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Biomedical subjects

D C Brown

Publications and source records attributed to D C Brown.

At least 55 records · Page 3Linked to original sources
PubMed1998

Implantable contact lens for moderate to high myopia: phase 1 FDA clinical study with 6 month follow-up.

PURPOSE: To assess the short-term safety and efficacy of the implantable contact lens (ICL) to treat moderate to high myopia. SETTING: Phase 1 U.S. Food and Drug Administration clinical study of the ICL conducted at four sites in the United States. METHODS: Ten patients with myopia of 7.00 diopters (D) or greater had implantation of a Staar Surgical ICL and were examined preoperatively (baseline) and 1 day, 1 week, and 1, 3, and 6 months postoperatively. Mean preoperative myopia was 7.75 D (range 7.25 to 9.37 D). RESULTS: Six months postoperatively, 5 of 10 eyes (50%) had an uncorrected visual acuity (UCVA) of 20/20 or better, and all eyes had a UCVA of 20/30 or better. All eyes had a best spectacle-corrected visual acuity (BSCVA) of 20/20 or better and 6 eyes (60%), of 20/15 or better. Six eyes (60%) had an improvement of one or more lines of BSCVA. Mean postoperative spherical equivalent was -0.025 D +/- 0.47 (SD). Eight eyes (80%) were within +/- 0.250 D of emmetropia, and all were within +/- 1.125 D. No intraoperative or postoperative complications or adverse reactions were observed. CONCLUSIONS: The results support the short-term safety, efficacy, and predictability of ICL implantation to treat moderate to high myopia.

Adult↗
PubMed1998

Unusual congenital portosystemic communication resulting from persistence of the extrahepatic umbilical vein.

An unusual congenital portosystemic shunt was identified in one dog and two cats with clinical signs and laboratory evidence of hepatic dysfunction. In all the animals, the abnormal vessel arose from the portal system between the left medial and quadrate liver lobes and travelled within the falciform fat, exiting the abdomen through the caudal ventral left diaphragm. The intrathoracic course of these vessels was not established. The anatomical location of this anomalous vessel may have hindered attempts at ultrasonographic identification since it was not visualised before surgery in any of the animals. In addition, while the anatomical location of the vessel may facilitate rapid identification and surgical attenuation, it could predispose the vessel to trauma during the coeliotomy approach. It is hypothesised that this form of portosystemic communication results from failure of a portion of the left umbilical vein to degenerate during embryogenesis. This is in contrast to other forms of congenital extrahepatic portosystemic shunt that are presumed to be developmental errors resulting in an abnormal communication between the embryonic vitelline and cardinal venous systems. The prognosis for animals with the vascular anomaly reported here is probably similar to that for animals with other forms of congenital portosystemic shunt.

Animals↗
PubMed1998

Correlation between longitudinal bone growth, growth hormone, and insulin-like growth factor-I in prepubertal dogs.

OBJECTIVE: To determine the association between longitudinal bone growth and concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in serum from prepubertal dogs. Animals-6 male 14-week-old German Shepherd Dogs. PROCEDURE: Blood was obtained every 30 minutes for 14 consecutive days. Concentrations of GH and IGF-I in serum were determined, using a canine-specific radioimmunoassay and conventional radioimmunoassay after acid-ethanol extraction, respectively. Simultaneous biplanar radiography was performed daily to measure bone growth. Spectral analysis was used to estimate specific features of GH secretion during an extended period. Multiple linear regression with different lag times between independent and dependent variables was used to determine the strongest predictors of bone growth. RESULTS: The power spectra of GH concentrations in serum had a primary peak at a frequency of 0.02 cycles/h or a periodicity of 50 h/cycle. A significant determinant of longitudinal bone growth was a lag time of 1 day in concentration of GH in serum. The relationship between IGF-I concentration in serum and bone growth was not significant. CONCLUSIONS: The primary frequency of GH secretion is outside the time frame of a single day and the concentration of GH in serum is a primary determinant of bone growth. CLINICAL RELEVANCE: A better understanding of the components of bone growth provide discernment to improved diagnosis and treatment of abnormal bone growth.

