCLUSION: Light therapy appears to be an effective treatment for pediatric SAD.

Adolescent↗
PubMed1997

Quantitative determination of theophylline by an automated chemiluminescent immunoassay in serum and plasma: comparison to other methods of analysis.

A chemiluminescent immunoassay for theophylline in serum or plasma was developed for the Ciba Corning ACS: 180 automated analyzer. The assay has a limit of quantitation of 0.2 microgram/ml, with a range up to 40 micrograms/ml. The cross-reactivity to metabolites 1,3-dimethyluric acid 3-methylxanthine was 3.4% and 2.5%, respectively. Overall means of 101.0% and 97.8% were determined from dilution linearity and addition studies, respectively. When compared to a high-performance liquid chromatography (HPLC) method, a linear regression of ACS Theophylline = 0.996 (HPLC) + 0.35, r = 0.991, n = 93, was obtained. Similar results were obtained when the ACS assay was compared to other immunoassays. Precision (within-run and total coefficient of variation or CV) was < 6% in the therapeutic range (10-20 micrograms/ml). The performance data demonstrate that the ACS Theophylline assay provides an additional choice for the clinical measurement of the drug.

Chromatography, High Pressure Liquid↗
PubMed1997

The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection.

Different patterns of viral replication correlate with the natural history of disease progression in humans and macaques infected with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), respectively. However, the viral and host factors influencing these patterns of viral replication in vivo are poorly understood. We intensively studied viral replication in macaques receiving identical inocula of SIV. Marked differences in viral replication patterns were apparent within the first week following inoculation, a time prior to the development of measurable specific immune effector responses to viral antigens. Plasma viral RNA levels measured on day 7 postinoculation correlated with levels measured in the postacute phase of infection. Differences in the susceptibility of host cells from different animals to in vitro SIV infection correlated with the permissiveness of the animals for early in vivo viral replication and hence with the postacute set point level of plasma viremia. These results suggest that host factors that exert their effects prior to full development of specific immune responses are critical in establishing the in vivo viral replication pattern and associated clinical course in subjects infected with SIV and, by extension, with HIV-1.

Animals↗
PubMed1997

A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.

An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and monocyte-derived macrophages and resisted neutralization by heterologous sera which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3 was infectious and induced AIDS when inoculated intravenously into pig-tailed macaques (Macaca nemestrina). Two of four infected macaques developed no measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV-induced meningoencephalitis by 14 and 33 weeks postinfection. The other two macaques developed antibodies reactive in Western blot and virus neutralization assays. One macaque was sacrificed at 1 year postinoculation, and the survivor has evidence of immunodeficiency, characterized by persistently low CD4 lymphocyte subsets in the peripheral blood. Plasma samples from these latter animals neutralized SIVsmE543-3 but with much lower efficiency than neutralization of other related SIV strains, confirming the difficulty by which this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a valuable reagent for studying SIV-induced encephalitis, mapping determinants of neutralization, and determining the in vivo significance of resistance to neutralization in vitro.

Amino Acid Sequence↗
PubMed1997

Obstructive lung disease deaths in the United States from 1979 through 1993. An analysis using multiple-cause mortality data.

We analyzed mortality trends among people who died with a diagnosis of obstructive lung disease from 1979 through 1993, using death certificate reports of 31,314,160 decedents in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics. Of all the decedents, 2,554,959 (8.2%) had a diagnosis of obstructive lung disease (ICD-9 490 to 493.9, 496) listed on their death certificates; of these 2,554,959 decedents, only 1,106,614 (43.3%) had obstructive lung disease listed as the underlying cause of death. The age-adjusted mortality rate increased 47.3%, from 52.6 per 100,000 in 1979 to 77.5 per 100,000 in 1993. The age-adjusted mortality rate increased 17.1% among men, from 96.3% per 100,000 in 1979 to 112.8 per 100,000 in 1993, whereas this rate increased 126.1% among women, from 24.5 per 100,000 in 1979 to 55.4 per 100,000 in 1993. Over the study period, white males had the highest mortality rates (98.8 to 115.5 per 100,000), followed by black males (77.5 to 100.2 per 100,000), males of other races (38.1 to 58.6 per 100,000), white females (25.5 to 57.7 per 100,000), black females (14.9 to 38.5 per 100,000), and females of other races (10.9 to 20.9 per 100,000). We conclude that mortality related to obstructive lung disease is under-estimated in studies that look at only the underlying cause of death. Mortality rates of obstructive lung disease are starting to stabilize among men, but continue to increase among women, reflecting historical smoking trends in these populations.

