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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 163 records · Page 9Linked to original sources
PubMed1999

Biochemical monitoring of treatment for galactosaemia: biological variability in metabolite concentrations.

Red cell galactose 1-phosphate (Gal-1-P) concentrations and urinary galactitol excretion have been suggested as biochemical indices of dietary compliance in classical transferase-deficient galactosaemia. We report our experience of measuring both in 32 patients over 0-10.9 years (median 3.45). A total of 438 blood specimens for Gal-1-P and 383 urine specimens for galacitol assay were received; 317 pairs of specimens were collected at the same time. Concentrations of both analytes fell rapidly over the first 2-3 months following dietary intervention, to mean (geometric SD) levels of 225 (1.60) mumol/L red cells for Gal-1-P and 388 (1.19) mumol/mmol creatinine for galactitol. Concentrations then fell exponentially over the next 7-8 years, with times to half-disappearance of 6.3 years for Gal-1-P and 6.4 years for galactitol, to levels of 104 (1.58) and 193 (1.36) respectively in patients aged over 10 years. Concentrations of both analytes were independent of the presence of the common Q188R mutation. Mean intra- and inter-individual coefficients of variation (CV) across the range of values studied were 36% and 61% for Gal-1-P, and 37% and 42% for galactitol. Analytical CVs were 3.6% for Gal-1-P and 5.5% for galactitol, indicating that the major source of variability is biological. The correlation coefficient between Gal-1-P and galactitol in paired samples overall was 0.33; the regression equation being [Galactitol] = 0.84[Gal-1-P] + 176. Serial measurements of both Gal-1-P and galactitol may be valuable in monitoring galactosaemia, but high intra-individual biological variability limits their usefulness. Standardization of sample collection times may improve this. Further work is needed to assess the predictive values of both analytes for long-term outcome.

Adolescent↗
PubMed1999

Population newborn screening for inherited metabolic disease: current UK perspectives.

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Humans↗
PubMed1999

A case-control study of melanomas of the soles and palms (Australia and Scotland).

OBJECTIVES: Because the factors that influence risk of acral melanomas on the soles and palms in White populations are unknown, we investigated these in a multi-center case-control study. METHODS: Cases of melanoma of the feet and hands diagnosed from 1987-93 in persons aged over 18 years were ascertained in eastern Australia and western Scotland. There were 275 cases of melanoma on the soles and palms matched to 496 controls (selected from the electoral roll) in Australia, and 36 cases matched to 72 controls (nominated by general practitioners) in Scotland. RESULTS: Acral melanoma was strongly associated with high total body nevus counts (adjusted relative risk [RR] = 6.3, 95% confidence interval [CI] = 2.5-15.6), and with nevi on the soles (RR = 7.5, CI = 3.0-18.6). There were also significant positive associations with a penetrative injury of the feet or hands (RR = 5.0, CI = 3.0-8.6) and with heavy exposure to agricultural chemicals (RR = 3.6, CI = 1.5-8.3). Sun-sensitive complexions, cumulative sun exposure and a past history of nonmelanoma skin cancer were also associated with increased risk of acral melanoma. Current cigarette smoking was inversely related to acral melanoma (RR = 0.6, CI = 0.4-0.9). CONCLUSIONS: Melanomas of the soles and palms resemble other cutaneous melanomas in their association with sun exposure, but are distinguished from them by their strong positive associations with nevi on the soles, previous penetrative injury, and exposure to agricultural chemicals, and by their inverse association with smoking.

Adolescent↗
PubMed1999

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome.

Proteins control cell function and measurement of their concentration is crucial for understanding their roles in health and disease. However, current methods for their detection in tissue sections are not quantitative. Radioimmunoluminography (RILG) is a system for direct measurement of quantity and distribution of protein in histological sections. Histological carcinomas were reacted with antigen-saturating concentrations of 125I-antibody to carcinoembryonic antigen (CEA). Antibody distribution and concentration was mapped by phosphor imaging. Radioactivity in each pixel of the digital image was proportional to antigen concentration, calculated from a standard line generated from a nitrocellulose CEA dot-blot assay. RILG gave a linear correlation with standards of known CEA concentration (r = 0.999). Six tumour xenografts with differing CEA concentrations by radioimmunoassay (RIA) were studied by RILG and immunohistochemistry (IHC). RILG gave a linear correlation with CEA by RIA (r = 0.994) but IHC failed to do so (r = 0.42). CEA levels measured by RILG, in cryostat (n = 15) and paraffin (n = 19) sections from colorectal cancer patients showed a range of CEA concentration (38.9-594 ng g(-1) and 22.5-212.5 ng g(-1) respectively). Tumour CEA concentration by RILG was significantly correlated with dose of antibody (% injected radioactivity kg(-1)) localized in tumour (P = 0.04 and P < 0.02 respectively), in patients receiving radioimmunoguided surgery. Clinical relevance of RILG is illustrated by identifying patients with high tumour CEA, most likely to benefit from antibody targeted therapy. Knowledge of the pathophysiology of many diseases may be enhanced by quantitative estimation of antigen concentration related to tissue morphology.

