Biomedical subjects
B Cox
Publications and source records attributed to B Cox.
Reduced risk of colorectal cancer among recent generations in New Zealand.
Male and female age standardised mortality and incidence rates of colorectal cancer have increased over the most recent 30 years in New Zealand. Among men and women aged 40 to 74, age standardised mortality and incidence rates increased 18 to 105%. However, age standardised mortality and incidence rates among younger men and women have declined from 14 to 69%. Analysis of trends in age specific mortality and incidence rates indicates that the occurrence of colorectal cancer has been declining equally for men and women in successive cohorts born about 1943 to 1953 in New Zealand. This decline in the frequency of colorectal cancer among recent generations was apparent for both the right and left sides of the colon and the rectum. Age-specific trends in coronary heart disease and breast cancer differed from those apparent for colorectal cancer, suggesting that the factors producing the reduction in colorectal cancer risk may affect these diseases among different age groups or may not be of major aetiological importance in these diseases. These trends provide empirical evidence that the occurrence of colorectal cancer can be reduced by at least 50% with a substantial component of the risk being determined before the age of 30. Further study is needed to establish whether changes in risk factors at older ages contribute to the prevention of the disease.
Projections of cervical cancer mortality and incidence in New Zealand: the possible impact of screening.
STUDY OBJECTIVE: The aim was to estimate the likely burden of cervical cancer in New Zealand over the next two decades, according to whether cervical screening services are made more effective. DESIGN: The study was based on national mortality and incidence data for the periods 1954-87 and 1954-86, respectively. An age-period-cohort model was used to estimate the contributions of age, time period, and birth cohort effects to the occurrence of cervical cancer. Using age specific estimates of the future female population of New Zealand, projections of cervical cancer mortality and incidence until the year 2008 were derived from the model. Projections were made assuming either that screening services will not be improved, or that an immediate improvement in the organisation of screening will lead to a decline in period effects for incidence of 15% per five year time period (with a slightly delayed effect on mortality). It was also assumed either that the risk in new birth cohorts will be similar to that in recent cohorts, or that their risk will be halved as a result of changes in sexual behaviour (due to education about AIDS or other factors). Combining these assumptions produced four sets of estimates, reflecting a range of possible scenarios. SETTING: Both the data used and the projections obtained related to the entire population of New Zealand women. MAIN RESULTS: For both mortality and incidence, projections were made of age specific rates, cumulative rates, and absolute numbers of deaths or new cases. With the first assumption about new birth cohorts, it was estimated that both mortality and incidence rates will increase if screening services are are not improved. In absolute terms, the present 100 deaths per year could increase to about 148 deaths per year, while there could be a much larger increase in incidence from 235 per year to about 440 per year). With improved screening, there could be a reduction in age specific mortality rates and a modest decline in the number of deaths, while a reduction in incidence rates would be accompanied by about the same number of new cases as at present. In comparison with improvements in screening, changes in the underlying risk in new birth cohorts would have much smaller effects on the occurrence of cervical cancer over the next two decades. CONCLUSIONS: Plausible improvements in cervical screening are likely to be accompanied by only small changes in the burden of cervical cancer over the next two decades. If screening services are not improved, however, there will be striking increases in both mortality and incidence.
Health reforms.
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Impact of psychiatric services on prison suicide.
Severe restrictions on the transfer of mentally disturbed prisoners to psychiatric hospital were introduced in Auckland in 1983, while policy in other parts of New Zealand was unchanged. Among male prisoners, the suicide rate (per 100,000 man-years) increased from 27.3 in 1973-82 to 178.0 in 1983-87--an increase in relative risk, compared with unconfined men, from 1.6 to 8.2. Auckland accounted for most of this increase, from 37/100,000 man-years in 1973-82 to 549/100,000 in 1983-87. This striking increase in prison suicide rate in Auckland underlines the importance of ready access to psychiatric care for prisoners.
Severe anomalies associated with ring chromosome 7.
A newborn infant with the polyasplenia sequence, intrauterine growth retardation, cutaneous nevi, and minor anomalies was found to have mosaicism for ring chromosome 7. This patient's anomalies are markedly different from those of previous patients reported with this cytogenetic anomaly.
