Search PubMed⌕ Search

Biomedical subjects

G Dean

Publications and source records attributed to G Dean.

At least 37 records · Page 2Linked to original sources

Primary liver cancer in two sisters in Holland with intermittent acute porphyria.

Two sisters living in Holland, with a niece now living in South Africa, were reported in 1958 to have inherited intermittent acute porphyria (IAP). In 1994 both sisters died from primary liver cancer. Other reports have also noted an increased mortality from carcinoma of the liver in porphyrics. Porphyria variegata has a high prevalence in white and coloured South Africans, and it would be relatively easy to ascertain whether those who have inherited the gene for this disorder, in South Africa, have a higher than reported mortality from liver cancer. If they do, consideration should be given to ways to reduce their risk of developing and dying from this cancer.

Barbiturates↗

Analysis of the C-terminal secretion signal of the Rhizobium leguminosarum nodulation protein NodO; a potential system for the secretion of heterologous proteins during nodule invasion.

We used deletions to analyze the domains required for secretion of the Rhizobium leguminosarum bv. viciae nodulation protein, NodO, by the sec-independent pathway. Deletion of the C-terminal 24 amino-acids (residues 261 to 284) reduced secretion by at least 95%. A monoclonal antibody that recognizes the C-terminal domain of NodO was used to identify four nested deletions that retained the C-terminal 24 residues of NodO but had lost up to 133 residues (amino acids 128 to 259); all four proteins were secreted into the growth medium with an efficiency between 50 and 90% of normal. A deleted derivative of NodO that retained residues 1 to 21 and 167 to 284 (and therefore lacked most of the N-terminal Ca(2+)-binding domain) was secreted at around 80% of normal efficiency. Taken together, these observations indicate that the C-terminal 24 amino acids are sufficient for NodO secretion although the region adjacent to this domain appears to affect secretion efficiency. A derivative of the Escherichia coli alkaline phosphatase (phoA) gene was cloned into two derivatives of nodO such that PhoA (lacking the N-terminal transit peptide) was in-frame at both ends, with the C terminus fused to either the last 24 or 50 amino acids of NodO. These fusion proteins were secreted at 40 and 80% of the wild-type level, respectively, and the larger of the two retained alkaline phosphatase activity. A hybrid protein, containing E. coli beta-glucuronidase (GUS) fused to the N terminus of NodO, was not secreted, and it reduced the levels of wild-type NodO secreted by R. leguminosarum bv. viciae. The nature of the NodO C-terminal secretion signal is discussed with regard to its use as a delivery system for heterologous proteins useful for investigating the Rhizobium-legume interaction.

Amino Acid Sequence↗

The meaning of cancer pain.

Pain is a common symptom in cancer and one experienced both by patients and family caregivers. A neglected area of pain management is enhancing the individual's ability to derive the meaning from pain and suffering associated with illness. Because pain is often a metaphor for impending death, the meaning derived from pain may contribute to the ultimate meaning of death for the individual. This article provides case examples and analysis of the search for meaning in cancer pain.

Adult↗

Prevalence of multiple sclerosis in the region of Osona, Catalonia, northern Spain.

To ascertain the prevalence of multiple sclerosis in the region of Osona in Catalonia, northern Spain, an intensive study was undertaken in a small population of 72,000 people over a period of five years, using many sources of information. Patients were classified according to the Poser criteria. Most of the patients presented with mild symptoms only and many had not seen a neurologist or attended a large hospital. The prevalence of definite and probable multiple sclerosis was 58 per 100,000. This is nine to 10 times higher than had been found previously in Catalonia and is a similar prevalence to that found in southern Spain, in Sicily, and in Greek speaking Cyprus.

Adolescent↗

Deaths from primary brain cancers, lymphatic and haematopoietic cancers in agricultural workers in the Republic of Ireland.

