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Biomedical subjects

D Thomson

Publications and source records attributed to D Thomson.

At least 19 recordsLinked to original sources
PubMed1992

Problem drug use in a central London general practice.

OBJECTIVE: To describe the profile of problem drug users presenting in general practice and to determine whether they can be cared for in general practice. DESIGN: Study of consultations by problem drug users. SETTING: Central London general practice. SUBJECTS: 150 problem drug users presenting over two years. MAIN OUTCOME MEASURES: Stopping drug use, alterations in lifestyle, obtaining paid work, and stopping drug related crime. RESULTS: Of the 150 patients, 111 were men and 39 women, and 106 were unemployed. 121 patients used heroin, 112 of whom injected. 145 patients accepted a methadone reduction programme and 81 completed it. A further 25 were stabilised on reducing doses of methadone, until places became available for them as inpatients at drug dependency units or rehabilitation projects. CONCLUSION: Withdrawal programmes for patients who misuse drugs can be successfully managed in general practice.

Family Practice↗
PubMed1992

MHC interaction and T cell recognition of carbohydrates and glycopeptides.

The T cell independence of complex polysaccharide Ag has suggested the possibility that carbohydrates may be incapable of T cell recognition because of a failure to interact with MHC restriction elements and/or a failure of MHC/carbohydrate complexes to interact with and be recognized by Ag-specific TCR. We have used two approaches to obtain information about T cell recognition of carbohydrate. First, we have determined the capacity of a series of oligosaccharides and glycolipids to bind a murine class II MHC molecule, IAd. No significant binding was observed with the 26 compounds tested, but the limitation to these studies was that there was a relatively limited collection of synthetic carbohydrate and glycolipid structures of limited complexity available for analysis. The second approach involved the study of the effect of glycosylation of a known peptide T cell epitope (OVA 323-339) on MHC binding of the peptide and on T cell recognition. Three patterns of effects were observed: 1) no effect on either binding or T cell recognition. This pattern was observed when the carbohydrate was located at residues removed from the core MHC-binding region. When the carbohydrate was located within the core MHC-binding regions, either 2) glycosylation destroyed both MHC binding and T cell recognition; or 3) glycosylation did not ablate MHC binding or T cell recognition. In this latter instance, there was evidence to indicate that the carbohydrate moiety was an important part of the antigenic determinant recognized by T cells.

Animals↗
PubMed1992

Inhibitory effects of glyceryl trinitrate on alpha-adrenoceptor mediated contraction in the human internal mammary artery.

1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta-adrenoceptor mediated relaxation and that alpha-adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha-adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA--coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40-90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/- 0.06 -log M) and 20-90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/- 0.16 -log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8-38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9-39.3% (P greater than 0.05). The alpha 1-adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Triple therapy for advanced squamous cell cancer of the head and neck.

This study presents the results of treatment for Stage III and IV squamous cell carcinoma of the head and neck at the Princess Alexandra Hospital and Queensland Radium Institute, Brisbane. Patients were treated using a programme of sequential chemotherapy, surgery and radiotherapy. Between 1980 and 1988, 116 patients commenced the programme and 85 completed the treatment as planned. The Price-Hill regimen of chemotherapy was used until 1986 after which time it was replaced by cisplatin/5-fluorouracil (5FU). Two courses were usually given achieving an overall response rate of 36% (12% complete response). Cisplatin/5FU produced an overall response rate of 56% compared with 24% for the Price-Hill regimen. Radical surgical resections were performed using a free flap reconstruction in the majority of patients. Radiotherapy fields usually covered the primary site and both cervical lymph node areas to a dose of 50-60 Gy in 5-6 weeks. The lengthy treatment was generally well tolerated although there were two chemotherapy and two perioperative deaths. The overall actuarial survival for the 85 patients completing the triple therapy was 60%. These patients were analysed in more detail for possible prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A three-step approach combining Bayesian regression and NONMEM population analysis: application to midazolam.

NONMEM, the only available supported program for population pharmacokinetic analysis, does not provide the analyst with individual subject parameter estimates. As a result, the relationship between pharmacokinetic parameters and demographic factors such as age, gender, and body weight cannot be sought by plotting demographic factors vs. kinetic parameters. To overcome this problem, we devised a three-step approach. In step 1, an initial NONMEM analysis provides the population pharmacokinetic parameters without taking into account the demographic factors. Step 2 consists of individual bayesian regressions using the measured drug concentrations for each subject and the population pharmacokinetic parameters obtained in step 1. The bayesian parameter estimates of the individual subject can be plotted against the demographic factors of interest. From the scatter plots, it can be seen which are the demographic factors that appear to affect the pharmacokinetic parameters. In step 3, the NONMEM analysis is resumed, and the demographic factors found in step 2 are entered into the NONMEM regression model in a stepwise manner. This method was used to analyze the pharmacokinetics of midazolam in 64 subjects from 714 plasma concentrations and 11 demographic factors. CL (elimination clearance) and V1 were found to be a function of body weight. Age and liver disease were found to decrease CL. Of the 11 demographic factors recorded for each patient, none was found to influence VSS or intercompartmental clearance.

