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Biomedical subjects

P M Webb

Publications and source records attributed to P M Webb.

At least 19 recordsLinked to original sources

Health effects of recreational exposure to Moreton Bay, Australia waters during a Lyngbya majuscula bloom.

A survey of residents in an area subject to annual toxic cyanobacterial blooms was undertaken to examine potential health effects of cyanobacteria toxins. The survey assessed the health of marine recreational water users in Deception Bay/Bribie Island area in northern Moreton Bay, Queensland, which is exposed to blooms of the nuisance and potentially harmful cyanobacterium Lyngbya majuscula. A postal survey was mailed to 5000 residents with a response rate of 27%. High numbers of people (78%) responding to the survey reported recreational water activity in Moreton Bay. Of those having marine recreational water activity, 34% reported at least one symptom after exposure to marine waters, with skin itching the most reported (23%). Younger participants had greater water exposure and symptoms than older participants. Participants with greater exposures were more likely to have skin and eye symptoms than less exposed groups, suggesting agents in the marine environment may have contributed to these symptoms. Of those entering Moreton Bay waters 29 (2.7%) reported severe skin symptoms, 12 of whom attended a health professional. Six (0.6%) reported the classic symptoms of recreational water exposure to L. majuscula, severe skin symptoms in the inguinal region. Participants with knowledge of L. majuscula were less likely to report less skin, gastrointestinal and fever and headache symptoms. In conclusion, high numbers of participants reported symptoms after exposure to waters subject to L. majuscula blooms but only a small number appeared to be serious in nature suggesting limited exposure to toxins.

Adolescent↗

Changes in survival after breast cancer: improvements in diagnosis or treatment?

We have compared 5-year survival rates in two cohorts of women diagnosed with breast cancer in Brisbane, Australia, between 1981-1984 and 1990-1994. Tumours diagnosed in the early 1990s were significantly smaller and less likely to have nodal involvement than those diagnosed 10 years earlier (P<0.0001). The size difference was particularly striking for women aged over 50 at diagnosis, those targeted for screening. Five-year survival was greater among women diagnosed in the 1990s (84% vs. 74%; hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.81). After adjusting for the effects of tumour size and nodal status this difference was reduced, but women diagnosed more recently still showed improved survival (HR 0.75; 95% CI 0.56-1.01) and disease-free survival (HR 0.72; 0.56-0.92) at 5 years. This suggests that both earlier diagnosis and changes in breast cancer treatment have contributed to improved breast cancer survival.

Adult↗

Effects of Helicobacter pylori eradication among adults with intellectual disability.

BACKGROUND: Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success of a standard H. pylori eradication protocol; (2) frequency of side-effects; and (3) impact of eradication on level of functional ability and maladaptive behaviour. METHOD: A cohort of adults with ID underwent assessment of their levels of function and maladaptive behaviour, medical history, physical examination, and H. pylori testing using serology and faecal antigen tests. Some received standard H. pylori eradication therapy. Twelve months later, participants underwent repeat assessment, were grouped by change in H. pylori status and compared. RESULTS: Of 168 participants, 117 (70%) were currently infected with H. pylori at baseline, and 96 (82%) of the 117 were given standard H. pylori eradication therapy. The overall eradication rate was 61% but 31% reported side-effects. Institutional status of the participants, their level of behaviour or function, and number of comorbid medical conditions were not associated with failure of eradication. There were no statistically significant differences in level of behaviour or function, ferritin, or weight between the groups in whom H. pylori was eradicated or stayed positive. CONCLUSION: Adults with ID have lower H. pylori eradication and higher side-effect rates than the general population. Levels of maladaptive behaviour and disability did not improve with eradication and thus greater levels of maladaptive behaviour or disability appear to be risk factors for, rather than consequences of, H. pylori infection.

Adult↗

Recurrence of Helicobacter pylori infection in adults with intellectual disability.

Although Helicobacter pylori infection is very common among particular groups of adults with intellectual disability, the rate of recurrence (reinfection or recrudescence) is unknown in this population. Thirty-six months after successful treatment of H. pylori, 28 adults with intellectual disability were retested using the faecal antigen test. Six (21%) of 28 patients tested positive, giving an approximate yearly recurrence rate of 7%, a rate considerably higher than that in the general population (<1%). It is recommended that adults with intellectual disability who have had successful treatment of H. pylori be retested for an interval of 3-5 years after treatment.

Adult↗

Environmental, medical, behavioural and disability factors associated with Helicobacter pylori infection in adults with intellectual disability.

