Biomedical subjects

D Downey

Publications and source records attributed to D Downey.

At least 19 recordsLinked to original sources

PubMed2006

Assessing the prognostic significance of transrectal ultrasound extracapsular extension in prostate cancer.

AIMS: To determine the prognostic value of transrectal ultrasound (TRUS)-detected extraprostatic disease for prostate cancer in patients receiving radical external-beam radiation therapy (EBRT). MATERIALS AND METHODS: A chart review of 181 patients treated with radical EBRT for prostate cancer was conducted. All patients underwent TRUS assessment by one radiologist. The median radiation dose delivered to the prostate was 66 Gy (range 53-70 Gy) in 33 fractions (range 20-39 fractions). Median follow-up time for all patients was 6.5 years. Sixty-four (35%) out of 181 patients were found to have extracapsular disease on TRUS. Clinical relapse was defined as the first occurrence of either salvage hormonal therapy administration by the treating oncologist or clinical, radiological, and/or pathologic evidence of recurrent or progressive disease. In terms of biochemical failure, two prognostic variable analyses were carried out using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus guidelines and the Houston definition of biochemical failure. The primary end point for the prognostic variable analyses was time to first clinical or biochemical failure (CBF). RESULTS: For time to CBF using the ASTRO consensus guidelines for biochemical failure, univariable analysis revealed that the prostate-specific antigen (PSA) (P = 0.018), clinical T stage (P = 0.002), Gleason score (P = 0.021), adjuvant hormonal therapy (P = 0.032) and TRUS T staging (P = 0.0001) were statistically significant prognostic factors. On multivariable analysis, clinical T stage (P = 0.051) was of borderline statistical significance, whereas PSA (P = 0.036), TRUS T stage (P = 0.0002) and adjuvant hormonal therapy (P = 0.015) were found to be independent prognostic factors. For time to CBF using the Houston definition of biochemical failure, univariable analysis revealed that PSA (P = 0.001), Gleason score (P = 0.026) and prostate volume (P = 0.013) were statistically significant prognostic factors. On multivariable analysis, PSA (P = 0.002), Gleason score (P = 0.012), and adjuvant hormonal therapy (P = 0.041) were found to be independent prognostic factors. TRUS T staging was not found to be independently significant. CONCLUSIONS: A clear role for TRUS staging as an independent prognostic factor, in the setting of other more established variables, such as Gleason grade, PSA, and digital rectal examination (DRE) T stage, was not confirmed in this study, population.

Aged↗

PubMed2004

A novel follicle culture system markedly increases follicle volume, cell number and oestradiol secretion.

This study reports a novel, simple method for culture of mouse follicles which results in follicles with cell numbers similar to in vivo fully grown follicles. Using this method, follicles (180-240 microm in diameter) were cultured in a 100 microl inverted drop of medium without oil and compared with culture in upright drops with and without a mineral oil overlay. Follicles, isolated from C57BL/6 x CBA/ca crossbred and MF1 inbred mice, were cultured individually at 37 degrees C in 96-well round-bottomed suspension cell tissue culture plates for 6 days. Follicles grown in the inverted drop culture system reached a markedly higher final diameter (means+/-s.e.m.; 471 +/- 6.0 microm) as compared with the upright with oil (363 +/- 2.7 microm) and without oil (358 +/- 4.0) systems. There was no significant effect of mouse strain on follicle diameter. Follicular secretion of oestradiol and lactate into the medium was measured on days 2, 4 and 6 of culture. Secretion of oestradiol per follicle on day 6 was 2.49 +/- 0.45 ng in the inverted and 0.90 +/- 0.17 ng in the upright without oil system (P < 0.001). Follicular secretion of lactate on a per unit of follicle volume basis remained constant in the inverted system over days 2, 4 and 6 and was less (P < 0.001) than secretion in both the upright with and without oil systems. Follicle cell proliferation was markedly increased in the inverted as compared with the upright with oil system; the increases in cell numbers were significant on day 3 (P < 0.01) and on all subsequent days (P < 0.001). These results are discussed in relation to the supply of oxygen to the follicle in culture.

Animals↗

PubMed2001

Oral, water-soluble combined estrogen/calcium preparation for postmenopausal therapy.

