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Biomedical subjects

D J Moore

Publications and source records attributed to D J Moore.

At least 145 records · Page 8Linked to original sources

Relative merits of ultrasound and intravenous urography in the investigation of the urinary tract.

Three hundred and fifty adult patients referred for intravenous urography were entered into a prospective double blind trial comparing intravenous urography with real time ultrasound. The study was performed to clarify the relative merits of the two techniques. Our results show that ultrasound and a plain abdominal radiograph should be the examination of first choice in most circumstances. This is particularly so in vague abdominal pain and in recurrent urinary tract infections where intravenous urography can usually be omitted or used only as a secondary investigation for further evaluation of abnormal ultrasound findings. In acute renal colic, intravenous urography should be the primary investigation. In macroscopic haematuria, initial examination by ultrasound would reliably diagnose mass lesions, show whether the lesion is cystic or solid and assess possible spread. Normal ultrasound does not exclude haematuria due to ureteric lesions or bladder lesions and intravenous urography is recommended.

Clinical Trials as Topic↗

In vitro cytotoxicity of pyrazine-2-diazohydroxide: specificity for hypoxic cells and effects of microsomal coincubation.

The antitumor drug pyrazine-2-diazohydroxide exhibits cytotoxicity to A204 tumor cells in vitro under acid conditions. The IC50 with a 1 hr drug exposure at pH of 7.4 was 61 micrograms/ml and at pH of 6.0 it was 31 micrograms/ml. It is suggested that the increased cytotoxicity is due to the acid catalyzed formation of a reactive pyrizinyldiazonium ion from pyrazine-2-diazohydroxide. Pyrazine-2-diazohydroxide is also more cytotoxic to A204 cells under hypoxic conditions in the presence of glucose with an IC50 at pH 7.4 of 22 micrograms/ml. The increased cytotoxicity of pyrazine-2-diazohydroxide under acid and hypoxic conditions may favor selective toxicity to solid tumors in vivo. Coincubation with rat hepatic microsomes increased the cytotoxicity of pyrazine-2-diazohydroxide to A204 cells. The effect did not require NADPH and was not due to formation of metabolites. There was an increased rate of degradation of pyrazine-2-diazohydroxide in the presence of microsomes, presumably with formation of the pyrizinyldiazonium ion. The final degradation product 2-hydroxypyrazine was not cytotoxic to A204 cells. The effect of microsomes on pyrazine-2-diazohydroxide cytotoxicity is probably of little in vivo significance.

Animals↗

Disposition and metabolism of the antitumor agent pyrazine-2-diazohydroxide in mouse and beagle dog.

The pharmacokinetics and metabolism of pyrazine-2-diazohydroxide have been studied in the beagle dog and mouse. When pyrazine-2-diazohydroxide was administered to beagle dogs at a dose of 18.6 mg/kg (428 mg/m2) by i.v. bolus, the plasma half-life (t1/2) was 7.3 min, the apparent volume of distribution (Vd) 577 ml/kg, and the total body clearance (Cl) 55 ml/min per kg. In mice given pyrazine-2-diazohydroxide by i.v. bolus at 100 mg/kg (428 mg/m2), the t1/2 was 5.8 min, the Vd 250 ml/kg, and the Cl 30 ml/min per kg. When [2-14C]pyrazine-2-diazohydroxide was infused i.v. to mice at 100 mg/kg over 8 h, the Cl for parent drug was 122 ml/min per kg. The major product formed from pyrazine-2-diazohydroxide was 2-hydroxypyrazine, which accounted for 80% of the total radioactivity in the plasma after a 6-h drug infusion. There were three other metabolites in plasma, two more polar than pyrazine-2-diazohydroxide, which accounted for 7% of the radioactivity, and one less polar, which accounted for 5% of the radioactivity. Following an i.v. bolus dose of [2-14C]pyrazine-2-diazohydroxide, 79% of the radioactivity was excreted in the urine in 24 h, 3% in the feces, and 0.4% in the expired air; 18% remained in the carcass. The liver and kidney showed the highest tissue levels of radioactivity. 2-Hydroxypyrazine accounted for 45% of the urinary radioactivity, pyrazine-2-diazohydroxide for 14%, and a glucuronide or sulfate conjugate of 2-hydroxypyrazine for 17%. Twenty-four percent of the radioactivity eluted near the void volume on high-performance liquid chromatography and was not identified.