Animals↗
PubMed1997

Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2.

All-trans retinoic acid (tRA) is a potent differentiation agent that is effective therapy for acute promyelocytic leukemia (APL). However, 5% to 25% of patients develop retinoic acid syndrome, a potentially life-threatening complication in which the pathogenesis relates to adhesive alterations of APL cells. Therefore, we investigated the relationship between tRA-induced differentiation and the adhesive properties of APL cells. After confirming differentiation-related morphological changes of NB-4 cells in response to tRA, we showed that homotypic aggregation of NB-4 cells grown in tRA for 72 hours is dose-dependent with a median effective dose of approximately 50 nmol/L. Maximal aggregation occurred at mean and peak therapeutic serum concentrations (100 and 1,000 nmol/L, respectively). Aggregation also increased with the length of tRA exposure over 168 hours. Aggregation was inhibited by neutralizing antibodies against LFA-1 and ICAM-2. Notably, antibodies directed against VLA-4, other beta2 integrins (Mac-1 and p150), or other potential LFA-1 counterstructures that were expressed on the cell surface (ICAM-1 and ICAM-3) did not block aggregation. Aggregation occurred with similar kinetics regardless of the presence of phorbol ester or the "activating" monoclonal antibody (MoAb) KIM 185, suggesting that the avidity of LFA-1 is not modulated on NB-4 cells in a manner similar to other leukocytes. Consistent with the prompt clinical effectiveness of methyl prednisolone sodium succinate (MPSS) in retinoic acid syndrome, MPSS rapidly inhibited homotypic aggregation in a dose-dependent manner. Thus, tRA alters the adhesive properties of APL cells by inducing the expression of high-avidity beta2 integrins, aggregation is inhibited by LFA-1 and ICAM-2 MoAb, and tRA effects are rapidly reversible by MPSS. Taken together, our findings provide a clinically relevant system for study of LFA-1/ICAM-2 interaction and suggest a mechanism in part for retinoic acid syndrome and the effectiveness of MPSS in ameliorating retinoic acid syndrome.

Antibodies, Monoclonal↗
PubMed1997

Epidemiologic evaluation of postoperative wound infections in dogs and cats.

OBJECTIVE: To determine postoperative wound infection rates in dogs and cats for various wound contamination categories and to identify factors that influence postoperative wound infection rates. DESIGN: Epidemiologic study. SAMPLE POPULATION: 1,574 wounds in 1,255 dogs and cats. PROCEDURE: Information recorded included signalment, nutritional status, surgery duration, surgical procedures, wound contamination classification, interval from clipping until surgery, blood pressure values, active infection at a distant site, endocrinopathy, and administration of immunosuppressive medications or antibiotics. Relative risk, 95% confidence intervals, and multiple regression analyses were performed. RESULTS: Postoperative infection was evident in 86 of 1,574 (5.5%) wounds, including 54 of 1,146(4.7%) and 13 of 259 (5.0%) animals with clean and clean-contaminated wounds respectively, and 12 of 100 (12.0%) and 7 of 69 (10.1%) animals with contaminated and dirty wounds, respectively. Animals with clean wounds that received antibiotics other than as prescribed in our perioperative protocol had a higher infection rate than animals that did not receive antibiotics. Surgical sites clipped before anesthetic induction were 3 times more likely to become infected than sites clipped after induction. Risk of wound infection increased with increasing duration of surgery. CLINICAL IMPLICATIONS: Wound contamination categories had too much variation to make them useful for predicting animals that would develop wound infections. Surgical sites should be clipped immediately prior to surgery, and intraoperative time should be kept to a minimum. Unless indicated for other current active infection, prolonged use of antibiotics after surgery should be avoided in animals with clean wounds.

