PubMed Health⌕ Search

Biomedical subjects

M Curran

Publications and source records attributed to M Curran.

At least 19 recordsLinked to original sources
PubMed2001

Investigation of infection with Campylobacter jejuni in a man with hypogammaglobulinaemia using PCR-single-stranded conformational polymorphism (PCR-SSCP) typing.

This study investigated several episodes of infection of Campylobacter jejuni in an immunocompromised male with hypogammaglobulinaemia, presenting with diarrhoea and bacteraemia over a 16-month period, by employing three phenotyping and four genotyping schemes, including the single-stranded conformational polymorphism (SSCP) technique to establish if infection was reinfection or persistent infection. Four isolates from blood culture and two faecal isolates of Campylobacter jejuni were obtained from the patient by direct selective plating on Skirrow Selective agar. Isolates were characterised at the sub-species level by Penner serology, Preston biotyping, Preston phage-typing, as well as E3CJC2 restriction fragment length polymorphism (RFLP), 16S ribotyping, flagellin (flaA) RFLP and single-stranded conformational polymorphism (SSCP) analyses. Phenotyping and genotyping sub-species analyses demonstrated that the patient was infected with at least two different strains of Campylobacter jejuni, i. e. one strain that persisted throughout the 16-month period and another strain that was transient suggesting reinfection from a different source. SSCP analysis was the most discriminatory of all the typing schemes examined and demonstrated an altered genotype of the persistent strain, whereby there were subtle modifications to the hypervariable regions of the flaA gene. Overall, as SSCP examines the hypervariable region of the flaA gene and as this technique can detect point mutations, differences between SSCP banding patterns may represent markers and thus examine mutations that occur under immune selection, thereby permitting the C. jejuni to evade the host immune response. In conclusion, this study describes the novel use of SSCP genotyping of C. jejuni and demonstrated that this method is a highly discriminatory technique which may be beneficial in outbreak characterisation, but which is not suitable to examine the clonal patterns of C. jejuni over a long period of time.

Agammaglobulinemia↗
PubMed2001

Fulvestrant.

Fulvestrant is a 7alpha-alkylsulphinyl analogue of estradiol that competes with endogenous estrogen for binding to the estrogen receptor. Once bound to the receptor, fulvestrant attenuates receptor dimerisation, effecting a rapid degradation of the estrogen receptor protein and inhibition of transcription. Fulvestrant is a potent inhibitor of the growth of human breast cancer cells in vitro and in vivo. It has demonstrated pure anti-estrogenic activity in animal systems. Intramuscular fulvestrant 250 mg once a month was as effective as the oral aromatase inhibitor anastrozole 1 mg/day in 2 phase III trials in postmenopausal women with advanced breast cancer who had received prior endocrine therapy. Median time to disease progression (the primary end-point) with fulvestrant and anastrozole was 5.4 and 3.4 months (North American trial) and 5.5 and 5.1 months (European trial). The median duration of response was 19.3 and 10.5 months (North American trial) and 14.3 and 14.0 months (European trial). The most common adverse events with fulvestrant are gastrointestinal disturbances and hot flushes. Fulvestrant showed similar tolerability to anastrozole in 2 phase III trials.

Antineoplastic Agents, Hormonal↗
PubMed2001

Valganciclovir.

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Parent-progeny recognition as a function of MHC odortype identity.

The several linked polymorphic genes of the MHC, which has been proposed as a prime determinant of sensed genetic individuality within species, is known to operate in mice by olfactory recognition in aspects of reproductive behavior that concern mate selection, thereby favoring outbreeding and heterozygosity, and also concern the maintenance of pregnancy. A single base-change can alter an individual MHC odortype, and the potential range of combinatorial MHC-determined odortypes is clearly vast. Following our findings that newborn mice already express their MHC odortype (which is detectable at 9 days of gestational age), we sought to determine whether MHC is involved in behavioral aspects of early development, such as rearing. In the studies presented herein, we report the ability and proclivity of mothers to recognize and preferentially retrieve syngeneic (genetically identical) pups from other pups differing only for MHC. Reciprocally, we report the ability of pups to recognize their familial environment, regardless of whether they had been nursed by their biological mothers or by foster mothers. Early learning experiences of the MHC environment are apparently a key element in survival, assuring maternal protection and promoting outbreeding.

