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Biomedical subjects

D B Johnson

Publications and source records attributed to D B Johnson.

At least 37 records · Page 2Linked to original sources

Changes in left ventricular mass and volumes in patients receiving angiotensin-converting enzyme inhibitor therapy for left ventricular dysfunction after Q-wave myocardial infarction.

OBJECTIVES: We evaluated global and segmental left ventricular (LV) mass and LV mass/volume ratio in patients with LV dysfunction receiving angiotensin-converting enzyme (ACE) inhibitor therapy after acute myocardial infarction (MI). BACKGROUND: ACE inhibitors attenuate LV dilatation and compensatory hypertrophy after acute MI in animal models. However, LV remodeling in patients after acute MI has been largely defined on the basis of changes in chamber volume alone. METHODS AND RESULTS: Twenty-nine patients with LV ejection fraction <40% received the ACE inhibitor ramipril (range 2.5 to 20 mg/day) within 5 days of their first Q-wave MI. Magnetic resonance imaging was performed at baseline and at 3 months, providing global and regional LV volumes and mass from summated serial short-axis slices. Mean arterial blood pressure was unchanged from baseline to 3-month follow-up (89 +/- 10 to 92 +/- 17 mm Hg). LV mass decreased (90 +/- 25 to 77 +/- 21 gm/m2, p < 0.0005) as LV end-diastolic volumes increased (65 +/- 13 to 73 +/- 22 ml/m2, p < 0.01). Global LV mass to volume ratio decreased from 1.40 +/- 0.28 to 1.08 +/- 0.18 gm/ml (p < 0.0001), as did circumferential wall thickness to volume ratio of noninfarcted myocardium at the base of the LV (0.06 +/- 0.02 to 0.05 +/- 0.02 mm/ml, p < 0.001). LV ejection fraction increased from 35 +/- 6 to 40 +/- 9% (p < 0.001) in the presence of an increase in calculated end-systolic wall stress (185 +/- 57 to 227 +/- 54 gm/cm2, p < 0.01). CONCLUSIONS: ACE inhibitor therapy was associated with improved LV function in the face of a decrease in mass to volume ratio of the LV as well as a decrease in wall thickness to volume ratio of noninfarcted myocardium. Whether ACE inhibitor therapy had direct or indirect effects on these changes in LV mass and function are open questions that require further investigation.

Adult↗

Extraskeletal mesenchymal chondrosarcoma of the rectus sheath.

Mesenchymal chondrosarcomas (MSCs) are a rare form of chondrosarcoma which usually arise in bone. Extraskeletal chondrosarcomas constitute a minority (14-25%) of MSCs. We describe the imaging features of an extraskeletal mesenchymal chondrosarcoma that arose from the rectus abdominus muscle.

Adult↗

Gadolinium-enhanced magnetic resonance angiography of renal transplants.

Our purpose was to investigate three-dimensional (3D) gadolinium-enhanced magnetic resonance angiography (Gd-MRA) in the evaluation of renal transplant arteries. Eleven MR angiography examinations were performed in nine renal transplant patients. Gd-MRA, three-dimensional phase contrast (3D-PC) post-gadolinium, and two-dimensional time-of-flight (2D-TOF) MR angiography were performed and independently reviewed by three vascular radiologists who, for each MR angiography sequence, separately graded occlusive disease in the ipsilateral iliac artery, the transplant artery anastomosis, and the transplant artery itself. The Gd-MRA and 3D-PC data were reviewed as maximum intensity projections (MIP) reconstructed in standard planes, and the 2D-TOF data were interpreted from source images. In addition, a single vascular radiologist prospectively interpreted the Gd-MRA and 3D-PC data together, hereinafter Gd/PC, from MIP reconstructions for each case. In all of these patients either surgical (n = 3) or angiographic studies (n = 8) were performed within 21 days following the MR examination, which served as a reference standard to determine sensitivity and specificity. The sensitivity/specificity for the detection of significant stenosis were as follows: Gd-MRA, 67/88; 3D-PC, 60.3/76.6; 2D-TOF, 47/81; and Gd/PC, 100/100. The kappa statistic (kappa) for interobserver agreement for the grading of stenoses by 2D-TOF, Gd-PC, and Gd-MRA was 0.48, 0.60, and 0.74, respectively. The percentage of all vascular segments seen well enough to grade (cumulative for all three observers) was 94%, 85%, and 79% for Gd-MRA, 3D-PC, and 2D-TOF, respectively. The combination of Gd-MRA and 3D-PC is a promising approach to the evaluation of transplant renal arteries.