OBJECTIVES: Estrogen is often prescribed for symptoms and sequelae of ovarian estrogen loss after menopause. METHODS: To assess efficacy and acceptability of a new, highly soluble estrogen-calcium preparation, we formulated a water-soluble powdered combination of estrogen (0.625 mg estrone piperazine sulfate) and calcium (1 g, ions) as the highly soluble glycerophosphate salt (Estrosol). Effects of once-daily administration on bone mineral turnover of Estrosol dissolved in water (n = 11) was compared with 0.625 mg conjugated estrogens (Premarin) + 1 g calcium (Tums 500 Calcium Supplement) (n = 8). All women had had a previous hysterectomy, were between the ages 40 and 75, within 25% of ideal body weight, and had not taken hormonal preparations for at least 3 months. Assessment of bone mineral turnover was by monitoring N-telopeptides and bone specific alkaline phosphatase (BSAP) on 5 occasions: pretreatment and once during each of the 4 months of treatment. RESULTS: Mean N-telopeptide values decreased (p = .005) in both groups: Estrosol, 29.2% (40 --> 29 mmol bone collagen equivalents (BCE)/mmol creatinine), and Premarin(R) + calcium, 44.8% (33 --> 18 mmol). Mean BSAP values also decreased (p = 0.007) in both groups: Estrosol, 12.6% (12.06 --> 10.54 mg/l), Premarin(R) + calcium, 19.1% (11.57 --> 9.36 mg/l). The difference between groups for both N-telopeptides and BSAP was not significant, although sample size was small. Symptoms (hot flashes, vaginal dryness) improved similarly in both groups. Symptoms during treatment (breast or nipple tenderness, bloating) also were similar in both groups. Both preparations were well-tolerated. There were no changes in CBC, liver function tests, electrolytes or urinalyses in either group . CONCLUSIONS: This pilot study indicates that the combined, highly water-soluble preparation of estrogen and calcium is effective in reducing bone mineral turnover, acceptable and well-tolerated. Use of this single aqueous preparation may lead to better compliance than using two separate pills.

Adult↗

PubMed2001

Evaluation of voxel-based registration of 3-D power Doppler ultrasound and 3-D magnetic resonance angiographic images of carotid arteries.

Spatial registration and fusion of ultrasound (US) images with other modalities may aid clinical interpretation. We implemented and evaluated on patient data an automated retrospective registration of magnetic resonance angiography (MRA) carotid bifurcation images with 3-D power Doppler ultrasound (PD US) and indirectly with 3-D B-mode US. Volumes were initially thresholded to reduce the uncorrelated noise signals. The registration algorithm subsequently maximized the mutual information measure between the PD US and 3-D MRA via iterative simplex search to find best "rigid body" transformation. We rated the performance of the algorithm visually on (n = 5) clinical MRA and 3-D PD US datasets. We also evaluated quantitatively the effect of thresholding, initial misalignment of the paired volumes and the reproducibility registration. We investigated the effect of image artefacts by simulation experiments. Preregistration misalignments of up to 5 mm in the transaxial plane, up to 10 mm along the axis of the carotids and up to 40 degrees resulted in 107 of 110 successful registrations, with translational and rotational errors of 0.32 mm +/- 0.3 mm and 1.6 +/- 2.1 degrees. The algorithm was not affected by missing arterial segments of up to 8 mm in length. The average registration time was 4 min. We conclude that the algorithm could be applied to 3-D US PD and MRA data for automated multimodality registration of carotid vessels without the use of fiducials.

Algorithms↗

PubMed2001

Porphyria: the road not traveled.

As our ability to evaluate patients with porphyria expands there have been some inconsistencies that are not easily explained. These inconsistencies are biochemical, enzymatic and genetic in nature. Recent work by others has led me to believe there is another way to look at the problem. I will propose how an evolutionary approach could reconcile these problems. In doing so it will imply that porphyria could potentially affect many more people than currently thought.

Humans↗

PubMed2001

Multiple focal nodular hyperplasia and steatosis: Atypical imaging characteristics.

Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A (99m)technetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the (99m)technetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

Adipose Tissue↗

PubMed2000

Nitric oxide, iNOS, and inflammation in cystic fibrosis.