In institutionalized adults with intellectual disability (ID), Helicobacter pylori infection occurs at approximately twice the rate it appears in the general population, and it may be responsible for the twofold higher rates of peptic ulcer disease and gastric cancer in this population. Medical, behavioural and additional environmental factors, as well as level of ID, may be related to the risk of infection with H. pylori. One hundred and sixty-eight adults with ID who were currently, had previously been or had never been institutionalized underwent a biopsychosocial evaluation. This included assessment of: level of ID using the Adaptive Behaviour Scale (ABS) Part I; levels of maladaptive behaviour using the ABS Part II; demographic, medical and environmental factors; as well as H. pylori tests using serology and faecal antigen. The overall rates of past or current infection with H. pylori in institutionalized and previously institutionalized participants were about twice that of the overall group of never-institutionalized participants, i.e. 87% and 79% compared to 44%, respectively (P < 0.001). The rates of H. pylori infection appeared to increase with age in the never-institutionalized group, but were consistently high across all ages in the other groups. The rate of infection was higher in those institutionalized for more than 5 years (95% versus 76%, P=0.02), in those with flatmates with excessive oral secretions (65% versus 21%, P < 0.001) or faecal incontinence (67% versus 27%, P < 0.001), and in those with more chronic illness and medications. All mean domain scores of the ABS Part I (Intellectual Disability) were significantly lower (indicating more severe ID) in the group currently infected with H. pylori compared to their non-infected counterparts. The majority of mean domain scores of the ABS Part II (Behaviour) were also worse, with half of these score differences reaching statistical significance in the currently infected group. The presence of alarm symptoms (e.g. vomiting, weight loss, haematemesis and melena), iron deficiency and body mass index were not significantly different in currently infected subjects. Adults with ID appear to be particularly at risk of infection with H. pylori. Environmental associations with infection include past or current institutionalization, a longer period of institutionalization, living with flatmates with excessive oral secretions and faecal incontinence. Medical associations include chronic disease and more medications, but not alarm symptoms or body mass index. Demographic associations may include increasing age in never-institutionalized adults, but no age effect in currently or previously institutionalized individuals. Psychosocial associations include more severe ID and maladaptive behaviour with current infection.

Adaptation, Psychological↗

Reproduction-related risk factors for mucinous and nonmucinous epithelial ovarian cancer.

The proposition that mucinous ovarian cancer has an etiology distinct from that of other histologic types has been evaluated using data from a population-based case-control study of epithelial ovarian cancer conducted in 1990--1993 among Australian women aged 18--79 years. The protective effects of parity and oral contraceptive use were greater in nonmucinous than in mucinous ovarian tumors. However, these differences appeared to be driven largely by the effect of ovulatory life, which was positively associated with nonmucinous tumors only. An association with family history of breast and/or ovarian cancer also appeared to be restricted to nonmucinous cancers. These results lend support to the hypothesis that mucinous and nonmucinous ovarian tumors develop via different causal mechanisms.

Adolescent↗

The microsomal epoxide hydrolase Tyr113His polymorphism: association with risk of ovarian cancer.

Functional significance has been demonstrated in vitro for the exon 3 T-->C Tyr113His amino acid substitution polymorphism of the microsomal epoxide hydrolase (EPHX) gene. The higher activity or fast TT genotype was previously reported to be associated with an increased risk of ovarian cancer, and this association may reflect enhanced activation of endogenous or exogenous substrates to more reactive and mutagenic derivatives. Components of cigarette smoke are examples of exogenous substrates subject to such bioactivation, and smoking exposure may thus modify the risk associated with the EPHX polymorphism. We examined 545 cases of epithelial ovarian cancer and 287 unaffected controls for this EPHX T-C genetic variant to investigate whether, in the Australian population, the TT genotype was associated with (i) specific ovarian tumor characteristics; (ii) risk of ovarian cancer, overall or for specific subgroups; and (iii) risk of ovarian cancer in smokers specifically. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Stratification of the ovarian cancer cases according to tumor behavior (low malignant potential or invasive), grade, stage, and p53 immunohistochemical status failed to show any heterogeneity with respect to the genotype defined by the EPHX polymorphism. There was a suggestion of heterogeneity with respect to histologic subtype (P=0.03), largely due to a decreased frequency of the TT genotype in endometrioid tumors. EPHX genotype distribution did not differ significantly between unaffected controls and ovarian cancer cases (overall, low malignant potential, or invasive) either overall or after stratification by smoking status. However, the TT genotype was associated with a decreased risk of invasive ovarian cancer of the endometrioid subtype specifically (age-adjusted odds ratio=0.38, 95% confidence interval=0.17-0.87). The results suggest that the proposed EPHX-mediated bioactivation of components of cigarette smoke to mutagenic forms is unlikely to be involved in the etiology of ovarian cancer in general but that a greater rate of EPHX-mediated detoxification may decrease the risk of endometrioid ovarian cancer. Mol. Carcinog. 30:71-78, 2001.

