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Biomedical subjects

A J Bell

Publications and source records attributed to A J Bell.

At least 73 records · Page 4Linked to original sources

Protein quantitation at the picomole level: an O-phthaldialdehyde-preTSK column-derivatization assay.

A fluorescent protein assay was described wherein an isocratic high-performance liquid chromatography system was used to separate the o-phthaldialdehyde-derivatized proteins from interfering components. Using a small TSK guard column equilibrated in 0.1% sodium dodecyl sulfate, it was demonstrated that all proteins and peptides examined, containing more than 22 residues, coelute in the excluded volume and were resolved from fluorescent signals contributed by commonly used reagents. The assay was linear over a useful range of 3 ng to 1 microgram of protein and required less than 15 microliter of sample.

Aldehydes↗

Ultrasound examination of the scrotum.

The technique of real time ultrasound examination of the scrotum is described. The examination was performed on 120 patients and was found to be a helpful diagnostic aid in scrotal swelling and in the acute painful scrotum. It is recommended as a useful investigation for scrotal abnormalities.

Genital Diseases, Male↗

Comparison of high and low sodium bicarbonate and acetate dialysis in stable chronic hemodialysis patients.

Eight stable center dialysis patients completed four, 10-week study periods in which either acetate or bicarbonate dialysis was used, each with high or low sodium concentration. During high sodium dialysis, blood pressure was better controlled, weight loss more easily tolerated and dialysis was most satisfactory from the patient's point-of-view with regard to dialysis-associated symptoms. Low sodium dialysis, whether with acetate or bicarbonate, was less satisfactory. In contrast to the beneficial effect of an increased sodium concentration, the use of bicarbonate instead of acetate appeared to make little difference either to the patient's symptoms, to the control of blood pressure or to changes in blood gases or biochemistry. Careful choice of dialysate sodium concentration appears to be important in lessening dialysis side-effects. Substitution of bicarbonate for acetate in chronic stable dialysis patients has comparatively little benefit and the choice can legitimately be made on the basis of cost and technical considerations.

Acetates↗

Relapse of lymphoma in the heart after a 10-year remission.

A 71-year-old woman presented with intractable cardiac failure 10 years after receiving treatment for lymphoma. Extensive investigations failed to demonstrate a recurrence of her disease, but resolution of her cardiac failure following a trial of chemotherapy and subsequently a cross-sectional echocardiogram suggested intracardiac relapse. This was later confirmed at autopsy. Cardiac metastases should be suspected in patients with malignant disease who develop signs or symptoms related to the heart.

Aged↗

Effects of verapamil and nifedipine on renal function and hemodynamics in the dog.

This study evaluates the direct effects of verapamil (5 micrograms/kg/min) or nifedipine (0.32 micrograms/kg/min) when infused into one renal artery for 2 h. The role of calcium in the systemic and renal vascular effects of angiotensin II (1 microgram/i.v. bolus) was examined in each period. Renal blood flow was increased 11% by verapamil and 29% by nifedipine. Unlike other vasodilators, these drugs markedly increased GFR (by 75% with verapamil and 50% with nifedipine), and both caused a profound natriuresis, which outlasted the renal hemodynamic changes. Further, they abolished the renal vascular responses to angiotensin II. These major direct effects on renal function and hemodynamics suggest that: (a) calcium blockers may affect the determinants of GFR differently from other vasodilators, and (b) they may interfere with proximal tubular Na+ transport.

Angiotensin II↗

Angiodysplasia of the colon in patients with hemostatic defects: risk of secondary hemorrhage after electrocoagulation treatment.

Angiodysplasia of the colon is a relatively common cause of blood loss in the elderly. Electrocoagulation through a colonoscope is a common mode of treatment for this condition. Three patients are presented who had associated hemostatic defects and electrocoagulation resulted in life threatening secondary hemorrhage. In two of these patients a right hemicolectomy was performed. On the basis of these findings we suggest that patients with angiodysplasia and associated hemostatic disorders have a greatly increased risk of secondary hemorrhage following electrocoagulation treatment. These patients should be followed closely for two-three weeks following this treatment.

Aged↗

Pulmonary effects in man of oral prizidilol hydrochloride (SK&F 92657), a new antihypertensive agent.

The effects on heart rate, blood pressure and pulmonary function of single oral doses of prizidilol hydrochloride (400 mg SK&F 92657) and propranolol (40 mg) were compared with placebo in nine healthy volunteers, in a double blind crossover study. Prizidilol had no effect on heart rate while propranolol caused a significant reduction compared with placebo. Diastolic blood pressure was lowered to the same extent by both prizidilol and propranolol. Propranolol significantly reduced the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the maximal expiratory flow at 50% vital capacity (MEF 50). Prizidilol had no effect on flow-volume loop parameters. Effective pulmonary blood flow was not altered by propranolol, but it was significantly increased by prizidilol. Oral prizidilol exerts its hypotensive effect by vasodilatation without reflex tachycardia. It does not cause airways obstruction in healthy subjects.

