Biomedical subjects

D Gilligan

Publications and source records attributed to D Gilligan.

15 recordsLinked to original sources

PubMed1999

Effect of recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol on the platelet storage lesion.

BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor (Mpl ligand). The receptor for this platelet growth factor (Mpl) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol (PEG-rHuMGDF), was added to apheresis platelets in vitro to determine whether Mpl ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of PEG-rHuMGDF (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of PEG-rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of PEG-rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, lactate dehydrogenase, mean platelet volume, glucose, lactate, osmotic recovery, morphology score, CD62P, and one-dimensional polyacrylamide gel electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three PEG-rHuMGDF doses and the control group, for any in vitro assay. One-dimensional polyacrylamide gel electrophoresis showed no changes among the platelet protein patterns for the three PEG-rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.

Blood Glucose↗

PubMed1998

Improving surgical resection rate in lung cancer.

BACKGROUND: Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (< 10%) than those achieved in Europe and the USA (> 20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries. METHODS: A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed. RESULTS: Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1-13). CONCLUSION: Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system.

Aged↗

PubMed1997

Step-gradient capillary electrochromatography.

The analytical benefits of using a step-gradient in capillary electrochromatography (CEC) are demonstrated. The application of step-gradient CEC to the analysis of six diuretics of widely differing lipophilicities was evaluated and shown to result in a marked reduction in the analysis time and an improvement in the peak shape for later-eluting lipophilic components. When the step-gradient approach was performed in an automated mode, the retention time RSD for repeated injections was below 1%.

Diuretics↗

PubMed1996

Application of a bromodeoxyuridine-Hoechst/ethidium bromide technique for the analysis of radiation-induced cell cycle delays in asynchronous cell populations.

A flow cytometric technique utilizing the continuous incorporation of bromodeoxyuridine (BrdU) into asynchronous cells to measure radiation-induced cell cycle delay is described. Following the incorporation of the BrdU label the cells are stained with ethidium bromide and the bis-benzimidazole Hoechst 33258. These fluorochromes have differential staining patterns. Hoechst 33258 fluoresces blue and is quenched by BrdU incorporated into cellular DNA during S phase. Ethidium bromide fluoresces red and is not quenched by BrdU. Therefore in cells that are cycling and synthesizing DNA new G1 and G2 compartments are created and this can be used to measure cell cycle delays following ionizing radiation to asynchronous cells. We have used this technique to evaluate two cell lines: a normal diploid human embryo fibroblast cell line MRC 5, which has inducible p53 and shows delays at both G1 and G2 checkpoints, and the human cervix carcinoma cell line HX 156. This cell line has been infected with human papilloma virus (HPV) 16, and therefore has inactivated p53 function and is blocked only at the G2 checkpoint. Using this method, cell cycle-dependent effects relating to the G2 block can be observed. The radiation-induced G2 block differs from that induced by drugs or heating in that cells are blocked in G2 irrespective of the phase of the cell cycle they are treated in. This method allows these different types of G2 block to be quantified.

Bisbenzimidazole↗

PubMed1994

The use of ultrasound to measure breast thickness to select electron energies for breast boost radiotherapy.

Ultrasound has been used in 30 patients to measure breast thickness as a means of selecting the most appropriate electron energy for the boost in breast conservation radiotherapy. When compared with electron energies selected on the basis of clinical examination, the target volume was underdosed in 21/30 patients. A major problem in the placement of an electron boost is the demarcation of the target volume.

Breast↗

PubMed1993

Identification of a mutation in the beta cardiac myosin heavy chain gene in a family with hypertrophic cardiomyopathy.

OBJECTIVE: To investigate the molecular genetic basis of the cause of disease in a family with hypertrophic cardiomyopathy. BACKGROUND: Mutation within the beta cardiac myosin heavy chain gene has been shown to be the pathogenetic mechanism underlying the disease in several families, though clear evidence of heterogeneity has been reported. PATIENTS: A family with a history of hypertrophic cardiomyopathy. RESULTS AND CONCLUSION: This paper reports a mutation at aminoacid position 908 within exon 23 of the beta cardiac myosin heavy chain gene, resulting in a conversion of a leucine to valine. This base substitution was identified in an individual with a confirmed family history but with equivocal symptoms of the disease. Inheritance of the mutation by his symptom free juvenile offspring demonstrates the application of the technique to presymptomatic diagnosis.

Adolescent↗

PubMed1992

Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy.

Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.

Adolescent↗

PubMed1992

QT-interval abnormalities in hypertrophic cardiomyopathy.

