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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 217 records · Page 12Linked to original sources

Ethylmalonic adipic aciduria--a treatable hepatomuscular disorder in two adult brothers.

An adult male presented at 28 years of age with muscle weakness and liver dysfunction. His brother had died suddenly 2 years earlier after presenting with Reye's syndrome. Urine organic acid analysis and muscle and cultured fibroblast fatty acid oxidation studies confirmed a diagnosis of ethylmalonic/adipic aciduria-an inherited defect of fatty acid oxidation. The patient responded favourably to treatment with a low fat/high carbohydrate diet supplemented with riboflavin. This case highlights the importance of considering inborn errors of metabolism, in particular fatty acid oxidation defects, in adults with liver disease, muscle disease or Reye's syndrome.

Adipates↗

Acute renal failure due to postinfectious glomerulonephritis during pregnancy.

Acute renal failure is a rare but potentially devastating complication of pregnancy. Among its many potential causes is acute postinfectious glomerulonephritis. We describe a case of acute renal failure during pregnancy, provide the histologic features of the renal biopsy, and discuss the differential diagnosis. Postinfectious glomerulonephritis can present rapidly after clinical infection and cause acute renal failure in pregnancy.

Acute Kidney Injury↗

Inhibition of growth and induction of differentiation of metastatic melanoma cells in vitro by genistein: chemosensitivity is regulated by cellular p53.

We have investigated the effect of the soybean isoflavone genistein on the growth and differentiation of human melanoma cells. Four human melanoma cell lines, either completely lacking or containing different levels of wild-type p53, were treated with genistein in vitro in culture. It has been found that genistein significantly inhibited cell growth and that the chemosensitivity might depend on cellular p53 content. Specifically, the data suggest that high levels of wild-type p53 expression make cells resistant to genistein's growth-inhibitory action. Further support for this observation came from the stable transfection studies in which p53 transfectants expressing high levels of wild-type p53 became resistant to genistein. With respect to cell differentiation, our study showed that genistein increased melanin content and tyrosinase activity and caused the cells to form dendrite-like structures. Cells lacking p53 responded more than cells with p53 to dendrite-like structure formation. We also observed that genistein-induced differentiation involved an increase in tyrosinase mRNA level; the mechanisms by which genistein increases tyrosinase transcripts remain to be elucidated. Genistein treatment of the melanoma cell lines resulted in cell cycle arrest at G2/M check point and no significant apoptosis was observed.

Antineoplastic Agents↗

A medical school's plan for anti-tobacco-use education in community schools and hospitals.

BACKGROUND: Tobacco use in the United States remains a significant health concern. In 1992, students at Dartmouth Medical School began a community service program that targeted the prevention of local tobacco use. METHODS: The program combined primary prevention, through education of school-aged children, with secondary prevention, through smoking cessation clinics. RESULTS: The program has received widespread community as well as national support for its actions. The program is in its initial stages of gathering data to determine whether there has been a significant impact on the tobacco use of the community. CONCLUSIONS: This paper is an introduction to the program's efforts, and a potential template for other medical schools to follow.

Adolescent↗

Wherein lies the truth? Assessment of agreement between parent proxy and child respondents.

BACKGROUND: The epidemiological study of diseases of childhood presents a special situation in that the principal respondent is almost always a person other than the index. Use of proxy respondents in paediatric epidemiology has been little studied compared with the use of surrogate respondents for adults. METHODS: Agreement between responses from children and their parents to identical questions about the children was assessed in a case-control study of childhood melanoma in Queensland, Australia. Weighted kappa and log-linear modelling techniques were used to measure agreement for ordinal data. RESULTS: Highest agreement was found for reports of unchanging physical characteristics such as eye colour (kappa = 0.88), hair colour (kappa = 0.76), and for history of residing on a farm (kappa = 0.84). Moderate agreement was seen for density of facial freckling (kappa = 0.62), propensity to sunburn (kappa = 0.46) and tanning ability (kappa = 0.47). Variables with low levels of agreement between parent proxy and child respondents included density of freckling on the shoulders (kappa = 0.28) and degree of moliness of the skin at age 5 years (kappa = 0.24). Agreement did not vary according to age or sex of the children. Log-linear modelling was performed to determine the type and magnitude of components of agreement. CONCLUSIONS: Agreement between responses from children and parent proxies depends largely upon the type of information sought, rather than characteristics of the respondents.