Animals↗

Childhood trichotillomania treated indirectly by punishing thumb sucking.

Trichotillomania was treated in a developmentally normal three-year-old by punishing thumb sucking. A behavioral analysis indicated a chain of behaviors that began with hair pulling and terminated in thumb sucking. The parents punished the thumb sucking by applying a bad tasting substance to the thumb. Both hair pulling and thumb sucking were rapidly eliminated. The child remained symptom free at 40 month follow-up. This study represents the third time trichotillomania has been treated in a preschooler indirectly by targeting finger sucking as the behavior to change. The significance of treating trichotillomania indirectly is discussed.

Behavior Therapy↗

Mitochondrial DNA of the human malarial parasite Plasmodium falciparum.

Covalently closed circular DNA molecules were isolated from Plasmodium falciparum total DNA by isopycnic centrifugation in CsCl gradients containing either ethidium bromide or 2',6-diamidino-2-phenylindole. The circular molecules had an average contour length of 11.1 +/- 0.5 micron, similar to the analogous molecules previously isolated from the simian malaria parasite P. knowlesi. Both circular molecules shared considerable sequence homology and conserved restriction sites. The nucleotide sequence of one 936 bp fragment of the P. falciparum molecule was determined and identified, by a data base homology search, as part of a mitochondrial small rRNA subunit, thus confirming the mitochondrial origin of the circular DNAs of both malarial species.

Animals↗

Breath hydrogen response to milk containing lactose in colicky and noncolicky infants.

In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.

Breath Tests↗

Assessment of arterial disease using digital systolic pressure measurement.

Digital systolic pressure measurements were made on 140 big toes using a photoplethysmographic technique before and after extrinsic heating of the foot. Most patients with apparent, critically ischemic feet demonstrated vasomotor activity, suggesting that much of the microcirculation of the foot was in fact intact. Significantly, nine of 21 feet which would have fallen into a critically ischemic category were recategorized after heating into a less severe group. These data confirm the value of toe pressure measurements in the assessment of severe ischemia but show that adequate foot vasodilation is essential to allow accurate conclusions to be drawn and to allow meaningful interpretation of results.

Adult↗

Duplex ultrasonography and selection of patients for carotid endarterectomy: plaque morphology or luminal narrowing?

Percentage of carotid stenosis and plaque morphology as determined by duplex scanning were correlated with symptoms and CT evidence of infarction in 108 patients. Severity of carotid stenosis less than 49% or greater than 50% narrowing was not associated with an increased risk of ipsilateral symptoms or CT infarction. However, a heterogeneous plaque appearance, suggesting intraplaque hemorrhage, did correlate with ipsilateral cerebral symptoms. Heterogeneous plaque appearance may be a more reliable indication for carotid endarterectomy than a hemodynamically significant stenosis.

Aged↗

The use of chlorhexidine in the management of gingivitis in children.

Two double-blind studies were conducted in 191 children in Mexico. Following a dental prophylaxis, either a 0.12% chlorhexidine gluconate mouthrinse or a placebo was used under supervised conditions in comparable groups twice per day. The chlorhexidine treatments resulted in a significant decrease of gingivitis when compared to the placebo rinse. Although superficial mucosal desquamations were seen in some chlorhexidine users, they were transient and without discomfort. The increase of cosmetic side effects, e.g., dental stain and supragingival calculus, was without consequence to the gingival health of the subjects. The use of a chlorhexidine rinse twice per day and as adjunct to regular oral hygiene procedures achieved a considerable benefit against gingivitis in children in two studies extending over ten and 12 weeks.