Adolescent↗

Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.

OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.

Angiotensin-Converting Enzyme Inhibitors↗

Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle-wasting disorder with an incidence of approximately 1/3,500 male births. Females are also affected, in rare instances. The manifestation of mild to severe symptoms in female carriers of dystrophin mutations is often the result of the preferential inactivation of the X chromosome carrying the normal dystrophin gene. The severity of the symptoms is dependent on the proportion of cells that have inactivated the normal X chromosome. A skewed pattern of X inactivation is also responsible for the clinical manifestation of DMD in females carrying X;autosome translocations, which disrupt the dystrophin gene. DMD may also be observed in females with Turner syndrome (45,X), if the remaining X chromosome carries a DMD mutation. We report here the case of a karyotypically normal female affected with DMD as a result of homozygosity for a deletion of exon 50 of the dystrophin gene. PCR analysis of microsatellite markers spanning the length of the X chromosome demonstrated that homozygosity for the dystrophin gene mutation was caused by maternal isodisomy for the entire X chromosome. This finding demonstrates that uniparental isodisomy of the X chromosome is an additional mechanism for the expression of X-linked recessive disorders. The proband's clinical presentation is consistent with the absence of imprinted genes (i.e., genes that are selectively expressed based on the parent of origin) on the X chromosome.

Blotting, Southern↗

A concept-based retrieval system for thoracic radiology.

Current digital information systems in radiology are insufficient to accommodate the retrieval needs of academicians. Significant efforts are required in retrieving clinical cases for teaching and research. We describe a prototype system that supports intelligent case retrieval based on a combined specification of patient demographics, radiologic findings, and pathologic diagnoses. The documents for these cases can be distributed among multiple heterogeneous data bases. The system features automatic indexing of radiology and pathology reports, a comprehensive lexicon for thoracic radiology, an interface to a hospital information system, radiology information system, and picture archiving and communication systems, and a graphical user interface for query formulation and results visualization. The prototype system was developed within the domain of thoracic radiology involving patients with lung cancer.

Abstracting and Indexing↗

Magnetic resonance imaging in the evaluation of cerebrospinal fluid fistulae.

Twenty-four patients with a clinical diagnosis of cerebrospinal fluid (CSF) fistulae who were assessed by MR are reported and the literature reviewed on the use of MR in the evaluation of CSF fistulae. Thirteen patients presented with rhinorrhoea, three had otorhinorrhoea and two had recurrent meningitis. Six patients had a combination of symptoms. Nine patients did not have active leakage of CSF at the time of MR scanning. The site of the CSF leak was identified in all 24 patients (100%) and was verified at operation in all patients. This study suggests that MR is a sensitive and accurate technique for detection of CSF leaks even in patients who are not actively leaking at the time of evaluation. MR imaging is a useful technique in the assessment of patients with CSF fistulae; it is non-invasive, offers excellent anatomical detail and has no radiation risk.

Adolescent↗

Cardiac hypertrophy and failure in hypertension.

Left ventricular hypertrophy is both a major adaptive response to chronic pressure overload and an important risk factor in patients with hypertension. It is now well appreciated that structural changes in the myocardium are mediated not only by the mechanical stress of pressure overload but also by various neurohormonal substances that exert trophic effects on myocytes and non-myocytes in the heart. Both earlier recognition and improved understanding of cardiac hypertrophy may lead to more effective therapeutic strategies for hypertension. This review focuses on the underlying mechanisms in hypertensive heart disease that lead to heart failure.

Animals↗

Prostate-specific antigen concentration: influence of age and ethnicity.

This pilot study evaluated the influence of age and ethnicity on serum prostate-specific antigen (PSA) concentration in Asian and white men without a clinical diagnosis of prostate cancer. Between October and December 1993, 1260 patients who underwent serum PSA determination (Hybritech Tandem-R assay, San Diego, California) at Straub Clinic & Hospital were retrospectively analyzed. Of these, 885 (70%) men aged 40 to 79 years were either Asian (Chinese, Filipino, Japanese, and Korean) or white and had a serum PSA less than 10.0 ng/ml. The PSA for the entire group was 2.1 +/- 2.0 ng/ml (mean +/- SD). PSA correlated with age (r = 0.31, p = 0.0001) and age accounted for 10% of the variance in serum PSA. Using the regression formula, serum PSA increased 2.5% (0.06 ng/ml) per year of age. The entire study group was about equally divided between whites (49%) and Asians (51%). Nearly three-fourths of the Asian men were Japanese. The mean PSA was very close in the Asian and white groups. There was no direct correlation between serum PSA and ethnicity (r = 0.03; p = 0.3201). Ethnicity contributed 0.1% of the variance in PSA. In conclusion, this preliminary study suggests serum PSA increases with age in Asian and white men without a clinical diagnosis of prostate cancer. No difference was found in PSA between men of Asian and white ethnicity.