Adolescent↗
PubMed1997

Emerging diseases--what veterinarians need to know.

The recent increase in emerging diseases can be attributed to a number of factors, all of which relate to some form of alteration in the way etiologic agents move around. Some of these factors responsible for altered agent trafficking include actual transport to a susceptible population or new species, environmental disruption that facilitates exchange of microbes, and a husbandry change that promotes new ways for microbes to move around. Given the exponential growth of the human population and all the attendant implications, including the mobility of this population, the ecological disruption that is accompanying the overall increase, and the necessity of exploring new agricultural technologies to feed a burgeoning population, it is a certainty that altered agent trafficking will not only continue but will undoubtedly increase. Veterinarians should be aware of the role they will be expected to play in this field.

Acquired Immunodeficiency Syndrome↗
PubMed1997

When to say stop.

The decision to say stop is unequivocally one for the patient alone. The general practitioner's role is to ensure that the patient understands the problem as fully as possible and appreciates the various treatment options and all their ramifications.

Decision Making↗
PubMed1997

Salvage intraperitoneal therapy of advanced epithelial ovarian cancer: impact of retroperitoneal nodal disease.

PURPOSE: The objective of this study was to evaluate the impact of retroperitoneal lymph node disease on the efficacy of salvage intraperitoneal (IP) chemotherapy for advanced epithelial ovarian cancer. METHODS: We retrospectively reviewed the records of 41 patients with advanced epithelial ovarian cancer treated between 9/83-7/95, who had undergone retroperitoneal nodal sampling prior to salvage intraperitoneal chemotherapy. RESULTS: Of the 41 patients treated with debulking surgery and platinum-based chemotherapy, 19 (46%) had disease noted in retroperitoneal lymph nodes at initial surgery or at reassessment laparotomy, while 22 (54%) had biopsy-proven negative nodes. The mean age of the node-positive group was 49 years. Residual disease prior to initiation of IP therapy was optimal (< or = 2 cm) in 16 patients and suboptimal in 3. Twenty-two patients with a mean age of 55 were found to be node-negative. Residual disease prior to initiation of intraperitoneal therapy was optimal (< or = 2 cm) in all 22 patients. All patients received salvage intraperitoneal chemotherapy. With a median follow-up of 26 months since surgical reassessment, the median survival in the node-positive group is 31 months compared to 40 months for the node-negative group (p = 0.47). CONCLUSIONS: The presence of retroperitoneal nodal disease does not appear to be a contraindication to the use of salvage IP chemotherapy in advanced ovarian cancer.

Adult↗
PubMed1997

Mismatches for two major and one minor histocompatibility antigen correlate with a patient's rejection of a bone marrow graft from a serologically HLA-identical sibling.

We describe the case of a patient with chronic myeloid leukemia who rejected a bone marrow (BM) graft from a sibling donor believed to be HLA identical. Sequencing of the HLA genes showed the mother to be heterozygous for two closely related HLA haplotypes that could not be resolved by serological typing. The donor and the recipient had each inherited a different maternal haplotype resulting in allelic mismatches for the HLA-B35 and the HLA-DR11 genes. T cell cytotoxicity directed towards the donor's B35 allele was detected in the patient, in addition to CTL specificity for an HLA-B7-restricted minor histocompatibility antigen carried by the donor, resulting in three histocompatibility mismatches between the BM donor and the recipient.

Adult↗
PubMed1996

Clinical presentations of major depression by African Americans and whites in primary medical care practice.