Adolescent↗
PubMed1991

Heterogeneity of glutathione S-transferase isoenzyme expression in renal disease.

Recent work has suggested that glutathione S-transferase (GST) enzymuria may be used to assess renal injury in transplant kidneys. There is little work investigating the possibility of using glutathione S-transferase enzymuria to assess other renal diseases and this study was undertaken to evaluate the localisation of GST isoenzymes in various glomerular and tubular pathologies so that the specificity of these enzymes as markers of tubular injury could be defined. Immunostaining was carried out to establish the location of alpha and pi class GST in renal biopsies from patients with a wide variety of renal diseases including membranous glomerulonephritis, minimal-lesion glomerulonephritis, mesangial proliferative glomerulonephritis, loin pain haematuria syndrome, and renal allograft rejection. In the cases of glomerulonephritis studied, alpha class GST was detected in proximal tubules and pi class GST in distal convoluted tubules, podocytes, and Bowman's capsule. The majority of cases of glomerulonephritis showed a heterogeneous pattern of expression of both isoenzymes: that is, there was variation in intensity of staining both in single tubules and also between tubules as opposed to the uniform staining pattern observed in normal kidneys. The location of enzymes in the cases of glomerulonephritis was the same as that in normal kidneys and we were unable to demonstrate any de novo expression of GST isoenzymes. However, seven out of ten renal allograft biopsies showed expression of pi class GST in proximal tubules which were atrophic. Provided there is no significant tubular atrophy, urinary release of these enzymes may be used to localise renal tubular injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group.

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The bidirectional cavopulmonary shunt.

The bidirectional cavopulmonary shunt improves systemic arterial oxygen saturation without increasing ventricular work or pulmonary vascular resistance. Since 1983, 17 patients have undergone a cavopulmonary shunt procedure (five primary operations, 12 secondary operations). Diagnoses were single ventricle complex (n = 4), hypoplastic right heart syndrome (n = 10), and hypoplastic left ventricle (n = 3). Age at primary operation ranged from 3 1/2 to 30 months (median 6 months). Weight ranged from 3.5 to 9.7 kg. Age at secondary operation ranged from 10 months to 14 years (median 15 months). Seven cavopulmonary shunt operations were performed without cardiopulmonary bypass (six via thoracotomy and one via sternotomy) and 10, with cardiopulmonary bypass. All patients in the bypass group had additional procedures: takedown of modified Blalock-Taussig shunt, seven patients; revision of right ventricular outflow tract, four patients; reconstruction of pulmonary arteries, four patients; tricuspid valvuloplasty, one patient; and Damus procedure, one patient. There was one (1/17) operative death (Damus procedure). One patient required early revision. Follow-up ranges from 1 to 53 months (median 23 months). Twelve of 16 had a good to excellent late result, with a rise in mean arterial oxygen saturation from 69% to 83%. Three patients died late (4 to 53 months) (pulmonary vascular disease, pulmonary arteriovenous malformations, and pneumonia, one patient each). There was one late failure (converted to Glenn shunt). The cavopulmonary shunt is an excellent palliative procedure when right atrium-pulmonary artery connection (modified Fontan) must be deferred because of age, weight, or anatomic considerations. Five patients have undergone right atrium-pulmonary artery connection later. In addition, at the time of the modified Fontan operation, the cavopulmonary shunt approach may optimize the anatomic connection (eight additional patients).

Adolescent↗
PubMed1990

The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting.

The purpose of this study was to identify factors associated with atrial fibrillation and flutter after coronary artery bypass grafting. The study group consisted of a consecutive series of 5807 patients who underwent coronary artery bypass grafting alone and who were in sinus rhythm preoperatively. Atrial fibrillation and flutter were identified during continuous monitoring or by clinical symptoms and signs; they occurred in 17.2% of the patients. The prevalence of atrial fibrillation and flutter was directly related to age at operation, varying from 3.7% in patients aged less than 40 years to 27.7% in patients aged 70 and over. In a multivariate analysis, age remained the most important independent predictor of atrial fibrillation and flutter (p less than 0.001). Other independent predictors of atrial fibrillation and flutter were chronic airflow limitation (p = 0.006), preoperative beta-adrenergic blockers (p = 0.011), and chronic renal failure (p = 0.04). Extent of coronary disease at catheterization, history of a previous myocardial infarction, heart size on chest x-ray film, and all operative factors measured, apart from year of operation, were unassociated with atrial fibrillation and flutter. Thus atrial arrhythmias after coronary artery bypass operations are most strongly related to advanced age and are unassociated with preoperative left ventricular function and extent of coronary disease.