Adult↗

The toxins of Lyngbya majuscula and their human and ecological health effects.

Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles.

Aerosols↗

Renal function in suckling and fasting pups of the northern elephant seal.

Elephant seals fast for prolonged periods without access to water. This is made possible, in part, by reductions in urine production. However, the mechanisms involved in reducing urine production are not understood. In this study, glomerular filtration rate (GFR) was measured in five northern elephant seal pups (Mirounga angustirostris) via the inulin clearance technique. Measurements were made during day 9 and day 18-22 of nursing and the second and eighth week of the postweaning fast. Plasma aldosterone and cortisol concentrations, quantified by radioimmunoassay, were measured in eight other weanlings during the second and eighth week of the fast. Mean GFR was 79.3+/-29.3 ml/min during the early suckling period and 78.2+/-17.1, 89.8+/-52.7, and 80.4+/-12.2 ml/min during the late suckling, early fasting and late fasting periods, respectively. Differences between nursing and fasting were insignificant, possibly because reduced protein oxidation during suckling and rapid recruitment of protein for tissue synthesis obviated the need for postprandial hyperfiltration. Alternatively, maintenance of GFR during fasting may facilitate urea concentration by compensating for reductions in the fractional excretion of urea. It is further hypothesized that aldosterone is primarily responsible for mediating renal water reabsorption in this system.

Aldosterone↗

Cigarette smoking and risk of epithelial ovarian cancer (Australia).

OBJECTIVES: We studied the association between cigarette smoking and ovarian cancer in a population-based case control study. METHODS: A total of 794 women with histologically confirmed epithelial ovarian cancer who were aged 18-79 years and resident in one of three Australian states were interviewed, together with 855 controls aged 18-79 years selected at random from the electoral roll from the same states. Information was obtained about cigarette smoking and other factors including age, parity, oral contraceptive use, and reproductive factors. We estimated the relative risk of ovarian cancer associated with cigarette smoking, accounting for histologic type, using multivariable logistic regression to adjust for confounding factors. RESULTS: Women who had ever smoked cigarettes were more likely to develop ovarian cancer than women who had never smoked (adjusted odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2-1.9). Risk was greater for ovarian cancers of borderline malignancy (OR = 2.4; 95% CI = 1.4-4.1) than for invasive tumors (OR = 1.7; 95% CI = 1.2-2.4) and the histologic subtype most strongly associated overall was the mucinous subtype among both current smokers (OR = 3.2; 95% CI = 1.8-5.7) and past smokers (OR = 2.3; 95% CI = 1.3-3.9). CONCLUSIONS: These data extend recent findings and suggest that cigarette smoking is a risk factor for ovarian cancer, especially mucinous and borderline mucinous types. From a public health viewpoint, this is one of the few reports of a potentially avoidable risk factor for ovarian cancer.

Adenocarcinoma, Mucinous↗

Body size and ovarian cancer: case-control study and systematic review (Australia).

OBJECTIVE: Although increased body mass is an established risk factor for a variety of cancers, its relation with cancer of the ovary is unclear. We therefore investigated the association between measures of body mass index (BMI) and ovarian cancer risk. METHODS: Data from an Australian case-control study of 775 ovarian cancer cases and 846 controls were used to examine the association with BMI. We have also summarized the results from a number of other studies that have examined this association. RESULTS: There was a significant increased risk of ovarian cancer with increasing BMI, with women in the top 15% of the BMI range having an odds ratio (OR) of 1.9 (95% confidence interval (CI), 1.3-2.6) compared with those in the middle 30%. Stratifying by physical activity showed a stronger effect among inactive women (OR = 3.0, 95% CI 1.3-6.9). The overall effect was consistent with the findings of most prior population-based case-control studies, while cohort studies reported positive effects closer to the null. Hospital-based studies gave variable results. CONCLUSIONS: Taken together, the evidence is in favor of a small to moderate positive relation between high BMI and occurrence of ovarian cancer.

Adolescent↗

Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype.