Adenocarcinoma↗
PubMed1999

GABA(B) receptors function as heterodimers.

Our current understanding is that functional GABA(B) receptors exist as heterodimers of two related seven-transmembrane proteins, GABA(B)-R1 and GABA(B)-R2. GABA(B)-R1 requires GABA(B)-R2 to be expressed at the cell surface as a mature glycoprotein. Cloning of the GABA(B) receptor has failed to provide molecular evidence to support the existence of true receptor subtypes. The discovery of the heterodimeric nature of the GABA(B) receptor has already changed the way we think about GPCR function and it is likely that future studies will change our understanding about how receptor subtypes can be formed.

Animals↗
PubMed1999

Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals.

DNA of a wide spectrum of epidermodysplasia verruciformis-associated human papillomavirus (HPV) types (EV-HPV) has been detected in skin lesions and plucked hairs from both immunosuppressed and a considerable proportion of non-immunosuppressed persons. Recently, the skin of psoriatic patients was claimed to be an important reservoir for a particular EV-HPV type, HPV 5, which is considered as a high-risk HPV type for skin carcinomas. In the present study, we analysed plucked hairs from immunosuppressed renal transplant patients and immunocompetent individuals, utilizing an HPV 5-specific nested polymerase chain reaction. HPV 5 was detected in hairs derived from 14 of 31 (45%) immunosuppressed patients and 21 of 135 (16%) immunocompetent individuals. Both the immunosuppressed and the immunocompetent groups consisted of individuals with and without non-melanoma skin cancer. HPV 5 DNA was detected in similar proportions of hair samples plucked from individuals with and without skin cancer in either group. Our results indicate that HPV 5 is commonly present in the population. The role of HPV 5 in the pathogenesis of skin carcinomas and psoriasis remains to be established.

Adult↗
PubMed1999

Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients.

INTRODUCTION: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early death due to these complications has been described. DESIGN: We report a study on the prevalence and mortality of HHT in a Danish population based on two cross-sectional surveys in combination with a long-term follow-up study. SETTINGS AND SUBJECTS: Prevalent cases of HHT as of 1 January 1974 in the County of Fyn, Denmark, were identified. In 1995-97 a follow-up study of mortality was performed of the initial patient sample, and a new point prevalence rate of HHT as of 1 January 1995 was calculated. All live patients and their families were invited to attend a detailed clinical examination. RESULTS: The prevalence of HHT in the County of Fyn was 13.8 per 100,000 on 1 January 1974 and 15.6 per 100,000 on 1 January 1995. In the HHT group as a whole, we found a slightly increased mortality; however, amongst the HHT patients younger than 60 years at inclusion the mortality of HHT patients was twice the expected. The excess mortality could be fully explained by severe HHT symptoms. CONCLUSION: This study suggests that HHT is more prevalent than previously believed. In young patients the disease is associated with an excess mortality which is fully attributable to HHT. Future research should aim at the identification of HHT patients at particular risk of developing severe complications.

Adolescent↗
PubMed1999

Photobiological aspects of sunscreen re-application.

A single application of a high sun protection factor (SPF) sunscreen has been shown to prevent sunburn, but the existence of a further protective effect following re-application of sunscreen has received little attention. The aim of this study was to quantify the ultraviolet radiation (UVR) protection against sunburn afforded by a re-application of sunscreen relative to a single application. The study methods were based on the Australian Standard SPF testing regimen, using human volunteers, standardized applications of sunscreen and an artificial solar simulating UVR source. Sunscreen was initially applied, followed by a suberythemal UVR dose; sunscreen was then re-applied, followed immediately by a second period of controlled UV exposure sufficient to induce mild erythema. Compared to the first application, the second sunscreen application afforded 3.1 times more protection against minimal UVR-induced erythema. The combined effect of two sunscreen applications gave on average 2.5 times better protection from UVR than a single sunscreen application. Health authorities worldwide have recommended sunscreen re-application for the prevention of sunburn for some time. This is the first quantitative study to substantiate such recommendations.

