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Biomedical subjects

J Halliday

Publications and source records attributed to J Halliday.

At least 19 recordsLinked to original sources

Psychological impact of genetic testing for hereditary non-polyposis colorectal cancer.

The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending familial cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p < 0.001) and 4 months post-notification of result (t = -3.22; p = 0.002). For non-carriers, significant decreases in mean scores for intrusive and avoidant thoughts about colorectal cancer were observed at all follow-up assessment time points relative to baseline. Non-carriers also showed significant decreases from baseline in mean depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.

Adult↗

Implementation of HaemScreen, a workplace-based genetic screening program for hemochromatosis.

There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace.

Adolescent↗

Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-control study.

BACKGROUND: That sexual dysfunction occurs in schizophrenia is not in doubt. Previous studies have had weaknesses such as the use of selected populations or the absence of a control group. AIMS: To measure rates of sexual dysfunction in people with schizophrenia compared with the general population. METHOD: Sexual dysfunction was assessed by a self-completed gender-specific questionnaire. Ninety-eight (73%) of 135 persons with schizophrenia and 81 (71%) of 114 persons recruited as controls returned the questionnaire. RESULTS: At least one sexual dysfunction was reported by 82% of men and 96% of women with schizophrenia. Male patients reported less desire for sex, were less likely to achieve and maintain an erection, were more likely to ejaculate more quickly and were less satisfied with the intensity of their orgasms. Female patients reported less enjoyment than the control group. Sexual dysfunction in female patients was associated with negative schizophrenic symptoms and general psychopathology. There was no association between sexual dysfunction and type of antipsychotic medication. CONCLUSIONS: People with schizophrenia report much higher rates of sexual dysfunction than do the general population. Men and women with schizophrenia have a different pattern of sexual dysfunction.

Adult↗

Inhibitors of sialyltransferases: potential roles in tumor growth and metastasis.

For over thirty years it has been evident that there is altered glycosyltransferase activity in neoplastic tissue when compared to healthy tissue. It has also long been speculated that disruption of the neoplastic expression of sialic acid on cellular glycoconjugates, is a valid target in anti-metastatic therapeutic development. Over the years attempts have been made to synthesize inhibitors of sialyltransferases in a effort to assist in the validation or dissolution of these enzymes as potential therapeutic targets.

Enzyme Inhibitors↗

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects.

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.

Blood Glucose↗

Measurement of human tricarboxylic acid cycle rates during visual activation by (13)C magnetic resonance spectroscopy.

Measurement by (13)C magnetic resonance spectroscopy (MRS) of the incorporation of label from [1-(13)C] glucose, initially into C4 of glutamate, allows the regional tricarboxylic acid (TCA) cycle flux (F(TCA)) to be determined in the human brain. In this study, a direct (13)C MRS approach was used at 3T, with NOE enhancement and (1)H decoupling with WALTZ16, to determine basal F(TCA) in six volunteers. The values found in the visual cortex are similar to those reported in previous (13)C MRS studies, and consistent with PET measurements of the cerebral metabolic rate for glucose, CMRglc. In two preliminary activation studies using light emitting diode (LED) goggles flashing at 8 Hz, compared to darkness as control, increases in F(TCA) were found from 0.60 +/- 0.10 to 0.94 +/- 0.03 micromol/min/g (56%) and from 0.34 +/- 0.14 to 0.56 +/- 0.07 micromol/min/g (65%). These are upper estimates, but they are similar to the increases in CMRglc reported in PET studies, and strongly suggest, in contrast to these PET studies, that cerebral glucose is metabolized oxidatively, even during intense visual stimulation. This is supported by the observation that very little (13)C label is incorporated into C3 lactate, as would be expected if glucose were metabolized anaerobically. There is evidence for incorporation of glucose into cerebral glycogen, but this is a relatively minor component of cerebral glucose metabolism.

Adult↗

Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists.