The phase II glutathione S-transferases (GSTs) GSTT1, GSTM1 and GSTP1 catalyse glutathione-mediated reduction of exogenous and endogenous electrophiles. These GSTs have broad and overlapping substrate specificities and it has been hypothesized that allelic variants associated with less effective detoxification of potential carcinogens may confer an increased susceptibility to cancer. To assess the role of GST gene variants in ovarian cancer development, we screened 285 epithelial ovarian cancer cases and 299 unaffected controls for the GSTT1 deletion (null) variant, the GSTM1 deletion (null) variant and the GSTP1 codon 104 A-->G Ile-->Val amino acid substitution variant. The frequencies of the GSTT1, GSTM1 and GSTP1 polymorphic variants did not vary with tumour behaviour (low malignant potential or invasive) or p53 immunohistochemical status. There was a suggestion that ovarian cancers of the endometrioid or clear cell histological subtype had a higher frequency of the GSTT1 and GSTM1 deletion genotype than other histological subgroups. The GSTT1, GSTM1 and GSTP1 genotype distributions did not differ significantly between unaffected controls and ovarian cancer cases (overall or invasive cancers only). However, the GSTM1 null genotype was associated with increased risk of endometrioid/clear cell invasive cancer [age-adjusted OR (95% CI) = 2.04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 may increase the risk of ovarian cancer of these histological subtypes specifically. This marginally significant finding will require verification by independent studies.

Adenocarcinoma, Clear Cell↗

No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer.

Epidemiological studies suggest that ovarian cancer is an endocrine-related tumour, and progesterone exposure specifically may decrease the risk of ovarian cancer. To assess whether the progesterone receptor (PR) exon 4 valine to leucine amino acid variant is associated with specific tumour characteristics or with overall risk of ovarian cancer, we examined 551 cases of epithelial ovarian cancer and 298 unaffected controls for the underlying G-->T nucleotide substitution polymorphism. Stratification of the ovarian cancer cases according to tumour behaviour (low malignant potential or invasive), histology, grade or stage failed to reveal any heterogeneity with respect to the genotype defined by the PR exon 4 polymorphism. Furthermore, the genotype distribution did not differ significantly between ovarian cancer cases and unaffected controls. Compared with the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk of ovarian cancer was 0.78 (0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14) for the TT genotype. In conclusion, the PR exon 4 codon 660 leucine variant encoded by the T allele does not appear to be associated with ovarian tumour behaviour, histology, stage or grade. This variant is also not associated with an increased risk of ovarian cancer, and is unlikely to be associated with a large decrease in ovarian cancer risk, although we cannot rule out a moderate inverse association between the GT genotype and ovarian cancer.

Base Sequence↗

Androgen receptor exon 1 CAG repeat length and risk of ovarian cancer.

Epidemiological studies indicate that ovarian cancer is an endocrine-related tumour. We conducted a case-control comparison to assess the androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAG(n)) as a risk factor for epithelial ovarian cancer. AR CAG(n) was determined for 319 case subjects with ovarian adenocarcinoma and 853 unaffected control subjects (comprising 300 unrelated adult female monozygotic twins, and 553 adult females sampled randomly from the population using the electoral rolls). The CAG(n) distributions of case subjects and control subjects were compared as a continuum, and by dichotomising alleles according to different CAG(n) cut-points. Logistic regression was used to calculate age-adjusted odds ratio (OR) estimates. Analyzed as a continuous variable, there was no difference between case subjects and control subjects for the smaller, larger or average allele sizes of the CAG(n) genotype, before or after adjusting for age. The mean (95% CI) for the average CAG(n) was 22.0 (21.8-22.2) for case subjects and 22.0 (21.9-22.1) for control subjects (p>.9). Analysis of CAG(n) as a dichotomous variable showed no difference between case subjects and control subjects for the median cutpoint (>/= 22), or for another cut-point previously reported to act as a modifier of breast cancer risk (>/= 29). Our data provide no evidence for an association between ovarian cancer risk and the genotype defined by the AR exon 1 CAG(n) polymorphism, although we cannot exclude small effects, or threshold effects in a small subgroup.

Adenocarcinoma↗

CYP17 promotor polymorphism and ovarian cancer risk.

The CYP17 gene encodes the cytochrome P450c17alpha enzyme, which functions at 2 different points in the steroid biosynthesis pathway, and is considered a candidate susceptibility gene for endocrine-related tumors. A T to C substitution polymorphism exists in the 5' promoter region of this gene, and creates an additional Sp1-type motif. Several studies have examined this polymorphism as a risk factor for breast cancer, but results have been conflicting. We examined 319 cases of ovarian cancer and 298 unaffected controls for the T-C polymorphism. There was no significant difference between cases and controls for the allele frequencies (p = 0.6), or for genotype distribution (p = 0.9). The odds ratio (95% confidence interval) for ovarian cancer was 1.13 (0.70-1.82) for the putative "cancer susceptibility" CC genotype and 1.07 (0.77-1.48) for any C allele (CC or CT genotype). Results were little different after adjustment for age. Stratification of the ovarian cancer cases according to form (benign, low malignant potential or invasive), histology, grade or stage failed to reveal any heterogeneity with respect to CYP17 genotype. Our data provide no evidence for an association between ovarian cancer risk and the genotype defined by the CYP17 5' promoter region T-C polymorphism.

