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Biomedical subjects

R Milroy

Publications and source records attributed to R Milroy.

At least 55 records · Page 3Linked to original sources
PubMed1990

Clinical and pharmacological study of a novel controlled release preparation of salbutamol.

This study compared the efficacy of 8 mg controlled release (CR) salbutamol tablets twice daily with standard 4 mg salbutamol tablets four times daily in patients with chronic obstructive airways disease. There was significant bronchodilation in both treatment groups as measured by standard spirometry (P less than 0.05). With the CR preparation there was significantly less wheeze (P less than 0.05) and significantly reduced requirement for rescue bronchodilator (P less than 0.05). Salbutamol levels measured hourly on the final day of each treatment period showed that the drug profile in the CR group was smoother, without the troughs and peaks seen with standard tablets.

Adult↗
PubMed1989

Effects of the pH dependence of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay.

The tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), is reduced by live but not dead cells, and this reaction is used as the end point in a rapid drug-screening assay. It can also be used for accurate determinations of drug sensitivity but only if a quantitative relationship is established between cell number and MTT-formazan production. We have shown that reduction of MTT to MTT-formazan by cells is dependent on the amount of MTT in the incubation medium. The concentration required to give maximal MTT-formazan production differs widely between cell lines. The absorption spectrum of MTT-formazan varies with cell number and with pH. At a low cell density or a high pH, the absorption maximum is at a wavelength of 560 to 570 nm. However, at a high cell density or a low pH, there are two absorption maxima; one at 510 nm and a second at about 570 nm. Measurements of absorbance at 570 nm underestimate MTT-formazan production and, hence, cell number at high cell densities. This error can result in a 10-fold underestimation of chemosensitivity. Addition of a buffer at pH 10.5 to the solubilized MTT-formazan product can overcome the effects of both cell density and culture medium on the absorption spectrum. Provided that sufficient MTT is used and the pH of the MTT-formazan product is controlled, dye reduction can be used to estimate cell numbers in a simple chemosensitivity assay the results of which agree well with a commonly used clonogenic assay.

Azo Compounds↗
PubMed1989

Mechanism of 201Tl uptake in tumours.

We have studied the mechanism of tumour uptake of 201Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n = 26), lung cancer (n = 56) and lymphoma (n = 15), the time course of tumour uptake of 201Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, 99mTc labelled microspheres and 201Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for 201Tl were one tenth of those for 99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with 201Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of 201Tl compared to the cells not so exposed (0.6% +/- 0.1% vs 11.8 +/- 0.7.2% of the administered dose). The mechanism of 201Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. 201Tl uptake may provide a useful means of studying tumour viability.

Breast Neoplasms↗
PubMed1989

Acute phase reaction during chemotherapy in small cell lung cancer.

We have measured the serum concentration of the acute phase reactant, C-reactive protein (CRP), in 20 patients with histologically proven small cell lung cancer undergoing their first pulse of induction cytotoxic chemotherapy. Baseline CRP concentrations were raised in 16 of 20 patients (median baseline CRP 18.5 mg l-1; normal range less than 10 mg l-1). CRP levels more than doubled in 11 of 20 patients during induction chemotherapy. This acute phase reaction was seen in seven of the 10 chemosensitive patients, but was not observed in any of the five non-responding patients. Five patients were non-evaluable for chemoresponse. These data indicate that there is a previously undescribed quantifiable acute phase response during chemotherapy for small cell lung cancer which has potential for predicting chemoresponse.

Acute-Phase Reaction↗
PubMed1988

Abnormal haemostasis in small cell lung cancer.

Disorders of haemostasis and altered platelet activity have been documented in patients with malignant disease but their relation to response to treatment and prognosis are not known. Thrombin activity (fibrinopeptide A (FpA), plasmin mediated fibrinolysis (B beta 15-42) antigen), and platelet alpha granule release (beta thromboglobulin) were studied in 37 patients with small cell lung cancer to find out whether these indices show a relationship to chemoresponse. There was evidence of considerably increased thrombin activity, with a median fibrinopeptide A concentration of 13.2 (normal less than 4) pmol/ml, but only modestly increased fibrinolysis, with a median B beta 14-42 antigen concentration of 5.6 (normal less than 3) pmol/ml. Thus the ratio of fibrinopeptide A to B beta 15-42 concentration (FpA:B beta) was raised, with a median value of 2.2 (normal less than 1.33). In addition, 57% of patients had increased platelet alpha granule release, the median beta thromboglobulin concentration being 50 (normal less than 50) ng/ml. There was a significant association between increased thrombin generation and lack of response to chemotherapy. Furthermore, non-responders had higher FpA:B beta ratios. The same haemostatic markers were studied in nine patients who have been in complete remission for at least two years after chemotherapy for small cell lung cancer. There was a significant difference in thrombin activity and also in the ratio of thrombin activity to lysis between the pretreatment group and the group of two year survivors. Lack of response to chemotherapy appears to be related to increased thrombin activity. Such an association has not previously been reported in patients with malignant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Gallium scintigraphy in small cell lung cancer.

We have undertaken gallium imaging studies in 49 patients with histologically proven small cell lung cancer. Tracer uptake in the primary tumour was seen in 98% of cases. Twenty five patients underwent repeat scanning after induction chemotherapy and a correlation was demonstrated between conventional parameters of response and gallium scan changes (P less than 0.01). There was no correlation between initial gallium activity and subsequent chemoresponse (which was evaluated in 32 patients) or survival (measured in 42 patients). Ten patients who had shown a complete response to induction treatment were followed up with gallium scans repeated at three monthly intervals. Such longitudinal studies were particularly helpful in excluding tumour activity when the appearance of the chest radiographs were difficult to interpret.