Nitric oxide (NO) is produced from three isoforms of nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). Cystic fibrosis (CF) patients have an increased bacterial load in the airways which stimulates iNOS and therefore NO production. Upregulation of iNOS in normal epithelial cells protects the lung from damage, but in CF cells, iNOS is not upregulated and NO production is reduced. Reduced iNOS expression is associated with neutrophil sequestration in the lung, thus increasing the potential damage from neutrophil proteases and reactive oxygen species. In contrast, high concentrations of NO may augment the inflammatory process in acute lung injury from sepsis. Meng et al. have shown that cystic fibrosis epithelial cells, when stimulated by a cytokine mix and co-cultured with activated neutrophils, have reduced iNOS expression compared to normal epithelial cells. Although iNOS expression may not accurately reflect activity and NO production may arise from elsewhere, this study suggests that reduced iNOS expression may play a part in the pathophysiological processes in cystic fibrosis.

Cystic Fibrosis↗

PubMed2000

Endothelins, their receptors, and retinal vascular dysfunction in galactose-fed rats.

PURPOSE: Endothelins are potent vasoactive factors that have been implicated in the pathogenesis of several vascular disorders. This study was conducted to determine the role that endothelins play in the development of retinal microangiopathy under hyperhexosemic conditions induced by galactose feeding. METHODS: Retinal blood flow was determined using Doppler sonography in galactose fed rats with or without an endothelin receptor antagonist (Bosentan) treatment and were compared to control rats after 1 and 6 months of follow-up. Levels of endothelin-1, endothelin-3, (ET-1, ET3) and receptors endothelin A, endothelin B, (ET(A), ET(B)) mRNA expression were determined by semiquantitative RT-PCR. Immunohistochemical distribution of ET-1 and ET-3, ligand binding, and autoradiography to determine ET receptor distribution were carried out. RESULTS: Retinal vasoconstriction measured by an increase in resistivity index (RI) was present in 1 month galactose feeding compared to controls, which was prevented by Bosentan treatment. After 6 months of follow up all animal groups exhibited higher RI compared to their 1 month counterpart, although they were not different from each other. Compared to the controls, after 1 month levels of mRNA for ET-1, ET-3, and ET(A) were increased in galactose-fed rats, whereas ET(B) mRNA production remained similar to controls. After 6 months, all four genes exhibited increased levels compared to the controls, and no effect of Bosentan treatment on gene expression was evident. Increased immunoreactivity of ET-1 and ET-3 was determined, as well as increased ET receptor concentration was further present in the retina of galactose-fed animals. CONCLUSION: The data suggests that endothelin production is increased under hyperhexosemic conditions and that the endothelins play an important role in regulating the hemodynamics of retinal blood flow.

Animals↗

PubMed2000

"Impact? What impact?" Epidemiological research findings in the public domain: a case study from north-east England.

This paper reflects on the dissemination of potentially controversial research evidence about industrial air pollution and health in north-east England. It draws on a participant observation study of the local impact of a four-year epidemiological research programme in Teesside. The difficulties in and obstacles to disseminating research findings are explored. It may thus be described as a study of the impact of a study. We look at institutional resistance (including from the funders of the research) to any evidence indicating adverse health effects from industrial pollution. We also look at the failure of researchers to surmount such resistance and to communicate effectively with those who lived in the vicinity of the major industrial operations. This leads us to consider how conflicting notions of accountability coloured dissemination strategies as well as researchers' judgements. We offer a critique of fashionable and unduly consensual notions of a 'user community', in a context where different 'user communities' had incompatible expectations about the purpose of a piece of research and the significance of the data to emerge from it. The study also highlights the difficulties of disseminating research findings when the topic has the potential to affect economic interests.

Air Pollution↗

PubMed2000

Mathematical modeling of the human body during water replacement and dehydration: body water changes.

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model.

Body Temperature Regulation↗

PubMed2000

Segmentation of carotid artery in ultrasound images: method development and evaluation technique.

Segmentation of carotid artery lumen in two-dimensional and three-dimensional ultrasonography is an important step in computerized evaluation of arterial disease severity and in finding vulnerable atherosclerotic plaques susceptible to rupture causing stroke. Because of the complexity of anatomical structures, noise as well as the requirement of accurate segmentation, interactions are necessary between observers and the computer segmentation process. In this paper a segmentation process is described based on the deformable model method with only one seed point to guide the initialization of the deformable model for each lumen cross section. With one seed, the initial contour of the deformable model is generated using the entropy map of the original image and mathematical morphology operations. The deformable model is driven to fit the lumen contour by an internal force and an external force that are calculated, respectively, with geometrical properties of deformed contour and with the image gray level features. The evaluation methodology using distance-based and area-based metrics is introduced in this paper. A contour probability distribution (CPD) method for calculating distance-based metrics is introduced. The CPD is obtained by generating contours of the lumen using a set of possible seed locations. The mean contour can be compared to a manual outlined contour to provide accuracy metrics. The variance computed from the CPD can provide metrics of local and global variability. These metrics provide a complete performance evaluation of an interactive segmentation algorithm and a means for comparing different algorithm settings.

