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C Brown

Publications and source records attributed to C Brown.

At least 19 recordsLinked to original sources
PubMed1999

Methods for evaluating treatment of uroliths.

Formation of uroliths is not a disease but rather a complication of several disorders. Some disorders can be identified and corrected (e.g., infection-induced struvite urolith formation), and some can be identified but not corrected (e.g., hyperuricosuria occurring in Dalmatians that form ammonium urate uroliths), although for others, the underlying etiopathogenesis is not known (e.g., calcium oxalate urolith formation in Miniature Schnauzers). A common denominator of these disorders is that from time to time, they can create oversaturation of urine with one or more crystal precursors, resulting in formation of crystals. To develop rational and effective approaches to treatment, abnormalities that promote urolith formation must be identified with the goal of eliminating or modifying them. It is therefore important to understand several basic concepts associated with urolithiasis.

Animals↗
PubMed1999

Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma.

The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1DH12, is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1DH12-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding.

Animals↗
PubMed1999

Injuries of the gastrointestinal tract from blunt trauma in children: a 12-year experience at a designated pediatric trauma center.

INTRODUCTION: Nonoperative management of solid organ injury from blunt trauma in children has focused concern on potential delays in diagnosis of hollow viscus injury with resultant increases in morbidity, mortality, and cost. This study of a large pediatric trauma database will review the issues of difficulty and/or delay in diagnosis as it relates specifically to definitive treatment and outcome. METHODS: We surveyed 11,592 consecutive admissions to a designated pediatric trauma center from 1985 to 1997 to identify children with documented injury of the gastrointestinal (GI) tract from blunt trauma. The records were extensively analyzed specifically in regard to mechanism of injury, type and site of injury, time to diagnosis, operative treatment, complications, and final outcome. RESULTS: The 79 children identified, 4 months to 17 years old, included 27 females and 52 males. Mechanism of injury included 15 restrained and 7 unrestrained passengers, 15 pedestrians, 15 child abuse victims, 10 bike handlebar intrusions, 8 discrete blows to the abdomen, 4 bike versus auto, 3 falls, and 2 crush injuries. There were 51 perforations, 6 avulsions, and 22 lesser injuries including contusions. Injury of the small bowel was most common, 44 cases, followed by the duodenum, 18 cases, colon, 17 cases, and stomach, 6 cases. In 45 children, diagnosis was made quickly by a combination of obvious clinical findings, plain x-ray and/or initial computed tomographic findings mandating urgent operative intervention. Diagnosis was delayed beyond 4 hours in 34 children, beyond 24 hours in 17 children and was made by persistent clinical suspicion, aided by delayed computed tomographic findings of bowel wall edema or unexplained fluid. The six deaths were caused by severe head injury. Complications included two delayed abscesses and two cases of intestinal obstruction. All 73 survivors left the hospital with normal bowel function. CONCLUSIONS: Injury to the GI tract from blunt trauma in children is uncommon (<1%). The majority of GI tract injuries (60%) are caused by a discrete point of energy transfer such as a seatbelt (19%), a handle bar (13%), or a blow from abuse (19%), or other blows and is unique to this population. Although diagnosis may be difficult and often delayed, this did not result in excessive morbidity or mortality. Safe and effective treatment of GI tract injuries is compatible with nonoperative management of most other injuries associated with blunt abdominal trauma in children, while reducing the risk of nontherapeutic laparotomy.

Adolescent↗
PubMed1999

Characterization of a novel simian immunodeficiency virus (SIV) from L'Hoest monkeys (Cercopithecus l'hoesti): implications for the origins of SIVmnd and other primate lentiviruses.