We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)). Microdialysis and high performance liquid chromatography were used to monitor changes in extracellular levels of striatal dopamine and its metabolites, glutamate, aspartate and gamma-amino-butyric acid (GABA). These data were correlated with changes in the striatal and cortical electroencephalographs and clinical signs. We found that, although neither dopamine receptor antagonist inhibited behavioural seizure activity, blockade of the dopamine D(1)-like receptor with SCH 23390 significantly reduced both the 'power' of the electrical seizure activity and the associated change in extracellular striatal concentration of glutamate, whilst increasing the extracellular striatal concentration of GABA. In contrast, blockade of the dopamine D(2)-like receptor with sulpiride significantly increased the extracellular, striatal content of glutamate and the dopamine metabolites. These results confirm previous evidence in other models of chemically-evoked seizures that antagonism of the dopamine D(1) receptor tends to reduce motor and electrographic seizure activity as well as excitatory amino-acid transmitter activity, while antagonism of the dopamine D(2) receptor has relatively less apparent effect.

3,4-Dihydroxyphenylacetic Acid↗

SCH 23390 affords protection against soman-evoked seizures in the freely moving guinea-pig: a concomitant neurochemical, electrophysiological and behavioural study.

We studied the role of striatal dopamine (DA) release in seizure activity evoked by the subcutaneous administration of the cholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman), in the guinea-pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the D(1)-like receptor antagonist SCH 23390 (0.5 mg kg(-1)) or the D(2)-like receptor antagonist sulpiride (30 mg kg(-1)). Microdialysis and HPLC with electrochemical detection were used to monitor changes in extracellular levels of striatal DA and its metabolites, acetylcholine and choline. These data were correlated with changes in the striatal and cortical electroencephalogram and observation of predefined clinical signs. We found that the blockade of the D(1) receptor with SCH 23390 can inhibit seizure activity, while blockade of the D(2) receptor with sulpiride can augment the evoked seizure activity. These results clarify the involvement of the dopaminergic system in soman-evoked seizures.

Animals↗

The increasing knowledge of the role of periconceptional folate in Victorian women of child-bearing age: follow-up of a randomised community intervention trial.

OBJECTIVES: To determine the changes since 1996 in knowledge of folate for the prevention of neural tube defects (NTDs) among women of child-bearing age and measure the residual effect of an earlier consumer-directed information campaign. DESIGN: A community, randomised trial with three matched pairs of geographically distinct local government areas in Victoria. INTERVENTION: Printed information recommending folate intake to decrease the risk of NTDs was disseminated in 1997 to women of child-bearing age. MAIN OUTCOME MEASURE: The proportion of women aware of the association between folate and spina bifida was established in 1996, 1997 and 2000 (approximately 200 respondents per local government area in each survey). RESULTS: 12.5% (adjusted for population sampling fraction) of 1,196 women interviewed in 1996, prior to the intervention, were aware of folate and NTDs. Independent surveys after the intervention in 1997 and again in 2000 showed that this had increased to 17.4% (n=1204) and 30.2% (n=1227) respectively. The intervention had a significant impact on folate awareness (a 4% difference in 1997 and a residual 3.3% in 2000, ORadj=1.24, 95% CI 1.19-1.37, p=0.007). CONCLUSIONS AND IMPLICATIONS: There has been a continuing increased awareness of folate in women of child-bearing age since 1996. Within this setting, the provision of printed educational material in a brief intervention in 1997 has caused enduring increased awareness of the association between folate and NTDs. The need for ongoing health promotion action on folate remains.

Adolescent↗

Assessment of education and counselling offered by a familial colorectal cancer clinic.