Adolescent↗

A high-performance liquid chromatography assay for measuring integrated biphenyl metabolism by intact cells: its use with rat liver and human liver and kidney.

A rapid, sensitive high-performance liquid chromatography assay with fluorescence detection for measuring biphenyl metabolism by intact cells has been developed. The assay does not require organic solvent extraction or enzymatic digestion for the measurement of hydroxybiphenyl conjugates. The lower limit of detectability for 4-hydroxybiphenyl is 5 pmol injected. Rat hepatocytes incubated with biphenyl form predominantly 4-hydroxybiphenyl sulfate with lesser amounts of 4-hydroxybiphenyl glucuronide and free hydroxybiphenyls, and small amounts of 3-hydroxybiphenyl sulfate and 3-hydroxybiphenyl glucuronide. Slices of fresh human liver incubated with biphenyl form predominantly 4-hydroxybiphenyl glucuronide with some free hydroxybiphenyl and small amounts of 4-hydroxybiphenyl sulfate. 4-Hydroxybiphenyl glucuronide formation by human liver shows a lag time that is not abolished by preincubating the liver without substrate. Human kidney slices incubated with biphenyl form 4-hydroxybiphenyl glucuronide and 4-hydroxybiphenyl sulfate at rates less than one-tenth those seen with human liver. Human kidney slices do not form detectable free hydroxybiphenyl. There is wide intersubject variability in the rates of hydroxybiphenyl metabolite formation by human liver and kidney.

Animals↗

Duplex scanning for noninvasive assessment of both carotid luminal diameter and atheromatous plaque morphology.

The value of Duplex scanning in 50 consecutive patients with symptomatic carotid stenosis was evaluated. Compared with contrast arteriography, the sensitivity of Duplex scanning, for a greater than 50% internal carotid diameter reduction, was 90% (66/73) with a specificity of 96% (26/27). The overall agreement between Duplex and contrast arteriography as measured by the Kappa value was K = 0.561. One of the 13 arteries felt to be occluded on Duplex scanning was radiologically found to be patent. Excluding the six normal and 13 occluded arteries, 81 carotid plaques were defined as either heterogeneous, suggestive of intraplaque hemorrhage or as homogeneous. Twenty-four of the 32 asymptomatic cerebral hemispheres were associated with ipsilateral homogeneous plaques, while 30 of the 49 symptomatic hemispheres had heterogeneous plaques in the ipsilateral carotid, (p less than 0.001). This study confirms the accuracy of duplex scanning in detecting internal carotid stenosis as well as in identifying plaques which are morphologically heterogeneous and more likely to be associated with ipsilateral cerebral hemispheric symptoms.

Aged↗

Gas chromatographic assay for the new antitumor agent pyrazine-2-diazohydroxide (diazohydroxide) and its stability in buffer, blood and plasma.

Diazohydroxide is a new antitumor agent being considered for clinical trial. A sensitive and specific assay for diazohydroxide in physiological media, plasma and blood has been developed based on conversion of diazohydroxide to 2-chloropyrazine in the presence of strong hydrochloric acid. The 2-chloropyrazine is extracted into the ethyl acetate and separated by capillary gas chromatography with nitrogen-phosphorus detection. Using 0.2 ml plasma the assay was linear up to 100 micrograms/ml diazohydroxide and had a lower limit of detectability for diazohydroxide of 50 ng/ml. The coefficient of variation of the assay at 1 micrograms/ml was 6.7%. Breakdown of diazohydroxide was rapid under mild acid conditions but slower under alkaline conditions,. The half-life of diazohydroxide in 0.1 M sodium phosphate buffer, pH 6.0, at room temperature was 5 min and at pH 8.0, 480 min. Breakdown of diazohydroxide in plasma was biphasic. In fresh mouse plasma diazohydroxide had a terminal half-life at 37 degrees C of 72 min while in fresh human plasma the terminal half-life was 23 min and in fresh blood 21 min. Diazohydroxide accumulated in red blood cells at 37 degrees C to a concentration 68% above the concentration in plasma. Diazohydroxide was 49% bound to human plasma proteins at room temperature.