Animals↗
PubMed2000

MHC-mediated fetal odourtypes expressed by pregnant females influence male associative behaviour.

Mice can recognize one another by individually characteristic phenotypic body odours (odourtypes) that reflect their genetic constitution at the highly polymorphic major histocompatibility complex (MHC) of genes on chromosome 17. We have shown previously that MHC-determined odours are produced by fetuses: house mice, Mus domesticus, can be trained to discriminate between genetically identical pregnant females carrying 9-18-day-old fetuses of differing MHC type. Theoretically, it should be possible for a mouse to determine the MHC type of the sire based on the odourtype of the pregnant female. In the current study we investigated whether untrained male mice show spontaneous discrimination between such pregnant mice. In experiment 1, sexually inexperienced male mice spent more time near pregnant females that carried fetuses most genetically different from the males themselves. Experiment 2, designed to evaluate possible experiential effects on this preference, tested males that were cohabiting and had impregnated a female that was either genetically identical to the test male (excepting X and Y chromosomes) or differed from him only at the MHC. Males in the former case performed virtually identically to those tested in experiment 1. In contrast males in the latter group did not display this preference. These studies reveal that among untrained male mice, fetal MHC type influences choice behaviour presumably via fetal odourtypes expressed in maternal secretions/excretions and that previous housing and/or mating experience modulates male choice. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2000

Effect of B2m gene disruption on MHC-determined odortypes.

Major histocompatibility complex (MHC) genes confer individual olfactory identity that can be detected with exquisite accuracy by mice. The fact that MHC genes themselves generate the characteristic odortype, rather than dedicated odor-determining genes, was supported in studies of point mutations in H2K and HLA transgenic mice, which evinced distinct odor profiles in olfactory assays. In this article we provide further evidence for a central role of MHC genes themselves in odortype specification by demonstrating that mice that are unable to express their genomic class I MHC genes because they lack beta2-microglobulin are distinguishable by scent from otherwise identical mice which possess an intact B2m gene. This odortype disparity appears at 9-12 days of gestational age, the period in which the MHC is first detectable in fetal cells of normal mice.

Animals↗
PubMed2000

Reconceptualising the outcomes of Continuing Professional Development.

This paper considers the potential outcomes, both positive and negative, of continuing professional development from the perspectives of practitioners and managers. Following a consideration of the literature it draws upon data collected during a 3-year evaluation of the English National Board Framework and Higher Award to highlight divergent views and tensions within Continuing Professional Development (CPD). Considerable discrepancies between practitioners and managers emerge which raise a number of searching questions about the value each group accords to continuing professional development. Based on the data a new framework for conceptualizing the outcomes of CPD is presented which fundamentally undermines a quasi-market approach.

Attitude of Health Personnel↗
PubMed2000

Sibling vesicoureteral reflux in multiple gestation births.

BACKGROUND: Vesicoureteral reflux (VUR) is the most commonly inherited disease of the genitourinary tract. Although the majority of evidence supports a genetic cause, the tendency for this condition to spontaneously improve over time has made it difficult to determine the actual mode of transmission. We report the incidence of VUR in siblings of multiple gestation births and for the first time compare the relative incidence of reflux between identical and fraternal twins. METHODS: A database consisting of all radionuclide cystograms and voiding cystourethrograms performed between the years 1986 and 1996 was searched for multiple gestation births. The medical records of each patient were evaluated for age at presentation, zygosity, reflux grade, and time to resolution. Children with secondary causes of VUR (eg, posterior urethral valves) were excluded. Triplets were treated as 2 pairs of twins for statistical analysis. RESULTS: Forty-six pairs met the inclusion criteria (31 dizygotic and 15 monozygotic). Overall, 23 (50%) of 46 siblings of index cases had demonstrable VUR. Comparison of VUR prevalence between identical and nonidentical twins was revealing with 80% (12/15) of identical twins and 35% (11/31) of fraternal twins having VUR. When only the youngest individuals in each group were considered, 100% (7/7) of the monozygotics and 50% (5/10) of the dizygotics demonstrated this trait. CONCLUSIONS: High concordance for VUR in identical twin siblings supports a genetic basis for the transmission of this disease. Results obtained from fraternal twin siblings provides convincing evidence that this trait is transmitted in an autosomal dominant fashion.

