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Biomedical subjects

G Dean

Publications and source records attributed to G Dean.

At least 19 recordsLinked to original sources

Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer.

We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.

Adult

The changing mortality from motor neurone disease and multiple sclerosis in England and Wales and the Republic of Ireland.

A study has been undertaken to ascertain the changes in mortality from motor neurone disease (MND) and from multiple sclerosis (MS) in England and Wales and in the Republic of Ireland. During the 20 years 1968-1987, 16,077 deaths were reported as being primarily due to MND in England and Wales with a male/female ratio of 1.22. There has been an increase in MND deaths from 3,185 in 1968-1972 to 5,241 in 1983-1987. The increase occurred in the death rates in both sexes and in all age groups, but particularly over the age of 65. In contrast, there was no increase in MS deaths and the MS death rates fell below the age of 55 but increased over this age, evidence that MS patients are living longer. A similar but more marked increase in MND mortality, and a considerable fall in MS mortality, occurred in the Republic of Ireland. The increase in MND mortality is not due to an increase in the number of neurologists, as there has been little increase in their numbers. The highest MND mortality was in Social Class IIIN males - skilled non-manual workers.

Age Factors

Follow up of a cohort of intravenous heroin users in north and south central Dublin and in Dun Laoghaire.

Three studies of intravenous heroin abusers, in electoral wards in the north and south of central Dublin and in Dun Laoghaire, were undertaken in 1982-84. One hundred and one out of the 203 intravenous injectors in these three studies are known to have been tested in Dublin for infection by the Human Immunodeficiency Virus (HIV) and 87 of the 101, or 86% are HIV Positive. Ninety two had also been tested for Hepatitis B infection (Hab) and 76 of the 92 were positive for the hepatitis antigen. The majority of those at present known to be HIV Positive in the Republic of Ireland are, or were, intravenous drug users.

Adolescent

Multiple sclerosis in Cyprus.

The prevalence of multiple sclerosis (MS) was studied in the Greek-speaking population in the southwestern district of Paphos and the eastern Famagusta area and in the Troodos mountains in Cyprus. Excluding refugees from the northern part of the island, the MS prevalence was 44.5 per 100,000. This is a similar prevalence to that found in Sicily and shows that, like Sicily, Greek-speaking Cypriots have a medium to high and not a low MS prevalence. There was no significant difference in MS prevalence between the warm Paphos and Famagusta areas and the much colder mountainous areas. In one village, Liopetri, there were five families with definite MS (CDMS), and one patient with clinically probable MS (CPMS). Excluding refugees, the prevalence for CDMS and CPMS in this village was 240 per 100,000. All six families are probably related.

Adolescent

Do nurses or doctors have an increased risk of developing multiple sclerosis?

A cluster of multiple sclerosis (MS) patients has been reported in seven of 307 nurses in Key West, Florida. The MS death rates in British nurses and qualified medical practitioners were looked at and no increased mortality from multiple sclerosis was found. Neither was there an increase in mortality from motor neuron disease (amyotrophic lateral sclerosis), the control disease. Death rates from MS vary with social class, being highest in social class IIIN (skilled non-manual) and lowest in social class II (intermediate). These different rates may be due to MS causing health related occupational mobility. Allowance for the inter-class variability in MS death rates did not materially affect the conclusion that death from MS appears to be no more common than expected among nurses and doctors than in the general population. Possible explanations for the cluster of multiple sclerosis among nurses in Key West are discussed.

Adult

Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies.

Multiple sclerosis (MS) is very uncommon among ethnic Asians in the Indian subcontinent, among Asians and Africans resident in the New Commonwealth countries of Africa and in the West Indies. It is also very uncommon among those who have migrated to England from those countries. In contrast, the children born in the United Kingdom of Asian, African and West Indian immigrants have, in the age groups available for study, a high prevalence of MS of a similar order to that occurring in the general population of England.

Adolescent

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Adjuvants, Immunologic

Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma.

We have studied the effects of low-dose recombinant interleukin-2 preceded by low-dose cyclophosphamide on malignant melanoma. Thirty eight outpatients aged from 25 to 75 years were treated with interleukin-2, 3.6 million Cetus units/m2 i.v. daily for five days on two successive weeks beginning three days after 350 mg/m2 of intravenous cyclophosphamide. This schedule was repeated at least twice more with a one-week interval between cycles, usually at the same dosage level. Ten of the 38 patients (26.3%) had clinically significant remissions: two complete (5.3%), seven partial (18.4%), and one ongoing, long-term (greater than 18 mo) "minor" response (2.6%). Four others (10.5%) had shorter minor responses and four (10.5%) a mixed response. One patient with disease restricted to the skin had a complete remission, while the other patient with a complete remission had had three lung nodules and an enlarged hilar lymph node. It was gratifying that one of the major sites of disease responding to treatment was the liver. Two complete and two partial remissions (i.e., greater than 50% regressions for greater than four weeks at this site) were obtained in 10 patients with liver involvement. Lung metastases also responded in four of 16 patients (one complete and three partial remissions). Subcutaneous nodules responded in seven of 21 patients (two complete, five partial remissions), while lymph node metastases diminished significantly in four of 14 patients (one complete, three partial remissions). The median duration of response was nine months (range, 1.5-20 months), with four patients treated for more than one year. Toxicity was moderate and controllable, and only two patients required hospitalization, both overnight. Lymphokine activated killer cell activation was induced in 24 of 38 patients, including all nine of the major responders. Conversely, none of 14 patients without lymphokine activated killer cell activation had a significant clinical remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of lymphokine activated killer cells, and was more tolerable than therapy with high doses of interleukin-2.

