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Biomedical subjects

J Maddock

Publications and source records attributed to J Maddock.

At least 37 records · Page 2Linked to original sources
PubMed1983

Determination of isosorbide dinitrate and its mononitrate metabolites in human plasma by high-performance liquid chromatography-thermal energy analysis.

An accurate and sensitive method for the simultaneous determination of isosorbide dinitrate and its 2- and 5-mononitrates in human plasma has been developed. Following extraction of 3.0 ml of plasma with 12.0 ml of dichloromethane-ethyl acetate (1:1) the extract is subjected to high-performance liquid chromatography employing a Zorbax NH2 column. The eluent stream is introduced into a thermal energy analyser, employing chemiluminescence as a specific means of detection. The minimum quantifiable level of the compound in plasma is 200 pg/ml allowing the quantitation of isosorbide dinitrate in human plasma following single oral administration. Nitroglycerin is employed as internal standard.

Chromatography, High Pressure Liquid↗
PubMed1983

On the treatment of migraine. Pharmacokinetic-pharmacodynamic relationships for a programmed release formulation of dihydroergotamine administered orally in the human.

With the combined pharmacokinetic-pharmacodynamic approach, the bioavailability and venoconstrictor effects of two DHE formulations (programmed release capsules and oral solution) have been compared after acute oral dose administrations in the healthy volunteer subjects. The bioavailability of DHE from programmed release capsules has been significantly greater than that shown by the oral solution. DHE capsules formulation has seemed to provide appropriate plasma concentrations for at least 10 h after administration. That may well account for its efficacy in the treatment of morning migraine.

Administration, Oral↗
PubMed1983

Pharmacokinetics of 14C CDP-choline.

The absorption, metabolism and excretion of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) were investigated in six adult healthy subjects after a single oral dose of 300 mg of the 14C-labelled compound. The compound was well tolerated by the subjects. Absorption was virtually complete with less than 1% of the dose being found in the faeces during the 5-day collection period. Two peaks were found in the plasma radioactivity time profile: the first at 1 h, and a second larger peak at 24 h post-dose. Elimination of the ingested dose occurred via respiratory CO2 and through urinary excretion; the former predominating, and both routes exhibited biphasic patterns characterized by an early phase followed by slower decline. It is postulated that in the healthy human subject CDP-choline is metabolized in the gut wall and in the liver; the products arising from the compound's extensive hepatic metabolism being subsequently available for diverse biosynthetic pathways, tissue metabolism, and excretion.

Adult↗
PubMed1983

CDP-choline: repeated oral dose tolerance studies in adult healthy volunteers.

Cytidine diphosphate choline (CDP-choline, citicoline, Somazina) was administered to 12 adult healthy volunteer subjects in two short-term chronic oral dose regimens (600 mg X day-1 and 1g X day-1), each of 5 consecutive days, and compared with a corresponding regimen of matched placebo. Transient headaches were the only untoward events recorded, occurring in 4 and 5 subjects, respectively, on the lower and higher dose regimens but in only one subject during placebo administration.

Adult↗
PubMed1982

Long-term monitoring of the effects of thymoxamine hydrochloride tablets in the management of patients with Raynaud's disease.

Seventeen patients with Raynaud's disease were followed whilst receiving treatment with 40 mg thymoxamine hydrochloride 4-times daily for period ranging between 11 and 19 months. Digital artery patency and blood flow changes, assessed by Doppler ultrasound techniques after different thermal stresses, were monitored regularly as were platelet aggregation to ADP and collagen, platelet adhesion to glass beads, measures of blood coagulation and fibrinolysis, and plasma viscosity. Significant clinical improvement noted at 1 month appeared to improve further at 3 months and was maintained thereafter. Vessel patency rates at 10 degrees C and 21 degrees C improved significantly during treatment and both collagen- induced aggregation and platelet retention were significantly inhibited. These unexpected effects on platelet function are not readily explained by the drug's documented activity as a selective alpha-adrenergic antagonist and they may represent other hitherto unrecognized pharmacological effects which merit further exploration. The study also confirmed the usefulness of Doppler techniques for continuous atraumatic evaluation of digital vessel patency and investigation of therapeutic regimens on intermittent digital artery obstruction in Raynaud's disease.

Adult↗
PubMed1978

Clinical therapeutic evaluation of methylcysteine hydrochloride in patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control.

A double-blind, between-patient, placebo controlled trial was carried out to investigate the effects of methylcysteine hydrochloride in patients with chronic obstructive bronchitis. After a 2-week washout period on placebo, 30 patients were allocated at random to treatment for 6 weeks with either methylcysteine (1200 mg daily in Week 1, 800 mg daily in Week 2, then 600 mg daily) or with identical placebo tablets on the same regimen. During the post-treatment period, all patients returned to a single-blind placebo regimen (6 tablets daily) for a further 14 days. Assessments were made at the start, at regular intervals during the trial, and at the end of the post-treatment period, of subjective and objective measures of clinical response, and measurements of pulmonary function and certain physico-chemical properties of sputum. The results showed that methylcysteine increased sputum volume, reduced the viscidity of sputum, and significantly improved the subjective assessments of ease of expectoration and severity and frequency of cough, leading to a definite improvement in the patients' clinical state. No side-effects of clinical significance were reported and no abnormalities were found in any of the haematological, hepatic and renal function tests carried out.