Child↗
PubMed1999

Maternal 1-deamino-8-D-arginine-vasopressin-induced sequential decreases in plasma sodium concentration: ovine fetal renal responses.

OBJECTIVE: Acute maternal plasma hypotonicity induces a reduced placental osmotic gradient that contributes to augmented maternal-to-fetal water flow. Subsequently, maternal plasma hyponatremia results in fetal plasma hyponatremia, increased fetal urinary flow, and ultimately increased amniotic fluid volume. We hypothesized that both the degree of reduction in the placental osmotic gradient and the degree of fetal plasma hyponatremia influence fetal urinary diuretic responses. To differentiate the roles of these factors, we determined fetal urinary responses to graded levels of plasma hyponatremia during a constant placental osmotic gradient. Furthermore, we sought to establish the minimum level of plasma hyponatremia necessary to facilitate an increase in fetal urine production. STUDY DESIGN: Seven pregnant ewes (130 +/- 2 days) were prepared with maternal and fetal vascular catheters and a fetal bladder catheter. After 6 days of recovery, fetal urinary flow and urine and plasma compositions were measured during a 2-hour control period. At 2 hours, tap water (2 L, 38 degreesC) with a 20-g bolus of 1-deamino-8-d-arginine-vasopressin was administered to the ewe. Maternal plasma sodium concentration was decreased from control by 5 to 7, 10 to 12, and 15 to 17 mEq/L, and held at each level (levels 1, 2, and 3) for 60 minutes. RESULTS: 1-Deamino-8-d-arginine-vasopressin administration induced sequential decreases in maternal and fetal plasma sodium concentrations (control 146.9 +/- 0.5 mEq/L and 141.0 +/- 0.5 mEq/L, respectively) at level 1 (140.1 +/- 0.6 mEq/L and 136.7 +/- 0.7 mEq/L, respectively), level 2 (132.5 +/- 0.7 mEq/L and 130.6 +/- 1.1 mEq/L, respectively), and level 3 (125.4 +/- 1.2 mEq/L and 123.0 +/- 1.5 mEq/L, respectively). The maternal-fetal placental osmolality and sodium gradients were constant at each hypotonicity level. Fetal urinary flow significantly increased in association with the degree of hyponatremia (from 0.17 +/- 0.03 mL/kg/min to 0. 26 +/- 0.04 mL/kg/min, 0.33 +/- 0.05 mL/kg/min, and 0.38 +/- 00.5 mL/kg/min at levels 1, 2, and 3, respectively). CONCLUSIONS: These results indicate the following: (1) Sequential decreases in maternal plasma tonicity result in parallel decreases in fetal plasma tonicity. (2) The fetal urinary diuretic response is highly correlated with the degree of fetal plasma hypotonicity, despite a constant placental osmotic gradient. A fetal therapeutic response (53% increase in fetal urine production) may be induced by a maternal plasma sodium concentration decrease of only 5 to 7 mEq/L.

Animals↗
PubMed1999

Assessing dehydroepiandrosterone in saliva: a simple radioimmunoassay for use in studies of children, adolescents and adults.

While salivary assays for some hormones are widely used, the availability of assays for salivary DHEA is limited. By adapting a commercially available radioimmunoassay serum kit, we developed a reliable, efficient and sensitive measure of DHEA in saliva that does not require separation or extraction. The minimum detection limit was 4.0 pg/ml. Intra-assay coefficients of variation (CV%) were on average 4.05, and inter-assay CVs averaged 9.70. Method accuracy, determined by spike recovery, and linearity, determined by serial dilution, averaged 99.55 and 92.03%. Levels in matched serum and saliva samples showed strong linear relationships for adult males and females. Specific guidelines are developed for sample collection, storage, and preparation procedures. Reference ranges for salivary DHEA levels are provided for 64 children ages 8-11, 96 adolescents ages 12-17 and 48 adults ages 30-45. Salivary DHEA levels are shown to reflect developmental, gender and diurnal differences.

