Search PubMed⌕ Search

Biomedical subjects

D Ross

Publications and source records attributed to D Ross.

At least 325 records · Page 18Linked to original sources

Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium.

Carcinogen-induced primary intestinal adenocarcinomas serve as a useful animal model for human colonic adenocarcinomas. Although striking similarities between this model and the human disease state exist, there are also troublesome discrepancies-a major one being the reported lack of an adenoma-carcinoma sequence in the experimental model. However, the original morphologic descriptions of these experimental neoplasms predated the development of presently accepted morphologic criteria that have been used to describe the adenoma-carcinoma sequence in humans. Therefore, the authors reevaluated the structural evolution of dimethylhydrazine-induced rat intestinal neoplasms, using the same criteria that were recently applied to evaluate human colonic adenocarcinomas. Such an approach shows that many dimethylhydrazine-induced intestinal adenocarcinomas have peripheral foci of adenomatous epithelium associated with them. In addition, the frequency of this association correlates inversely (P less than .001) with the depth of invasion. These findings are comparable to those which, in humans, have been used as evidence supporting the adenoma-carcinoma sequence. Thus, when assessed with equivalent criteria, dimethylhydrazine-induced intestinal adenocarcinomas appear to be similar, not dissimilar, to human colonic adenocarcinomas in their structural evolution. These data suggest that, at least in part, dimethylhydrazine-induced intestinal adenocarcinomas arise in foci of preexisting adenomatous epithelium.

Adenocarcinoma↗

The formation and metabolism of N-hydroxymethyl compounds--I. The oxidative N-demethylation of N-dimethyl derivatives of arylamines, aryltriazenes, arylformamidines and arylureas including the herbicide monuron.

The metabolism of the N-methyl moieties of aryldimethylamines and N-methyl compounds of the general formula Aryl-X-N(Me)2, where X is either -N=N-(3-aryl-1, 1-dimethyltriazenes). -NHCO- (N'-aryl-N,N-dimethylureas) or -N=CH- (N'-aryl-N,N-dimethylformamidines) was studied using mouse liver microsomes. Products of microsomal metabolism were reincubated with mouse liver homogenate devoid of microsomes and assayed colourimetrically for formaldehyde. This allows metabolically generated formaldehyde to be distinguished from formaldehyde precursors. Whereas the N-methyl moieties of the aryldimethyltriazenes, formamidines and amines were metabolised to formaldehyde, the aryldimethylureas formed stable formaldehyde precursors upon metabolism. The products of metabolism of one such aryldimethylurea, the herbicide monuron (N'-(4-chlorophenyl)-N, N-dimethylurea) were investigated using a high pressure liquid chromatographic method. Two metabolites were found on incubation of monuron with microsomes, one of which was identified as the N-desmethyl compound by mass spectrometry. The other product showed chromatographic properties similar to 4-chlorophenylurea but resembled the monomethylaryl urea on mass spectral analysis. It is concluded that this metabolite is likely to be N'-(4-chlorophenyl)-N-hydroxymethyl-N-methylurea. A urinary product of conjugative metabolism obtained after the administration of monuron to mice also gave the mass spectrum of the monomethyl compound after deconjugation which suggests that a conjugated N-hydroxymethyl compound may have been formed in vivo.

Amines↗

Studies of the mode of action of antitumour triazenes and triazines--IV. The metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene.

The metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene has been studied in vivo and in vitro in mice. This dimethyltriazene was extensively metabolised in vivo and HPLC analysis of the plasma revealed the presence of two metabolites, the monomethyltriazene, 1-(4-acetylphenyl)-3-methyltriazene, and the arylamine, 4-aminoacetophenone. The dimethyltriazene was also biotransformed in vitro by a 9000 g fraction of mouse liver homogenate to products which were selectively toxic to TLX5 lymphoma cells. HPLC analysis of the products of in vitro metabolism under these conditions showed the presence of the monomethyltriazene but in an amount insufficient to account for the observed cytotoxicity. The monomethyltriazene was itself rapidly biotransformed by a 9000 g fraction of mouse liver homogenate, and by isolated mouse hepatocytes.

