ISB Clinical Biomechanics Award 1997.
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Journal Article↗
Biomedical subjects
R Norman
Publications and source records attributed to R Norman.
Contrasting actions of pressor agents in severe autonomic failure.
BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.
Aged↗
Skin cancer prevention: still missing the target!
Skin cancer is a significant public health issue in Australia due to the preventable nature of the disease, its high incidence rate, and its effects on mortality and morbidity. What public health strategies are being used to target this disease, and is this important health issue being dealt with adequately? This paper highlights three areas where skin cancer prevention programs have failed. Firstly, health education is not successful for individuals in low socio-economic groups where financial and social resources are limited. Secondly, the common ideology that equates a suntan with youth, vigour and health needs to be challenged. Finally, there has been a failure to reorient and use the significant resources available in our health institutions for skin cancer education and prevention.
Humans↗
An investigation into movement planning and execution deficits in individuals with schizophrenia.
The purpose of this study was to examine whether individuals with schizophrenia demonstrate slowing in movement planning (reaction time), or in movement execution (movement time and velocity), in comparison to normals. Twelve schizophrenic and 12 control right-handed males performed aiming movements with a mouse (controlled by either the left or right hand) on a graphics tablet towards targets of differing sizes and distances appearing on a computer screen. Results showed that, for reaction time, the controls were faster than the schizophrenics and the latter had a left hand advantage for movement preparation while the controls showed no such differences. For movement time, no group differences were found. However, as expected, movement times were shorter (i.e., movements were faster) to the large, and near targets. These results support Fitts' law (Fitts, 1954) which describes a relationship where aiming movement time decreases as target distance decreases, and target size increases. We provide evidence here for a movement planning deficit in schizophrenic patients with no decrement in movement execution compared to controls.
Adult↗
Smoking and schizophrenia.
Individuals with schizophrenia have a high prevalence of smoking compared with the general population and little is known about why so many people with schizophrenia smoke. This paper reviews suggestions of differences in motivation for smoking. Possible explanations for smoking include psychological reasons, together with possible effects on positive and negative symptoms of schizophrenia and reduced side-effects of neuroleptics. Understanding complex issues related to smoking and schizophrenia is important prior to developing health promotion strategies.
Humans↗
Assessment of physical work load in epidemiologic studies: common measurement metrics for exposure assessment.
There are many possible means of determining exposure ranging from self-reports of physical exposure to measures of muscle activations and estimated spinal loads. In epidemiologic studies, issues of validity make instrumented measures preferable, however issues of cost and practicability tend to force investigators to less costly but less valid and less reliable measures of exposure, such as self-report questionnaires. This paper presents a method by which estimates of exposure from self-report questionnaires, expert observers, work sampling, video analysis and electromyograms can be reported in a common metric, Newtons of force on a tissue, and show, as an example of its application, estimation of spinal compression on auto workers. A common metric allows a flexible approach to selection of measurement methods in occupational settings: no matter which instrument is used the results can be combined to provide an overall picture of exposure. This approach to exposure assessment for the low back allows for comparability across studies and settings.
Automobiles↗
The epidemiology of louping-ill, a tick borne infection of red grouse (Lagopus lagopus scoticus).
The epidemiology of louping-ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in louping-ill within Britain was small.
Animals↗
A common major histocompatibility complex class II allele HLA-DQB1* 0301 is present in clinical variants of pemphigoid.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons. It is characterized clinically by the development of tense bullae and by the presence of an antibasement membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAg1 and BPAg2. We have compared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicatricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel of 218 haplotypes of normal individuals. We found that the three diseases (BP, OCP, and OP) have significant association with DQB1*0301 (P = 0.005, P < 0.0001, and P = 0.001, respectively). The frequencies of alleles DQB1*0302, 0303, and 06, which share a specific amino acid sequence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also increased (P = 0.01). We suggest that an identical major histocompatibility complex class II allele (DQB1*0301) is a common marker for enhanced susceptibility and that the same amino acid residues in positions 71-77 (DQB1*0301, -0302, -0305, -0602, -0603 alleles) are found in patients with BP, OCP and OP. Our findings propose that the autoimmune response in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a peptide from the basement membrane of conjunctiva, oral mucosa, and skin.