The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) appear to have originated by cross-species transmission of simian immunodeficiency virus (SIV) from asymptomatically infected African primates. Few of the SIVs characterized to date efficiently infect human primary lymphocytes. Interesting, two of the three identified to infect such cultures (SIVsm and SIVcpz) have appeared in human populations as genetically related HIVs. In the present study, we characterized a novel SIV isolate from an East African monkey of the Cercopithecus genus, the l'hoest monkey (C. l'hoesti), which we designated SIVlhoest. This SIV isolate efficiently infected both human and macaque lymphocytes and resulted in a persistent infection of macaques, characterized by high primary virus load and a progressive decline in circulating CD4 lymphocytes, consistent with progression to AIDS. Phylogenetic analyses showed that SIVlhoest is genetically distinct from other previously characterized primate lentiviruses but clusters in the same major lineage as SIV from mandrills (SIVmnd), a West African primate species. Given the geographic distance between the ranges of l'hoest monkeys and mandrills, this may indicate that SIVmnd arose through cross-species transmission from close relatives of l'hoest monkeys that are sympatric with mandrills. These observations lend support to the hypothesis that the primate lentiviruses originated and coevolved within monkeys of the Cercopithecus genus. Regarded in this light, lentivirus infections of primates not belonging to the Cercopithecus genus may have resulted from cross-species transmission in the not-too-distant past.

Amino Acid Sequence↗
PubMed1999

Anxiety disorders among African-American and white primary medical care patients.

The prevalence of current anxiety disorders and associated clinical patterns was examined in a sample of 125 African American and 120 white primary medical care patients between ages 18 and 64. Patients who indicated they had at least one mood or anxiety symptom in response to a screening questionnaire were interviewed to determine the presence of a DSM-IV anxiety, mood, or possible alcohol abuse disorder. Demographic data and data on mental- and physical-health-related functioning and health service utilization were also collected. The authors found no racial differences in the proportions of patients who met DSM-IV criteria for the disorders, nor in their symptom patterns, level of functional disability, or rates of health and mental health service utilization.

Adult↗
PubMed1999

Pathogenesis of Newcastle disease in chickens experimentally infected with viruses of different virulence.

Groups of 4-week-old White Rock chickens were inoculated intraconjunctivally with nine isolates of Newcastle disease virus representing all pathotypes. Birds were monitored clinically and euthanatized sequentially, with collection of tissues for histopathologic examination and in situ hybridization using an anti-sense digoxigenin-labeled riboprobe corresponding to the sequence of the gene coding for the matrix protein. Disease was most severe with velogenic viscerotropic pathotypes and was characterized by acute systemic illness with extensive necrosis of lymphoid areas in the spleen and intestine. Viral nucleic acid was detected in multiple tissues but most prominently in macrophages associated with lymphoid tissue. Velogenic neurotropic isolates caused central nervous system disease despite minimal amounts of viral nucleic acid detected in neural tissue. Mesogenic and lentogenic pathotypes caused no overt disease; however, viral nucleic acid was present in myocardium and air sac epithelium following infection with these isolates. Compromise of air sac and myocardium may predispose mesogen- and lentogen-infected chickens to secondary infection and/or decreased meat and egg production.

Air Sacs↗
PubMed1998

High-level expression of secreted glycoproteins in transformed lepidopteran insect cells using a novel expression vector.

An expression cassette for continuous high-level expression of secreted glycoproteins by transformed lepidopteran insect cells has been developed as an alternative to baculovirus and mammalian cell expression systems. The expression cassette utilizes the promoter of the silkmoth cytoplasmic actin gene to drive expression from foreign gene sequences, and also contains the ie-1 transactivator gene and the HR3 enhancer region of BmNPV to stimulate gene expression. Using an antibiotic-resistance selection scheme, we have cloned a Bm5 (silkmoth) cell line overexpressing the secreted glycoprotein juvenile hormone esterase (JHE-KK) at levels of 190 mg/L in batch suspension cultures. A baculovirus (AcNPV) expressing the same gene under the control of the p10 promoter of AcNPV produced only 4 mg/L active JHE in static cultures of infected Sf21 cells. A cloned Bm5 cell line overexpressing a soluble isoform of the alpha-subunit of the granulocyte-macrophage colony stimulating factor receptor (solGMRalpha) was also generated and produced five times more solGMRalpha in static cultures than a cloned BHK cell line obtained by transformation with a recombinant expression cassette utilizing the human cytomegalovirus (CMV) enhancer-promoter system. Finally, we show that recombinant protein expression levels in transformed Bm5 cells remain high in serum-free media, that expression is stable even in the absence of antibiotic selection, and that lepidopteran cells other than Bm5 may be used equally efficiently with this new expression cassette for producing recombinant proteins.