Adrenergic beta-Antagonists↗

Attenuation of nephrotoxic acute renal failure in the dog with angiotensin-converting enzyme inhibitor (SQ-20,881).

Angiotensin-converting enzyme inhibitor was used in dogs with uranyl nitrate-induced acute renal failure to evaluate (1) a possible protective effect of angiotensin blockade and (2)the role of angiotensin II in the generation of renal failure in this model. Angiotensin-converting enzyme inhibitor treatment attenuated the fall in glomerular filtration rate and renal blood flow during the first 6 hours after injection of the nephrotoxic agent. A protective effect of similar magnitude was observed whether angiotensin-converting enzyme inhibitor treatment preceded, or shortly followed, the administration of uranyl nitrate. This indicates that angiotensin-converting enzyme inhibitor delivery to its intrarenal site of action remains effective after administration of the nephrotoxin. In addition, protection of glomerular filtration rate correlated with sodium and renal solute excretion. However, combined treatment with angiotensin-converting enzyme inhibitor and furosemide enhanced solute excretion but did not further improve the protection of renal function. Finally, the protective effects of angiotensin-converting enzyme inhibitor on renal function and hemodynamics were abolished by intravenous indomethacin. In conclusion, early, continuous blockade of angiotensin II protects partially against th initiation of acute renal failure. These findings support a major pathogenic role for angiotensin II in the generation phase of acute renal failure in this model. Furthermore, they suggest that an imbalance between vasoconstrictive (angiotensin II) and vasodilating factors (prostaglandins) may be operative in the early phase of uranyl nitrate-induced acute renal failure in the dog.

Acute Kidney Injury↗

Cardiovascular effects in man of intravenous prizidilol hydrochloride (SK&F 92657); a new antihypertensive agent.

1 Cardiovascular responses to intravenous prizidilol hydrochloride (SK&F 92657) 0.86 mg/kg were studied in eight supine resting healthy volunteers. Five subjects were slow and the remaining three were fast acetylators of sulphamethazine. Compared with pre-infusion values, mean resting systolic and diastolic blood pressures were significantly reduced, while mean resting pulse rate was significantly increased at 30 min after the start of the twenty minute infusion. 2 During the 6 h study period the lowest mean +/- s.e. mean systolic blood pressure (108.8 +/- 1.7) was recorded 30 min after the start of the infusion. This represented a mean reduction of 5.2 mmHg. Reductions in mean diastolic blood pressure were greater and of longer duration, the lowest mean value (44.8 +/- 2.0 mmHg) being recorded 3.5 h after the start of the infusion and representing a reduction of 18.5 mmHg from the pre-dosing value. At 6 h after the start of the infusion mean diastolic blood pressure was still significantly reduced (by 15.3 mmHg). 3 The maximum mean +/- s.e. mean resting pulse rate (79.3 +/- 4.4 beats/min) occurred 3 h after the start of the infusion, an increase of 23.0 beats/min over the pre-infusion value. At the end of the study the pulse rate was still significantly raised (by 17.7 beats/min). 4 The left ventricular ejection fraction, evaluated in five subjects, 45 min after the start of the infusion, was not altered by prizidilol hydrochloride, but the left ventricular area decreased significantly. 5 Intravenous prizidilol hydrochloride decreases resting blood pressure and left ventricular area, increases pulse rate and has virtually no effect on left ventricular ejection fraction.

Adolescent↗

Organisation of inverted repeat sequences in hamster cell nuclear DNA.

Hamster cell nuclear DNA is shown to contain inverted repeat (foldback) sequences, in some respects similar to the foldback fraction in DNA from other animal cell types. Using electron microscopy the majority of foldback duplexes are shown to be located in simple hairpin-like DNA structures, formed from individual pairs of complementary inverted repeated sequences 50--1000 nucleotides in length, in some cases arranged in tandem, and in other cases separated by intervening sequences, up to 16000 nucleotide residues long. In addition, a novel class of foldback structure, referred to as 'bubbled hairpins' is reported, which appear to be formed from clusters of inverted repeat sequences that are separated from adjacent clusters of complementary inverted repeats by large intervening sequences which vary in length from 5000 to over 20000 nucleotide residues. Due to the special pattern of distribution of these latter inverted repeat sequences, 'bubbled hairpins' are observed only in long foldback DNA. Evidence is presented that the distribution of foldback sequences in hamster cell DNA is highly ordered. The lengths of the intervening single chains in foldback structures appear to vary non-randomly. This gives rise to a localised periodic pattern of organisation that is believed to be a consequence of regular alternating arrangements of foldback and non-foldback sequences in the segments of DNA from which foldback structures are derived.

Animals↗

Characterization of foldback sequences in hamster DNA using electron microsocpy.