STUDY OBJECTIVE: To ascertain if agricultural workers in the Republic of Ireland had a higher than expected mortality from brain and haematopoietic cancers than occurred in the general population. DESIGN: The Central Statistics Office of Ireland provided computer analysis of all deaths coded as cancer of the brain, ICD 191, and of lymphatic and haematopoietic cancers, ICD codes 200-208, by socioeconomic, sex, and age groups, from 1971 to 1987. The deaths were then analysed by socioeconomic group and compared with the expected number of deaths in the general population. SETTING: A cluster of four deaths from primary brain cancer, three from leukaemia, and one from Hodgkin's disease, occurred in the research and technical staff of the former Agricultural Institute of the Republic of Ireland in men under the age of 65. This raised the question, were farmers more likely to get these forms of cancer due to exposure to herbicides or fertilisers? SUBJECTS: All deaths in the Republic of Ireland from 1971 to 1987 by socioeconomic group. MAIN RESULTS: Although deaths reported as due to primary brain cancers had increased in all socioeconomic groups in the two time periods studied, there was no greater increase in farmers and a smaller increase in other agricultural workers and fishermen. Deaths from Hodgkin's disease and multiple myeloma, and to a smaller extent from leukaemia, had also increased. The increase in reported mortality of these haematopoietic cancers in farmers was no greater and in other agricultural workers it was less than in the general population. CONCLUSION: There was no evidence that farmers had any greater increase in mortality from these cancers than the general population. The cluster of brain and haematopoietic cancers in research and technical staff at the Agricultural Institute of the Republic of Ireland does not reflect a high risk of these cancers among the general farming population, but strongly supports the need for a compilation of a register of causes of death of laboratory workers in a number of countries.

Adolescent↗

Motor neuron disease in a defined English population: estimates of incidence and mortality.

Linked statistics from hospital records and death certificates were used to study the incidence of and mortality from motor neuron disease in a defined English population. The incidence of motor neuron disease, measured as first-admission rates for the disease, was studied from 1963 to 1985 and death certificates for the patients admitted to hospital were obtained to the end of 1990. The average annual first-admission rate for motor neuron disease was 2.1/100,000 men (95% confidence interval (CI) 1.9 to 2.4) and 1.7/100,000 women (95% CI 1.5 to 1.9). First-admission rates increased with age and peaked in the age range 65-84 years. Motor neuron disease was recorded on the death certificate for 86% of patients who died while they had the disease and there was no appreciable change over time in the recording of motor neuron disease as the underlying cause of death. The admission and mortality data derive from different sources, hospital statistical abstracts and death certificates respectively, but trends over time in the two data sets were similar. There was an increase in mortality during the period covered by the study, as there has been in mortality from motor neuron disease nationally, and the increase in mortality in the Oxford region was accompanied by an increase in first-admission rates. It is concluded that the increase in mortality from motor neuron disease probably occurred as a result of an increase in the diagnosed incidence of the disease rather than changes in death certification practice.

Adult↗

Multiple sclerosis in black South Africans and Zimbabweans.

Multiple sclerosis is rare among the indigenous black people of Africa. The first account of a black patient with multiple sclerosis in South Africa was published as late as 1987. Since then a search to find black patients with multiple sclerosis in Southern Africa has continued. Seven black patients have now been traced in South Africa and five in Zimbabwe in whom a diagnosis of multiple sclerosis can be accepted. Six of the 12 patients became blind, or nearly so, from severe optic neuritis. Multiple sclerosis in these few black patients more often resembled the disorder as it occurs in oriental people than among white people in southern Africa or the black people of North America or the Caribbean.

Adolescent↗

Sustained regression of a primary choroidal melanoma under the influence of a therapeutic melanoma vaccine.