Animals↗
PubMed1998

Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D.

Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus. On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism. The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D. Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.

Animals↗
PubMed1998

Prevention of allogeneic fetal rejection by tryptophan catabolism.

In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation. Rapid T cell-induced rejection of all allogeneic concepti occurred when pregnant mice were treated with a pharmacologic inhibitor of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme expressed by trophoblasts and macrophages. Thus, by catabolizing tryptophan, the mammalian conceptus suppresses T cell activity and defends itself against rejection.

Animals↗
PubMed1998

Randomised controlled trial of the READER method of critical appraisal in general practice.

OBJECTIVE: To evaluate the READER model for critical reading by comparing it with a free appraisal, and to explore what factors influence different components of the model. DESIGN: A randomised controlled trial in which two groups of general practitioners assessed three papers from the general practice section of the BMJ. SETTING: Northern Ireland. SUBJECTS: 243 general practitioners. MAIN OUTCOME MEASURES: Scores given using the READER model (Relevance, Education, Applicability, Discrimination, overall Evaluation) and scores given using a free appraisal for scientific quality and an overall total. RESULTS: The hierarchical order for the three papers was different for the two groups, according to the total scores. Participants using the READER method (intervention group) gave a significantly lower total score (P < or = 0.01) and a lower score for the scientific quality (P < or = 0.0001) for all three papers. Overall more than one in five (22%), and more men than women, read more than 5 articles a month (P < or = 0.05). Those who were trainers tended to read more articles (P < or = 0.05), and no trainers admitted to reading none. Overall, 58% (135/234) (68% (76/112) of the intervention group) believed that taking part in the exercise would encourage them to be more critical of published articles in the future (P < or = 0.01). CONCLUSION: Participants using the READER model gave a consistently lower overall score and applied a more appropriate appraisal to the methodology of the studies. The method was both accurate and repeatable. No intrinsic factors influenced the scores, so the model is appropriate for use by all general practitioners regardless of their seniority, location, teaching or training experience, and the number of articles they read regularly.

Education, Medical, Continuing↗
PubMed1998

Diagnosis and treatment of depression in primary medical care practice: the application of research findings to clinical practice.

Approximately 50% of persons experiencing clinical depression seek help for this disorder from their primary care physician. This pattern of help-seeking has stimulated interest in providing appropriate treatment for depressed primary medical care patients. While the efficacy of both psychotherapy and pharmacotherapy for depression have been demonstrated in the mental health specialty sector, current research endeavors to establish the effectiveness of such treatments when provided to primary medical care patients. We review and discuss the clinical, practical, and methodological issues pertaining to the transfer of depression research to routine primary care practice. Possible directions for future research which will inform the continued applicability of research findings to routine practice are discussed.

Delivery of Health Care↗
PubMed1998

Perseverative writing errors in a patient with Alzheimer's disease.

This study reports the writing performance of a dysgraphic patient with Alzheimer's disease and moderate dementia who frequently perseverated on strokes and letters. Letter formation errors were also frequently produced. Oral spelling was superior to written spelling. The habitual style of writing (cursive writing) was significantly more prone to perseverations than writing in uppercase letters, a form of writing less frequently used by the patient. Central (linguistic) spelling processes were relatively preserved. The pattern of preserved and impaired functions is consistent with impairment of the peripheral mechanism that generates the graphic motor patterns code. We suggest that damage to the peripheral orthographic mechanism may cause deficits in some patients with Alzheimer's disease.

Aged↗
PubMed1998

A phase II trial of intraperitoneal cisplatin and etoposide as consolidation therapy in patients with Stage II-IV epithelial ovarian cancer following negative surgical assessment.

