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Biomedical subjects

M L Clark

Publications and source records attributed to M L Clark.

At least 127 records · Page 7Linked to original sources
PubMed1976

Chlorpromazine metabolism VII: new quantitative fluorometric determination of chloropromazine and its sulfoxide.

A new, sensitive assay is described for chlorpromazine and/or its sulfoxide. The method is based on reacting the tertiary amine base with 9-bromomethylacridine to form a quaternary compound which, on photolysis, yields highly fluorescent products that are determinable fluorometrically. The procedural steps were standardized, and an optimum assay procedure was developed. The method shows a less than 3% coefficient of variation when applied directly to chlorpromazine samples and is capable of determining 15-20 ng of the drug. The method is readily adaptable to clinical and bioavailability studies.

Chemical Phenomena↗
PubMed1976

Chlorpromazine metabolism VIII: blood levels of chlorpromazine and its sulfoxide in schizophrenic patients.

A procedure was standardized for extracting chloropromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans.

Chlorpromazine↗
PubMed1976

Food antibodies in patients with dermatitis herpetiformis and adult coeliac disease - relationship to jejunal morphology.

Serum antibodies to a variety of dietary proteins were investigated in 26 patients with adult coeliac disease (ACD, 14 untreated and 17 treated with a gluten-free diet) and 38 patients with dermatitis herpetiformis (DH) with varying small bowel abnormalities. The incidence of one or more positive tests was highest in untreated ACD (73.4%) and DH with subtotal villous atrophy (57.4%). This incidence fell with morphological improvement, being 56.4% in treated ACD patients with partial villous atrophy (PVA), and 33.4% in DH with PVA, and 0% in DH with normal biopsies. The height of the serum antibody titre also fell with morphological improvement. These results show that there is an abnormally high incidence of dietary antibodies in patients with DH, and this correlates with the degree of small bowel damage.

Adult↗
PubMed1975

Malabsorption.

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Humans↗
PubMed1975

A study of the renal handling and intestinal absorption of dibasic amino acids in a patient with genotype +/11 heterozygous cystinuria and idiopathic hypercalcuria.

A case is reported of a patient with idiopathic hypercalcuria who was referred for investigation of renal calculi. Studies of urinary amino acid excretion in the patient and all living members of his family, as well as studies of endogenous renal clearances of dibasic amino acids and cystine in the patient and his daughter, indicated that the patient had genotype +/11 heterozygous cystinuria. Intestinal perfusion studies showed however that the patient was able to absorb L-lysine, L-arginine normally from the jejunum and ileum. This suggests that a difference exists between renal and intestinal handling of lysine and arginine in cystinuria.

Adult↗
PubMed1975

Loxapine in newly admitted chronic schizophrenic patients.

The standard drug Stelazine (STEL), at a dose of 50 mg/day, exhibited therapeutic activity significantly different from placebo (PL) activity on several variables, most notably BPRS, attesting to the sensitivity of the experiment. On the other hand, the investigational drug, loxapine (LOX), in doses of 100 mg/day for four weeks, could be differentiated from PL as treatment in the described population on only one variable (NGI-Imp.) and one item of the BPRS. On several variables, positive trends were noted, but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05. One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose.

Adult↗
PubMed1975

Ammonia and urea transport by the excluded human colon.

1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of (15N)-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesing limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of 'juxtamucosal' (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.

Ammonia↗
PubMed1975

A study of relations between the absorption of amino acids, dipeptides, water and electrolytes in the normal human jejunum.

1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-L-alanine and its constituent amino acids on water and electrolyte absorption from iso-osmotic solutions in the upper jejunum of normal human subjects. 2. There was no significant absorption of water and electrolytes from sodium chloride solution (150 mmol/l) but the presence of the dipeptide or its constituent amino acids stimulated water and electrolyte absorption. 3. Water absorption reached a peak at increasing amino acid and dipeptide concentrations and then tailed off. Our data suggest that the tailing off is not solely due to the diminished sodium content of the solutions. 4. During perfusion of the dipeptide-sodium chloride and amino acid-sodium chloride solutions solute and water were absorbed as an iso-osmotic solution. Analysis of the results indicates that this could occur at high dipeptide concentrations only if the majority of the dipeptide enters the cell intact.

Adult↗
PubMed1975

Jejunal absorption of an amino acid mixture simulating casein and an enzymic hydrolysate of casein prepared for oral administration to normal adults.

1. An intestinal perfusion technique was used in six normal human subjects to study absorption of sixteen individual amino acids from an amino acid mixture simulating casein and from an enzymic hydrolysate of casein, prepared for oral administration to these subjects, which consisted of a mixture of oligopeptides and free amino acids. 2. Total absorption of alpha-amino nitrogen was greater from the casein hydrolysate than from the amino acid mixture, and the considerable variation in percentage absorption of individual amino acids from the amino acid mixture was much reduced when the enzymic hydrolysate solution was perfused, as a number of amino acids which were poorly absorbed from the amino acid mixture were absorbed to a greater extent from the casein hydrolysate. 3. These findings indicate that after extensive intestinal resections or in malabsorption there might be significant nutritional advantages in the administration of protein hydrolysates rather than amino acid mixtures.

Administration, Oral↗
PubMed1975

Antireticulin antibodies in dermatitis herpetiformis and adult coeliac disease. Their relationship to a gluten free diet and jejunal histology.