Age Factors↗
PubMed1989

[3H]MK-801 binding sites in neonate rat brain.

[3H]MK-801 binding sites are present in neonate rat brain as early as 3 days after birth. Immature hippocampus and cortex contain approximately one sixth the concentration of binding sites of the adult, while brainstem concentration is twice as high as that of adult. [3H]MK-801 binding is stimulated by glutamate and glycine and blocked by phencyclidine and Mg2+ both in 7-day-old neonate and adult, indicating that as early as 7 days postnatally, the N-methyl-D-aspartate-type glutamate receptor and MK-801 binding site are functionally coupled.

Animals↗
PubMed1989

Parameters influencing the response time of volatile anesthetics monitors.

In a given inhalational anesthetic analyzer, response (RT) is usually thought to be a constant value, however, several factors may influence RT. RT's measured under ideal conditions for the Beckman LB 2, the Normac (Datex), the Servo S 120 (Siemens) and the Irina (Dräger) were 107 +/- 5, 589 +/- 14, 538 +/- 30, and 166 +/- 15 msec, respectively. In addition, we investigated the RT of a Beckman LB 2 analyzer under conditions which may occur in clinical practice (non ideal conditions). Increasing aspirating flow (AF) resulted in shorter RT's, the effect being most pronounced when AF was below 200 ml/min. Interposing a filter prolonged RT by 80%. The type of the inhalational anesthetic (halothane or isoflurane), humidity and temperature of the carrier gas as well as size and direction of the concentration step change did not influence RT. Increasing length or internal diameter (ID) of the sample tube resulted in longer RT's. Changing the sample tube material from glass to Teflon or polyethylene resulted in a slight increase of RT, but the increase was dramatic when rubber or silicone tubes were used. The partition coefficient of halothane in the material of a particular sample tube was directly correlated to the corresponding RT in this sample tube. The influence of different sampling places was studied by interposing copper or corrugated rubber tubing between the place where the concentration step change occurred and the place where the gas was sampled, the measured time was called total response time (TRT). Using corrugated rubber tubes instead of copper tubes increased TRT two to four times. More distal gas sampling and/or lower flow rates caused longer TRT's. Compared with sampling in its center, gas sampling near the walls of the tube resulted in an increase in TRT of 13-45%. It is concluded that the response time of an infrared inhalational anesthetic analyzer is not a constant parameter, but varies between 100 and 4000 msec depending on the characteristics of the analyzer, the sample line, and the place of gas sampling.

Anesthesia, Inhalation↗
PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Localization of S-100 protein in a Leydig and Sertoli cell tumour of testis.

A Sertoli-Leydig cell tumour of testis presented some diagnostic difficulties. The tumour cells showed strong expression of S-100 antigen. Preliminary study of non-neoplastic testis suggests that Leydig cells and, to a lesser extent, Sertoli cells express S-100 antigen; its localization may be of value in the diagnosis of sex cord-stromal tumours of testis.

Adult↗
PubMed1989

Heart transplantation for Churg-Strauss syndrome.

A patient with heart failure caused by Churg-Strauss syndrome was successfully treated with transplantation. The case was unusual because there was little evidence of Churg-Strauss syndrome in the lung. The patient remains well on standard transplant immunotherapy.

Adult↗
PubMed1989

Cardiac allograft ischemic time. Relation to graft survival and cardiac function.

Organ donor scarcity has resulted in an increasing number of long-distance cardiac allograft procurements. The effect on short-term (90-day) survival and cardiac function was assessed in a consecutive series of 167 heart transplants performed between April 1981 and July 1988. During that time, total allograft ischemic time was more than 4 hours in 22% of cases and more than 5 hours in 7%. In 1988, total ischemic times have been more than 4 hours in 38% of cases. Ninety-day graft loss (any cause) was 11% for ischemic times 0-120 minutes, 27% for ischemic times 121-240 minutes, 17% for ischemic times 241-300 minutes, and 0% for ischemic times greater than 300 minutes. In 107 patients who survived 3 months, cardiac function was assessed at 1 week by resting hemodynamics and at 3 months by treadmill testing (Bruce protocol), supine rest and exercise radionuclide angiography, and supine rest and exercise right-heart hemodynamics. Treadmill exercise duration was similar in the four groups of patients. Resting ejection fraction was also not different among the groups. Exercise ejection fraction did not rise in the group with ischemic times greater than 3 hours, but the difference did not achieve statistical significance. Resting right atrial pressure was not different among groups at 1 week and decreased significantly in all groups at 3 months. During supine exercise, right atrial pressure rose markedly in each group but was not different among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