Foldback sequences in nuclear DNA from cultured Hamster fibroblasts (BHK-21/C13 cells) have been characterized by electron microscopy. One half of the structures observed when denatured hamster DNA is allowed to anneal in the range O less than Cot1 less than 1 x 10(-4) M sec result from the annealing of inverted sequences forming foldback DNA. The remainder have a probable bimolecular origin. arising from rapidly-annealing sequences of satellite-like complexity. The average length of the inverted sequences in the foldback molecules is about 0.9 kilobases. There is estimated to be about 42,000 such sequences (21,000 pairs) in the hamster genome, approximately 45% of which form looped structures with a mean loop length of 1.74 kilobases. Contrary to previous reports, binding of the renatured duplex molecules to hydroxyapatite results in a poor recovery of structures containing identifiable foldback sequences, due to preferential enrichment of the bound fraction with duplexes formed by intermolecular annealing.

Base Sequence↗

Peripheral blood stem cell autografting.

Transplantation of haemopoietic stem cells provides a means whereby patients with malignant disease may be treated with increased doses of chemotherapy or chemoradiotherapy. Until recently, the bone marrow has been the sole source of these cells. However, haemopoietic progenitors can also be demonstrated in the blood and it has been known for more than twenty years that peripheral blood mononuclear cells are capable of repopulating the marrow in animals. This phenomenon has recently been reproduced in man. The use of peripheral blood rather than bone marrow for autologous stem cell rescue may have advantages in terms of ready access, availability in patients with compromised pelvic bone marrows, a lower risk of tumour contamination and more rapid granulocyte and immune recovery. However, clinical experience with peripheral blood stem cell autografting is still very small. This review discusses the characteristics of circulating stem cells, the methods by which they can be collected and stored and the information which has come from recent studies of their transplantation in man.

Humans↗

Correlation between histology and immunophenotype in a series of 322 cases of non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms displaying a wide variation in cell morphology, histological patterns, immunological phenotype and prognosis. In this paper we compare the results of phenotypic investigation of 322 tissue biopsies with the histology based on the Kiel classification. Immunological analysis revealed that 81 per cent of these tumours were of B cell origin, 12 per cent of T cell origin and the remaining 7 per cent could not be characterized as representing either cell lineage. This last group included a number of cases which had received a histological diagnosis of true histiocytic lymphoma. The original morphological diagnosis, based on routine haematoxylin and eosion sections correlated with the immunologically determined phenotype in 86 and 93 per cent of the T- and B-cell cases respectively. The B cell tumours were phenotypically heterogenous with respect to immunoglobulin (Ig) heavy chain and B lymphocyte subset marker expression. IgG was most often found associated with NHL of cb/cc histology and a small subgroup of lymphocytic NHL. IgA expression was uncommon and occurred in combination with IgD and G in three cases and alone in two cases of NHL. The most common immunoglobulin isotype expressed was IgM this isotype occurred with IgD most often in lymphocytic and centrocytic NHL and less often in tumours of cb/cc histology. Whilst greater than 90 per cent of the lymphocytic NHLs expressed the CD5 antigen, between 20 and 75 per cent of B-cell tumours of other histologies also expressed this epitope. The CD10 antigen and the epitope recognized by the monoclonal reagent FMC7 were widely distributed on tumour cells from all histologies. TdT expression commonly regarded as a marker for immature cells was found in one case of follicle centre cell lymphoma. All cases of T cell NHL displayed marked heterogeneity for both pan T and T subset antigens which is significant in terms of the routine diagnosis of T NHL and with regard to the rational classification of node based T NHL. Unlike resting peripheral blood T cells, MHC class II, OKT 10 and CD25 epitopes were expressed reflecting activation of tumour populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Pharmacokinetics of cilazapril during repeated oral dosing in healthy young volunteers.

The pharmacokinetics of cilazapril and its active metabolite cilazaprilat in plasma were investigated in an open study of 13 healthy male volunteers, aged 18 to 43 years. One capsule containing 2.5 mg cilazapril was administered to each volunteer daily for 8 days. Plasma samples were obtained after the first and eighth doses. Concentrations of cilazapril, cilazaprilat and activities of angiotensin converting enzyme (ACE) were measured by radioenzymatic methods. For cilazapril, the values of apparent plasma clearance (about 15 l/h) and volume of distribution (around 28 l) were sufficiently high to suggest that significant pre-systemic hydrolysis to cilazaprilat occurred. There were no significant changes in these values after repeated dosing. There were small, but statistically significant, increases in mean peak concentrations, mean areas under concentration-time curves and mean trough concentrations from the first to the eighth dose. A steady state was achieved after eight doses with an accumulation of 20-30%. The mean effective half-life was approximately 9 h. Despite the accumulation of cilazaprilat in plasma, there were no significant differences in plasma ACE inhibition from the first to the eighth dose.

Administration, Oral↗