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Biomedical subjects

J Yuen

Publications and source records attributed to J Yuen.

At least 19 recordsLinked to original sources

Risk perceptions and behavioral intentions for Hepatitis B: how do young adults fare?

Young adults are at risk for Hepatitis B infection. Little is known about their attitudes and beliefs concerning Hepatitis B, which are determinants of getting immunized. This investigation examined risk perceptions and behavioral intentions concerning Hepatitis B among a convenience sample of 1070 young adults, 18-24 years old who participated in a Hepatitis B campaign that aired a prevention-based advertisement in movies. The campaign did not produce any significant effects. Therefore, analyses presented in this paper explored whether risk perceptions and intentions vary by sociodemographic characteristics. Most young adults do not perceive themselves to be at risk for Hepatitis B, but perceive other people to be at risk. Gender and ethnic differences in behavioral intentions to seek out Hepatitis B information were also observed. This study offers insight about important factors to consider when designing Hepatitis B prevention interventions for young adults and suggests that increasing health-promotion efforts for this group, while accounting for differences in age, culture and gender, are warranted.

Adolescent↗

Efficacy and safety of radiofrequency ablation for perivascular hepatocellular carcinoma without hepatic inflow occlusion.

BACKGROUND: The role of radiofrequency ablation (RFA) for perivascular (up to 5 mm from the major intrahepatic portal vein or hepatic vein branches) hepatocellular carcinoma (HCC) is unclear because of possible incomplete tumour ablation and potential vascular damage. This study aimed to evaluate the safety and efficacy of RFA for perivascular HCC without hepatic inflow occlusion. METHODS: Between May 2001 and November 2003, RFA using an internally cooled electrode was performed on 52 patients with perivascular HCC (group 1) through open (n = 39), percutaneous (n = 9), laparoscopic (n = 2) and thoracoscopic (n = 2) approaches. Hepatic inflow occlusion was not applied during the ablation procedure. The perioperative and postoperative outcomes were compared with those of 90 patients with non-perivascular HCC (group 2) treated by RFA during the same period. RESULTS: The morbidity rate was similar between groups 1 and 2 (25 versus 28 per cent; P = 0.844). One patient in group 1 (2 per cent) and two in group 2 (2 per cent) had developed thrombosis of major intrahepatic blood vessels on follow-up computed tomography scan. There were no significant differences between groups 1 and 2 in mortality rate (2 versus 0 per cent; P = 0.366), complete ablation rate for small HCC (92 versus 98 per cent; P = 0.197), local recurrence rate (11 versus 9 per cent; P = 0.762) and overall survival (1-year: 86 versus 87 per cent; 2-year: 75 versus 75 per cent; P = 0.741). CONCLUSION: RFA without hepatic inflow occlusion is a safe and effective treatment for perivascular HCC.

Adolescent↗

A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer.

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m(-2), respectively) (n=59) or the daily x 5 Mayo Clinic schedule (425 and 20 mg m(-2), respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79-1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71-1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred.

Adult↗

Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia.

Epidemiological studies have consistently shown elevated rates of breast cancer among female blood relatives of patients with ataxia telangiectasia (AT), a rare autosomal recessive disease. A large proportion of the members of AT families are carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and it has been hypothesised that these otherwise healthy carriers are predisposed to breast cancer. This is an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT in 66 Nordic families. Blood relatives were identified through population registry linkages, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. The ATM mutation carrier probabilities of relatives were assigned from the combined information on location in family, consanguinity, if any, and supplementary carrier screening in some families. Among the 1445 blood relatives of AT patients, 225 cancers were observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of 1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in 34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. We concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. The findings of breast cancer risk in mothers, but not other likely mutation carriers, in this and other studies raises questions about the hypothesis of a simple causal relationship with ATM heterozygosity.

Adult↗

Impact of radiofrequency ablation on the management of patients with hepatocellular carcinoma in a specialized centre.