Adenocarcinoma↗

Respiration and heart rate at the surface between dives in northern elephant seals.

All underwater activities of diving mammals are constrained by the need for surface gas exchange. Our aim was to measure respiratory rate (fb) and heart rate (fh) at the surface between dives in free-ranging northern elephant seals Mirounga angustirostris. We recorded fb and fh acoustically in six translocated juveniles, 1.8-2. 4 years old, and three migrating adult males from the rookery at Año Nuevo, California, USA. To each seal, we attached a diving instrument to record the diving pattern, a satellite tag to track movements and location, a digital audio tape recorder or acoustic datalogger with an external hydrophone to record the sounds of respiration and fh at the surface, and a VHF transmitter to facilitate recovery. During surface intervals averaging 2.2+/-0.4 min, adult males breathed a mean of 32.7+/-5.4 times at a rate of 15. 3+/-1.8 breaths min(-)(1) (means +/- s.d., N=57). Mean fh at the surface was 84+/-3 beats min(-)(1). The fb of juveniles was 26 % faster than that of adult males, averaging 19.2+/-2.2 breaths min(-)(1) for a mean total of 41.2+/-5.0 breaths during surface intervals lasting 2.6+/-0.31 min. Mean fh at the surface was 106+/-3 beats min(-)(1). fb and fh did not change significantly over the course of surface intervals. Surface fb and fh were not clearly associated with levels of exertion, such as rapid horizontal transit or apparent foraging, or with measures of immediately previous or subsequent diving performance, such as diving duration, diving depth or swimming speed. Together, surface respiration rate and the duration of the preceding dive were significant predictors of surface interval duration. This implies that elephant seals minimize surface time spent loading oxygen depending on rates of oxygen uptake and previous depletion of stores.

Animals↗

Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and serum pepsinogens: an international study. The Eurogst Study Group.

BACKGROUND & AIMS: CagA-positive Helicobacter pylori infection has been more closely associated with gastric disease than CagA-negative infection. This study evaluated whether geographic variation in the prevalence of CagA could explain variation in gastric cancer rates. METHODS: The Eurogast study was conducted in 17 centers in 13 countries. Gastric cancer rates were calculated for each center, and serum samples from approximately 2850 subjects were assayed for immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C. RESULTS: The proportion of CagA-positive H. pylori infections varied across the centers, but this variation did not explain any more of the variation in gastric cancer rates than H. pylori alone. Subjects with CagA-positive infection had, however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio than subjects with CagA-negative infection; this pattern was observed consistently across the study centers. CONCLUSIONS: Variation in the seroprevalence of CagA did not explain geographic variation in gastric cancer rates any better than H. pylori alone. However, the consistent variation in pepsinogen levels with CagA status across the study centers supports the importance of the role of CagA in the development of gastric disease.

Adult↗

Comparability of a computer-assisted versus written method for collecting health behavior information from adolescent patients.

PURPOSE: To investigate the comparability of health behavior data obtained from adolescents via notebook computer versus those obtained via written questionnaire. METHODS: We interviewed adolescent patients (ages 13-20 years) receiving services at community adolescent health clinics. Participants anonymously completed either a computer-assisted self-interview (CASI) or a self-administered questionnaire (SAQ), both assessing health-protective behaviors, substance use (i.e., tobacco, alcohol, marijuana) and sexual behaviors. From a pool of 671 adolescent participants (348 completing CASI, 323 completing SAQ), we matched 194 SAQ participants with 194 CASI participants on the basis of gender and race. We could not match individually on the basis of age, but were able to match each gender-race subgroup by mean age. RESULTS: Across the majority of health behaviors (i.e., all health-protective behaviors, tobacco use, sexual behaviors), mode of administration made no significant difference in the reporting of information by adolescents. However, girls reported a greater frequency of alcohol use and marijuana use on CASI than on SAQ, whereas boys reported a lower frequency of alcohol use and marijuana use on CASI than on SAQ. CONCLUSIONS: The findings of this study suggest that there may be gender-related differences between modes of anonymous collection of specific adolescent health behaviors such as alcohol and marijuana use. Future studies should incorporate direct questions regarding adolescents' attitude and comfort levels toward completing different modes of data collection.

Adolescent↗