To examine whether QTc and QTc dispersion across the leads of a surface electrocardiogram (ECG) are different in patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, we measured QT and calculated QTc in all 12 leads of a surface ECG in 24 patients with HCM and in 20 age- and sex-matched normal control subjects. Maximal QTc was prolonged in HCM patients (465 +/- 24 ms) compared with controls (410 +/- 20 ms) (p < 0.001). QTc dispersion defined as the difference of maximum-minimum QTc was also greater in HCM patients (71 +/- 21 ms) compared with normals (35 +/- 11 ms) (p < 0.001). A correlation was found between the degree of left ventricular hypertrophy expressed by the maximal wall thickness and maximal QTc (r = 0.48, p < 0.02). However, QTc dispersion did not correlate with maximal wall thickness. Thus, patients with HCM show a prolonged QTc (> 440 ms) and increased QTc dispersion compared with normal subjects. In addition, the degree of left ventricular hypertrophy correlates with maximal QTc. The presence of a prolonged QT with increased regional dispersion may be associated with the occurrence of serious ventricular arrhythmia and sudden death in HCM.

Adult↗

PubMed1992

Amiodarone reduces QT dispersion in patients with hypertrophic cardiomyopathy.

To compare QT interlead variability (dispersion) in patients who receive a class III antiarrhythmic with those not on antiarrhythmic therapy, we measured QT in all 12 leads of a standard ECG in 24 patients with hypertrophic cardiomyopathy, 12 (50%) of whom were on amiodarone monotherapy and 12 (50%) who were not on amiodarone or other cardioactive medication which could affect QT. Age, functional class, chamber dimension or the degree of left ventricular hypertrophy expressed by maximal wall thickness (21 +/- 5 vs 20 +/- 4 mm; p = NS) was not different between the amiodarone and the non-amiodarone group. Maximal corrected QT (QTc) was greater in patients receiving (488 +/- 25 ms) compared to those not receiving amiodarone (451 +/- 23 ms) (p less than 0.001). However, QTc dispersion defined as the difference of maximum minus minimum QTc was decreased in the amiodarone (48 +/- 10 ms) compared to the non-amiodarone group (78 +/- 17 ms) (p less than 0.001). We conclude that in patients with hypertrophic cardiomyopathy, amiodarone prolongs QTc but reduces QTc dispersion. These results agree with expected changes in ventricular recovery time in patients who receive Class III antiarrhythmic agents and provide further support to the theory that QTc dispersion reflects regional differences in ventricular recovery time.

Adolescent↗

PubMed1991

Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses.

Mucosal melanoma is rare and is traditionally treated by radical surgery. A retrospective survey was made of 28 cases of malignant mucosal melanoma of the nasal cavity and paranasal sinuses treated by definitive radiotherapy. Initial complete regression was observed in 22 out of 28 cases (79%). Absolute local control by radiotherapy alone was achieved in 17 out of 28 cases (61%) but follow-up was limited in many cases by early death due to metastatic disease; actuarial local disease-free survival was 49% at 3 years. The approach of radical radiotherapy for melanoma of this site can be justified on the basis of the local control achieved, low treatment morbidity in patients who are typically elderly and the propensity to disseminated disease. Doses of radiotherapy required to achieve local control need to be radical; the influence of dose per fraction is uncertain.

Aged↗

PubMed1990

Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori.

Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single-blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer-healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice-daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients.

Anti-Ulcer Agents↗

PubMed1989

Ear lobe crease and coronary artery disease in patients undergoing coronary arteriography.

An association between the ear lobe crease and coronary heart disease has been documented. A prospective study of 125 consecutive patients undergoing coronary arteriography was carried out to evaluate the ear lobe crease with the presence and extent of coronary artery disease. An ear lobe crease was observed in 65 patients, but this trait was not related to age, sex, smoking history, previous myocardial infarction, history of hypertension, family history of heart disease, body mass index or angiographically defined coronary artery disease. We conclude the ear lobe crease is not related to coronary heart disease.

Adult↗

PubMed1987

Campylobacter pylori and recurrence of duodenal ulcers--a 12-month follow-up study.

In 39 patients with endoscopically healed duodenal ulcers repeat endoscopy and two antral biopsies after 1 year showed a relapse rate of 59%. Only post-treatment Campylobacter pylori status was a significant predictor of endoscopic relapse. 79% of patients who remained culture positive had a relapse, compared with 27% of culture-negative patients. Relapse was more likely (66%) in patients with a recurrence of C pylori after apparent eradication of the organism than in those who remained negative for C pylori (10%). No patient who remained negative for C pylori had histological gastritis, whereas all with recurrence of C pylori showed histological gastritis. These findings suggest an important role for C pylori in duodenal ulcer relapse in the year after treatment.

Adult↗

PubMed1983

Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma.

A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44 000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47 000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements.

Alanine Transaminase↗

PubMedDate not supplied

Recent developments in the diagnosis and treatment of lung cancer.

Lung cancer is responsible for 25% of all cancer deaths in the UK and it is estimated that over 80% of lung cancers are related to smoking. Despite numerous health education campaigns, large numbers of young people take up smoking, particularly girls. In the past there has been a somewhat nihilistic attitude to the management of lung cancer, but this is changing due to the emergence of sub-specialisation in oncology and the development of new techniques and treatment, which are beginning to show promise.

Carcinoma, Non-Small-Cell Lung↗