Adult

Increased risk of cataract in patients receiving radiotherapy to the eye: a pilot study.

Of 507 persons in England and Wales identified as having had radiotherapy to the eye or eyes some years previously (after excluding those who had died and were not traced), information suitable for analysis could be obtained on 165. Of these, 23 had developed other eye disease so that the lens could not be examined. Of the other 142, 32 had certainly and one had probably developed cataract. A cataract operation had been performed on 19 persons, compared with an expected operation rate of four out of 142. The increased risk of cataract after radiotherapy to the eye is probably higher than the fivefold excess these figures for operations suggest.

Cataract

HLA associations with multiple sclerosis in Sicily and Malta.

The islands of Sicily and Malta have very different prevalence rates for multiple sclerosis (MS): at least 44 per 100,000 in Sicily and only 4 per 100,000 in Malta. In Northern Europe, MS is associated with HLA-DR2/Dw2. The other components of the commonest DR2-containing haplotype of this region, HLA-A3-B7-DR2-Dw2, also tend to be present at higher frequency in MS patients. HLA Class I and II antigen frequencies and associations in controls and MS patients from Sicily and Malta were studied to discover whether they might account for the difference in MS prevalence. In Sicilian MS patients, DR2 is increased in frequency compared with controls and four out of five DR2-positive patients also type as Dw2. In the Maltese population, DR2 is present at high frequency but approximately half of the DR2 positive individuals do not type as Dw2 so that DR2 is probably most commonly present as part of Class II haplotypes other than those commonly associated with MS. Additional differences in HLA profile of the Sicilian and Maltese populations were found when HLA-A, -B, and B-DR antigen associations were examined. Therefore, some of the difference in MS prevalence might be explained by genetic factors.

Cross-Sectional Studies

To tell or not to tell the diagnosis of multiple sclerosis.

167 patients disabled by multiple sclerosis were interviewed to ascertain their views about being told the name of the disease causing their disability. 30 were ignorant of the nature of their disease. 83% favoured knowing the diagnosis, 13% were indifferent, and less than 4% preferred not to know the diagnosis. Almost a quarter of the patients had discovered the diagnosis for themselves. All the respondents thought that the consultant was the person who should convey the diagnosis of multiple sclerosis.

Attitude to Health

Causes of death of blue-collar workers at a Dublin brewery, 1954--73.

The suggested association between high consumption of beer and an increased risk of death from cancer of the colon and rectum was investigated among blue-collar workers at a Dublin brewery, who consume more than average amounts of beer, usually in the form of stout. A study of their mortality between 1954 and 1973 showed that they had as good an expectation of life as all Dublin males, with no increased risk of death from cancer of the oesophagus, pharynx, liver or of cirrhosis of the liver, accidents or suicide, conditions normally associated with the high consumption of alcohol. They had significantly increased risk of death from cancer of the rectum and also from diabetes mellitus. Twenty per cent of the workers, differentiated by their place of work within the brewery, had a much higher risk of death from cancer of the rectum.

Adolescent

Multiple sclerosis in southern Europe. I: Prevalence in Sicily in 1975.

Previous reports on large population groups have suggested that the prevalence of multiple sclerosis (MS) in Sicily and southern Italy is low, of the order of 4-8 per 100 000. In contrast, immigrants from Italy resident in Greater London, many of whom are from southern Italy and Sicily, had a hospitalised MS prevalence similar to that found among people born in the United Kingdom (1960-72). The present study shows that in Enna city (population 29 000) in central Sicily, the prevalence of probable MS was 53 per 100 000, which is of the same order of magnitude as has been reported from the United Kingdom and northern Europe. The high prevalence of MS found in Enna city may be due, at least in part, to the fact that the population studies was small. Because Enna is on high ground, similar studies are being undertaken in two small coastal towns of Sicily.

Adult

Multiple sclerosis in southern Europe. II: Prevalence in Malta in 1978.

After an intensive survey only 14 patients have been found with a diagnosis of probable multiple sclerosis (MS) in the islands of Malta. This is a low prevalence of 4.2 per 100 000. The low prevalence of MS is confirmed by the small number of deaths certified as due to MS--six in 11 years--and by the absence of Maltese MS patients resident in England among the MS patients admitted to hospital in Greater London and the West Midlands (1960-72). The low prevalence of MS found in Malta can be contrasted with the high prevalence found in Enna city in central Sicily. The genetic and environmental reasons for this difference in MS prevalence between the neighbouring islands of Sicily and Malta require further study.

England