BACKGROUND: Radiofrequency ablation (RFA) has been used increasingly in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to investigate changes in the treatment pattern of primary HCC following the implementation of RFA in a specialized surgical centre. METHODS: This was a retrospective analysis of all 894 patients admitted for treatment of primary HCC over 36 months. RESULTS: There was no difference in the age, sex ratio, liver function according to Child-Pugh grade, serum alpha-fetoprotein concentration, hepatitis B surface antigen status and tumour size among patients before and after the introduction of RFA therapy. Fifty-one patients (10.6 per cent) with primary HCC received RFA treatment after its implementation. There was a 6.8 per cent reduction in the number of patients who had supportive treatment (P = 0.041) and a 3.2 per cent reduction in surgical treatment. The hospital mortality rates for RFA and surgery were 2.0 and 4.9 per cent respectively. The overall survival rates at 6, 12 and 18 months for patients treated with RFA were 92.2, 73.4 and 61.2 per cent respectively. The corresponding survival rates for the 213 patients who had surgery were 88.0, 77.0 and 71.5 per cent. These values were no different from those in patients who had RFA (P = 0.718). Patients treated with RFA or surgery survived longer than those who had other treatments. CONCLUSION: RFA had a significant impact on the management of primary HCC, increasing the number of patients suitable for liver-directed therapy and leading to survival benefit. RFA may become the treatment of choice for patients with irresectable HCC.

Adolescent↗

Improved detection rate of prostate cancer using the 10-core biopsy strategy in Singapore.

OBJECTIVES: To evaluate if changing the biopsy regime to 10 cores might improve the positive predictive value (PPV) of elevated prostate-specific antigen [PSA, elevated range, 4 to 20 ng per ml, normal range, < 4 ng per ml] for the diagnosis of prostate carcinoma. METHODS: From February 2000 to April 2001, 191 patients, mean age 64 years [range, 38 to 85 yr], underwent transrectal ultrasound [TRUS] for either elevated PSA [elevated range, 4 to 20 ng per ml] and/or abnormal digital rectal examination [DRE]. A 10-core TRUS-guided biopsy of the prostate was performed. This included the standard sextant biopsy and two additional cores for each far lateral zone. RESULTS: Using this technique, 47 out of 191 patients [24.6%] had prostate cancer. The PPV for PSA levels of 4.1 to 10.0 ng per ml and 10.1 to 20.0 ng per ml were 19.3% and 35.4%, respectively. The lateral cores contributed 21.3% of the cancer cases, which would have been missed if only sextant biopsies were performed. CONCLUSIONS: With the 10-core biopsy method, the PPV for prostate cancer for patients with a PSA in the range of 4 to 20 ng per ml was in the range of 25%. This is significantly different from previous reports. The reason for this may be due to the adoption of a better, more uniform and systematic biopsy strategy for patients with elevated PSA, or it may be a true reflection of the current population incidence. Hence, this biopsy strategy is highly recommended.

Adult↗

Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study.

The extremely high risk reported for some types of cancer among patients with common variable immunodeficiency (CVID) is based on a limited number of investigations. Therefore, we examined the risks for cancer among 562 Danish and Swedish patients with CVID or IgA deficiency and 2071 relatives in 1958-96. The patients were identified through an Immunodeficiency Register and hospital records, while the relatives were traced through population registers. Cancer incidence was assessed by linkage to the Cancer Registries and compared with that in the general population. Among 386 patients with IgA deficiency, the incidence of cancer was not increased (standardized incidence ratio (SI) = 1.0); but two cases of stomach cancer were found, resulting in a non-significant increase in risk (SIR = 5.4; 95% CI = 0.7-19.5). Among 176 patients with common variable immunodeficiency (CVID), the incidence of cancer at all sites combined was increased (SIR = 1.8; 95% CI = 1.0-2.9), which was due mainly to significant excesses of malignant lymphoma (obs = 4; SIR = 12.1; 95% CI = 3.3-31.0) and of stomach cancer (obs = 3; SIR = 10.3; 95% CI = 2.1-30.2). Among the 626 relatives of patients with CVID, no increase in risk was found for these types of cancer or for cancer overall (obs = 53; SIR = 1.0; 95% CI = 0.8-1.3). Our data show that the risks for malignant lymphoma and stomach cancer among patients with CVID may be lower than reported previously. The absence of an increased risk among relatives suggests that the increased cancer morbidity in patients with CVID is related to the immunodeficiency per se rather than to specific genetic traits shared with their relatives.

Adult↗

RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III.

The heterotrimeric G-protein Gs couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha-subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the alpha(s) family member alpha(olf) links odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours.

Adenylyl Cyclase Inhibitors↗

Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.

BACKGROUND: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. METHODS: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. RESULTS: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. CONCLUSIONS: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.