This study compared the psychiatric history and presenting clinical characteristics of 119 African American and 153 white patients assessed for and participating in a randomized control trial of treatments for major depression in primary care practice. African Americans and whites participated equally in the assessment process, and both groups presented with similar psychiatric treatment histories, severity of depression, level of psychosocial functioning, and severity of medical illness. However, racial differences were evident in the comorbidity of psychiatric disorders, severity of somatic symptoms, self-reported physical functioning, life stress, and health beliefs. Implications for the recognition of depression in African American primary care patients are discussed.

Adolescent↗
PubMed1996

Phosphorylation and activation of p42 and p44 mitogen-activated protein kinase are required for the P2 purinoceptor stimulation of endothelial prostacyclin production.

Extracellular ATP and ADP, released from platelets and other sites stimulate the endothelial production of prostacyclin (PGI2) by acting on G-protein-coupled P2Y2 and P2Y2 purinoceptors, contributing to the maintenance of a non-thrombogenic surface. The mechanism, widely described as being dependent on elevated cytosolic [Ca2+], also requires protein tyrosine phosphorylation. Here we show that activation of both these P2 receptor types leads to the tyrosine phosphorylation and activation of both the p42 and p44 forms of mitogen-activated protein kinase (MAPK). 2-Methylthio-ATP and UTP, selectively activating P2Y1 and P2Y2 purinoceptors respectively, and ATP, a non-selective agonist at these two receptors, stimulate the tyrosine phosphorylation of both p42mapk and p44mapk, as revealed by Western blots with an antiserum specific for the tyrosine-phosphorylated forms of the enzymes. By using separation on Resource Q columns, peptide kinase activity associated with the phosphorylated MAPK enzymes distributes into two peaks, one mainly p42mapk and one mainly p44mapk, both of which are stimulated by ATP with respect to kinase activity and phospho-MAPK immunoreactivity. Stimulation of P2Y1 or P2Y2 purinoceptors leads to a severalfold increase in PGI2 efflux; this was blocked in a dose-dependent manner by the selective MAPK kinase inhibitor PD98059. This drug also blocked the agonist-stimulated increase in phospho-MAPK immunoreactivity for both p42mapk and p44mapk but left the phospholipase C response to P2 agonists essentially unchanged. Olomoucine has been reported to inhibit p44mapk activity. Here we show that in the same concentration range olomoucine inhibits activity in both peaks from the Resource Q column and also the agonist stimulation of 6-keto-PGF1, but has no effect on agonist-stimulated phospho-MAPK immunoreactivity. These results provide direct evidence for the involvement of p42 and p44 MAPK in the PGI2 response of intact endothelial cells: we have shown that both the endothelial P2Y purinoceptors are linked to activation of MAPK, and that activation of this pathway is a requirement for the stimulation by ATP/ADP of endothelial PGI2 production.

Adenosine Triphosphate↗
PubMed1996

Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells.

Osteoclastogenesis is a complex process that is facilitated by bone marrow stromal cells (SCs). To determine if SCs are an absolute requirement for the differentiation of human hematopoietic precursors into fully mature, osteoclasts (OCs), CD34+ cells were mobilized into the peripheral circulation with granulocyte colony-stimulating factor, harvested by leukapheresis, and purified by magnetic-activated cell sorting. This procedure yields a population of CD34+ cells that does not contain SC precursors, as assessed by the lack of expression of the SC antigen Stro-1, and that differentiates only into hematopoietic cells. We found that CD34+, Stro-1- cells cultured with a combination of granulocyte/macrophage colony-stimulating factor, interleukin 1, and interleukin 3 generated cells that fulfill current criteria for the characterization of OCs, including multinucleation, presence of tartrate-resistant acid phosphatase, and expression of the calcitonin and vitronectin receptors and of pp60c-src tyrosine kinase. These OCs also expressed mRNA for the noninserted isoform of the calcitonin receptor and excavated characteristic resorption pits in devitalized bone slices. These data demonstrate that accessory SCs are not essential for human osteoclastogenesis and that granulocyte colony-stimulating factor treatment mobilizes OC precursors into the peripheral circulation.

Acid Phosphatase↗