Administration, Topical↗
PubMed1999

Do people who apply sunscreens, re-apply them?

Little is known about Australians' practices regarding sunscreen re-application, yet it is routinely advised and has recently been shown to increase the protective efficacy of sunscreens. A baseline survey of sunscreen application and re-application behaviour was therefore conducted in a Queensland community using a standard self-administered questionnaire. Other sun protection methods were also assessed. Of a total of 669 adult respondents, 76% reported using sunscreen and of those, 61% reported re-applying sunscreen. Significantly more women (66%) than men (55%) reported re-applying sunscreen and re-application was inversely related to age (79% of those aged less than 45, 57% of those 45-59 years old and 46% of those over 60 years). Increased rates of re-application were reported during times of increased sun exposure, as well as by those with greater knowledge of the benefits of sunscreen re-application. A recent personal history of non-melanoma skin cancer did not lead to improved rates of sunscreen application, sunscreen re-application, or most forms of physical sun protection.

Adult↗
PubMed1999

Suppression of cell proliferation and telomerase activity in 4-(hydroxyphenyl)retinamide-treated mammary tumors.

The detection of telomerase activity has been proposed as a biomarker of breast cancer development and progression. In this study, we used cell proliferation and telomerase in MNU (N-methyl-N-nitrosourea)-induced mammary carcinomas as targets for assessing the response of tumor cells to 4-(hydroxyphenyl)retinamide (4-HPR), a known inhibitor of mammary carcinogenesis in animal models and premenopausal women. In mammary tumors of rats treated for 1, 2, 4 or 6 weeks with 4-HPR, we observed that telomerase activity decreased progressively with the extension of 4-HPR administration. A marked reduction in telomerase activity was already observed by 2 weeks after treatment and the lowest level was found at 6 weeks after initiation of 4-HPR treatment. The changes in telomerase activity were preceded and accompanied by a significant decrease in the percentage of proliferating cells as evaluated by 5-bromodeoxyuridine (BrdU)-labeling. However, when the values of telomerase activity in the individual tumors were compared with the percentage of proliferating cells, no significant correlation was found. These data suggest that the decreased telomerase activity in the animals treated with 4-HPR is not a simple consequence of the changes in cell proliferation, but a more complex phenomenon involving different cellular mechanisms and pathways. The time-dependent and consistent decrease of telomerase activity in the tumors treated with 4-HPR suggests that, in addition to the percentage of proliferating cells, telomerase activity could also be used as an endpoint in breast cancer chemotherapy studies.

Animals↗
PubMed1999

4-(hydroxyphenyl)retinamide selectively inhibits the development and progression of ductal hyperplastic lesions and carcinoma in situ in mammary gland.

In most previous chemoprevention studies on inhibition of mammary carcinogenesis, the formation of palpable tumors has been used as an end-point. Little is known about whether chemopreventive agents may similarly or selectively suppress hyperplastic and premalignant stages of the neoplastic process. In this study, we evaluated the effect of 4-(hydroxyphenyl)retinamide (4-HPR) on the development and progression of hyperplastic lesions and carcinoma in situ (CIS) in the N-methyl-N-nitrosourea (MNU) mammary carcinogenesis model in rats. 4-HPR was used as the chemopreventive agent because of its proven inhibitory effect on both the early and late phases of mammary carcinogenesis. Treatment with 4-HPR (2.0 mM/kg diet), beginning 2 days after MNU administration and administered continuously for 10 weeks, suppressed all mammary gland lesions (hyperplasia, CIS and invasive carcinoma) in 35% of animals. In the remaining 65%, 4-HPR allowed the development of hyperplastic lesions, alone or combined with CIS, and/or invasive carcinomas (CA). 4-HPR also increased by 2-fold the ratio between CIS and CA (0.75 per animal in control versus 1.5 in 4-HPR-treated animals), suggesting that it may also suppress the transition of CIS into CA. 4-HPR, when administered beginning 4 weeks after MNU administration [when hyperplastic and premalignant (CIS) lesions are present in the mammary gland], inhibited the frequency of terminal end bud hyperplasia (TEBH) and CA but did not significantly suppress ductal hyperplasia, ductal alveolar hyperplasia, alveolar hyperplasia and CIS. In these animals, 4-HPR induced partial disintegration of mostly peripheral areas of lesions, including carcinomas. Taken together, our data indicate that 4-HPR selectively suppresses the development and progression of hyperplastic lesions and CIS in TEBs. Furthermore, it appears that, in addition to mammary carcinomas, TEBH and CIS could also be used as end-point biomarkers in breast cancer chemoprevention studies.