Adult↗

Stereoselective pharmacokinetics and interconversions of flosequinan enantiomers containing chiral sulphoxide in rat.

1. In order to study the pharmacokinetics of flosequinan enantiomers ((+-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) containing chiral sulphur, plasma levels of (+)-(R)- and (-)-(S)-flosequinan (R-FSO and S-FSO) and two metabolites (flosequinan sulphide (FS) and flosequinan sulphone (FSO2)) were measured after oral and i.v. administration of racemic flosequinan (rac-FSO), R-FSO and S-FSO in male rat. 2. The pharmacokinetic parameters of the enantiomers were different after oral and i.v. administration of R-FSO and S-FSO. The plasma clearance of R-FSO was higher than S-FSO. 3. The major metabolites of boh R-FSO and S-FSO was FSO2. A minor metabolite, FS, was also detected in plasma. 4. Interconversions occurred after the oral and i.v. administration of R-FSO and S-FSO. The amount of interconversion from S-FSO and R-FSO was greater than that from R-FSO to S-FSO. The rate of interconversion after oral administration was higher than that after i.v. administration. 5. After i.v. administration of FS, R-FSO and S-FSO were detected in plasma, suggesting that the interconversion occurred via formation of FS. 6. The pharmacokinetic parameters of R-FSO after administration of rac-FSO differed from that after administration of R-FSO, indicating the interaction between each enantiomer.

Administration, Oral↗

Carmustine, Ara C, cyclophosphamide and etoposide with autologous bone marrow transplantation in relapsed or refractory lymphoma: a dose-finding study.

The purpose of this study was to define the dose-limiting non-hematologic toxicity of carmustine, Ara C, cyclophosphamide and etoposide (BACE). Between October 1986 and March 1990, 37 patients with relapsed or refractory lymphoma received escalating doses of combination chemotherapy followed by autologous bone marrow transplant (ABMT). Twenty patients with Hodgkin's disease (HD) and 17 patients with intermediate or high grade non-Hodgkin's lymphoma (NHL) initially received conventional-dose therapy with either a 7 week course of modified MACOP-B or a single dose of cyclophosphamide (CY) at 2 g/m2 depending on prior therapy and response. Regardless of response, patients then received escalating doses of BACE, toxicity permitting. Ten patients obtained complete responses (CR) and 12 patients were partial responders (PR), CR+PR (75%) with modified MACOP-B and 7 (64%) patients obtained PR with CY. The maximum-tolerated dose (MTD) for BACE was determined to be carmustine 700 mg/m2, Ara C 1500 mg/m2, CY 150 mg/kg and etoposide 1500 mg/m2. When Ara C was escalated from 1500 mg/m2 to 3000 mg/m2 holding the other drugs at the prior doses, the next two patients died secondary to diffuse alveolar damage. Overall and event-free survivals are identical with 14 of 37 patients (38%) alive with a median follow-up of 61 months (range 38-79 months). Ten patients were treated at the MTD, none of whom died a toxic death and 3 (30%) are alive with a median follow-up of 42 months (range 38-52 months). We defined the MTD and BACE showing pulmonary toxicity to be the dose-limiting non-hematologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microbiological and chemical characteristics of an acidic stream draining a disused copper mine.

Water samples draining a disused copper mine (Parys Mountain) in Anglesey, North Wales, were analysed for distribution of acidophilic bacteria (iron oxidising and heterotrophic) and for changes in physicochemical composition along the length of the drainage stream. Ten samples were taken at regular distance intervals along a 1 km stretch from the source of the acid mine drainage. The stream remained highly acidic (pH < 2.8) although a slight decrease (0.6 pH unit) in acidity with distance from source was observed. Concentrations of most metals measured decreased with distance along the length of the stream, although some showed a gradual increase and others peaked at c. 200 m from source. Most dissolved iron was in the ferrous form in the upper reaches of the stream, but ferric iron became increasingly dominant downstream as a result of microbial oxidation. Although concentrations of nutrients such as nitrogen and phosphorus were low in the acid mine drainage, they were not limiting rates of bacterial iron oxidation, which appeared to be limited more by temperature. The iron oxidising bacteria Thiobacillus ferrooxidans and Leptospirillum ferrooxidans were both isolated from all sampling sites, although their relative abundances varied; L. ferrooxidans accounted for 57% of all iron oxidising isolates. Numbers of iron oxidising bacteria decreased with distance from drainage source, in contrast to those of acidophilic heterotrophic bacteria which increased. The diversity of heterotrophic isolates also increased with distance. The relationship between the chemistry and microbiology of the stream is discussed.