Adolescent↗

Gastric graft-versus-host disease: a blinded histologic study.

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.

Adolescent↗

Breastfeeding, menopause, and epithelial ovarian cancer.

No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval (CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.

Adult↗

Relation between HLA antigens and skin cancer in renal transplant recipients in Queensland, Australia.

On the basis of previous studies that showed a negative association between HLA-A11 and skin cancer in renal transplant recipients and a positive association with HLA-B27 and HLA-DR7, we performed a study in Queensland with 1098 recipients to address the question of whether the same associations could be found. The influence of HLA mismatching and HLA homozygosity on the risk of skin cancer was also studied. In contrast to earlier studies, HLA-A11 was associated with an increased risk of skin cancer. On the other hand, we confirmed that the HLA-B27 antigen was associated with the development of skin cancer, but only when the development of basal cell carcinomas alone was considered, and we confirmed that there is a weak but not statistically significant association with HLA-DR7. No association between HLA mismatching or HLA homozygosity and the development of skin cancer was observed. Environmental factors such as different levels of exposure to sunlight and infection with human papillomaviruses are factors that are most likely to be involved. We hypothesize that human papillomavirus-induced antigens prevail in the skin cancers in the recipients living in the Netherlands, whereas antigens induced by solar radiation, the so-called "photo-antigens," may be more common in the skin cancers of the recipients living in Queensland. Exposure to sunlight can also induce immunologic unresponsiveness, and excessive exposure to sunlight in Australia may, therefore, simply override the risk factors that are important in countries with a more temperate climate.

Basal Cell Carcinoma↗

Cancer and diabetes--a follow-up study of two population-based cohorts of diabetic patients.

OBJECTIVES: To study the occurrence of cancer amongst patients with diabetes mellitus (DM). DESIGN: Population based cohort study. SETTING: Denmark. SUBJECTS: Two cohorts of patients with DM were identified. One cohort comprised 1659 conscripts diagnosed with type I DM before the age of 20 years. Another cohort comprised 1499 men and women with insulin treated DM identified by means of medical prescriptions on 1 July 1973. Both cohorts were followed until the end of 1992. MAIN OUTCOME MEASURES: The relative risk of cancer in the two cohorts was estimated as the ratio of observed to expected number of cancers in the cohort (SIR). RESULTS: No unusual risk of cancer was observed amongst the conscripts (SIR 0.9, n = 13) or amongst patients with onset of DM before the age of 30 years in the prescription cohort (SIR 0.9, n = 32). Amongst those aged 30 years or more at DM onset in the prescription cohort, the overall risk of cancer did not depart from normal (SIR 1.0, n = 103), however, pancreatic cancer occurred in excess both immediately (< 1 year) (SIR 190, n = 1), and during 1-9 years after DM onset (SIR 9.0, n = 4). Similarly, the risk of non-Hodgkin's lymphoma was increased significantly (SIR 3.3, n = 6), all cases occurring more than 10 years after DM onset. CONCLUSIONS: Our data suggest that there is no unusual risk of cancer associated with type I DM. Type II DM may be the first symptom of pancreatic cancer and may be associated with an increased risk of non-Hodgkin's lymphoma.

Adult↗

Validity of self-reported hysterectomy and tubal sterilisation. The Survey of Women's Health Study Group.

Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self-reports of these procedures, we assessed their reliability and validity using data obtained in a case-control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self-reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long-term effects of these procedures to be studied with reasonable accuracy from self-reports.

Adolescent↗

Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells.