Animals↗

Aortic regurgitation in tetrad of Fallot and pulmonary atresia.

Data on 18 patients, aged 12 to 42 years, with documented aortic regurgitation and tetrad of Fallot or pulmonary atresia with ventricular septal defect were reviewed. In two patients, aortic regurgitation was caused by surgical repair but in the others it was present before operation. There was increased volume overload from a long-standing surgical shunt (8 to 30 years' duration) or congenital systemic collateral vessels in 14. Six patients with a history of infective endocarditis had aortic cusp perforations. Failure to detect the presence of aortic regurgitation before radical repair in six patients contributed to operative problems and postoperative morbidity and mortality. Aortic valve surgery was performed in 13 patients. Aortic regurgitation is an acquired complication that should be specifically excluded by routine retrograde ascending aortography in all adolescents or adults with tetrad of Fallot or pulmonary atresia with ventricular septal defect. Earlier radical repair in the first decade of life may prevent the complication.

Adolescent↗

N-methylformamide: antitumour activity and metabolism in mice.

The antitumour activities of N-methylformamide, N-ethylformamide and formamide against a number of murine tumours in vivo (Sarcoma 180, M5076 ovarian sarcoma and TLX5 lymphoma) have been estimated. In all cases N-methyl-formamide had significant activity, formamide had marginal or no activity and N-ethylformamide had no significant activity. N-methylformamide and N-ethylformamide were equitoxic to the TLX5 lymphoma in vitro. Formamide was found as a metabolite in the plasma and urine of animals given N-methylformamide and N-ethylformamide, but excretion profiles do not support the hypothesis that formamide is an active antitumour species formed from N-alkylformamides. No appreciable metabolism of N-methylformamide occurred under a variety of conditions with liver preparations in vitro. N-methylformamide, but not N-ethylformamide or formamide, reduced liver soluble non-protein thiols by 59.8% 1 h after administration of an effective antitumour dose.

Animals↗

Isolation and characterization of cDNA clones for human apolipoprotein A-I.

We have isolated cDNA clones encoding human apolipoprotein (apo) A-I. Twenty putative apo A-I cDNA clones were selected by screening 10,000 clones of an adult human liver cDNA library with an oligonucleotide probe. The probe was a mixture of synthetic 14-base-long DNA oligomers constructed to correspond to the codons for apo A-I amino acids 105-109. Four of these clones were examined further and showed 600- to 800-base-pair (bp) inserts. Preliminary restriction mapping and partial DNA sequence analysis indicated that the shorter inserts were a subset of the longer DNA inserts. DNA sequence analysis of the clone with an insert of approximately equal to 600 bp, designated pAI-113, revealed that it contained a DNA sequence corresponding to apo A-I amino acids 94-243. The DNA base sequence of this clone also contained a standard termination codon, polyadenylylation signal, and poly(A) tail. Partial DNA sequence of a second clone that contained an 800-bp insert, designated pAI-107, showed that it corresponded to apo A-I amino acids 18-243 and also included the 3' untranslated region. Isolation of these cDNA clones will facilitate molecular analyses of apolipoproteins in normal and disease states.

Amino Acid Sequence↗

Antiarrhythmic efficacy of amiodarone in recurrent ventricular tachycardia evaluated by multiple electrophysiological and ambulatory ECG recordings.

Thirty-three patients with recurrent drug-refractory ventricular tachycardia were treated with oral amiodarone during an average period of 6.1 months. In-hospital monitoring for two weeks or more, electrophysiological tests and ambulatory ECG were used to evaluate the results. Twenty patients are still using the drug with complete control of the arrhythmia. Eleven have failed the drug, ten due to recurrence of documented ventricular tachycardia. Only three patients failed after the first month of therapy. Two patients died, one suddenly. The drug was discontinued in a further two patients due to side-effects. Other side-effects were tolerable or manageable by dose adjustments alone. Five patients showed evidence of inadequate arrhythmia control between days 15 and 32 of therapy but subsequently responded to the drug for 4-9 months, giving further support to the concept that in some patients at least 30 days of therapy is necessary for the full effect of the drug to appear. In 16 of the 20 patients tested by arrhythmia induction study while on the drug, ventricular tachycardia could still be induced. Seven (44%) of these eventually failed the drug. Arrhythmia recurred in one of those four in whom tachycardia could not be induced. Amiodarone is a valuable drug in the management of recurrent ventricular tachycardia, refractory to other antiarrhythmic drugs.