Animals↗
PubMed1999

Epidemiology of type 1 (insulin-dependent) diabetes mellitus: public health implications in the Middle East.

Recent estimates suggest that more than 100,000 inhabitants in the Middle East suffer from type 1 diabetes and that about 6000 subjects in the region develop the disease each year. This paper illustrates how epidemiological principles and methods may assist in a rational assessment of the public health impact of type 1 diabetes in the Middle East. Making a series of assumptions, it is estimated that the future prevalence of type 1 diabetes in the region will increase slightly, but that the increase may be more pronounced if the disease incidence is increasing and the prognosis improved. It is recommended that more valid information is established on the basic epidemiological features of type 1 diabetes in the Middle East, as this will provide the basis of more rational planning of the current and future diabetes healthcare in the region.

Adolescent↗
PubMed1999

Prospectively measured levels of serum follicle-stimulating hormone, estradiol, and the dimeric inhibins during the menopausal transition in a population-based cohort of women.

The aims of this study were: 1) to describe, in relation to the date of final menses, the average hormone levels of women in the years before and after this date and to determine the extent to which these average levels were dependent on age and body mass index (BMI); and 2) to determine the degree of tracking in residual hormone levels [i.e., the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses]. Serial levels of serum FSH, circulating estradiol (E2), and the dimeric inhibins (INH) A and B were measured annually in 150 women who experienced a natural menopause during 6 years of follow-up. Means of the log-transformed hormonal levels were analyzed as a double-logistic function of time relative to FMP, as well as age and BMI and correlations between repeated hormonal levels, were measured. Mean FSH levels started to increase from about 2 years before the FMP, increased most rapidly about 10 months before the FMP, and had virtually plateaued by 2 years after the FMP. FSH levels were, on average, 3% greater for each year of age and 2% lower for each kg/m2 of BMI. After adjusting for time relative to the FMP, logFSH showed modest tracking. Age-adjusted values of logFSH were moderately correlated across time, and much of this tracking was explained by the actual timing of a woman's FMP. Mean E2 levels started to decrease about 2 years before the FMP, decreased most rapidly around the time of the FMP, and had virtually plateaued by 2 years after the FMP. E2 levels were lower, on average, by about 9% per year of age, and residual values showed weak tracking. Levels of both INHA and INHB decreased, on average, in the years before the FMP and were undetectable (INHA, < 10 pg/mL; INHB, < 25 pg/mL) in the majority of women by the time of the FMP and in almost all women by 4 years post-FMP. Significant negative correlations between log serum FSH and log E2 (r = -0.73) and log INHA (r = -0.41) and log INHB (r = -0.36) were observed. It is concluded that substantial changes in reproductive hormone levels occur within 1-2 yr on each side of the FMP, that falling concentrations of E2 and the INH contribute to the rising concentrations of FSH, and that there is no single reliable hormonal marker of menopausal status for an individual woman.

Aging↗
PubMed1999

On discriminating and not discriminating between affect and representation.

The topic involves two issues. They can be related either to different clinical pictures or to divergent opinions about the same clinical facts. But the above mentioned opposition can be found in Freud's work. Listening in analysis differentiates between situations where the distinction of affect and representation is blurred within the general frame of communication and others where this distinction imposes itself because of the critical or chronic character of the predominance of affect. Problems about the discrimination between affect and representation in the unconscious are elucidated in the light of their structural differences. The notion of the psychical representative of the drive announces the reference to the further notion of instinctual impulse. Later on, in Freud's theory, the notion of instinctual impulse has encompassed the distinction between affects and representation. Contemporary authors have, in their vast majority, chosen to refer preferably to object relationships. Nevertheless, the problems raised by Freud remain unanswered. It is with the clinical picture of borderline personality disorders that the lack of discrimination between affect and representation becomes evident. A detailed description is presented of the forms of transference where the irrepresentable prevails, accompanied by feelings of being overwhelmed, repetition compulsion, acting out and somatic reactions. In the countertransference, the affects of helplessness, despair and even the impossibility of grasping the meaning of the patient's communication are frequently met in the analyst. In these clinical pictures, intermediary formations, i.e. psychic organisations where primary processes structures the unconscious, are impaired. One is struck by the limitation of the capacities of representation and by the importance of phenomena related to negative hallucinations specially focused on thought processes, The communication is frequently self-contradictory, the transference oscillating between disembodiment and primitive fusion. The object has a paradoxical status; it is at the same time everything and nothing, the transference being incomprehensible and unanalysable. Different hypotheses are presented to explain the importance of destruction. Finally, the author presents a hypothesis for the deficiency of these intermediary formations because of the absence of continuing cathexis from the primary object at certain important moments of the relationship. It is the establishment of theses intermediary formations that will permit the acceptance of the separation from the object, the child now being able to rely on his own internal creations. However important the influences of the relationship to the other in the genesis of affects, the internal orientation towards the body of the psychic processes is what constitutes the core of the primordial psychic world.