We have evaluated whether or not client expectations, in terms of education and information needs, have been met by a multi-disciplinary familial colorectal cancer clinic. The study used a pre- and post-clinic questionnaire design and 126 (84 women, 42 men) clients of the clinic participated. The most common reason for coming to the clinic is to 'find out whether there is a gene for colorectal cancer in the family', followed by 'to reduce risk for bowel cancer' and 'concern for children's risk'. Clients would have preferred to receive more information before attendance at the clinic to help with preparation. Information given during the clinic increased knowledge of bowel cancer genetics and had a positive effect on the accuracy of some clients' perceptions of their risk of developing cancer. In multivariate analysis, higher risk perceptions, higher education level and greater baseline knowledge predicted post-clinic knowledge of bowel cancer genetics and an increase in knowledge. Client reports of the presence of a genetic counsellor or medical geneticist in the session also predicted post-clinic knowledge and an increase in knowledge. Most participants felt they received enough information during the clinic session on various aspects of familial colorectal cancer, but the desire for more written information on prevention, including lifestyle actions, was expressed by many.

Adult↗

Cancer worries, risk perceptions and associations with interest in DNA testing and clinic satisfaction in a familial colorectal cancer clinic.

Multi-disciplinary familial cancer clinics are becoming an integral part of cancer services. It is, therefore, important to assess how attendance at these clinics impacts on cancer-related concerns, risk perceptions and behavioural intentions, and how the clinic services are being received by those using them. This study has assessed a familial colorectal cancer clinic with respect to cancer-related worries and risk perceptions and their impact on interest in DNA testing and overall satisfaction with the clinic. Pre- and post-clinic questionnaires were completed by 127 patients and relatives attending the clinic. After attending the clinic, the proportion of people 'very' or 'extremely' worried about developing bowel cancer reduced from 49 (pre-clinic) to 34% (p = 0.002). Worry about bowel cancer was positively associated with younger age, higher education level and higher perceived risk of developing cancer. A reduction in level of risk perception correlated with a lower likelihood of feeling 'very worried' about developing bowel cancer. Of those intending to go ahead with DNA testing, 58% were 'very worried' about bowel cancer compared with 15% of those not intending to proceed with testing, suggesting that worry was a motivation for interest in DNA testing. One-third of participants indicated another session of genetic counselling would be helpful. Within this group, a higher proportion was very worried about bowel cancer (43%) than for those who did not want another session (17%). Attendance at this familial colorectal cancer clinic alleviated worry for many individuals, partly due to improved information about risk of colorectal cancer.

Adult↗

Vaginal births after Caesarean (VBAC): a population study.

This paper describes delivery outcomes for women from Victoria, Australia, who gave birth in 1995 and whose immediately previous (penultimate) delivery, within a 5-year search period, was a Caesarean section. Because of the large numbers of records involved, dedicated computer software for record linkage was used to identify the previous delivery and link it with the woman's current birth in 1995. Overall, 79% of the records from multiparous women were linked successfully. Approximately 15% were not linked because the previous birth was before the search period or was an abortion that would not have been reported to the Perinatal Data Collection Unit. Reasons for not being able to link the last 6% of the records include the previous pregnancy being overseas or interstate. Women who had a vaginal birth as the penultimate birth or a multiple birth at either event were excluded, resulting in a study population of 4663 linked records. More women (68%) had a repeat Caesarean than went into labour and, of the remaining women who laboured, 56% delivered vaginally. Overall, 18% of the women delivered vaginally. For the women who went into labour, the reported number experiencing a uterine rupture was two per 1000 births. Uterine rupture was not reported in the two-thirds who did not labour but had a repeat Caesarean. A review of the perinatal deaths identified only two deaths, one baby being born by elective Caesarean and one by a vaginal birth after a previous Caesarean (VBAC) where the choice of delivery methods may have contributed to the death. This large study is one of the few in the literature to provide population-based information on vaginal births after a previous Caesarean and related outcomes.

Adolescent↗

Is sudden infant death syndrome still more common in very low birthweight infants in the 1990s?

