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S Dische

Publications and source records attributed to S Dische.

At least 19 recordsLinked to original sources

Pharmacokinetics of nicotinamide and its effect on blood pressure, pulse and body temperature in normal human volunteers.

The pharmacokinetics of nicotinamide were studied in four human volunteers after oral doses of 1-6 g. Plasma concentrations and clearance rates of the vitamin were found to be dose-dependent, with a half-life of approximately 7-9 h for the two highest doses administered (4 and 6 g), approximately 4 h with 2 g and approximately 1.5 h with a 1-g dose. Peak concentrations ranged from 0.7 to 1.1 mumol.ml-1 after a 6-g dose. The time to reach peak plasma concentration was dose independent with a broad range from 0.73 to 3 h. In this study, nicotinamide had no detectable effect on blood pressure, pulse or body temperature.

Administration, Oral

A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin.

Following stimulation with pilocarpine, the secretion from eccrine sweat glands produces characteristic imprints in hardening silicone polymers applied to the skin. This permits an accurate determination of the numerical density of functional eccrine glands in irradiated skin which can be compared to non-irradiated skin. A description of this inexpensive, noninvasive, and quantitative technique is presented as well as preliminary results determined in six normal subjects and 28 irradiated patients. Eleven patients, with atrophy and telangiectasia after radiotherapy to the skin to a high dose, were found to have no functional eccrine glands by this technique. A range of results from normal numbers of eccrine glands through partial and, rarely, complete loss was observed in patients given lower doses and in whom the skin was visually normal. When the irradiated side outside the boost area in 16 breast cancer patients who received postoperative radiotherapy was compared to an equivalent area on the untreated, contralateral side, 11 showed a greater than 50% reduction in the density of functional eccrine glands. The method appears to be a sensitive, quantitative assay for a permanent change in skin and so ought to facilitate meaningful comparison of different regimens of radiotherapy. Further studies are required to determine the dose-response relationship, latency and progression of the observed changes.

Breast

Changes in serum and salivary amylase during radiotherapy for head and neck cancer: a comparison of conventionally fractionated radiotherapy with CHART.

The changes in serum amylase that occur when radiotherapy is given in the treatment of head and neck cancer has been studied in 41 patients, 29 treated by CHART and 12 by conventionally fractionated radiotherapy. The peak rise in serum amylase following the start of treatment is seen earlier and is greater in the patients receiving continuous hyperfractionated accelerated radiotherapy (CHART). The serum amylase returns to normal earlier in the CHART patients so that the area under the curve is the same for both groups. The difference probably reflects the more rapid delivery of treatment to the patients receiving CHART. A close correlation between the peak rise in serum amylase and the amount of parotid tissue in the treatment volume is demonstrated. For six patients the total amount of amylase secreted by the parotid gland during CHART was measured and found to decline rapidly within a few days of the start of radiotherapy. The rise in serum amylase that results from the irradiation of salivary tissue provides a unique biochemical measure of an early radiation effect in a normal tissue. This probably reflects the interphase cell death of serous salivary cells. Although these immediate changes are of considerable interest they may not relate to the late effects of radiation on salivary gland function.

Amylases

Tumor cell kinetics, local tumor control, and accelerated radiotherapy: a preliminary report.

The local tumor control achieved in patients treated in a pilot study of continuous, hyperfractionated, accelerated radiotherapy has been related to the tumor cell kinetics evaluated by in vivo administration of bromodeoxyuridine and flow cytometry. In 42 of 50 patients with advanced squamous cell carcinomas in the head and neck region it was possible to sample the primary tumor prior to treatment. In three further cases, involved regional nodes were studied: in the remaining five, tissue was obtained subsequently either from a local recurrence or from a distant metastasis. Successful cell kinetic measurements were made in 38 (90%) of the 42 primary tumors. The median values of the labelling index, the duration of the DNA synthetic phase and, thus, the potential doubling time for all primaries were 7.1%, 9.8 hr, and 3.9 days, respectively. Complete regression was achieved in 28 (74%) of the primary tumors and in 23 (61%) this was maintained to the time of observation for this report. There was no significant influence of any of the cell kinetic parameters upon the immediate or longer term local tumor control. This result is compatible with the overcoming of cellular repopulation by the acceleration of radiotherapy.