Alleles↗
Markers for cardiovascular and renal morbidity: expectations for an intervention programme in an Australian aboriginal community.
1. Australian Aborigines have high rates of both cardiovascular mortality and renal failure and the usual male dominance in these conditions is respectively reduced and effaced. 2. In one Aboriginal community, we have demonstrated a strong association between albuminuria and cardiovascular risk factors and a relationship of both with insulin resistance, which is more pronounced in females than males. 3. We propose that albuminuria is a component of Syndrome X and that reduction in levels of albuminuria should prove to be a useful marker of effectiveness in treatment programmes targeting cardiovascular risk as well as renal disease.
Albuminuria↗
Interfering with nature.
Certain kinds of medical treatment are often held to be morally unacceptable because they are an 'interference with nature'. I suggest a way in which we can make sense of such ideas. We can make significant choices only against a background of conditions which we regard as 'natural', and these will typically include such facts as those of birth and death, of youth and age, and of sexual relations. I argue, however, that such ideas, though intelligible, do not establish any valid moral objection to, for instance, the use of ovarian tissue for assisted conception.
Biomedical Technology↗
Genetic hypertension. A direct link to salt.
The basis of one type of inherited hypertension has been discovered-it is caused by mutations in the gene for the beta subunit of a renal sodium channel.
Amino Acid Sequence↗
Differential distribution of mRNA for the alpha- and beta-subunits of chorionic gonadotrophin in the implantation stage blastocyst of the marmoset monkey.
We studied the expression of mRNA encoding the alpha- and beta-subunits of marmoset chorionic gonadotrophin (mCG) in implantation stage blastocysts and in a trophoblastic cell line derived from such blastocysts. In this investigation in situ hybridization was carried out using digoxygenin-labelled riboprobes to localize the subunit transcripts. The trophoblastic cell line, known to secrete bioactive mCG, was used as a positive control. Marmoset uterine embryos were cultured to hatched blastocysts and following growth on Matrigel or plastic were processed for in situ hybridization at developmental stages ranging from 13-15 days post-conception. In serial sections mCG-beta mRNA was detected mainly in polar trophoblast. The mRNA for mCG-alpha was expressed more uniformly in polar and mural trophoblast. Transcripts for the beta-subunit were not expressed, or present as weak signals, in the inner cell mass (ICM) and endoderm. However, low levels of mRNA for mCG-alpha were detected in the ICM and visceral endoderm. We have concluded that mRNA for mCG-beta was primarily localized to patches of syncytiotrophoblast at the embryonic pole and sparsely distributed in mural trophoblast, while the transcripts for mCG-alpha were distributed more uniformly in differentiating cytotrophoblast and syncytium, and at much lower levels in ICM and early endoderm.
Animals↗
Is the human chorionic gonadotropin secreted by ectopic trophoblast different from that in normal intrauterine pregnancies?
OBJECTIVE: To determine whether different isoforms of hCG are secreted by trophoblast tissue from ectopic pregnancy (EP). DESIGN: Retrospective study of surgically confirmed EPs compared with normal pregnancies. SETTING: Teaching hospital in South Africa. PATIENTS: One hundred patients with EPs and 120 patients with normal pregnancies. MAIN OUTCOME MEASURES: Isoforms of hCG were measured by specific immunoassays, lectin binding, and examination of disappearance rates of hCG after surgical clearance of EP. RESULTS: There were no obvious differences between the two types of pregnancy apart from a lower binding of beta-subunit immunoactivity to ricin 120. No clinically useful diagnostic measures to distinguish hCG from normal and EPs were found. CONCLUSIONS: No obvious differences were found in the isoforms of hCG between the two types of pregnancy using these methods.
Blood↗
Persistence and transmission of tick-borne viruses: Ixodes ricinus and louping-ill virus in red grouse populations.
The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes louping-ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with louping-ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.
Animals↗
Electrocardiographic and echocardiographic characteristics of female athletes.
