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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 415 records · Page 23Linked to original sources

A longitudinal study of the prostaglandin content of central nervous system tissues from guinea pigs with acute experimental allergic encephalomyelitis (EAE).

The levels of prostaglandins (PGs) E, F2 alpha and 6-oxo-PGF1 alpha, in spinal cords and cerebellums of guinea pigs were measured during the development of experimental allergic encephalomyelitis (EAE). The earliest change observed was an elevation of PGE in spinal cords, but not cerebellums , 5-7 days post-inoculation (PI) and prior to the appearance of clinical symptoms. PGE content of spinal cords continued to rise until days 12-14 PI when the animals displayed paralytic EAE. In contrast, PGF2 alpha and 6-oxo-PGF1 alpha levels in spinal cords peaked on days 9-11, when the animals exhibited initial clinical signs, but fell to lower values by days 12-14 PI. In cerebellums , the PGE content increased more slowly than in spinal cords, consistent with the lower numbers of mononuclear cell infiltrates, whereas PGF2 alpha and 6-oxo-PGF1 alpha levels remained unaltered. The relationships between the observed changes in prostanoid levels, lesion development and the appearance of clinical symptoms are discussed.

6-Ketoprostaglandin F1 alpha↗

Subacute apomorphine injections in rats: effects on components of behavioral stereotypy.

This study was aimed at documenting the changes in the frequency and duration of bouts of behavior of Sprague-Dawley male rats in the open-field following each of four injections of apomorphine (Apo, 5 mg/kg, sc, immediate), or normal saline, delivered at 3-day intervals. Independent quantification of locomotion, sniffing, rearing, grooming, inactivity, gnawing, nodding, and jumping was obtained continuously throughout the 78-min sessions. Apo eliminated grooming and inactivity on all sessions. The large increases in locomotion and sniffing seen in the Apo rats compared to the saline rats on the first session were sustained throughout subsequent sessions. However, the Apo-induced potentiation of nodding of the head and gnawing, seen acutely, declined across sessions. These observations reconcile inconsistencies in the literature on subacute Apo effects. Finally, the individual differences in behavioral scores of Apo-treated rats were more stable than were those of saline-treated rats. This finding supports evidence in the literature that individual differences in neurochemistry are more likely to be predicted from the behavioral scores of Apo-challenged rats than from the scores of untreated rats.

Animals↗

Transient hypercalciuria after commencing total intravenous nutrition.

A study of 28 patients receiving a standard regimen of total intravenous nutrition (I.V.N.) for periods of > 14 days has shown the transient development of hypercalciuria in 14 patients (50%). The peak incidence of hypercalciuria occurred in 11 patients (39%) after 1 week of I.V.N. and hypercalciuria persisted for 1-4 weeks. In only one patient was hypercalciuria present at the end of the treatment period. Urine calcium (Ca) and nitrogen (N) excretion rates correlated significantly (r = 0.48 p < 0.001) and urine N excretion varied from week to week in parallel with urine Ca excretion in the hypercalciuric group of patients. There was no significant difference in urine Ca excretion between 12 patients who received 3.75 mmol Ca/day and 16 patients who received 8.75 mmol Ca/day. It is concluded that transient hypercalciuria may be related to increased protein catabolism and N excretion and that it probably does not indicate a major problem in mineral metabolism.

Journal Article↗

Pseudoaneurysm of the pulmonary artery after the banding procedure: two-dimensional echocardiographic description.

This report describes an infant with double-outlet right ventricle who underwent pulmonary artery banding as palliation for excessive left to right shunting through a ventricular septal defect. Three weeks after this procedure, there was abrupt clinical deterioration, and two-dimensional echocardiography clearly defined a large pseudoaneurysm arising from a breach in the posterior pulmonary artery wall, just proximal to the band. The diagnosis was confirmed at surgery, during which total correction was performed with successful outcome. The two-dimensional echocardiographic features of a pseudoaneurysm of the pulmonary artery are shown and the role of this noninvasive technique in the evaluation of pulmonary artery bands is discussed.

Aneurysm↗

Pseudolymphoma of the tongue mimicking Hodgkin's disease. (A case report).

We have presented a case of what we believe to be pseudolymphoma arising on the dorsal aspect of the anterior part of the tongue in a middle-aged male with histological features initially suggestive of Hodgkin's disease. The nature and significance of pseudolymphoma have been discussed, together with a critical review of the relevant literature and a suggested outline of management for patients with this type of lesion.

Diagnosis, Differential↗

Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route.

The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Animals↗

Synthesis and kinetic studies of protease substrates containing the 1-methyl-6-aminoquinolinium ion as a fluorogenic leaving group.