Age Factors↗
PubMed1997

IL-6 and TNFalpha expression in brains of twitcher, quaking and normal mice.

Cytokines have been postulated to play a pathogenic role in twitcher mice, which are an animal model of globoid cell leukodystrophy. In particular, TNFalpha promotes oligodendrocyte and myelin pathology, and IL-6 expression is induced in astrocyte and microglial cultures that have been incubated with TNFalpha or myelin debris, respectively. It is unknown whether these cytokines are expressed in twitcher mice. The objectives of the present study were to develop an immunohistochemical method to detect TNFalpha and IL-6 in the mouse CNS, and then utilize this method to identify the cell types expressing these cytokines, and their spatial distribution, in the brains of normal, twitcher and quaking mice. In normal mice, IL-6 was found in ependymal cells, Bergmann glia, in processes that were adjacent or attached to the ventricles or pial surface, and in lightly stained processes in white matter. These processes were identified to belong to astrocytes and microglia. IL-6 staining was dramatically increased in twitcher mice. Astrocytes, with reactive features, and microglia were labeled in the cerebral cortex, basal ganglia, subcortical white matter, pons, medulla and cerebellar white matter. IL-6-positive reactive astrocytes were less abundant in quaking mice than twitcher mice. Cells expressing TNFalpha were rare or absent in normal and quaking mice. In twitcher mice, TNFalpha-positive macrophages were present at a lower concentration in cerebral white matter than in the pons and medulla, which have more advanced demyelination. These data demonstrate that pathological events induce the expressions of TNFalpha and IL-6 in the CNS of twitcher mice.

Animals↗
PubMed1997

Assessment of health risks due to hazardous air pollutant emissions from electric utilities.

Hazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environmental and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.

Air Pollutants↗
PubMed1996

Ability of 5-HT4 receptor ligands to modulate rat striatal dopamine release in vitro and in vivo.

1. The ability of 5-HT4 (5-hydroxytryptamine4) receptor ligands to modify dopamine release from rat striatal slices in vitro and in the striatum of freely moving rats was assessed by the microdialysis technique. 2. The release of dopamine from slices of rat striatum continually perfused with Krebs buffer was enhanced by 5-HT4 receptor agonists; 5-HT (10 microM), 5-methoxytryptamine (5-MeOT; 10 microM), renzapride (10 microM) and (S)-zacopride (10 microM) maximally increased dopamine release by 133 +/- 5, 214 +/- 25, 232 +/- 29 and 264 +/- 69%, respectively (mean +/- s.e.mean, n = 3-8). The drug-induced responses were maximal within the first 2 min of drug application, and subsequently declined. The non-selective 5-HT3/5-HT4 receptor antagonist, SDZ205-557 (10 microM), failed to modify basal dopamine release from striatal slices but completely antagonized the (S)-zacopride (10 microM)-induced increase in dopamine release. 3. To allow faster drug application, the modulation of dopamine release from rat striatal slices in a static release preparation was also investigated. The 5-HT4 receptor agonist, renzapride (10 microM) also enhanced dopamine release in this preparation (maximal increase = 214 +/- 35%, mean +/- s.e.mean, n = 14), whilst a lower concentration of renzapride (3 microM) was less effective. The renzapride-induced response was maximal within the first 2 min of drug application, before declining. In this preparation, the stimulation of dopamine release by renzapride (10 microM), was completely antagonized by the selective 5-HT4 receptor antagonist, GR113808 (100 nM). In addition, both the Na+ channel blocker, tetrodotoxin (100 nM) and the non-selective protein kinase A inhibitor, H7 (100 nM) completely prevented the stimulation of dopamine release induced by renzapride (10 microM). 4. In vivo microdialysis studies demonstrated that the 5-HT4 receptor agonists, 5-MeOT (10 microM), renzapride (100 microM) and (S)-zacopride (100 microM) maximally elevated extracellular levels of dopamine in the striatum by 220 +/- 20, 161 +/- 10 and 189 +/- 53%, respectively (mean +/- s.e.mean, n = 5-9). A lower concentration of renzapride (10 microM) was less effective. The elevation of extracellular striatal dopamine levels induced by either renzapride (100 microM) or (S)-zacopride (100 microM) were completely antagonized by the non-selective 5-HT4 receptor antagonist, SDZ205-557 (100 microM). In addition, the elevation of extracellular levels of dopamine induced by either 5-MeOT (10 microM) or renzapride (100 microM) was completely prevented by the selective 5-HT4 receptor antagonist, GR113808 (1 microM) and the renzapride (100 microM)-induced response was also completely prevented by the non-selective protein kinase A inhibitor, H7 (1 microM). In this in vivo preparation, both GR113808 (1 microM) and H7 (1 microM), when perfused alone, reduced extracellular levels of dopamine. 5. In conclusion, the present study provides evidence that the 5-HT4 receptor facilitates rat striatal dopamine release in vitro and in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Ability of angiotensin II to modulate striatal dopamine release via the AT1 receptor in vitro and in vivo.