Adult↗

Cancer incidence and work place exposure among Swedish biomedical research personnel.

OBJECTIVE: This cohort study aimed to elucidate cancer occurrence in relation to occupational exposure to specific chemical, biological and physical agents among biomedical research laboratory personnel in Sweden. METHODS: Standardized incidence ratios (SIRs) for the period 1970-1994 were calculated for specific exposures in the laboratory group (n = 3,277) and for personnel working in non-laboratory departments (n = 2,011), as an internal reference group. Expected numbers were based on national cancer rates. RESULTS: The total number of cancer cases was lower than expected in both laboratory and non-laboratory personnel. Elevated SIRs were noted for malignant melanoma among female laboratory employees for whom use was reported of solvents (SIR 2.73; CI 1.10-5.63) and of selected carcinogenic (International Agency for Research on Cancer (IARC) group 2B) agents (SIR 3.15; CI 1.16-6.85). A light increase of the risk estimate for breast cancer was also observed. CONCLUSIONS: In general, there were few cases of cancer in this comparatively young cohort, but the findings give some indication of increased risks for malignant melanoma in female laboratory personnel after exposure to organic solvents or substances classified by IARC as being possibly carcinogenic.

Breast Neoplasms↗

Single nucleotide polymorphisms of the fukutin gene.

Mutations in the LMNA gene, which encodes nuclear lamins A and C, underlie both Emery-Dreifuss muscular dystrophy (EMD2) and Dunnigan-type familial partial lipodystrophy (FPLD). This indicates that one gene can cause different phenotypes characterized by tissue degeneration. The gene for one form of Berardinelli-Seip-type congenital total lipodystrophy (BSCL) has been mapped to chromosome 9q34. Based on the observation that one gene caused both FPLD and EMD2, we considered that a known gene for muscular dystrophy at or near the BSCL locus on chromosome 9q would be an appropriate candidate for BSCL. The gene encoding fukutin, which is mutated in Fukuyama congenital muscular dystrophy has been mapped to 9q31. We thus developed amplification primers for the coding regions of the fukutin gene. We found no putative disease mutations, but through screening of diseased and normal subjects, we identified three novel single nucleotide polymorphisms (SNPs). We conclude that mutations in fukutin are not present in subjects with BSCL. However, the identification of SNPs provides tools to investigate this protein for association with other phenotypes.

Base Sequence↗

Single-nucleotide polymorphisms of the nuclear lamina proteome.

Familial partial lipodystrophy (FPLD) has been shown to be due to mutations in the LMNA gene encoding nuclear lamins A and C, indicating that defective structure of the nuclear envelope can produce this unique phenotype. Some patients with inherited partial lipodystrophy have normal LMNA coding, promoter, and 3'-untranslated region sequences. This suggests that the FPLD phenotype is genetically heterogeneous. Among the candidate genes to consider for the non-LMNA-associated forms of FPLD are other components of the inner nuclear membrane, such as lamin B1 and B2 and the lamin B receptor. We developed amplification primers for the coding regions of LMNB1, LMNB2, and LBR, which encode lamin B1, lamin B2, and the lamin B receptor, respectively. We found no putative disease mutations in any of these proteins in subjects with non-LMNA FPLD, but, through the screening of diseased and normal subjects, we identified several single-nucleotide polymorphisms (SNPs); specifically, five SNPs in LMNB1 and four SNPs in LBR. The LMNB2 gene was monomorphic in screening experiments. We conclude that mutations in other constituent proteins of the nuclear envelope are not present in subjects with non-LMNA-associated FPLD. However, the identification of amplification primers and SNPs provides tools to investigate these proteins for their association with other phenotypes.

Base Sequence↗

A pilot study of pentoxifylline in the treatment of radiation-induced trismus.