Several sensitive substrates for porcine pancreatic elastase, chymotrypsin, and trypsin were prepared that utilize the permanently charged, fluorogenic cation 1-methyl-6-aminoquinoline (MAQ+) as the leaving group. Kinetic rates for the hydrolysis of substrates were determined fluorimetrically and compared with analogues having 6-aminoquinoline (6-AQ) as an uncharged leaving group. It was found that substrates containing the quaternized leaving group generally have a higher kcat/Km ratio. An exception to this trend was noted with a trypsin substrate, Bz-DL-Arg-MAQ+. During the course of this investigation, several significant advantages of the MAQ+ ion as a fluorogenic leaving group in protease substrates were found: (a) its appearance can be measured fluorimetrically using wavelengths of light that result in its maximal fluorescence, while under these conditions, the unhydrolyzed substrate is essentially nonfluorescent, (b) it confers a high degree of water solubility to hydrophobic peptides, thereby eliminating the need for organic cosolvents to dissolve substrates, and (c) quaternized substrates can be prepared readily and in good yield from the corresponding 6-(peptidylamido)quinolines. These positively charged synthetic fluorogenic substrates are, therefore, useful probes for investigating the steric and electronic properties of the active-site environment of proteolytic enzymes.

Aminoquinolines↗

Treatment of inoperable non-small cell carcinoma of the lung with radiation therapy, with or without levamisole. A randomized trial of the Southeastern Cancer Study group.

In a randomized trial, 251 patients with inoperable non-small cell lung cancer received radiation therapy (RT) with or without levamisole (2.5 mg/kg twice weekly for 1 year, or until progression). Radiation therapy was delivered to 6000-6500 rad for Stages I and II, and 4000-4500 rad by continuous or split course for Stage III disease. Responses were observed in 40% of patients receiving placebo, and in 29% of patients taking levamisole. Relapse occurred at local sites only in 53% of the placebo- and 75% of the levamisole-treated patients. The frequency of relapse in distant sites was lower (25%) in the levamisole group as compared with the placebo group (47%). No significant difference in survival was observed between the placebo and levamisole-treated groups (median survival, 48.2 and 45 weeks, respectively). Responders to radiotherapy survived significantly longer than nonresponders (median survival, 73 vs. 33.3 weeks, p = 0.001). Among responders, the median survival of patients treated with levamisole was shorter (63.9 weeks) than that of patients receiving placebo (92.7 weeks). Toxicity attributable to levamisole included severe granulocytopenia in five patients and severe nausea and vomiting in nine. It is concluded that levamisole is without significant benefit in this setting.

Adenocarcinoma↗

Contrasting effects of subcutaneous pulsatile GnRH therapy in congenital adrenal hypoplasia and Kallmann's syndrome.

A patient with congenital adrenal hypoplasia (AH) and hypogonadotrophic hypogonadism was treated with pulsatile subcutaneous GnRH therapy for 16 weeks in an attempt to induce puberty. No rise in serum LH or FSH concentrations occurred despite increasing doses of GnRH (2.8 micrograms/pulse-22.4 micrograms/pulse). In contrast a similar programme of therapy successfully initiated the biochemical changes of puberty in a patient with Kallmann's syndrome. Both patients before therapy had low basal serum LH and FSH concentrations with blunted LH and FSH responses to GnRH stimulation. After 1 week, serum LH and FSH rose into the normal adult range in the patient with Kallmann's syndrome. This study fails to confirm a previous report which suggested that intermittent low dose GnRH therapy may be of value in inducing puberty in AH. The reasons for the difference of pituitary responsiveness to GnRH in AH and Kallmann's syndrome are unclear at present.

Adrenal Glands↗

Dialysis access fistulas: treatment of stenoses by transluminal angioplasty.

Fifty-six balloon dilatations in 51 patients with upper-extremity dialysis access fistulas were performed over a 4-year period. Forty-four venous anastomotic lesions in patients with either internal or graft fistulas were dilated. Three arterial anastomotic lesions and nine distant venous stenoses were treated. Thirty-nine of 56 (70%) dilatations were initially successful. Of the initial successes, 28/35 (80%) were patent at 3 months, 19/27 (70%) at 6 months, 12/22 (55%) at 1 year, 7/14 (50%) at 2 years, and 3/9 (33%) at 3 years. Three complications (5%) were encountered. These included two graft thromboses and one pseudoaneurysm at the dilatation site. The procedure may be performed on an outpatient basis.

Adult↗

Effects of saline infusion on titratable acid generation and ammonia secretion.

