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Biomedical subjects

S Lindsay

Publications and source records attributed to S Lindsay.

At least 19 recordsLinked to original sources
PubMed2003

Randomised crossover trial to assess the tolerability of LHRH analogue administration.

Luteinising hormone releasing hormone (LHRH) analogues are routinely used in the treatment of patients with advanced prostate cancer. This randomised crossover trial was conducted to compare patient comfort and tolerability between two commonly used LHRH analogues: goserelin acetate and leuprorelin acetate. A total of 50 patients were randomised into two groups, each receiving 6-monthly injections of leuprorelin acetate (a liquid presentation) and goserelin acetate (a depot pellet) and crossing over between treatments. Patients completed a simple visual analogue score for the discomfort felt from the injections. An analysis of variance model was used, and the results found that patients do tolerate leuprorelin acetate (0.589) better than goserelin acetate (1.343) (P < 0.001, CI = 95%).

Aged↗
PubMed2001

Hydrogen peroxide formation during iron deposition in horse spleen ferritin using O2 as an oxidant.

The reaction of Fe2+ with O2 in the presence of horse spleen ferritin (HoSF) results in deposition of FeOH3 into the hollow interior of HoSF. This reaction was examined at low Fe2+/HoSF ratios (5-100) under saturating air at pH 6.5-8.0 to determine if H2O2 is a product of the iron deposition reaction. Three methods specific for H2O2 detection were used to assess H2O2 formation: (1) a fluorometric method with emission at 590 nm, (2) an optical absorbance method based on the reaction H2O2 + 3I- + 2H+ = I3- + 2H2O monitored at 340 nm for I3- formation, and (3) a differential pulsed electrochemical method that measures O2 and H2O2 concentrations simultaneously. Detection limits of 0.25, 2.5, and 5.0 microM H2O2 were determined for the three methods, respectively. Under constant air-saturation conditions (20% O2) and for a 5-100 Fe2+/HoSF ratio, Fe2+ was oxidized and the resulting Fe3+ was deposited within HoSF but no H2O2 was detected as predicted by the reaction 2Fe2+ + O2 + 6H2O = 2Fe(OH)3 + H2O2 + 4H+. Two other sets of conditions were also examined: one with excess but nonsaturating O2 and another with limiting O2. No H2O2 was detected in either case. The absence of H2O2 formation under these same conditions was confirmed by microcoulometric measurements. Taken together, the results show that under low iron loading conditions (5-100 Fe2+/HoSF ratio), H2O2 is not produced during iron deposition into HoSF using O2 as an oxidant. This conclusion is inconsistent with previous, carefully conducted stoichiometric and kinetic measurements [Xu, B., and Chasteen, N. D. (1991) J. Biol. Chem. 266, 19965], predicting that H2O2 is a quantitative product of the iron deposition reaction with O2 as an oxidant, even though it was not directly detected. Possible explanations for these conflicting results are considered.

Air↗
PubMed2001

Psychological influences on acceptance of postsurgical treatment in cancer patients.

OBJECTIVE: Many cancer patients fail to complete treatment for reasons that are unclear in previous research which, nevertheless, suggested hypotheses for this study about the characteristics of the patients and their consultations. METHOD: 158 adults with breast cancer or other cancers who had been chosen for postsurgical treatment in the Lister Hospital or the Mount Vernon Hospital had completed published questionnaires to assess either (n=74) personal attributes or circumstances viz. locus of health control, health habits, support, affiliative drive, anxiety, depression, or (n=84) their attitudes to cancer or their consultations, viz. the Mental Attitudes to Cancer Scales, Trust in Physicians, Perceived Empathy, and Satisfaction With Recent and Diagnostic Consultations. RESULTS: 32% then failed to complete treatment. In logistic multiple regression analyses, only diagnosis (P=.0001), gender (P=.005), and treatment center (P=.0002) predicted this although the effect of gender was not significant among patients without breast cancer. Among the patients without breast cancer intended for the Mount Vernon Hospital, a National Cancer Centre, fewer completed treatment than those did not complete. CONCLUSION: The breast cancer patients, unlike women with other cancers, and patients referred to the local hospital rather than the regional cancer center, were more likely to complete treatment. Thus, uptake of treatment may be favored by accessibility and familiarity of its source and by the unique impact in women of breast cancer and the wider public attention given to that illness. Research on patients' expectations, fears, and corresponding experiences of treatment, rather than personal attributes, should clarify failure to complete cancer treatment especially in patients without breast pathology.