Journal Article↗

Isolation and characterization of an acidophilic, heterotrophic bacterium capable of oxidizing ferrous iron.

A heterotrophic bacterium, isolated from an acidic stream in a disused pyrite mine which contained copious growths of "acid streamers," displayed characteristics which differentiated it from previously described mesophilic acidophiles. The isolate was obligately acidophilic, with a pH range of 2.0 to 4.4 and an optimum pH of 3.0. The bacterium was unable to fix carbon dioxide but oxidized ferrous iron, although at a slower rate than either Thiobacillus ferrooxidans or Leptospirillum ferrooxidans. Elemental sulfur and manganese(II) were not oxidized. In liquid media, the isolate produced macroscopic streamerlike growths. Microscopic examination revealed that the bacterium formed long (greater than 100 microns) filaments which tended to disintegrate during later growth stages, producing single, motile cells and small filaments. The isolate did not appear to utilize the energy from ferrous iron oxidation. Both iron (ferrous or ferric) and an organic substrate were necessary to promote growth. The isolate displayed a lower tolerance to heavy metals than other iron-oxidizing acidophiles, and growth was inhibited by exposure to light. There was evidence of extracellular sheath production by the isolate. In this and some other respects, the isolate resembles members of the Sphaerotilus-Leptothrix group of filamentous bacteria. The guanine-plus-cytosine content of the isolate was 62 mol%, which is less than that recorded for Sphaerotilus-Leptothrix spp. and greater than those of L. ferrooxidans and most T. ferrooxidans isolates.

Bacteria↗

Ferric iron reduction by acidophilic heterotrophic bacteria.

Fifty mesophilic and five moderately thermophilic strains of acidophilic heterotrophic bacteria were tested for the ability to reduce ferric iron in liquid and solid media under aerobic conditions; about 40% of the mesophiles (but none of the moderate thermophiles) displayed at least some capacity to reduce iron. Both rates and extents of ferric iron reduction were highly strain dependent. No acidophilic heterotroph reduced nitrate or sulfate, and (limited) reduction of manganese(IV) was noted in only one strain (Acidiphilium facilis), an acidophile which did not reduce iron. Insoluble forms of ferric iron, both amorphous and crystalline, were reduced, as well as soluble iron. There was evidence that, in at least some acidophilic heterotrophs, iron reduction was enzymically mediated and that ferric iron could act as a terminal electron acceptor. In anaerobically incubated cultures, bacterial biomass increased with increasing concentrations of ferric but not ferrous iron. Mixed cultures of Thiobacillus ferrooxidans or Leptospirillum ferrooxidans and an acidophilic heterotroph (SJH) produced sequences of iron cycling in ferrous iron-glucose media.

Journal Article↗

Mitogenic induction of ornithine decarboxylase in human mononuclear leukocytes: relationships with adenosine diphosphate ribosyltransferase.

1. Relationships between ornithine decarboxylase (ODC) and adenosine diphosphate ribosyl transferase (ADPRT) in human mononuclear leukocytes (HML) were tested by statistical comparisons of their values in a group of 46 people, and by use of inhibitors of ADPRT. 2. ODC was assayed following exposure of HML, for 20 hr, to mitogens [phytohemagglutinin (PHA) and pokeweed mitogen]; ADPRT was measured following exposure of HML to H2O2 (100 microM) for 1 hr (activated ADPRT), and in parallel cultures without H2O2 (constitutive ADPRT). 3. Significant correlations were found between ODC and ADPRT values; the effects of smoking disturbed the correlations. PHA induction of ODC was negatively influenced by age (standardized beta coefficient = -2.95, P = 0.005), while age also influenced ADPRT values negatively in non-smokers (for H2O2 activated ADPRT, standardized beta coefficient = -2.74, P less than 0.008). 4. Inhibitors of ADPRT, nicotinamide, caffeine and benzamide inhibited the induction of ODC by PHA in a concentration-dependent manner, in the range (0.6-10 mM) known to inhibit ADPRT.

Age Factors↗