Short-term hyperchloremic metabolic acidosis can decrease sodium reabsorption by the superficial proximal tubule (PT), increase tubular fluid flow rate, and stimulate aldosterone release. We studied the effects of increased tubular fluid delivery (graded saline infusion) and mineralocorticosteroid administration on tubular fluid pH (TFpH), titratable acid (TA) generation, and ammonium (NH+4) secretion by superficial proximal and distal tubules (DT) of acidotic, phosphate-loaded rats. The TFpH was 6.4 +/- 0.1 at the late proximal tubule (LP); it was unaltered at the early (ED) or late distal tubule (LD), but urine pH (UpH) was 1 unit lower. The major fraction of TA or NH+4 was formed in the superficial PT. There was no net TA generation by the superficial DT even during supplemental mineralocorticosteroid and increased Pi delivery during saline infusion. TA excretion was increased only slightly by saline infusion in acidotic rats despite increased buffer delivery (caused by decreased Pi reabsorption, primarily in the loop segment) because this was offset by a rise in UpH. Ammonia was secreted into tubular fluid in the superficial PT and DT; there was loss of NH+4 in the loop segment and addition after the LD. Saline infusion did not modify TFpH in the PT or DT but increased NH+4 secretion by the DT in direct proportion to tubular fluid flow. DOCA administration increased the addition of NH+4 between the LD and the urine. In conclusion 1) the superficial PT is of major importance for acidification, generation of TA, and secretion of NH+4 in short-term metabolic acidosis. 2) The superficial DT does not generate TA even during dramatically high rates of buffer delivery and mineralocorticosteroid administration. 3) Excretion of NH+4 is increased by saline infusion, which leads to flow-dependent NH+4 secretion by the superficial DT. 4) Chronic administration of DOCA stimulates NH+4 secretion predominantly in the terminal or deep nephrons.

Acidosis, Renal Tubular↗

Sudden infant death syndrome: abnormalities in short term fluctuations in heart rate and respiratory activity.

In order to test the hypothesis that a defect in cardiorespiratory regulation contributes to death of infants from sudden infant death syndrome (SIDS), we analyzed the power spectra of heart rate and respiratory activity during 256-sec epochs of quiet sleep. Data were obtained from pneumogram recordings performed for 12 h at night on eight infants who subsequently died from SIDS and 22 age-matched control infants. We computed the heart rate and respiratory power spectra from a single epoch on each infant using an algorithm developed for an 8085 microprocessor system dedicated to this investigation. There was no statistically significant difference between SIDS and controls based on mean respiratory and heart rates. Spectral analysis revealed enhancement of low frequency power in the 0.02 to 0.1 Hz band in the heart rate power spectrum in the SIDS group compared to control (p less than 0.002) and dispersion in respiratory frequency as determined by the respiratory band width (p less than 0.00001). These data suggest that a predisposition to SIDS manifests itself in an abnormal pattern of fluctuations in heart rate and respiratory activity.

Female↗

Catheter separation during coronary angiography.

Complete fracture and separation of a right coronary Judkins catheter during coronary angiography is presented. The possible mechanism underlying the separation and retrieval of the catheter fragment is described.

Angiography↗

The epidemiology of plasma renin.

1. The epidemiological characteristics of plasma renin activity (PRA) were established in 1999 members of occupational groups in North and West London. 2. The main finding was that PRA was inversely associated with systolic blood pressure in men, the percentage fall in PRA (on a log scale) being 8.4% for each increase of one standard deviation in systolic blood pressure. There was a less obvious inverse relationship in women. 3. However, blood pressure accounted for less than 1% of the variance in PRA. 4. Mean PRA in both smokers and ex-smokers was about 20% higher than in non-smokers. 5. PRA fell with increasing age, was lower in women than in men and considerably lower in blacks (of either sex) than whites. 6. PRA was lower in the first quarter of the menstrual cycle than in the rest of the cycle. 7. Haemoglobin, blood cholesterol, leucocyte count and Factor VIII were positively correlated with PRA. 8. PRA was lower in men with diagnosed hypertension than in those without; there was no significant difference in the women. 9. PRA was lower in those who had had myocardial infarcts in the past than in those who had not. 10. The data as a whole suggest that it may be low, not high, levels of PRA which are associated with increased risks of cardiovascular disease in which hypertension is a predisposing factor. 11. The explanation may be a homoeostatic fall in PRA in response to a rise in blood pressure rather than a major causal role for PRA in the pathogenesis of essential hypertension and target-organ damage.

Adult↗

Calcium antagonists and the acutely ischemic heart: experimental effects on ventricular fibrillation and enzyme release.

To investigate and to compare the protective action of verapamil, nifedipine and diltiazem on the acutely infarcting myocardium, we studied effects on cellular damage and mechanical function in the isolated working rat heart preparation subjected to left main coronary artery ligation. First, the fall in the ventricular fibrillation threshold (VFT) was diminished by all three agents, but non-specific effects of these agents were operating at least in part. All three compounds afforded substantial dose-dependent reduction of lactate dehydrogenase release, which was taken as an index of cellular damage, and preserved ATP stores in the infarcting myocardium. The range of effective concentrations was small and close to doses which produced atrioventricular conduction disturbances (verapamil, diltiazem) or LV pump failure (nifedipine). It is argued that these concentrations may be therapeutically relevant, whereas the concentration of a beta-adrenoceptor antagonist agent required comparably to inhibit enzyme release was supra-therapeutic (metoprolol 10(-4) M). There are substantial differences between such animal models and the situation in acute myocardial infarction in man, where preliminary data show benefits both for beta-adrenergic blockade by sotalol and for calcium antagonism by nifedipine.

Adrenergic beta-Antagonists↗