Adult↗
PubMed1978

Effects of progestogens on serum lipids in the post-menopause.

Measurement of serum cholesterol, triglycerides, and phospholipids was undertaken in patients with a natural menopause or following oöphorectomy who received cyclical oestrogen regimens for six consecutive months. The regimen employed was either a 'high' or 'low' dose of equine conjugated oestrogens, piperazine oestrone sulphate or oestradiol valerate. After six months a change was made to cyclical sequential oestrogen/progestogen regimens for varying periods. Patients with a natural menopause given either 'high' or 'low' dose regimens showed no significant changes in serum cholesterol, triglyceride or phospholipid levels compared to baseline values. However, the serum cholesterol levels of the oöphorectomized subjects were significantly elevated in comparison with the perimenopausal group. The addition of progestogen to the oestrogen did not cause any significant alterations.

Adult↗
PubMed1978

Endometrial factors under treatment with oestrogen and oestrogen/progestogen combinations.

In a continuing prospective study, uterine curettage was undertaken on sixty-four patients attending a Menopause Clinic prior to consideration of gonadal hormone therapy. Two of these patients (3.1%) were found to have endometrial hyperplasia, and subsequently they were not given gonadal hormone therapy. Sixty-two patients with normal endometrium at pre-treatment curettage received cyclical oestrogen regimens or sequential oestrogen/progestogen treatments. Four (30.8%) of the thirteen patients in receipt of cyclical 'high-dose' oestrogens developed cystic glandular hyperplasia, whereas none of the patients taking either cyclical 'low-dose' oestrogens (thirty patients) or cyclical-sequential oestrogen/progestogen regimens (nineteen patients) developed endometrial hyperplasia. Among the patients with a normal endometrium, both before and during cyclical gonadal hormone therapy, regular withdrawal bleeding was experienced by thirty-two patients (51.6%). Breakthrough bleeding occurred in nine (14.5%), while twenty-one patients (33.9%) had no vaginal bleeding. Of the four patients with normal endometrium at pre-treatment curettage who subsequently developed endometrial hyperplasia during cyclical 'high-dose' oestrogen therapy, regular withdrawal bleeding was experienced by two patients, and in one of these breakthrough bleeding also occurred. Furthermore, in the four patients who developed endometrial hyperplasia, this condition occurred within six months in two patients and within 9 and 10 months respectively in the remaining two. In the nineteen patients receiving cyclical sequential oestrogen/progestogen regimens, all had regular withdrawal bleeding, while one patient had breakthrough bleeding during sequential therapy. It is concluded that in those climacteric patients who present with severe menopausal symptoms which necessitate the administration of high-dose oestrogen regimes it is necessary either to undertake both pretreatment uterine curettage or to add a progestogen to the oestrogen in a sequential regimen.

Climacteric↗
PubMed1976

Evaluation of tolmetin in the treatment of arthritis: open and controlled double-blind studies.

In a 6-week open study in 24 patients with rheumatoid arthritis, tolmetin was shown to have analgesic and anti-inflammatory activity at daily doses in excess of 1200 mg per day and produced statistically significant reductions in overall joint pain, walking time and articular index. The drug was well tolerated, but 2 patients were withdrawn because of persistent indigestion and 1 because of an urticarial type rash. In a double-blind crossover comparison against indomethacin and placebo in 22 patients, 1400 mg tolmetin daily showed efficacy comparable with that of 150 mg indomethacin daily. Few side-effects were reported and did not necessitate any patients being withdrawn.

Adult↗
PubMed1975

Lactic acidosis complicating treatment of ketosis of labour.

Hypertonic glucose, fructose, and sorbitol solutions were given intravenously to women in the first stage of labour who had ketonuria and ketonaemia as evidenced by a raised blood acetoacetate and 3-hydrosybutyrate. There was no difference in the antiketogenic action of these, which was rapid and effective, but when compared with a control group who were given normal saline they had a high incidence of hyperlactataemia, and nine out of 28 patients developed lactic acidosis after the infusions. The "lactatogenic" effect was shared by all three substrates, and when they are used in the treatment of ketosis of labour, and the mother develops lactic acidosis, they might exacerbate pre-existing lactic acidosis and precipitate fetal distress.

Acetoacetates↗
PubMed1975

Long-term study of indomethacin and alclofenac in treatment of rheumatoid arthritis.

Indomethacin and alclofenac were compared for 13 months under double-blind conditions in 109 patients with active, classical, or definite rheumatoid arthritis at a relatively early stage of the disease. Both indomethacin and alclofenac were clearly effective: most patients either improved or remained as well controlled as on entry. Alclofenac proved the more effective drug, however, producing a significantly greater reduction in morning stiffness, articular index, and erythrocyte sedimentation rate, and only in the alclofenac-treated group did functional capacity improve and latex-agglutination titres diminish. Comprehensive laborabory tests showed no significant deviation from normal which could have been attributed to either drug.

Administration, Oral↗
PubMed1975

A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis.

In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself.

Adult↗