Affect↗
PubMed1999

Sun exposure, skin cancers and related skin conditions.

Skin cancer is the most commonly occurring cancer in humans. Solar keratoses are related benign tumours that are at least ten times commoner than skin cancers and photoageing of the skin is still more common. Descriptive studies show that incidence rates of the main types of skin cancer, basal cell carcinoma, squamous cell carcinoma and melanoma are maximal in populations in which ambient sun exposure is high and skin (epidermal) transmission of solar radiation is high, suggesting strong associations with sun exposure. Analytic epidemiological studies confirm that exposure to the UV component of sunlight is the major environmental determinant of skin cancers and associated skin conditions and evidence of a causal association between cumulative sun exposure and SCC, solar keratoses and photodamage is relatively straightforward. Results for BCC and melanoma are complicated by several factors including the existence of subgroups of these diseases which do not appear to be caused by sun exposure yet have been included in most aetiological studies to date. Complementary to epidemiological data is the molecular evidence of ultraviolet (UV) mechanisms of carcinogenesis such as UV-specific mutations in the DNA of tumour suppressor genes in skin tumours. With increased UV irradiation resulting from thinning of the ozone layer, skin cancer incidence rates have been predicted to increase in the future--unless, as is hoped, human behaviour to reduce sun exposure can offset these predicted rises.

Australia↗
PubMed1999

Long-term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose.

Adipocyte glucose transport can be impaired by prolonged hyperglycemic conditions. However, at the whole body level, lipolysis is quantitatively a more important function of adipocytes than glucose uptake. We have therefore investigated the effect of prolonged high glucose and insulin on adipocyte lipolysis in basal conditions or with maximal concentrations of adenosine deaminase (ADA), dibutyryl cyclic-AMP (dbcAMP), or isoproterenol (ISO). Neither insulin nor glucose alone affected basal or maximally stimulated lipolysis. However, insulin plus glucose increased the rate of ADA-, dbcAMP-, and ISO-stimulated lipolysis by 40-65%, and the effect was maximal by 8 h. When insulin was kept constant, the half-maximally effective concentration (EC50) of glucose was approximately 2.5 mmol/l. We also demonstrated that the effect is not glutamine-dependent and does not induce insulin resistance of lipolysis. Because the effect of insulin and glucose was evident whether lipolysis was stimulated by ADA, dbcAMP, or ISO, we hypothesized that the expression of the rate-limiting enzyme for lipolysis, hormone-sensitive lipase (HSL), was increased. Our results show that insulin plus glucose-treated cells contain approximately 40% more HSL protein than control cells, in good agreement with the increase in maximally stimulated lipolysis. We conclude that hyperglycemic-hyperinsulinemic conditions increase basal and maximal adipocyte lipolysis by a mechanism that is not glutamine-dependent and involves maintenance of cellular concentrations of HSL. The results also provide evidence that factors other than translocation of HSL to the lipid droplet are necessary to activate the enzyme.

Adenosine Deaminase↗
PubMed1999

A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis.

Cri du chat syndrome is associated with a deletion on the short arm of chromosome 5. The main diagnostic feature is a high pitched, cat-like cry which has recently been localised to 5p15.3 and is separate from the remaining clinical features of the syndrome, which have been localised to 5p15.2. The present study describes a family of four who have a deletion slightly distal (5p15.3) to the critical region. Detailed neuropsychological evaluations indicated a similar pattern of cognitive performance to that reported for subjects with typical CDCS but with only minimal intellectual impairment. In addition, in this family the 5p deletion is transmitted in an autosomal dominant fashion, contrasting with most cases of CDCS, which are either de novo or occur as an unbalanced product of a balanced translocation in a normal parent. This study confirms the importance of differentiating between 5p deletions that coincide with the typical cri du chat phenotype which includes severe to profound learning disability and deletions that only delete the distal critical region that coincides with a milder degree of cognitive impairment and a much improved prognosis.

Adolescent↗