Aged↗
PubMed2001

Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation.

The first haematopoietic stem cells in mammalian and non-mammalian vertebrates are derived from mesoderm, therefore genes that are important in mesoderm patterning and formation might also play an essential role in haematopoietic stem cell commitment and differentiation. Several members of the Wnt gene family are expressed in very specific patterns in embryonic mesoderm and have previously been shown to act as haematopoietic growth factors. In order to investigate in detail the role that such secreted proteins play in the biology of early haematopoietic commitment we have used in vitro differentiation of murine embryonal stem (ES) as a model system. Using reverse-transcriptase polymerase chain reaction analysis we identified several candidate Wnt genes whose expression pattern was consistent with a role in generation, maintenance and/or differentiation of early haematopoietic progenitor cells including three genes previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b). The most interesting candidate was Wnt3, because of its strong and regulated expression during in vitro differentiation of murine ES cells as well as its early embryonic expression in mesoderm. Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells. In addition, overexpression of Wnt3 caused a marked upregulation of Brachyury expression, thus providing some evidence that Brachyury may be one of the target genes for the Wnt3 signalling pathway.

Animals↗
PubMed2001

Development of a questionnaire to measure concern for dental appearance.

100 adults, selected for cosmetic dental treatment in a general dental practice, completed a 42-item questionnaire designed, on the basis of previous research and the author's clinical experience, to measure concern for dental appearance. This had high internal consistency and was reduced to a questionnaire of 23 items with internal consistency shown by a standardised Cronbach alpha of .84. An exploratory factor analysis with varimax rotation identified six factors, the main one appearing to be a measure of concern for dental appearance. The high internal consistency suggests that the total score for the revised questionnaire is a measure of a construct, concern for dental appearance. Although the simplest measure of that may be contained in the items for the first factor, a much larger sample would be necessary to confirm the complex factor structure and so the questionnaire's total score is probably the more reliable measure at present. A study is summarised showing that the total score provides a measure that, in statistical regression analysis, may predict the intentions of adults to take care of the appearance of their teeth.

Adult↗
PubMed2000

Helicopter in transit care of the critically ill--the Whangarei experience.

AIMS: To describe our experience in transit care of the critically ill in Northland and to highlight the multidisciplinary co-operation which renders this an efficient model of transit care in suburban and rural areas. METHODS: Since its inception in 1988, Northland's wholly community owned rescue helicopter has played an integral part in transit Intensive Care in Northland. This aids in transportation of medical and nursing intensive care staff to outlying primary hospitals for patient stabilisation, subsequent transfer of the patient to the intensive care unit (ICU) in Whangarei and, occasionally, for transfer to specialised critical care services in Auckland. RESULTS: As of August 1999, over 3,900 helicopter missions have been accomplished. A doctor, vetting each request for Medevac, minimises over-triage, thus ensuring adequate levels of transit care and effective utilisation of expensive resources. More than 90% of non-obstetric adult patients were ventilated and the number of Medevac missions increased over the years. The Accident Compensation Corporation (ACC) funds 40% of all flights, another 40% of flights are funded by Northland Health and the Order of St John funds the remainder. CONCLUSIONS: With a widespread geography, efficient transit care of the critically ill is imperative to quality hospital care and ensures equity of access to the rural populace. The Whangarei system of transit intensive care is an ideal template for suburban and rural areas.

Air Ambulances↗
PubMed2000

Effect of pregnancy on exposure to malaria mosquitoes.

Pregnant women attracted twice the number of Anopheles gambiae complex--the predominant African malaria-carrying mosquito--than did their non-pregnant counterparts. We postulate that physiological and behavioural changes that occur during pregnancy are responsible for increased attractiveness, which could be important in intervention strategies aimed at protecting this high-risk group against malaria.

Analysis of Variance↗
PubMed2000

The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome.