OBJECTIVE: To determine the rate of sudden infant death syndrome (SIDS) in very low birthweight children (VLBW) relative to children with low (LBW) and normal birthweights. DESIGN, SETTING AND SUBJECTS: Cohort study of consecutive live births in Victoria, 1993-1997 inclusive. MAIN OUTCOME MEASURES: All sudden unexpected deaths in early childhood over this five-year period; all deaths from SIDS (defined as a sudden unexpected death without a definite pathological explanation); and the proportion of SIDS in live births in three birthweight subgroups (VLBW, 500-1499 g; LBW, 1500-2499 g; and normal birthweight, > 2499 g). RESULTS: There were 316,028 live births (with known birthweight) in Victoria over the five-year period; 224 (0.71 per 1000 live births) died unexpectedly. In 10 of these deaths there was a definite pathological explanation, giving a rate of SIDS of 0.68 per 1000 live births. The rate of SIDS in VLBW children was 2.52 per 1000 live births, lower than the rate reported before the 1990s. The rate of SIDS in VLBW children was not significantly different from the rate in LBW children of 1.98 per 1000 live births (difference per 1000 live births, 0.53; 95% CI, -1.45 to 2.52), but was significantly higher than the rate in normal birthweight children of 0.59 per 1000 live births (difference per 1000 live births, 1.93; 95% CI, 0.06-3.79). CONCLUSIONS: The rate of SIDS in VLBW children has fallen in the 1990s, along with the overall fall in the rate of SIDS, but remains higher than that in normal birthweight children.

Humans↗

Perinatal and obstetric outcomes of donor insemination using cryopreserved semen in Victoria, Australia.

This study compared the perinatal and obstetric outcomes of 1552 donor insemination pregnancies in Victoria, Australia, with a control group of 7717 normally conceived pregnancies from the general population. Data on the outcomes of pregnancies of at least 20 weeks gestation, for both groups, were obtained from the same population-based birth registry. The study showed that there were no significant differences between the donor insemination and control groups in the incidence of preterm birth, low birthweight, multiple birth, perinatal death and birth defects, or in the sex ratio. Pregnancies conceived by donor insemination were significantly more likely than controls to have an induced labour (OR = 1.6, 95% CI 1. 4-1.8), a forceps delivery (OR = 1.5, 95% CI 1.3-1.8) and/or a Caesarean section (OR = 1.6, 95% CI 1.4-1.9) and to develop pre-eclampsia (OR = 1.4, 95% CI 1.2-1.8) after adjusting for maternal age, multiple birth, parity and presentation. Reasons for the higher rate of induced and operative deliveries are not clear. Overall, the study's findings are reassuring for couples considering infertility treatment with donor insemination. The study illustrates the importance of complete follow-up in studies of pregnancy outcomes after assisted conception and the use of appropriate population-based control groups with comparable ascertainment of outcomes.

Case-Control Studies↗

Changes in the sexual lifestyles of young people in Somerset, 1990-1996.

OBJECTIVES: The immediate objective was to up-date knowledge of the socio-sexual lifestyles and AIDS awareness of young people (16-24 years of age) in Somerset, and to compare these 1996 survey findings to the Somerset Survey findings from 1990. The ultimate objective was to provide information to assist the continuing development of HIV risk-reduction and sexual health promotion strategies for young people. DESIGN: An identical schedule-structured survey strategy to that employed in 1990 was undertaken in May to July 1996 among 498 young people throughout Somerset. A quota sampling strategy was undertaken in 50 electoral wards, randomly selected in proportion to population size. The interviews, undertaken in respondents' homes, involved a combined personal interview and self-completion booklet. RESULTS: Between 1990 and 1996 broad shifts in sexual lifestyles were identified, involving earlier ages of first intercourse, slight increases in numbers of sexual partners and more 'casual-recreational' sexual attitudes. These changes were accompanied by a substantial increase in condom use. CONCLUSIONS: The trend among youth in Somerset is towards more open sexual lifestyles, but with the positive public health implications of higher levels of 'safer sex' practice.

Acquired Immunodeficiency Syndrome↗