Antireticulin antibody was present in 17% of sera from thirty-five patients with dermatitis herpetiformis, 45% from twenty-eight patients with adult coeliac disease and none of thirty healthy controls. There was a higher incidence of antireticulin antibody(a) in patients on normal diets than in those on gluten free diets, and (b) in patients with subtotal villous atrophy than in those with partial villous atrophy. Two patterns of tissue staining were demonstrated, one of which was almost invariably associated with jejunal subtotal villous atrophy. The Ig class of the antibody was IgG in all instances but in 64% antibody of the IgA class was also present.

Adolescent↗
PubMed1975

Absorption of two proline containing peptides by rat small intestine in vivo.

1. Glycyl-L-proline and L-prolyl-glycine are two dipeptides that are poorly hydrolysed by brush border peptide hydrolases in vitro. The present study was undertaken to investigate in vivo intestinal absorption of the two dipeptides in male Wistar rats. A steady-state perfusion technique has been used and jejunal and ileal absorption studied by comparing rates of absorption of constituent amino acids from dipeptide and equivalent equimolar amino acid solutions. 2. Glycine and proline were absorbed at the same or faster rates during perfusion of 10 mM glycyl-L-proline than during perfusion of 10 mM-L-prolyl-glycine than during perfusion of its equivalent equimolar amino acid solution. Conversely, the two constituent amino acids were absorbed at slower rates during perfusion of its equivalent amino acid solution. As expected very low concentrations of free amino acids were detected during the jejunal dipeptide perfusions but higher concentrations were detected during the ileal perfusions. 3. The addition of 40 mM L-prolyl-glycine to the 10 mM glycyl-L-proline solution did not affect the rates of disappearance of glycyl-L-proline. The addition of 40 mM glycyl-L-proline to 10 mM L-prolyl-glycine however had a significant inhibitory effect on the disappearance of L-prolyl-glycine. It is concluded that the two dipeptides may be absorbed by different peptide transport systems.

Animals↗
PubMed1975

Ileal function in patients with untreated adult coeliac disease.

A double-lumen perfusion technique has been used to investigate jejunal and ileal absorption of glucose, water, and electrolytes in a group of patients with untreated adult coeliac disease. Correct positioning of the tube was confirmed by measuring the differential jejunal and ileal handling of bicarbonate. Eight control subjects and eight patients with coeliac disease were perfused with an isotonic electrolyte solution containing 50 mM glucose and 25 mM bicarbonate. The group of coeliac patients had impaired jejunal absorption of glucose (P less than 0.001), water (P less than 0.01), sodium (P less than 0.02), and chloride (P greater than 0.05) compared with the control group. In contrast the group of coeliac patients had normal ileal glucose and water absorption and increased ileal sodium (P greater than 0.01) and chloride (P greater than 0.05) absorption compared with the controls. Evidence for ileal adaptation was found in three individual patients who had absorptive values outside 2SD of the normal mean. The results indicate that the distal small intestine in coeliac disease has the ability to adopt to the damage and loss of absorptive capacity in the proximal small intestine.

Adolescent↗
PubMed1975

Pimozide in chronic schizophrenic outpatients.

In a double blind placebo controlled clinical evaluation of maintenance therapy in chronic schizophrenic female outpatients, thiordazine in single daily doses not exceeding 375 mg./day for 6 months was shown to be effective maintenance treatment compared with PL, thereby establishing the sensitivity of the experiment. Pimozide was also shown to be effective in a single oral dose not exceeding 16 mg./day and comparable overall to the standard drug. The experimental design was based on the anticipated retrogression of PL treated subjects during the 6-month study period, which was reflected in 5 of 9 (56%) "treatment failures" in the PL group compared to 2 of 14 (14%) and 2 of 12 (17%) in the THI and PIM groups, respectively. In addition, in some instances improvement over baseline evaluations was noted in both drug groups, particularly on global impression. Though some items of the BPRS exhibited Drug: PL differences, the scale in general was felt to be rather insensitive for this kind of study. Social adjustment ratings on a special scale completed by the patients and families alike, were also found to be insensitive to treatment differences. Side effects most often seen with THI were sedation, EKG and liver function abnormalities. Headache and restlessness occurred most often with PIM. Extrapyramidal symptoms and insomnia were seen most often with PIM and PL equally.

Adult↗
PubMed1975

Jejunal and ileal absorption of dibasic amino acids and an arginine-containing dipeptide in cystinuria.

Ileal transport of dibasic amino acids has not previously been studied in the intestine of healthy volunteers or cystinuric patients. Experiments have therefore been designed to compare ileal and jejunal absorption of lysine and arginine both in normal subjects and cystinuric patients. In addition, jejunal perfusion experiments have been carried out to investigate absorption of the dipeptide L-arginyl-L-leucine. The results indicate that, at the concentrations studied (4.2 mM lysine, 1 mM arginine), severe transport defects exist throughout the whole small intestine for both amino acids in cystinuria. Despite the transport defect for free arginine, cystinuric patients absorbed the dipeptide L-arginyl-L-leucine normally. Because of the transport defect for free arginine, it has been possible to show that during absorption of L-arginyl-L-leucine in cystinuria approximately 30% of dipeptide-bound arginine can be recovered from the gut lumen in the free form. These findings indicate that the prime function of specific amino acid transport systems during the absorption of protein digestion products may be as a "recapture mechanism" for amino acids liberated as a result of mucosal cell peptide hydrolysis.

Adult↗