Turner syndrome is characterized by short stature and is frequently associated with a variable spectrum of somatic features including ovarian failure, heart and renal abnormalities, micrognathia, cubitus valgus, high-arched palate, short metacarpals and Madelung deformity. Madelung deformity is also a key feature of Leri-Weill syndrome. Defects of the pseudoautosomal homeobox gene SHOX were previously shown to lead to short stature and Leri-Weill syndrome, and haploinsufficiency of SHOX was implicated to cause the short stature phenotype in Turner syndrome. Despite exhaustive searches, no direct murine orthologue of SHOX is evident. SHOX is, however, closely related to the SHOX2 homeobox gene on 3q, which has a murine counterpart, Og12x. We analysed SHOX and SHOX2 expression during human embryonic development, and referenced the expression patterns against those of Og12x. The SHOX expression pattern in the limb and first and second pharyngeal arches not only explains SHOX -related short stature phenotypes, but also for the first time provides evidence for the involvement of this gene in the development of additional Turner stigmata. This is strongly supported by the presence of Turner-characteristic dysmorphic skeletal features in patients with SHOX nonsense mutations.

Adult↗
PubMed2000

SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development.

SRY, SOX9, and DAX1 are key genes in human sex determination, by virtue of their associated male-to-female sex reversal phenotypes when mutated (SRY, SOX9) or over-expressed (DAX1). During human sex determination, SRY is expressed in 46,XY gonads coincident with sex cord formation, but also persists as nuclear protein within Sertoli cells at 18 weeks gestation. High-level SOX9 expression in the sex cords of the testis parallels that seen during mouse development, however in humans, SOX9 transcripts also are detected in the developing ovary. Low-level DAX1 expression predates peak SRY expression by at least 10 days, and persists in Sertoli cells throughout the entire sex determination period. In Dosage Sensitive Sex reversal, the anti-testis properties of DAX1 over-expression could act prior to the peak effects of SRY and continue during the period of SOX9 expression. These findings highlight expression differences for the SRY, SOX9, and DAX1 genes during sex determination in humans and mice. These results provide a direct framework for future investigation into the mechanisms underlying normal and abnormal human sex determination.

Animals↗
PubMed2000

Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes.

Our understanding of early human development has been impeded by the general difficulty in obtaining suitable samples for study. As a result, and because of the extraordinarily high degree of evolutionary conservation of many developmentally important genes and developmental pathways, great reliance has been placed on extrapolation from animal models of development, principally the mouse. However, the strong evolutionary conservation of coding sequence for developmentally important genes does not necessarily mean that their expression patterns are as highly conserved. The very recent availability of human embryonic samples for gene expression studies has now permitted for the first time an assessment of the degree to which we can confidently extrapolate from studies of rodent gene expression patterns. We have found significant human-mouse differences in embryonic expression patterns for a variety of genes. We present detailed data for two illustrative examples. Wnt7a, a very highly conserved gene known to be important in early development, shows significant differences in spatial and temporal expression patterns in the developing brain (midbrain, telencephalon) of man and mice. CAPN3, the locus for LGMD2A limb girdle muscular dystrophy, and its mouse orthologue differ extensively in expression in embryonic heart, lens and smooth muscle. Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution.

5' Untranslated Regions↗
PubMed2000

Autosomal dominant sacral agenesis: Currarino syndrome.

Autosomal dominant sacral agenesis is characterised by a partial agenesis of the sacrum typically involving sacral vertebrae S2-S5 only. Associated features include anorectal malformation, a presacral mass, and urogenital malformation. Together, these features have been defined as the Currarino syndrome. Recently, HLXB9 has been identified as the major causative gene in Currarino syndrome allowing identification of asymptomatic heterozygotes. In this review, we have performed an analysis of medical publications, and our own additional cases, to identify the range of malformations and complications that occur. We have also estimated risks of malformation in heterozygotes by using Weinburg's proband method on families personally known to us in order to provide accurate genetic counselling information.

Anal Canal↗
PubMed2000

Patient Care Bridge--mobile ICU for transit care of the critically ill.

We describe the development and introduction of a Patient Care Bridge--a mobile ICU for the transit care of the critically ill. This stretcher-mounted Patient Care Bridge is being used for intensive transit care of the critically ill in Northland, New Zealand. It carries all the basic intensive care monitoring accoutrements, is lightweight and is suited for pre-hospital, inter-hospital and intra-hospital transit care. It is ideal for patient evacuation from the scene of motor vehicle and sporting accidents, surface transportation of patients by surface ambulance and aeroevacuation of patients by the Helicopter Emergency Medical Service. This economic and space efficient unit has been used for transfer of more than one thousand critically ill patients.