PURPOSE: To determine whether active specific immunotherapy with lysates of cutaneous melanoma cells, administered with immunologic adjuvant DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT), is effective in shrinking a primary choroidal melanoma, in an elderly patient already blind in the nontumorous eye. An 81-year-old man was referred with a primary choroidal melanoma of the left eye, with virtual blindness of the right eye due to macular degeneration. He was begun on active specific immunotherapy with an experimental melanoma vaccine (melanoma theraccine) and DETOX on weeks 1, 2, 3, 4, and 6, respected after a hiatus of 2 weeks. After a response was noted, monthly injections were given. RESULTS: The patient had a significant shrinkage of his choroidal melanoma from a height of 4.2 mm to 2.4 mm within 2 months. This was sustained by continual treatment for 21 months until September 1991. After the patient failed to return for 9 months while recuperating from a stroke, the lesion regrew to a height of 3.7 mm and developed an additional lobe. On resumption of monthly treatments, the lesion shrank to 3.4 mm within 3 months, lost the additional lobe, and has since remained stable. No metastases have been found over a period of nearly 4 years on quarterly computed tomographic (CT) scanning of the chest and abdomen, and magnetic resonance imaging of the head. CONCLUSION: Active specific immunotherapy with cutaneous melanoma lysates has caused a clinically useful protracted regression of a primary choroidal melanoma in an elderly patient in whom surgery and radiation therapy were contraindicated. This may represent the first case of a primary choroidal melanoma, and perhaps the only primary tumor, successfully treated with systemic immunotherapy alone. A formal trial of active specific immunotherapy for primary choroidal melanoma in selected patients may be warranted.

Adjuvants, Immunologic↗

Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.

PURPOSE: To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS: Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS: Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION: These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.

Adult↗

The prevalence of multiple sclerosis in the Sanitary District of Vélez-Málaga, southern Spain.

Since little is known about the prevalence of multiple sclerosis (MS) in Spain, we undertook an epidemiologic study to ascertain the prevalence of MS in the Sanitary District of Vélez-Málaga, close to the city of Málaga, in southern Spain. The crude prevalence rate of MS in Vélez-Málaga was 53 per 100,000, twice as high as the prevalence previously reported in both the city and province of Málaga. The MS prevalence in the Sanitary District of Vélez-Málaga is similar to that in Sicily and in Cyprus.

Adult↗

Mast cells in the synovium and synovial fluid in osteoarthritis.

SF and synovium from normal individuals and patients with OA, RA and traumatic arthritis (TA) were studied for the presence of mast cells (MC). When compared with normals, patients with OA had large numbers of intact and degranulated MC in the synovium and SF of diseased joints. The numbers of MC are comparable with those in RA where they have been implicated in the pathogenesis of joint damage. These data raise the possibility that in OA too MC may participate in the pathological processes in articular and periarticular tissues.

Adult↗

Motor neuron disease and multiple sclerosis among immigrants to England from the Indian subcontinent, the Caribbean, and east and west Africa.

The mortality from motor neuron disease (MND) and multiple sclerosis (MS) was studied among immigrants to England and Wales from the Indian subcontinent, the Caribbean, and East and West Africa during the 10 years 1979-88. The MND mortality among ethnic Asian males was only half and for females one fifth of that expected at English rates. MND mortality in Caribbean immigrants was somewhat lower than expected. White immigrants from the Indian subcontinent had the expected MND mortality. MS mortality was low among Asian, West Indian, and African immigrants. This study is evidence that MND mortality is not the same in all ethnic groups.

Adolescent↗

Motor neuron disease and multiple sclerosis mortality in Australia, New Zealand and South Africa compared with England and Wales.

There has been a marked increase in the reported mortality from motor neuron disease (MND) but not multiple sclerosis (MS) in England and Wales and in a number of other countries. A comparison has been made of the mortality from MND and from MS for two time periods in Australia, New Zealand and South Africa. An increase in MND mortality occurred in Australia and New Zealand between 1968-77 and 1978-87, greater than that which occurred in England and Wales, but there was no increase in MS mortality. Among the white population of South Africa, the MND mortality was half of that in England and Wales, Australia and New Zealand in both time periods. Both MND and MS mortality is higher in the English-speaking than in the Afrikaans-speaking white South African-born. The marked increase in MND mortality which has now been reported from many countries, is good evidence that an environmental factor is important in causing this disease. The large differences in MND mortality in different populations may be important clues to the environment factors causing the disease.

Adult↗

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↗