Adult↗

Open aortic valvotomy for congenital aortic stenosis. Late results.

Forty-nine consecutive patients, aged 2 to 28 years, were followed after open aortic valvotomy. Three late deaths occurred in relation to reoperation. Seventeen reoperations were performed 2 to 14 years after valvotomy for severe stenosis in 12 patients, aortic regurgitation in three patients, and aortic stenosis and regurgitation in two patients. Among the 12 patients who required reoperation for severe obstruction, five aged over 19 years had calcified valves with normal aortic roots and valve replacement was simple. Seven had tunnel obstruction with a hypoplastic aortic root, constituting a difficult surgical problem, and necessitating total aortic root replacement in four. The postoperative course after simple aortic valvotomy is determined by several factors; the basic pathological form of the obstruction is the most important. Those who present in the first decade with lumpy valves and small aortic roots tend to form a diffuse tunnel obstruction when residual stenosis remains after valvotomy; older patients with pliable domed valves slowly develop calcified cusps and present less problems as the aortic root is usually a good size. Although aortic valvotomy offers good early results with a low mortality, it should be regarded as palliative as all patients will ultimately require reoperation. Younger patients with lumpy valves and a small aortic root have more problems and may require different initial management.

Adolescent↗

Homograft replacement of aortic root with reimplantation of coronary arteries. Results after one to five years.

Between 1976 and 1980, 26 patients aged 7 to 36 years had complete replacement of the aortic root with a valved homograft into which the coronary arteries were reimplanted. The main indication was the tunnel type of obstruction combining a hypoplastic valve ring, often with supra and subvalvar stenosis. Nineteen had previous operations for congenital left ventricular outflow obstructions. There was one perioperative death and one late death from progressive pulmonary vascular disease. Relief of left ventricular outflow tract obstruction was achieved in a majority of cases and the valves were entirely competent. With increasing experience, the initial problems of malalignment and torsion of the coronary arteries and complete heart block have been largely overcome. This operation provides an alternative technique for the management of diffuse left ventricular outflow tract obstruction and related problems in young patients. The long-term results of aortic homografts are well documented, and by eliminating the problems of aortic regurgitation it is anticipated that this may represent an advance in treatment.

Adolescent↗

Plasma concentrations of LH, prolactin, oestradiol and progesterone in female red deer (Cervus elaphus) during pregnancy.

Peripheral blood samples were collected throughout pregnancy from 11 red deer hinds. During the same period, 6 other hinds which mated but failed to produce calves were also sampled. Pretreatment of some of these hinds included synchronization of oestrus alone (N = 3) or with injection of 1000 i.u. PMSG (N = 9). During early and mid-pregnancy, LH and prolactin were frequently undetectable. Prolactin concentrations in pregnant and non-pregnant hinds were high (greater than 250 ng/ml) in December-January. The results of the hormone analyses suggested that the amount of progesterone in plasma correlates with the number of corpora lutea (CL) present. The concentrations of oestradiol and progesterone were low from mid-winter onwards in the non-pregnant hinds, suggesting a reduction in ovarian activity at this time. In pregnant animals, progesterone concentrations were high for the first 200 days of gestation. Oestradiol rose to peak values concomitant with declining progesterone concentrations just before parturition.

Animals↗

Studies of the pharmacology of N-methylformamide in mice.