1. The ability of angiotensin II to modulate dopamine release from rat striatal slices in vitro and in the intact rat striatum in vivo was assessed by the microdialysis technique. 2. In slices of rat striatum, angiotensin II (0.1-1.0 microM) induced a concentration-related increase in endogenous dopamine release which was maximal (approximately 250% above basal levels) within the first 2-4 min of agonist application and subsequently declined to near basal values. The angiotensin II-induced increase in dopamine release was Ca(2+)-dependent and was completely antagonized by the selective AT1 receptor antagonist, losartan (1.0 microM). In contrast, the AT2 receptor antagonist, PD123177 (1.0 microM) failed to modify the angiotensin II-induced response. Neither antagonist alone modified basal dopamine release from striatal slices. 3. In freely moving rats, angiotensin II (1.0-10 microM; administered via the microdialysis probe) induced a concentration-related increase in extracellular levels of dopamine which was maximal (approximately 150% above basal levels) within 20-40 min of agonist application and subsequently declined. The angiotensin II (10 microM)-induced increase in extracellular levels of dopamine was completely antagonized by the AT1 receptor antagonist, losartan (0.1-1.0 microM; administered via the microdialysis probe) but not by the AT2 receptor antagonist, PD123177 (1.0 microM; administered via the microdialysis probe). Neither antagonist alone modified basal extracellular levels of dopamine. 4. Homogenate radioligand binding studies with [125I]-angiotensin II (0.1 nm) identified relatively low levels of specific binding sites in rat striatal homogenates compared to homogenates of pyriform cortex (51.3 +/- 9.2 and 651.3 +/- 55.1 fmol g-1 wet weight, respectively, mean +/- s.e.mean, n = 3; non-specific binding defined by unlabelled angiotensin II). The majority of the specific [125I]-angiotensin II (0.1 nM) binding in the striatal and pyriform cortex homogenates was sensitive to the selective AT1 receptor antagonist, losartan (1.0 microM). 5. In conclusions the present study provides direct evidence that angiotensin II acting via the AT1 receptor subtype facilitates the release of dopamine in the rat striatum in vitro and in vivo. This receptor-mediated response may account for the modulation of dopamine-mediated behavioural responses by antagonists of the AT1 receptor and inhibitors of angiotensin converting enzyme.

Angiotensin I↗
PubMed1996

Differentiation of normal male prepuberty and hypogonadotrophic hypogonadism using an ultrasensitive luteinizing hormone assay.