Antineoplastic Agents↗
PubMed1987

Phase II clinical and pharmacological study of oral 4-demethoxydaunorubicin in advanced non-pretreated small cell lung cancer.

4-Demethoxydaunorubicin (4-DMDNR) is an oral anthracycline with antitumour activity demonstrated in a number of clinical studies. We have assessed the usefulness of 4-DMDNR in 16 patients with advanced small cell lung cancer, none of whom had received previous chemotherapy. There were no complete or partial responders among the 14 evaluable patients, but 9 patients showed a minor radiographic improvement and 6 reported transient symptomatic improvement. Side effects were mostly minor or moderate, although one patient succumbed to septicaemia during neutropenia following treatment. There was no evidence of cardiotoxicity in any patient. Pharmacological studies were undertaken in 8 patients. A previously undescribed metabolite, identified as the 7-deoxyaglycone of 4-demethoxydaunorubicinol, was detected in 3 patients and these 3 patients all showed some anti-tumor response.

Administration, Oral↗
PubMed1987

Method for the determination of 4-demethoxydaunorubicin, its quinone and hydroquinone metabolites in human plasma and urine by high-performance liquid chromatography.

4-Demethoxydaunorubicin (4-DMDNR) is a new orally active analogue of daunorubicin (DNR). We have developed a high-performance liquid chromatography (HPLC) method capable of separating and identifying 4-DMDNR, five possible fluorescent quinone metabolites and three possible non-fluorescent hydroquinone metabolites. Methods are described for high-yield synthesis of reference metabolites. The limit of detection of the fluorescence assay was less than 1 ng/ml after extraction of 1 ml plasma or urine with chloroform/propan-2-ol (2:1), with coefficients of variation in k' (HPLC column capacity factors) of less than 3% throughout the day. Efficiency of the extraction method described exceeded 80% in control experiments. Blood and urine samples were analysed from four cancer patients who had received 50 mg/m2 orally as three divided doses every 8 h. A typical urinary profile of the drug and its metabolites was: parent drug, 13%; 4-demethoxydaunorubicinol (4-DMDNOL), 80%; 4-DMDNR 7-hydroxyaglycone, 4% and 4-DMDNOL 7-hydroxyaglycone, 3%. 4-DMDNOL was the major metabolite detected in plasma. A further metabolite identified as the 7-deoxyaglycone of 4-DMDNOL was detected in plasma of two patients at concentrations equal to or greater than the parent drug. In the other two patients no trace of the metabolite was detected.

Carcinoma, Small Cell↗
PubMed1986

Secondary amyloidosis in association with Aspergillus lung disease.

Three patients with amyloidosis secondary to bronchiectasis are described: in two patients bronchiectasis was secondary to allergic bronchopulmonary aspergillosis and in the third, post-tuberculous bronchiectasis was complicated by asthma and allergy to Aspergillus. We suggest that chronic Aspergillus allergy may cause amyloidosis and that some cases of amyloidosis ascribed to tuberculosis in the past may in fact have been secondary to Aspergillus allergy.

Amyloidosis↗
PubMed1986

Mediastinal imaging in lung cancer.

Sixty-six patients with lung cancer underwent mediastinal staging with gallium scanning, CT scanning and mediastinal exploration at mediastinoscopy and/or thoracotomy. Histological findings at time of mediastinal exploration were correlated with the results of the non-invasive staging scans. Gallium scanning had an accuracy of 78.8 per cent and CT scanning had an accuracy of 77.3 per cent. There was no evidence of increased test accuracy by performing both scans in the same individual. Either scanning technique may be utilised as a simple non-invasive mediastinal staging procedure, and where negative it is appropriate to proceed directly to thoracotomy.

Gallium Radioisotopes↗
PubMed1983

Detecting a repeated tone burst in repeated noise.

Samples of wideband noise 0.05, 0.1, 0.2, or 0.4 s in duration were digitized and then replayed cyclically to produce repeated-noise maskers. The signal was a repeating tone burst (0.4 or 1.6 kHz). It was half the duration of the noise sample, centered in the noise temporally, and it was repeated at the same point in each repetition of the noise. In the antiphasic conditions of the experiment, either the noise sample or the tone burst was inverted in alternate repetitions of the masker; in the homophasic conditions both the tone burst and noise, or neither, were inverted in alternative repetitions. If the auditory system were capable of storing detailed waveforms of sufficient length, alternate repetitions could be added or subtracted and we might expect a release from masking in the antiphasic conditions. The results show a small but significant advantage for the antiphasic conditions when the signal frequency was 0.4 kHz, but no difference with the 1.6-kHz signal.

Adult↗
PubMed1982

The deterioration of hearing with age: frequency selectivity, the critical ratio, the audiogram, and speech threshold.

The frequency selectivity of the auditory system was measured by masking a sinusoidal signal (0.5, 2.0, or 4.0 kHz) or a filtered-speech signal with a wideband noise having a notch, or stopband, centered on the signal. As the notch was widened performance improved for both types of signal but the rate of improvement decreased as the age of the 16 listeners increased from 23 to 75 years, indicating a loss in frequency selectivity with age. Auditory filter shapes derived from the tone-in-noise data show (a) that the passband of the filter broadens progressively with age, and (b) that the dynamic range of the filter ages like the audiogram. That is, the range changes little with age before 55, but beyond this point there is an accelerating rate of loss. The speech experiment shows comparable but smaller effects. The filter-width measurements show that the critical ratio is a poor estimator of frequency selectivity because it confounds the tuning of the system with the efficiency of the signal-detection and speech-processing mechanisms that follow the filter. An alternative, one-point measure of frequency selectivity, which is both sensitive and reliable, is developed via the filter-shape model of masking.

Adult↗