Transcript mapping reveals different expression strategies for the bicistronic RNAs of the geminivirus wheat dwarf virus.
We have characterised the major transcripts of the Czech isolate of wheat dwarf virus (WDV-CJI) which show that WDV uses two different mechanisms for expressing overlapping open reading frames (ORFs). Mapping of the virion sense RNAs identified a single polyadenylated transcript of 1.1kb spanning the overlapping ORFs V1 and V2 which encode cell-cell spread functions and the coat protein respectively. This finding distinguishes WDV from other monocot-infecting geminiviruses studied so far which were shown to encode two 3' co-terminal transcripts capable of expressing either the V1 or V2 ORF. A survey of codon usage at the junction between the V1 and V2 ORF has led us to propose that translational frame shifting analogous to that in the yeast Ty element may occur. Analysis of polymerase chain reaction (PCR) amplified complementary sense cDNA clones has revealed the presence of mature spliced and unspliced RNAs which could encode products of an intron mediated C1:C2 ORF fusion or the C1 ORF product alone. Mapping of the 5' and 3' extremities of the major WDV encoded transcripts has allowed us to identify putative transcription regulatory sequences and the presence of multiple overlapping transcripts may suggest temporal regulation of transcription.
The effect on the stratum-specific odds ratios of nondifferential misclassification of a dichotomous covariate.
Precise measurement of confounding or effect modifying variables is seldom possible. Nondifferential misclassification of such a variable can introduce bias in the odds ratios within the strata of the confounding variable. For two strata, the effect on the odds ratios is dependent on separate measures of the degree of nondifferential misclassification of the confounding variable. The authors investigate the bias in the stratum-specific odds ratios from nondifferential misclassification of a confounder in a case-control study, and show how estimates of the true stratum-specific odds ratios can be derived. For one stratum, the degree of bias introduced in the odds ratio is dependent only on the sensitivity of the measure of the confounding variable while only the specificity of this measure determines the bias introduced in the other stratum-specific odds ratio. The results are applied to a case-control study of fenoterol prescription and asthma death.
Suicide in New Zealand 1957-1986: the influence of age, period and birth-cohort.
New Zealand suicide rates from 1957 to 1986 were analysed for age, period and cohort effects. Cumulative suicide rates were relatively stable but more complex patterns were revealed by detailed analysis. There was a steadily increasing rate in young men and a recent increase in elderly men. Reduced mortality rates in equivalent categories of accidental and "undetermined" deaths could have accounted for only a proportion of these increases. A cohort effect was noted in men, with increasing risks of suicide in the young for successive birth-cohorts born from 1947 onwards. In women a period effect was likely, with increasing rates for all age-groups between 1957-61 and 1962-66, followed by a decline recently among all except the youngest age-groups. These trends in women may have been largely due to changes in barbiturate prescribing. In both sexes poisoning declined as a method of suicide, while hanging and carbon monoxide poisoning increased. Firearm suicides also increased in men. The implications of these results for prevention are considered.
Dosing schedule for recombinant hepatitis B vaccine.
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A feasibility study of organised cervical screening in southern New Zealand.
The 1985 electoral roll was used as a register to invite 1013 women to participate in a screening program. Appointment times and a choice of venues for having a smear were not provided. Overall, 26 per cent of the women sent invitations registered with the program. After adjustment for the prevalence of hysterectomy, the proportion who registered with the program was about 32 per cent. The low level of registration and difficulties experienced in tracing registrants and nonregistrants over time using the electoral roll resulted in the cessation of the program after 3 years. An assessment of the original invitation was made using a small case-control study, and associations between the screening history stated at interview and screening over the duration of the program were examined in nonregistrants.
Pharmacological studies in vivo with ICI 169,369, a chemically novel 5-HT2/5-HT1C receptor antagonist.