When 400 mg/kg of 14C-methyl-labeled N-methylformamide (NMF) was injected ip into mice, the curve for plasma concentration of radioactivity versus time was superimposable on the curve obtained by measuring unmetabolized NMF with gas-liquid chromatography during the first 24 hrs. Radioactivity in plasma was measurable for 8 days after NMF administration, but NMF was not measurable by gas chromatography beyond 24 hrs after administration. Radioactivity was eliminated from the plasma after 60 hrs, with an apparent half-life of 71.1 hrs. Of the radioactivity injected with NMF, 73.6% was recovered in the urine in 24 hrs; 26.4% of this was unchanged NMF. Three percent of the administered radioactivity was exhaled as 14CO2 in 7 hrs at a constant rate of 0.007% per min. One urinary metablite was a stable precursor of formaldehyde, which decomposed to formaldehyde only after alkaline hydrolysis and may well be N-(hydroxymethyl)-formamide. The areas under the plasma concentration versus time curve were estimated after ip, iv, and oral administration of NMF. The bioavailability of NMF was 1.01 after oral administration and 1.10 after ip administration.

Administration, Oral↗

[Nerve transplantations in the upper extremity with autologous grafts].

The paper deals with the technique and indications of interfascicular nerve grafting. The operative technique and problems as well as new ideas are described. When the results published in this operative technique are compared, the following tendency is seen: some teams of microsurgeons have nearly the same excellent results after transplantation as after primary suture, while other teams have significantly more failures with transplantation. The problems with follow-up studies and the different methods of postoperative examination are discussed, as are the results of some of the teams.

Arm↗

Malignant ventricular tachyarrhythmias associated with the use of encainide.

In patients treated with the antiarrhythmic drug, encainide, the agent appeared to cause or exacerbate malignant ventricular tachyarrhythmias in 11 cases. The most common type of arrhythmia associated with encainide toxicity was polymorphic ventricular tachycardia (VT) resulting in cardiac arrest. In contrast to drug-induced arrhythmias commonly encountered with quinidine and other type I antiarrhythmic drugs, encainide-induced rhythm was not associated with marked QT prolongation, was not necessarily initiated by R-on-T premature ventricular beats, and usually did not self-terminate. Two patients could not be resuscitated from the rhythm, and several others required prolonged or multiple resuscitations. The risk of encainide-induced ventricular tachyarrhythmias was 11% in 90 patients receiving the drug for recurrent sustained VT and/or fibrillation (VF), 2.2% in 47 patients receiving the drug for chronic complex ventricular ectopic activity. Encainide-induced arrhythmias occurred 29.8 +/- 11.3 hours (range 17 to 48 hours) after starting chronic oral maintenance doses or after dose increases, or 1 to 2 hours after single large doses. Patients experiencing this adverse effect could not be distinguished from those who did not on the basis of encainide dose, degree of QRS widening, or clinical status. We recommend that patients with history of sustained VT or VF have encainide therapy started only in a hospital setting with continuous ECG monitoring and capabilities for cardiopulmonary resuscitation. Dose changes should not be made more frequently than every 48 hours, and patients should not be discharged from the hospital until they have been on stable dose of encainide for a minimum of 48 hours.

Adult↗

Observations on spontaneous termination of atrioventricular nodal reentrant tachycardia.

Unusual mechanisms of spontaneous termination of atrioventricular (A-V) nodal reentrant tachycardia were observed in two patients during programmed electrical stimulation of the heart. In both patients the mechanism of termination was based on the use of another reentrant pathway than the use used during tachycardia. This pathway was located extranodally in one patient and intranodally in the other. The observations illustrate some of the complexities of reentry in the human heart and how they can play a role in spontaneous termination of A-V nodal tachycardia.

Adult↗

Electrophysiological effects of lorcainide, a new antiarrhythmic drug. Observations in patients with and without pre-excitation.

The electrophysiological effects of the intravenous administration of a new antiarrhythmic drug, lorcainide, were evaluated by programmed electrical stimulation of the heart in 23 patients with atrioventricular conduction disturbances (four patients), ventricular tachycardia (five patients), and accessory atrioventricular pathway (14 patients). Lorcainide did not affect the refractory period of the atrium, ventricle, atrioventricular node, or the AH interval. It lengthened the duration of the HV interval, the refractory period of the accessory pathway, and the width of the QRS complex. The drug terminated ventricular tachycardia in four of five patients. It is concluded that the drug may be of potential benefit in patients with ventricular tachycardia or accessory atrioventricular pathways (especially those with a short refractory period). Lorcainide is contraindicated in patients with bundle-branch block and prolonged HV interval.

Adult↗