BACKGROUND AND OBJECTIVE: To assess how the Delfia time-resolved immunofluorometric assay can most conveniently and economically be used to differentiate normal prepuberty from complete idiopathic hypogonadotrophic hypogonadism (IHH, Kallmann's syndrome). SUBJECTS: 42 prepubertal boys aged 8.06-14.1 years and 11 adult male patients with IHH. DESIGN AND MEASUREMENTS: Blood samples were withdrawn at 20-min intervals for 8 h from 23.00 to 07.00. Samples from the 6 h commencing 1 h after sleep onset were analysed for LH by Delfia. RESULTS: Mean LH over this 6-hour period discriminated between IHH and normal prepuberty after the age of 12.5 years (no IHH subject > 0.31 U/l, no prepubertal subject < 0.33 U/l). The maximum hourly mean LH value for each subject gave a greater degree of mutual exclusivity (no IHH subject > 0.45 U/l, no prepubertal subject < 0.50 U/l). CONCLUSION: Kallmann's syndrome patients can be distinguished from prepubertal boys aged 12.5 years or over by blood sampling every 20 min for 6 h, commencing 1 h after sleep onset. The pooling of these samples into six 1-hour samples and subsequent Delfia assay will yield six 1-hour mean LH concentrations for each subject. The highest of these six concentrations will give a value with mutual exclusivity between the two groups.

Adolescent↗
PubMed1996

MR diagnosis of bone contusions of the knee: comparison of coronal T2-weighted fast spin-echo with fat saturation and fast spin-echo STIR images with conventional STIR images.

OBJECTIVES: Bone contusions consist of posttraumatic marrow change resulting from a combination of hemorrhage, edema, and microtrabecular injury and are depicted on MR images as geographic, nonlinear areas of abnormally increased T2 marrow signal intensity. Detection of bone contusions is important, not only in that they are frequently a sign of more serious associated injury, but in that isolated contusions may account for clinical symptoms and thereby obviate further workup. We evaluated two promising rapid imaging sequences, T2-weighted fast spin-echo with fat saturation and fast spin-echo short inversion time (T1) inversion recovery (STIR) and compared their efficacy to that of conventional STIR for the diagnosis of bone contusions in knees. SUBJECTS AND METHODS: Fifty-one consecutive military, retired military, and military-dependent patients were prospectively entered. Imaging consisted of three experimental sequences: coronal T2-weighted fast spin-echo with spectroscopic fat saturation, fast spin-echo STIR, and STIR, as well as conventional T1, proton density, and T2. Each examination was interpreted by three radiologists, for a total of 153 interpretations. Each interpretation consisted of the conventional sequences plus one of the three experimental sequences, blinded to the other two, specifically addressing menisci, ligaments, bones, and soft tissues. A positive test result was defined as a diagnosis of bone contusion on any one of the three independent interpretations of a given examination. Our gold standard was the consensus opinion of all three radiologists in a retrospective, unblinded evaluation of all imaging sequences. Sensitivity and specificity of fast spin-echo with fat saturation and fast spin-echo STIR were then calculated and compared with STIR. RESULTS: Sensitivity and specificity for bone contusion diagnosis in the three experimental sequences were as follows: fast spin-echo with fat saturation, 91% sensitivity and 86% specificity; fast spin-echo STIR, 96% sensitivity and 96% specificity; and conventional STIR, 83% sensitivity and 93% specificity. Our results showed no statistically significant difference between either of the fast spin-echo sequences and conventional STIR (p > .05). CONCLUSION: Because of their comparable accuracy and short imaging time characteristics, coronal fast spin-echo with fat saturation and fast spin-echo STIR sequences are superior to conventional STIR sequences for the diagnosis of bone contusions in knees.

Adolescent↗
PubMed1996

Smoking cessation in pregnancy.

Smoking during pregnancy harms the fetus, newborn infant, young child, and mother. Smoking during the last two trimesters greatly increases the risk of stillbirth, spontaneous abortion, premature delivery, neonatal death, and low birth weight. Risk is in direct proportion to cigarette smoke exposure.

Cost-Benefit Analysis↗
PubMed1995

Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumopericardium associated with positive-pressure ventilation in a cat.

Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumopericardium with hypotension and tachycardia were observed after endotracheal intubation and during positive-pressure ventilation in a previously healthy cat anesthetized for ovariohysterectomy. Potential causes included tracheal tearing during intubation, a closed pop-off valve while using high oxygen flows, and preexisting acquired or congenital abnormalities in the respiratory tract. The cat responded well to conservative management, including cessation of positive-pressure ventilation and use of increased inspired oxygen concentration.

Animals↗
PubMed1995

ICF syndrome (immunodeficiency, centromeric instability and facial anomalies): investigation of heterochromatin abnormalities and review of clinical outcome.

A further patient with the ICF syndrome (immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9 and 16 and facial anomalies) is described. This case is the second to be reported with consanguinity of the parents. This lends support to the theory of autosomal recessive inheritance. The features of the 15 published cases are reviewed. The clinical and cytogenetic characteristics of the syndrome are discussed, and new evidence provided as to the role of centromeres and centric heterochromatin in the production of chromosome aberrations. Correspondence with other authors has made possible a review of the clinical outcome in this condition.

Abnormalities, Multiple↗
PubMed1995

Characterization of murine mannose-binding protein genes Mbl1 and Mbl2 reveals features common to other collectin genes.

Mannose-binding protein (MBP) is a member of a family of collagenous lectins (collectins), which are believed to play an important role in first-line host defense. In this study, the two genes encoding MBP in mice--Mbl1 and Mbl2--have been isolated and their exon-intron structure studied to understand their evolutionary relationship to the single human (MBL) and the two rat MBP genes. Mouse Mbl1 and Mbl2 have five and six exons, respectively. The structure of the mouse Mbl genes is similar to that of the rat and human MBP genes and shows homology to the other collectin genes, with the entire carbohydrate recognition domain being encoded in a single exon and all introns being in phase 1. The MBP encoded by mouse Mbl1 with three cysteines in the first coding exon, like the rat Mbl1 and human MBL, is capable of a higher degree of multimerization and has apparent ability to fix complement in the absence of antibody or C1q. However, the structural features of other exons, that is, the larger size of collagen domain region in the first coding exon (64 bp in Mbl2 vs 46 bp in Mbl1) and the smaller size of the exon encoding the trimerization domain (69 bp in Mbl2 vs 75 bp in Mbl1) reveal that the single human MBL gene is closely related to rodent Mbl2 rather than rodent Mbl1. The findings in this study suggest that in contrast to the evolution of another collectin gene--bovine surfactant protein-D--which duplicated in bovidae after divergence from humans, MBP gene most likely duplicated prior to human-rodent divergence, and that the human homolog to Mbl1 was perhaps lost during evolution.

Amino Acid Sequence↗
PubMed1995

Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction.

BACKGROUND: Animal studies have shown that malignant cells are shed into the blood stream during surgical resection of a primary tumor and that this may enhance the development of metastases. The evidence for tumor cell dissemination during surgical manipulation of human cancer is unclear. We have applied the technique of reverse transcription and polymerase chain reaction to detect circulating tumor cells in peripheral venous blood of patients with breast cancer perioperatively. METHODS: To target breast-specific gene transcription complementary DNA was prepared by reverse transcription of blood messenger RNA with oligonucleotide primers unique to CK18 and DF3 antigens. Preliminary assessment of specificity showed that the DF3 antigen was more suitable than CK18 for the purpose of this study. Assessment of sensitivity showed that as few as 10 tumor cells per 5 ml blood could be identified by this method. Peripheral blood samples were obtained by venepuncture from patients before, during, and 24 hours after breast surgery (nine malignant and three benign). RESULTS: In the group of patients with malignant disease, tumor cells were detected in one patient before operation and four patients during operation. No tumor cells were detected in the postoperative samples nor in any of the samples of patients with benign disease. CONCLUSIONS: These findings suggest that tumor manipulation during operation encourages tumor cell dissemination.

Breast Neoplasms↗