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Biomedical subjects

G W Middleton

Publications and source records attributed to G W Middleton.

At least 19 recordsLinked to original sources

Investigating lymphadenopathy--report on the first 12 months of the lymph node diagnostic clinic at the Royal Marsden Hospital.

The lymph node diagnostic clinic was set up at the Royal Marsden Hospital to provide a direct access service for general practitioners. In the first year 82 patients were seen. The malignancy pick-up rate was 19.5% which compares very favourably to rates in breast and colorectal clinics. Patient and general practitioner satisfaction with the service was high.

Adolescent↗

Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma.

PURPOSE: To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma. MATERIALS AND METHODS: Between October 1986 and June 1997, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP (mitomycin-C 8 mg/m2 q. six weeks, vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three weeks) chemotherapy and assessed for objective response and relief of symptoms. RESULTS: Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months: only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain (79%). These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60% of patients with radiological no change obtained useful symptom control. The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea. CONCLUSIONS: MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit. These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint.

Aged↗

Interference from duodeno-gastric reflux of 99Tcm radiopharmaceuticals in SPET myocardial perfusion imaging.

Single photon emission tomographic (SPET) myocardial perfusion imaging was performed on 76 patients using 99Tcm-sestamibi (99Tcm-MIBI). Retrospective analysis of the data showed good cardiac uptake and adequate hepatobiliary clearance. However, duodeno-gastric reflux of the activity excreted from the liver and gallbladder was seen in 34% of the studies. This reflux was considered to be severe in 16% of the studies, resulting in interference with the myocardial uptake and requiring three studies to be repeated. In an attempt to minimize interference from duodeno-gastric reflux, a further 86 patients (18 using 99Tcm-MIBI and 68 using 99Tcm-tetrofosmin) were imaged after lying on their right side for 20 min prior to imaging. Good cardiac uptake with adequate hepatobiliary clearance was again achieved. The incidence of duodeno-gastric reflux was significantly lower (P < 0.001), occurring in 22% of studies, while severe reflux occurred in 6% of studies with no studies being repeated. There was no significant difference in the incidence of reflux between the two agents. Duodeno-gastric reflux of 99Tcm-MIBI and 99Tcm-tetrofosmin is common and can result in significant interference with myocardial uptake. It is concluded that having patients lie on their right side for 20 min prior to imaging is a simple and effective method for significantly reducing the likelihood of such interference.

Duodenogastric Reflux↗

Role of CD34+ cells in engraftment after high-dose melphalan in multiple myeloma patients given peripheral blood stem cell rescue.

During the period December 1992 to June 1995, 95 patients were treated with high-dose melphalan (HDM) with peripheral blood stem cell rescue (PBSCR). Sixty-five had received previous treatment and 28 had relapsed. Among patients who had relapsed 21/28 had received HDM previously including one who received HDM twice during the course of the study. Seventy-five patients were given HDM/PBSCR for the first time. Comparisons have been made between engraftment times for platelets and neutrophils among patients who received less than or greater than 2 x 10(6) CD34+ cells at rescue. Analyses have also been done to evaluate the effect of previous HDM on recovery. Mobilization of progenitor cells was done with granulocyte colony-stimulating factor (G-CSF). Patients received only PBSCR. No growth factors were given to the PBSCR recipients during the recovery period. The percentage of patients from whom the number of CD34+ cells mobilized was > 2 x 10(6)/kg was similar in patients who received HDM for the first time (23%) compared with those who had had it previously (19%). The yield of CD34+ cells correlated with the number of granulocyte-macrophage colony forming units (CFU-GM). Although the number of CD34+ cells infused was < 2 x 10(6)/kg in 77% of patients, all engrafted for neutrophils to > 0.5 x 10(9)/l. This was delayed in patients who had had previous HDM (P < 0.02). Platelet recovery to > 25, 50 and 100 x 10(9)/l was delayed in all patients who received < 2 x 10(6) CD34+ cells/kg infused (P < 0.02). In patients who had had previous HDM both neutrophil (P < 0.05) and platelet recovery (P < 0.007) were delayed compared with recovery in patients who had not had HDM. In patients who had had previous HDM and received < 2 x 10(6) CD34+ cells/kg infused only 3/17 regained platelets to > 100 x 10(9)/l compared with 3/4 who had > 2 x 10(6) CD34+ cells/kg infused (P < 0.05 Fisher's exact test). There was no evidence that low numbers of CD34+ cells in the PBSCR were associated with early death. The data show that previous treatment with HDM had adverse effects on the subsequent engraftment of platelets among patients given HDM/PBSCR. The data suggest that additional measures are needed to achieve platelet reconstitution in these heavily pre-treated patients.

Antigens, CD34↗

Significant gastric reflux of technetium-99m-MIBI in SPECT myocardial imaging.

We present a case in which significant gastric reflux of 99mTc-methoxy isobutylisonitrile (MIBI) was observed in a patient who underwent stress/rest 99mTc-MIBI SPECT myocardial perfusion imaging for suspected coronary artery disease. The intense gastric activity partially obscured myocardial uptake of 99mTc MIBI, particularly in the inferolateral wall of the left ventricle. The presence of significant gastric activity should be considered when performing SPECT myocardial imaging with 99mTc MIBI, and, where necessary, steps should be taken to minimize this activity prior to commencing acquisition.