Animals↗

Percutaneous laser thermal angioplasty: initial clinical results with a laser probe in total peripheral artery occlusions.

A metal-tipped laser fibre was used during percutaneous angioplasty of femoral/popliteal or iliac artery occlusions in 56 patients. Primary success was achieved in 50 (89%) of these total occlusions, providing a channel for subsequent balloon dilatation. Before the procedure, 18 lesions had been judged untreatable by conventional angioplasty and four of the six failures were in these. Complications directly attributable to the laser probe were one case of vessel perforation and two cases of entry into vessel walls; these had no sequelae. Other acute complications were a distal thrombosis in a non-heparinised patient, requiring local streptokinase treatment, and two reocclusions and one transient peripheral embolic episode in the first 24 hours. The laser probe technique has potential for increasing the proportion of patients suitable for angioplasty.

Aged↗

Herpes simplex oesophagitis in young children.

Herpes simplex oesophagitis is usually associated with debilitated, traumatized or immunologically-compromised hosts. We report here two cases of severe self-limiting oesophagitis in immunologically competent young children that were caused by herpes simplex type 1. This diagnosis should be considered in the differential diagnosis of acute severe pain on swallowing in children for whom oral and pharyngeal pathology have been excluded.

Child↗

Disposition and metabolism of the antitumor glycoside phyllanthoside in mouse and beagle dog.

Phyllanthoside is a naturally occurring glycoside with activity against IP transplantable murine tumors. Phyllanthoside administered IV, to mice at a nontoxic dose of 16 mg/kg could not be detected in blood or plasma even 30 s after administration. There was rapid formation of a less polar metabolite, which disappeared with a half-life of about 10 min. When phyllanthoside was administered as an IV bolus to beagle dogs at doses of 0.1, 0.5, and 3.0 mg/kg the mean half-life of phyllanthoside elimination from plasma was 1.3 min and total body clearance 85.8 ml min-1 kg-1. A second phase of elimination was seen but could not be accurately defined. Only trace amounts of the less polar metabolite were detected in dog plasma. Infusion of phyllanthoside to beagle dogs at doses of 0.5 and 3.0 mg/kg over 70 min gave values for an initial half-life of 0.3 and 0.6 min, a terminal half-life of 99.4 and 16.5 min, and a total body clearance of 11.2 and 49.2 ml min-1 kg-1, respectively. The highest nontoxic dose of phyllanthoside in dog was 0.1 mg/kg, while doses of 0.5 mg/kg and 3.0 mg/kg resulted in ataxia and death of the dog. There was no difference in toxicity to dog according to whether phyllanthoside was given by IV bolus or continuous infusion. Isolated hepatocytes from rat metabolized phyllanthoside at a rate of 4.4 micrograms/min per 10(6) cells to form the less polar metabolite. Coculture with isolated hepatocytes decreased the cytotoxicity of phyllanthoside to A204 human rhabdomyosarcoma cell line growing in soft agarose. It is suggested that rapid metabolism of phyllanthoside in mouse as against dog might account for the lower toxicity of phyllanthoside in mouse, and might also account for the reported poor antitumor activity of IV-administered phyllanthoside in the mouse.

Animals↗

Angiographically-induced infection of the aorta.

We present three cases of infection of the native aorta following angiography. The infection was an incidental finding at operation in two patients, while a third presented with fulminant sepsis. All had debridement of the retroperitoneum and underwent successful extraanatomic bypass. We feel caution is warranted in placing a retroperitoneal graft even in suspected aortic sepsis. Prophylactic antibiotics may be advisable to protect against infection of atherosclerotic plaque during angiography.

Aged↗