ICI 169,369 (2-(2-dimethylaminoethylthio-3-phenylquinoline hydrochloride) has been tested in vivo for its potency and selectivity as an antagonist at 5-HT2 and 5-HT1C receptors. It caused a 50% inhibition of 5-HTP-induced head twitches in mice and fenfluramine-induced hyperthermia in the rat at approximately 1 mg/kg following parenteral administration. Results showed that ICI 169,369 had good oral bioavailability, since in the fenfluramine test the oral and s.c. ID50 values were similar. ICI 169,369 was a selective antagonist of 5-HT-induced bronchoconstriction in the guinea-pig and 5-HT-induced pressor effects in the anaesthetised dog. In a series of other tests in vivo the compound was shown to be devoid of significant activity at alpha 1- and alpha 2-adrenoceptors, dopamine (D2), muscarinic (M1) and histamine (H1) receptors at 30-100 times its ID50 values used in the 5-HT tests. Thus, ICI 169,369 is a selective, orally active 5-HT2/5-HT1C antagonist that should prove useful in the analysis of the role of 5-HT in physiological and pathological states.
Structural instability of human tandemly repeated DNA sequences cloned in yeast artificial chromosome vectors.
The suitability of yeast artificial chromosome vectors (YACs) for cloning human Y chromosome tandemly repeated DNA sequences has been investigated. Clones containing DYZ3 or DYZ5 sequences were found in libraries at about the frequency anticipated on the basis of their abundance in the genome, but clones containing DYZ1 sequences were under-represented and the three clones examined contained junctions between DYZ1 and DYZ2. One DYZ3 clone was quite stable and had a long-range structure corresponding to genomic DNA. All other clones had long-range structures which either did not correspond to genomic DNA, or were too unstable to allow a simple comparison. The effects of the transformation process and host genotype on YAC structural stability were investigated. Gross structural rearrangements were often associated with re-transformation of yeast by a YAC. rad1-deficient yeast strains showed levels of instability similar to wild-type for all YAC clones tested. In rad52-deficient strains, DYZ5 containing YACs were as unstable as in the wild-type host, but DYZ1/DYZ2 or DYZ3 containing YACs were more stable. Thus the use of rad52 hosts for future library construction is recommended, but some sequences will still be unstable.
Comparative trial of low-dose, intradermal, recombinant- and plasma-derived hepatitis B vaccines.
The immunogenicity and reactogenicity of low-dose, recombinant DNA and plasma-derived hepatitis B vaccines were investigated in a prospective, double-blind, randomized, controlled trial. Volunteers (153) received either recombinant vaccine, 10 micrograms in 1 ml intramuscularly; plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally or recombinant vaccine, 1 microgram in 0.1 ml intradermally at 0, 30, and 150 days. Peak geometric mean concentrations of antibody to hepatitis B surface antigen at day 200 were 1094, 387, and 43 mIU/ml, respectively. By day 360, these concentrations had fallen to 346, 124, and 19 mIU/ml, respectively (P less than .05 between groups both dates). Number of subjects with antibody greater than or equal to 10 mIU/ml at day 200 was similar between the 10-micrograms recombinant and 2-micrograms plasma-derived groups (94% vs. 90%), while only 78% of the 1-microgram recombinant group had protective concentrations of antibodies (P less than .05). Erythema and induration occurred in most subjects in both intradermal groups, while pain was prominent at the intramuscular site especially after the second dose. Thus, plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally, appears to be an acceptable cost-saving method for hepatitis B immunization, while recombinant-derived vaccine, 1 microgram in 0.1 ml intradermally, produced less satisfactory results.
Inside politics.
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Suppressant effects of selective 5-HT2 antagonists on rapid eye movement sleep in rats.
The effects of the novel, highly selective serotonin-2 (5-HT2) antagonists, ICI 169,369 and ICI 170,809, on 24 h EEG sleep-wake activity were studied in the rat. Both compounds caused a dose-related increase in the latency to rapid eye movement sleep (REMS) and significantly suppressed cumulative REMS time up to 12 h postinjection. In contrast, neither drug disrupted slow-wave sleep continuity in as much as the latency to non-REMS (NREMS) and cumulative NREMS time were unchanged. However, at the highest dose tested (20 mg/kg) ICI 170,809 did produce a significant increase in total NREMS time during the second half of the sleep-awake cycle. These results demonstrate effects of selective 5-HT2 antagonists on sleep in rats which appear to be specific for REMS behavior, suggesting that the priming influence of serotonin on REMS may involve 5-HT2 receptor subtypes. The relationship between the REMS suppressant actions of these compounds and their consideration as therapeutic agents in depression is discussed.