Aneuploidy

The role of radiotherapy in carcinoma of the thoracic oesophagus: an audit of the Mount Vernon experience 1980-1989.

All 244 patients with carcinoma of the thoracic oesophagus registered at the Mount Vernon Centre for Cancer Treatment during the decade from 1 January 1980 to 31 December 1989 have been audited. We have made a detailed analysis of 110 (45%) with localized disease considered unsuitable for surgery, who completed treatment solely by radiotherapy. The median survival of this group of patients was 8.2 months (range 0.2-54 months). Dysphagia was improved by radiotherapy in 77.3% of cases, the median duration of relief was 24 weeks (range 0-208 weeks) and was maintained until death in 40%. Life table analysis showed that radical compared with less than radical regimens of radiotherapy gave significantly superior relief of dysphagia. This result is unlikely to be due to case selection.

Age Factors

The problem of cigarette smoking in radiotherapy for cancer in the head and neck.

Smoking cigarettes during radiotherapy prolongs the period of reaction and may reduce the chance of cure. Of a group of 48 patients with advanced head and neck cancer 35 were smoking at the time of diagnosis, but 17 were persuaded to stop, although 7 relapsed later. Interviews conducted in 35 of the 48 patients revealed the problems which must be overcome if such patients are to cease smoking.

Adult

Chest radiography or computed tomography in the assessment of lung cancer prior to radiography.

A series of 93 patients with lung cancer were considered for intensive radiotherapy, and investigated by chest radiography and computed tomographic (CT) scan. Spread of tumour was detected radiologically to lymph nodes, pleura or chest wall on 98 occasions. Of these, 16 were shown by both investigations, but in 82 the spread was revealed only by CT examination. Clear visualization of the tumour prior to radiotherapy is important to select those patients who would benefit from radical radiotherapy, to allow accurate treatment planning, and to allow, in subsequent follow-up, monitoring of the response to radiotherapy. In this study tumour was clearly visualized in 59 patients treated, but in 31 (53%) of these only by the use of computed tomography.

Aged

Chest radiography or computed tomography to assess the response of lung cancer to radiotherapy.

In 58 patients with lung cancer the response of the primary tumour to treatment with CHART was followed by both chest radiograph and computed tomographic (CT) scan. Clear evidence of complete response was seen by chest radiograph in 11 patients and by CT scan in 20. If all studies showing no definite tumour, regardless of the quality of the study, were included then complete response was considered to have occurred in 25 as indicated by chest radiograph and in 22 by CT scan. The validity of the observations was tested by life table analysis comparing the survival of those showing complete regression with those whose response was incomplete. Comparison based on the CT scan findings showed the greatest significance (P = 0.0001), while that based on the chest radiograph findings showed the least (P = 0.044).

Aged

Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck.

The two techniques of flow cytometry analysis (FCM) and immunohistochemical localisation of bromodeoxyuridine (BrdUrd) incorporation after in vivo administration, were combined to study proliferation in squamous cell carcinoma of the head and neck region. Care was taken in this study to ensure that similar material was processed using both techniques such that comparisons could be made. FCM underestimated the labelling index (LI) in tumours classified as diploid compared to the histological evaluation of the tumour cells within those tumours (4.6% vs 17.1%). However, in aneuploid tumours, the FCM LI (10.7%) was similar to that obtained from histology (13.5%). Indeed, proliferation assessed by the combination of histology LI and FCM duration of S-phase (Ts) indicated that diploid tumours had a shorter median potential doubling time (Tpot) of 2.1 days compared to aneuploid (2.8 days). Despite the heterogeneity of proliferation evident histologically within the specimens, there was not a wide variation in the results of FCM analysis when multiple samples from resections were studied. Using FCM data alone, 46% of the tumours showed a Tpot of less than 5 days. When the Ts from the FCM data was combined with the average histological LI, 84% were less than 5 days and with the maximum LI, 99% were within this time interval. Compared with previous estimates, the proportion of tumours possessing proliferative characteristics which may indicate the need for acceleration of treatment seems to be much larger.

Aneuploidy

Parotid gland function following accelerated and conventionally fractionated radiotherapy.