Because metallothionein (MT) is elevated and may be protective in UV-irradiated skin, we have studied the effects of UV and other agents on MT transcription using the sheep MT 1A promoter, linked to the beta-galactosidase gene and stably transfected into human cell lines. beta-galactosidase reporter activity was inducible by adding Zn2+ ions to the medium (100 microM for 2-4 h). Two differentiating agents, butyric acid and azelaic bishydroxamic acid (ABHA), significantly increased the response to Zn2+ in a melanoma cell line (MM96L-gal). UVB (280-315 nm) had two distinct, time-dependent effects. During the first 4 h after irradiation, high doses of UVB inhibited induction by Zn2+, an effect that was made more acute by simultaneous exposure to the differentiating agents. These changes in reporter activity were not due to alterations in Zn2+ transport into the cell. The UVB-depressed MT response subsequently recovered and by 24 h was double the control, yet remained sensitive to ABHA. Reporter activity in transfected HeLa cells differed from that in MM96L, being depressed 4 and 24 h after UVB and insensitive to ABHA at both times. Galactosidase reporter activity driven by non-MT promoters was not affected by these treatments. Dependence of MT transcriptional activity on UV-related DNA damage could be inferred because equitoxic UVC (254 nm) affected the response to Zn2+ in a similar fashion, whereas UVA, cisplatin and a methylating agent had no effect. The MT response was partly dependent on the PKC signal transduction pathway because it was inhibited by phorbol ester in HeLa, and by bisindolyl maleimide in HeLa and MM96L. The biphasic MT transcriptional response may model a signal transduction pathway that gives an early, depressed response to acute UV damage, with exacerbation by concurrent differentiation stimuli, but switches to a positive, cell-specific and potentially protective response at later times.

Animals↗

Sun exposure, sunscreen and their effects on epidermal Langerhans cells.

This study examined the effects of chronic and current sun exposure on the number of Langerhans cells in epidermal sheets of UV-exposed and unexposed skin of the arms and assessed the effect of sunscreens. Participants were enrolled in a skin cancer prevention trial and had been using sunscreen daily for the previous 3 years. There were significantly fewer Langerhans cells on the exposed (463 cells/mm2) than on the unexposed forearm (528 cells/mm2) (P = 0.0001). High sun exposure in the previous 2 weeks and a history of predominantly outdoor occupations were both associated with a reduced number of Langerhans cells, although age and other biological indicators of chronic exposure were not associated. Sunscreen use was protective against the effects of current but not chronic sun exposure, with a suggestion of a greater effect at higher levels of exposure. Unexpectedly, people with a past history of nonmelanoma skin cancer had more Langerhans cells in both the exposed and the unexposed skin. These results emphasize the need for continued public health education to protect the immune system from the damaging effects of UV radiation.

Adult↗

Long-term influence of insulin dependent diabetes mellitus on refraction and its components: a population based twin study.

AIM: To study whether refraction of the eye, or some of its components is influenced by duration of insulin dependent diabetes mellitus. METHODS: From the young cohort of the population based Danish Twin Register, containing 20,888 twin pairs born between 1953 and 1982, all twin pairs having one or both partners affected with IDDM were searched. Autorefraction, autokeratometry, and ultrasonic biometric measurements were carried out on 45 twin pairs: 16 monozygotic (MZ) twin pairs, 14 dizygotic twin pairs of same sex (DZss), and 15 dizygotic twin pairs of opposite sex (DZos). To obtain an estimate of the influence of duration of diabetes, the intrapair differences in duration of diabetes were correlated with intrapair differences in refraction and each of its components. RESULTS: Refraction was statistically significantly negatively correlated with duration of diabetes in the DZss group, and axial length correspondingly positively correlated. Surprisingly, refraction and axial length in the MZ group, adjusted for confounding factors, were correlated with diabetes duration in the opposite direction than in the DZss group, although not reaching statistical significance. Lens thickness was statistically significantly positively correlated with duration of diabetes in both MZ and DZ twins. Anterior chamber depth was negatively correlated with duration of diabetes in all the zygosity groups. CONCLUSIONS: Studies of relations between refraction and duration of diabetes show diverging results. In the MZ group, a tendency to reduced axial length and corresponding hyperopia with increasing duration of diabetes was found. However, in the DZ group of same sex the opposite tendency was found. Increasing lens thickness and decreasing anterior chamber depth with increasing duration of diabetes have been confirmed in this study.

Adolescent↗

Germline duplication of chromosome 2p and neuroblastoma.

A child with a germline duplication of chromosome 2p, 46,XY,der(13)t(2;13)(p23;q34), who developed a fatal neuroblastoma confirmed at necropsy is reported. Fluorescent in situ hybridisation studies showed chromosome 2p (p23-pter) duplicated on chromosome 13 (q34). The clinical features of the present case shared many similarities to previous reports of trisomy 2p and there have been two cases described with neuroblastoma. Germline duplication of chromosome 2p including the N-myc proto-oncogene may have pre-disposed to the development of neuroblastoma in this case.

Chromosomes, Human, Pair 13↗