This study examined electrocardiographic and echocardiographic characteristics of endurance- and resistance-trained female athletes. The subjects were 10 varsity caliber endurance-trained athletes, 10 resistance-trained athletes, and 10 nonathletes. Data collection included anthropometric measurements, VO2max, standard 12-lead ECGs and left ventricular dimensions measured by M-mode and two-dimensional echocardiography. For endurance-trained athletes, absolute left ventricular end-diastolic volume and values normalized for lean body mass were significantly greater than in nonathletes. An interstudy comparison of female vs male endurance-trained athletes from the same population also revealed significantly lower values for M-mode left ventricular mass expressed per kilogram of lean body mass in the former. Absolute and normalized wall thicknesses were not significantly greater in resistance-trained athletes compared to the other two groups. Wall thickness indexed for lean body mass was similar for the three groups. Sinus bradycardia was observed in all endurance athletes and in four resistance-trained athletes. ECG criteria were unreliable for the prediction of left ventricular enlargement. It appears that both female resistance- and endurance-trained athletes exhibit a lesser degree of enlargement of left ventricular wall thickness and mass than male athletes. A close relationship between skeletal and cardiac muscularity in resistance-trained athletes of both genders also was supported.
Adult↗
The population dynamics of microparasites and vertebrate hosts: the importance of immunity and recovery.
The models of Anderson and May on the dynamics of vertebrate (1979, Nature 280, 361-367) and invertebrate (1981, Philos, Trans. R. Soc. 291, 451-524) populations and their microparasites have been extended and elaborated. Hence, in a series of models the effects of a range of biological factors have been considered. These models taken together clarify in particular the effects of recovery from the disease back to a state of susceptibility and the additional effects of recovery to a state of immunity. In general recovery increases both the threshold density and the equilibrium density but does not alter the prevalence of infection or the region in parameter space in which the host is regulated. Immunity causes a further increase in the equilibrium density, does not alter either the prevalence of infection or the threshold density, but reduces the region in which there is regulation. In both cases exceptions tend to occur when there is density dependence.
Animals↗
Assessment of risk factors for development of work-related musculoskeletal disorders (RSI).
This paper describes an approach to assessing the exposure to risk factors for the development of work-related chronic musculoskeletal disorders (repetitive strain injuries) of the upper limbs and low back. Instrumentation has been developed that combines a video image of the worker performing the task with superimposed quantitative information on risk factors. A description of the methodology, the rationale for the quantities displayed and workplace examples are presented. Continuous monitoring with both muscle activation and video has been found to be useful for identifying risk factors for both acute and chronic injuries in many workplaces. The approach gives information on chronic low-level loading not easily identified with observational methods. The methods presented give quantified information necessary for exposure measures in epidemiological studies. They also give semi-quantified information useful for identifying risks and justifying changes as well as for presentation to non-technical audiences.
Journal Article↗
Prenatal diagnosis and successful intrauterine treatment of a female fetus with 21-hydroxylase deficiency.
OBJECTIVE: To present the first reported Australian case of prenatal treatment of a female fetus with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. CLINICAL FEATURES: A couple whose son had congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency sought prenatal diagnosis and treatment in their next pregnancy. INTERVENTION: Maternal treatment with dexamethasone was commenced at seven weeks' gestation to suppress androgen production by the fetal adrenal glands and prevent virilisation of an affected female fetus. At ten weeks' gestation chorionic villus sampling demonstrated a female fetus, who was shown subsequently to be affected by means of a linkage method in which probes to HLA genes DQA and DRB were used as markers for the 21-hydroxylase genes. Increased 17-hydroxyprogesterone and androstenedione immunoactivity in amniotic fluid obtained at 14.5 weeks confirmed the fetus to be affected and demonstrated incomplete suppression of fetal adrenal androgen production. Dexamethasone was continued to term and maintained suppression of the fetal and maternal adrenal glands. OUTCOME: The infant was born with normal female genitalia. Growth retardation was present but the relationship between this and the dexamethasone treatment remains uncertain. The mother had excessive weight gain during pregnancy. CONCLUSION: Dexamethasone treatment commenced in the first weeks of pregnancy can prevent or reduce virilisation of female fetuses with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency.
Adrenal Hyperplasia, Congenital↗