Adult↗

Is gall bladder ejection fraction a reliable predictor of acalculous gall bladder disease?

The use of quantitative 99Tcm-EHIDA imaging with cholecystokinin and the measurement of gall bladder ejection fraction in a prospective study of 89 patients with right upper quadrant pain is described. Correlation with surgical and histological findings and clinical follow-up suggests that gall bladder ejection fraction < or = 35% is a reliable and accurate indicator of acalculous gall bladder disease.

Cholecystokinin↗

A multiple regression analysis for accurate background subtraction in 99Tcm-DTPA renography.

A technique for accurate background subtraction in 99Tcm-DTPA renography is described. The technique is based on a multiple regression analysis of the renal curves and separate heart and soft tissue curves which together represent background activity. It is compared, in over 100 renograms, with a previously described linear regression technique. Results show that the method provides accurate background subtraction, even in very poorly functioning kidneys, thus enabling relative renal filtration and excretion to be accurately estimated.

Humans↗

Prediction of outcome in Graves' disease after carbimazole treatment.

In a prospective study to determine which factors would predict remission or relapse, 65 patients with hyperthyroid Graves' disease were treated for six months with a blocking replacement regimen of carbimazole, 40 mg daily, and triiodothyronine (T3). They were followed for one year after stopping treatment, by which time 32 (49 per cent) had relapsed. Although the treatment protocol, relapse rate and frequency of the HLA-DR3 antigen in this population were similar to those of a regionally separate Graves' population investigated previously, the predictive value of HLA-DR3 status together with thyroid stimulating antibody (TSAB) levels was strikingly different. In the present study there was no significantly abnormal distribution of any HLA antigen in the relapse group compared with those patients who achieved remission. Thyroid stimulating antibodies were detected in 62 patients (95 per cent) and fell significantly (p less than 0.05) after carbimazole treatment, irrespective of DR3 status or outcome; TSAB levels only became undetectable in nine patients (28 per cent) who subsequently relapsed and in nine patients (30 per cent) who maintained remission. T3-suppressed 20 min 123I uptake fell equally after treatment in the relapse and remission groups but continued to fall thereafter in the group which maintained remission. In these patients, 123I uptake was significantly lower at the end of the study period than at the end of treatment (p less than 0.05). Serum free T4 levels were higher before treatment in the patients who later relapsed than in those whose disease remitted (p less than 0.02). This proved the only significant marker associated with outcome but was of little predictive value in any patient. This study highlights the problem in predicting the outcome of antithyroid drug treatment, since even within the same country under similar conditions, divergent results have been obtained. It appears that the loci controlling the immune response in Graves' disease are likely to include genes lying outside the HLA-DR region. The results also suggest that the immunological effects of antithyroid drugs are maintained after stopping treatment in those patients whose disease remits.

Adult↗

Analysis of T cell subsets in Graves' disease: alterations associated with carbimazole.

Conflicting data on subpopulations of peripheral blood lymphocytes in patients with autoimmune disease largely reflect variations in methods of study. An investigation was therefore conducted aimed at avoiding this difficulty. Serial samples of peripheral blood mononuclear cells from 42 patients with hyperthyroid Graves' disease were collected at monthly intervals before, during, and for 12 months after a six month course of carbimazole. Samples were stored in liquid nitrogen until completion of the study, when they were thawed and all samples from each patient analysed within the same assay using mouse monoclonal antibodies to human cell subsets and a fluorescence activated cell sorter. Proportions of cytotoxic/suppressor (OKT8) positive cells before treatment (mean 17.4 (SEM 0.8)%) were significantly lower (p less than 0.001) than those in normal controls (29.8 (1.9)%; n = 10) and returned to normal by the end of treatment. In contrast, the proportions of activated T cells (OKIa-OKM1) were significantly raised before treatment as compared with normal (14.4 (0.6)% versus 4.6 (0.8)%; p less than 0.001) and fell to normal by the end of treatment. Proportions of OKT3 and OKT4 positive T cells remained unchanged throughout treatment and in the succeeding 12 months. In patients who relapsed after treatment there was a rise in the proportion of activated T cells and a fall in OKT8 positive T cells, which returned towards normal with retreatment. The explanation for the alterations in numbers of circulating T cells remains to be determined but they may provide a means for predicting more accurately the outcome of Graves' disease after treatment with carbimazole.

Antibodies, Monoclonal↗

Spontaneous renal rupture in pregnancy.

A review of the literature reveals 9 cases of spontaneous renal rupture in pregnancy, to which we add another case. Most cases occurred in hydronephrotic kidneys. Four cases consisted of renal rupture without associated infection, or tumor, 3 were associated with abscesses, and 3 ruptured through renal hamartomas. Previously, all ruptured kidneys were removed. In our case the kidney was salvaged satisfactorily by prompt placement of a nephrostomy tube and drainage of the perirenal tissue. Attempt at renal salvage is urged for renal supture in pregnancy.

Adult↗

Long-term followup of anterior urethral transposition in female patients with neurogenic bladder.

Between 1961 and 1976, 13 carefully selected female patients with neurogenic bladders and incontinence refractory to other conservative therapy (9 patients) or deteriorating upper urinary tracts (4 patients) underwent anterior urethral transposition. Followup averaging 6 years revealed minimal stomal problems and excellent preservation of renal function. The surgical technique with modifications is presented.

Adolescent↗