The function of the parotid glands in patients treated by three different schedules of radiotherapy was studied 9 months or more after its conclusion. All had received radiotherapy for a malignancy confined to one side of the head and neck region and only the gland on the side of the lesion was in the treatment volume; the contralateral gland acted as an internal control. Saliva was selectively collected from the parotid glands and the stimulated flow rate and pH of the saliva determined. Flow rates were expressed in each case as a percentage of that of the contralateral ("untreated") gland. Twelve glands that had received conventionally fractionated radiotherapy to a dose of 60-66 Gy showed a mean percentage flow of 20% and a significant fall in the pH of the saliva produced. Six glands that had received CHART and eight conventionally fractionated radiotherapy to a dose of 35-40 Gy showed mean percentage flows of 57 and 65%, respectively, with only slight and non-significant falls in saliva pH. The results show that in the treatment of squamous cell carcinoma in the head and neck the use of CHART can lead to considerably less late change in the function of the parotid gland.

Aged

A comparison of the late radiation changes after three schedules of radiotherapy.

The late radiation change observed in 15 patients treated for carcinoma of oral cavity or oropharynx using continuous hyperfractionated accelerated radiotherapy (CHART) was compared to that seen in 15 similar patients treated with conventional radiotherapy. The average follow up was, 31 and 33 months, respectively. A new dictionary for the recording of radiation morbidity, developed in our centre, was employed and proved highly satisfactory in the recording of the changes observed in these patients and also in a third group treated by a combination of chemotherapy and hypofractionated radiotherapy in hyperbaric oxygen. The dictionary was able to record all the morbidity clinically seen with these three treatment schemes. The late changes observed in skin and mucosa with CHART were similar to those observed with conventional radiotherapy, but hair regrowth was observed in six out of 10 men treated with CHART compared with persistent, partial or complete hair loss in all nine men treated with the conventional scheme; after CHART there was also a trend towards less taste impairment and less severe dryness of mouth.

Adult

Hypoxia and local tumour control. Part 2.

The failure so far of the clinical effort to exploit laboratory knowledge as to the importance of hypoxia as a cause for radiation failure may have been the pursuit of this approach in isolation from other causes for radioresistance. In particular a capacity for rapid repopulation may be shown by a tumour showing resistance due to hypoxia. A knowledge of all the factors affecting radiosensitivity is required before the rational testing of hypoxic cell sensitisers can be planned.

Cell Hypoxia

Radiotherapy and anaemia--the clinical experience.

Review of the literature shows good evidence of an impaired outlook for anaemic compared with apparently similar, but non-anaemic patients, treated by radiotherapy for tumors at a number of sites. Some of the adverse associations, may be because anaemic patients, compared with the non-anaemic at the same site and with the same clinical stage, may have in actuality a more advanced disease. However, there is good evidence, especially in carcinoma of the cervix, that there occurs an impairment of the response of tumor to radiotherapy in anaemic patients. Where cure is the object of radiotherapy, restoration of the haemoglobin level is necessary before the course is begun. During the past 60 years there has been much interest in the relationship between anaemia and response to radiotherapy. In 25 series of cases where an effect of anaemia has been sought an adverse influence has been found in 23. An examination of these papers, however, reveals a complex pattern demanding some analysis. Anaemia itself requires definition. As can be seen in Fig. 1, there are different normal ranges for men and women and there is some variation in what is accepted as normal. Haemoglobin levels are commonly given in g%, but they are also expressed as mmol/l. There are also reports which refer to the haematocrit. The haemoglobin value at first presentation may be recorded, but the picture may change by the time treatment is instituted, either because of haemorrhage or because of blood transfusion. In examining reports it is sometimes not easy to know which value is related to response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia

What have we learnt from hyperbaric oxygen?

The 15 randomised controlled clinical trials of hyperbaric oxygen in radiotherapy yielded three with highly significant benefit and six with useful margins not reaching statistical significance. The increase in tumour control was partly negated by an increase in normal tissue effect. Now simple carbogen breathing in animal tumour models has shown high efficiency and there is the potential for its use in man as a simple means of hypoxic cell radiosensitization.

Cell Hypoxia