Algorithms↗

PubMed1999

Diabetes-induced vascular dysfunction in the retina: role of endothelins.

AIMS/HYPOTHESIS: Vasoactive factors like endothelins, by virtue of the microvascular regulation as well as by other effects, possibly play important parts in the pathogenesis of diabetic retinal microangiopathy. We investigated retinal vascular dysfunction in streptozotocin-induced diabetes and its relation with endothelins in short- and long-term diabetes. METHODS: Diabetic rats with or without an endothelin receptor antagonist (bosentan) treatment were investigated after 1 month and 6 months of follow-up. Retinal blood flow was measured and compared with age- and sex-matched non-diabetic control animals. Retinal tissues were analysed for endothelin-1, endothelin-3, endothelin A and endothelin B mRNA. Distribution of endothelin-1 and endothelin-3 was investigated by immunocytochemistry and that for endothelin receptors by ligand binding and autoradiography. RESULTS: Diabetic animals showed hyperglycaemia, glycosuria, elevated glycated haemoglobin values and reduced body weight gain. Retinal blood flow showed an increased resistivity index, an indicator of vasoconstriction, after 1 month of diabetes which was prevented by treatment with bosentan. This functional change in diabetes was eliminated after 6 months of follow-up. The retina from the diabetic animals showed increased mRNA expression for endothelin-1, endothelin-3 and endothelin A after one month. In addition, endothelin B mRNA expression was increased after 6 months. Furthermore, endothelin-1 and endothelin-3 immunoreactivity and endothelin receptor concentrations were increased in the retina of diabetic rats. CONCLUSION/INTERPRETATION: The results from this study indicate that the endothelin system is of importance in mediating retinal changes in diabetes although mechanisms of the endothelin system alteration as well as their effects might vary depending on the duration of diabetes. [Diabetologia (1999) 42: 1228-1234]

Animals↗

PubMed1998

Three-dimensional ultrasound imaging of the vasculature.

With conventional ultrasonography, the diagnostician must view a series of two-dimensional images in order to form a mental impression of the three-dimensional anatomy, an efficient and time consuming practice prone to operator variability, which may cause variable or even incorrect diagnoses. Also, a conventional two-dimensional ultrasound image represents a thin slice of the patients anatomy at a single location and orientation, which is difficult to reproduce at a later time. These factors make conventional ultrasonography non-optimal for prospective or follow-up studies. Our efforts have focused on overcoming these deficiencies by developing three-dimensional ultrasound imaging techniques that are capable of acquiring B-mode, colour Doppler and power Doppler images of the vasculature, by using a conventional ultrasound system to acquire a series of two-dimensional images and then mathematically reconstructing them into a single three-dimensional image, which may then be viewed interactively on an inexpensive desktop computer. We report here on two approaches: (1) free-hand scanning, in which a magnetic positioning device is attached to the ultrasound transducer to record the position and orientation of each two-dimensional image needed for the three-dimensional image reconstruction; and (2) mechanical scanning, in which a motor-driven assembly is used to translate the transducer linearly across the neck, yielding a set of uniformly-spaced parallel two-dimensional images.

Algorithms↗

PubMed1998

[Consensus guidelines for respiratory endoscopy issued by the Argentine Society of Bronchoesophagology].

The international consensus is that guidelines for respiratory endoscopy are inadequate, regarding such issues as institutional requirements, benefits, risks and limitations of the procedure, training programs and accreditation, with the result that the way or performing endoscopy varies according to how an operator was trained. The absence of precise recommendations means that practice is highly diverse and inappropriate use of the procedure has increased. The Argentine Consensus Group for Normalization of Respiratory Endoscopy was created in 1995 to unify criteria for several aspects of endoscopic practice. The official recommendations of the Group and of the Argentine Society of Bronchoesophagology define the indications (diagnostic, therapeutic and investigative) and contraindications (absolute, relative and high risk) for bronchoscopy. Required pre-bronchoscopic studies for routine and special cases are defined, as are indications for premedication, intubation and general anesthesia. Requirements for the setting, support personal and instruments are specified. Guidelines for topical anesthesia and techniques for insertion of the endoscope are suggested. The technique, indications and limitations of bronchoalveolar lavage, bronchial brushing and biopsy and transbronchial needle biopsy are defined. The utility and limitations of the various therapeutic techniques of bronchoscopy (laser, radiotherapy and stents) are defined. Norms to safeguard the patient, instruments and operator are emphasized.