PURPOSE: To determine the efficacy of three courses of intraperitoneal (i.p.) cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following pathologically negative second-look surgical reassessment for Stage IIC-IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between September 1988 and April 1996, 40 patients were treated with three cycles of i.p. CDDP (100 mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that of a group of 46 contemporaneous patients undergoing observation only. RESULTS: Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7), 3 (25), and not recorded (2); and residual disease at completion of initial surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46 patients who did not receive consolidation was 52 years (range, 27-80 years); stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5), 2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46 (54%) of those undergoing observation alone. Median disease-free survival (DFS) for the observed patients is 28.5 months and has not been reached in the consolidation group. Disease-free survival distribution between the two groups was compared using the log-rank test and was found to be significant (P = 0.03). Multivariate analysis revealed that the only significant predictor of improved DFS was protocol treatment (P < 0.01). CONCLUSION: Intraperitoneal consolidation with CDDP/VP-16 following negative second-look reassessment in patients with advanced EOC resulted in a significant increase in DFS compared to nonprotocol patients treated concurrently who underwent observation alone.

Adult↗
PubMed1998

Neoral induction in pediatric renal transplantation.

Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4-6 weeks, trough levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number of blood pressure medications was significantly higher in the Neoral group. At 5.5 +/- 1.1 months' followup, a single patient in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection. We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need to be adjusted accordingly.

Blood Pressure↗
PubMed1998

Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission.

Sexually transmitted diseases, genital ulcer disease, and progesterone therapy increase susceptibility to lentivirus transmission. Infection of cells by human immunodeficiency virus (HIV) is dependent on expression of specific chemokine receptors known to function as HIV co-receptors. Quantitative kinetic reverse transcription-polymerase chain reaction was developed to determine the in vivo expression levels of CCR5, CXCR4, CCR3, CCR2b, and the cytomegalovirus-encoded US28 in peripheral blood mononuclear cells and cervical biopsies from 12 women with and without sexually transmitted diseases, genital ulcer disease, and progesterone-predominant conditions. Our data indicate that CCR5 is the major HIV co-receptor expressed in the female genital tract, and CXCR4 is the predominantly expressed HIV co-receptor in peripheral blood. CCR5 mRNA expression in the ectocervix was 10-fold greater than CXCR4, 20-fold greater than CCR2b, and 100-fold greater than CCR3. In peripheral blood, CXCR4 expression was 1.5-fold greater than CCR5, 10-fold greater than CCR2b, and 15-fold greater than CCR3. US28 was not expressed in cervical tissue despite expression in peripheral blood mononuclear cells from five individuals. CCR5 was significantly increased (p < 0.02) in biopsies from women with sexually transmitted diseases and others who were progesterone predominant. In vitro studies demonstrate that progesterone increases CCR5, CXCR4, and CCR3 expression and decreases CCR2b expression in lymphocytes and monocytes/macrophages. Characterization of chemokine receptors at the tissue level provides important information in identifying host determinants of HIV-1 transmission.

Adult↗
PubMed1998

Thoracoscopic anterior spinal procedures in children.

METHODS: From February 1996 through July 1997, 20 patients were determined to be appropriate for a thoracoscopic approach for the anterior portion of their spinal surgery. Ages ranged from 8 to 17 years of age and weight from 20 to 70 kg. The diagnosis included severe idiopathic and neurogenic scoliosis or kyphosis (n = 20) and congenital hemivertebra (n = 4). The procedures performed included diskectomy and anterior release from two to nine vertebral levels, hemivertebrectomy, and epiphysiodesis. Four patients also had an open lumbar exposure and all had a posterior fusion. RESULTS: All procedures were completed successfully endoscopically. Surgical times for the thoracoscopic portion of the procedure averaged 106 minutes and total procedure times were comparable with the standard open technique. Three patients were extubated at the end of the procedure with the majority extubated on postoperative day 1. Average intensive care unit stay was 1.8 days, and chest tubes were removed between postoperative day 1 and 5 (average, 2.2 days). In follow-up, surgical correction was deemed to be acceptable and equivalent to open techniques in all cases. CONCLUSION: This technique has proven to be safe and effective in children and appears to be associated with less pain and morbidity as evidenced by earlier extubation and chest tube removal and shorter ICU stay.

Adolescent↗