Air Ambulances↗
PubMed1999

Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination.

The transcription factors SF-1 and WT1 play pivotal roles in mammalian gonadal development and sexual differentiation. In human embryos, both SF-1 and WT1 are expressed when the indifferent gonadal ridge first forms at 32 days post-ovulation. As the sex cords develop - providing morphological evidence of testis differentiation - SF-1 localises predominantly to developing Sertoli cells in the sex cords, whereas WT1 retains a broader pattern of expression. Later, SF-1 localises predominantly to steroidogenic Leydig cells, and WT1 localises to the sex cords. In the ovary, SF-1 and WT1 transcripts persist in the gonadal ridge from the earliest developmental stages throughout the critical period of sex determination. These studies, which delineate for the first time the sequential expression profiles of SF-1 and WT1 during human gonadal development, provide a framework for understanding human sex reversal phenotypes associated with their mutations.

DNA-Binding Proteins↗
PubMed1998

Glypican 3 and glypican 4 are juxtaposed in Xq26.1.

Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) gene cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS; ). The next centromeric gene detected is another glypican, glypican 4 (GPC4), with its 5' end 120763bp downstream of the 3' terminus of GPC3. One recovered GPC4 cDNA with an open reading frame of 1668nt encodes a putative protein containing three heparan sulfate glycosylation signals and the 14 signature cysteines of the glypican family. This protein is 94.3% identical to mouse GPC4 and 26% identical to human GPC3. In contrast to GPC3, which produces a single transcript of 2.3kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses show that GPC4 produces two transcripts, 3.4 and 4.6kb, which are very widely expressed (though at a much higher level in fetal lung and kidney). Interestingly, of 20 SGBS patients who showed deletions in GPC3, one was also deleted for part of GPC4. Thus, GPC4 is not required for human viability, even in the absence of GPC3. This patient shows a complex phenotype, including the unusual feature of hydrocephalus; but because an uncle with SGBS is less affected, it remains unclear whether the GPC4 deletion itself contributes to the phenotype.

Abnormalities, Multiple↗
PubMed1998

Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung.

The Wnt gene family encodes a set of signalling molecules, thought to play an important role in key processes of embryonic development. In vertebrates as a whole 20 different Wnt genes have been identified to date, however, a complement of only 16 have been identified in man and for some of these the complete coding sequences are unavailable. We have recently isolated the full-length cDNA sequence of a new human WNT gene, WNT11, investigated its genomic organisation and performed detailed expression studies in early human embryos. These have shown that the expression of human WNT11 is restricted to the perichondrium of the developing skeleton, lung mesenchyme, the tips of the ureteric buds and other areas of the urogenital system and the cortex of the adrenal gland. This, for the first time, provides information for the embryonic expression of human WNT11. We have mapped WNT11 to 11q13.5 and this together with its expression in the perichondrium of the developing skeleton, makes it a plausible candidate gene for HBM, which has been previously linked to markers from this region.

Amino Acid Sequence↗
PubMed1998

Utrophin mRNA expression in muscle is not restricted to the neuromuscular junction.

Utrophin is normally present exclusively in synaptic regions of skeletal muscle fibers, although it is expressed extrasynaptically in certain pathological situations, where it has been proposed to compensate for the absence of dystrophin in Duchenne muscular dystrophy patients and mdx mice. Recently there have been conflicting reports regarding the preferential expression of utrophin mRNA at the neuromuscular junction. Using in situ hybridization with RNA probes, we show a clear accumulation of autoradiographic labeling at more than 90% of neuromuscular junctions (identified by histochemical demonstration of cholinesterase activity). The intensity of this labeling is proportional to the number of junctional myonuclei in the section. Some clusters of labeling were found associated with nonmuscle nuclei (e.g., blood vessels, nerves), where utrophin is present. In addition, labeling for utrophin mRNA was associated with about 25% of extrajunctional myonuclei, where the protein is not present. The mean labeling per nucleus at junctional myonuclei was at least 10 times greater than at extrajunctional myonuclei. We discuss the possible regulatory mechanisms involved in the heterogeneous expression of utrophin mRNA in skeletal muscle.

Amino Acid Sequence↗