Anesthesia, General↗

PubMed1998

Pneumatic sequential compression reduces the risk of deep vein thrombosis in stroke patients.

OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs) combined with subcutaneous heparin and antiembolic hose reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND: DVTs and PEs are serious complications among hospitalized stroke patients. Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known if SCDs combined with subcutaneous heparin can improve the protection afforded by heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke patients admitted to the neurology service from October 1988 through June 1996. From October 1988 through April 1991 (233 patients), and during February 1993 (16 patients), patients received 5,000 U subcutaneous heparin twice daily and antiembolic hose. From June 1991 through January 1993 and from March 1993 through June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS: Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233 and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty-two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory) treated with SCDs as well as heparin. The addition of SCDs resulted in more than a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke patients have an increased risk for DVT and PE. Adding SCDs to treatment with subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs should be considered for adjunctive DVT prophylaxis in nonambulatory stroke patients.

Aged↗

PubMed1998

Sonographic demonstration of Couinaud's liver segments.

The segmental localization of liver tumors is critical to planning appropriate resection. Couinaud's nomenclature is a surgically relevant system of hepatic segmental anatomy, which defines the liver segments by their relationships to vascular structures, hepatic ligaments, and the gallbladder. We demonstrate a way to accurately localize hepatic masses with sonography.

Hepatectomy↗

PubMed1997

Dose-related suppression of serum luteinizing hormone in women by a potent new gonadotropin-releasing hormone antagonist (Ganirelix) administered by intranasal spray.

OBJECTIVE: To determine if the GnRH antagonist (GnRH-a) Ganirelix (Syntex Research, Palo Alto, CA), administered by intranasal (IN) spray to normal women, is absorbed into the systemic circulation and suppresses LH secretion. DESIGN: A single center, open label, nonrandomized, dose-escalation study. SETTING: Academic research environment. PATIENT(S): Normal female volunteers ages 23 to 43 years. INTERVENTION(S): Ganirelix was administered as a single dose by IN spray. The administered doses and the number of women receiving each of them were 0.1 mg (n = 1), 0.3 mg (n = 1), 1 mg (n = 2), 3 mg (n = 5), and 6 mg (n = 5). Blood samples were collected from -15 minutes to 24 hours after dosing. MAIN OUTCOME MEASURE(S): Serum concentrations of Ganirelix and LH. RESULT(S): Ganirelix was absorbed rapidly. The mean time to maximal serum levels in the 3- and 6-mg groups was 0.67 and 0.53 hour, respectively. Mean serum LH levels were suppressed by > or = 35% relative to baseline from 2 to 12 hours after dosing in both groups. The mean maximal percent decrease in serum LH was -62% (at 8 hours after dosing) and -74% (at 6 hours after dosing) in the 3- and 6-mg groups, respectively. CONCLUSION(S): Single dose IN administration of 3 or 6 mg of Ganirelix suppressed serum LH levels in women, further enhancing the potential clinical utility of this potent GnRH-a. This is the first clinical report of a GnRH-a reducing the secretion of a pituitary gonadotropin when administered by an IN delivery system. Based on the duration and extent of LH suppression observed in this study, Ganirelix, administered by twice daily IN spray, may be effective for the treatment of gonadal hormone-dependent disorders in women.

Administration, Intranasal↗

PubMed1996

Porphyrin enzyme analysis in an oral pathology practice: a look back over four years.

The porphyrias are defined by specific enzymes having diminished activity. More enzymes have become available for routine testing. Measurement of urine and stool porphyrin and porphyrin precursor elevations are important, but in many instances are not found or found in confusing patterns. The use of enzyme analysis can often be helpful in identifying those patients with a genetically diminished enzyme activity level. Looking back over the last four years, modifications in evaluating patients for porphyria were developed and are related in this article. In 91 patients, patterns of enzyme deficiencies were seen that have been observed by others; however, new observations have been made. While many of the enzymes in the porphyrin pathway are available for testing, others need to come on line as soon as possible, particularly protoporphyrinogen oxidase.

Adolescent↗