Radiation-induced trismus has a significant impact on the quality of life of patients receiving radiotherapy for head and neck cancers. Pentoxifylline has immunomodulatory activities that downregulate certain cytokines that have been implicated as mediators of fibrogenic reactions after radiation. A pilot study was therefore conducted to evaluate the efficacy of pentoxifylline in the treatment of radiation-induced trismus. Twenty patients with severe trismus (dental gap < or = 25 mm) after receiving radiotherapy for nasopharyngeal carcinoma were enrolled onto the study. Four patients were excluded from analysis because of poor drug compliance. The remaining 16 evaluable patients completed an 8-week course of pentoxifylline at a dose of 400 mg two to three times daily. Changes in dental gap were recorded by measuring the distance between left upper and lower incisor before and after treatment. At the end of treatment, 10 patients had a measured increase in dental gap ranging from 2 to 25 mm. Six patients had an increment of 5 mm or more. The mean dental gap before treatment was 12.5 mm compared with 16.5 mm at the end of treatment (p = 0.023). The mean difference in dental gap was 4 mm, with a 95% confidence interval of 0.6 to 7.4 mm. The drug pentoxifylline appears to exert a modest therapeutic effect in patients with radiation-induced trismus, although our findings need to be confirmed by a randomized placebo-controlled study. While awaiting more evidence from clinical studies, a therapeutic trial of pentoxifylline is worth considering in patients experiencing radiation-induced trismus.

Adult↗

[Ataxia-telangiectasia surveyed in Sweden].

Ataxia-telangiectasia (AT) is a rare autosomal recessive disease with a complex phenotype involving cerebellar degeneration, immunodeficiency, cancer risk and radiosensitivity. Our aim has been to identify Swedish AT patients in order to study the possible "Swedish phenotype" of the disease. In the 19 patients identified in Sweden we found a phenotype fairly similar to what has been described internationally, with the exception of some differences including lower cancer incidence in patients and their relatives and somewhat more pronounced immunodeficiency and concomitant susceptibility to infections.

Adolescent↗

Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. The protein truncation test (PTT), fragment length and heteroduplex analyses of large (0.8-1.2 kb) cDNA fragments were used. In total, 67 of 82 (82%) of the disease-causing alleles were characterized. Thirty-seven unique mutations were detected of which 25 have not previously been reported. The mutations had five different consequences for the ATM transcript: mutations affecting splicing (43%); frameshift mutations (32%); nonsense mutations (16%); small in-frame deletions (5%); and one double substitution (3%). In 28 of the probands mutations were found in both alleles, in 11 of the probands only one mutated allele was detected, and no mutations were detected in two Finnish probands. One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygote with at least one identified allele. Ten alleles were found more than once; one Norwegian founder mutation constituted 57% of the Norwegian alleles. Several sequence variants were identified, none of them likely to be disease-causing. Some of them even involved partial skipping of exons, leading to subsequent truncation of the ATM protein.

Alternative Splicing↗

Critical leg ischemia resulting from interruption of collaterals by harvest of the rectus abdominis free flap: endovascular salvage.

In the setting of aortoiliac occlusive disease, the inferior epigastric artery may be an important pathway for collateral blood supply to the lower extremities. A 72-year-old man developed critical ischemia of both legs after harvest of a rectus abdominis free flap as a result of interruption of the inferior epigastric artery. In patients with aortoiliac occlusive disease, the contribution of the inferior epigastric artery to lower extremity blood flow should be evaluated noninvasively. In the setting of reversed flow, the inferior epigastric artery usually should not be divided.

Abdominal Muscles↗

Cancer risk in patients with earlier diagnosis of cutaneous melanoma in situ.

We calculated the short-term and long-term risks of developing cancer among 3,766 patients with a diagnosis of cutaneous melanoma in situ in Sweden from 1958 to 1992. In total, 393 patients developed a primary cancer at any site compared with an expected number of 177 [standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) = 2.0-2.4]. Patients below 60 years of age at diagnosis had the highest SIR (2.7, 95% CI = 2.3-3.2). The overall risks were similar between men and women. The highest risk was seen during the first year of follow-up, though the risk remained elevated also after 15 or more years of follow-up. For specific sites, the highest SIR was found for developing invasive cutaneous malignant melanoma (SIR = 22.2). The risk of subsequent primary non-melanoma skin cancer was elevated 8-fold in men and almost 7-fold in women. An elevated risk was also found for female breast cancer (SIR = 1.4). Especially among women, other sites with increased cancer risk (though not significant) were non-Hodgkin's lymphoma (SIR = 1.9), multiple myeloma (3.2) and cancers of the colon (1.6) and pancreas (1.6). In conclusion, patients with melanoma in situ run a generally increased risk of developing primary cancers, especially cutaneous malignant melanoma and non-melanoma skin cancer. The increased long-term risk of cancer after diagnosis of melanoma in situ may be due to continuing carcinogenic exposure or to intrinsic tumor susceptibility.

Adult↗