Adolescent↗
PubMed1999

The prevalence of chronic knee injury in triathletes.

OBJECTIVES: To add to the area of triathlon research by providing much needed prevalence data on knee injury in triathletes. METHOD: An incidental "in field" sampling technique was used to interview 58 triathletes aged between 15 and 55 years about knee injury during a triathlon event. The sample comprised 46 men and 12 women. RESULTS: Most knee injuries occurred during the running event (72%) and affected the lateral side of the knee (38%). In all, 78% of the sample sought treatment from a healthcare professional. CONCLUSION: The study has provided much needed prevalence data on chronic knee injury in triathletes.

Adolescent↗
PubMed1998

National influenza surveillance 1997.

In 1997 information from several sources was combined to detect trends in influenza activity in Australia. Data was included from laboratories, general practitioners and a national employer. Laboratory surveillance documented two consecutive outbreaks, influenza B in July followed by influenza A (H3N2) in August. Some of the influenza A (H3N2) viruses isolated, represented by the A/Sydney/5/97 strain, showed significant antigenic drift from the A/Wuhan/359/95 vaccine strain. Influenza activity was also reflected in the consultation rates recorded by sentinel general practitioner reporting schemes. The peak consultation rate recorded by the Australian Sentinel Practice Research Network was higher and later than in recent years, occurring in early August. Tropical Influenza Surveillance in the Northern Territory demonstrated an early outbreak in March followed by a second rise later in the year. There was no rise in absenteeism rates recorded by a national employer.

Adolescent↗
PubMed1997

Nonphosphorylated peptide ligands for the Grb2 Src homology 2 domain.

Critical intracellular signals in normal and malignant cells are transmitted by the adaptor protein Grb2 by means of its Src homology 2 (SH2) domain, which binds to phosphotyrosyl (pTyr) residues generated by the activation of tyrosine kinases. To understand this important control point and to design inhibitors, previous investigations have focused on the molecular mechanisms by which the Grb2 SH2 domain selectively binds pTyr containing peptides. In the current study, we demonstrate that the Grb2 SH2 domain can also bind in a pTyr independent manner. Using phage display, an 11-amino acid cyclic peptide, G1, has been identified that binds to the Grb2 SH2 domain but not the src SH2 domain. Synthetic G1 peptide blocks Grb2 SH2 domain association (IC50 10-25 microM) with a 9-amino acid pTyr-containing peptide derived from the SHC protein (pTyr317). These data and amino acid substitution analysis indicate that G1 interacts in the phosphopeptide binding site. G1 peptide requires a YXN sequence similar to that found in natural pTyr-containing ligands, and phosphorylation of the tyrosine increases G1 inhibitory activity. G1 also requires an internal disulfide bond to maintain the active binding conformation. Since the G1 peptide does not contain pTyr, it defines a new type of SH2 domain binding motif that may advance the design of Grb2 antagonists.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Australia's notifiable diseases status, 1996. Annual report of the National Notifiable Diseases Surveillance System.

In 1996 there were 65,024 notifications to the National Notifiable Diseases Surveillance System. The record high number of Ross River virus infection notifications was of particular note. The highest rates were recorded in Western Australia, where an outbreak was documented in the South West, and in Queensland. Most cases occurred in the late summer and early autumn months. The number of measles cases has continued to fall markedly following the outbreak in 1993 and 1994. Rubella notifications also fell in 1996. The number of cases of pertussis remained at a similar level to that recorded in recent years, the highest notification rate being recorded for children under the age of one year. A peak in late 1996 marked a resurgence in the pertussis epidemic which has continued into 1997. Notifications of Haemophilus influenzae type b continued to decline reaching a record low rate of 0.3 notifications per 100,000 population. For the enteric diseases, the number of cases of campylobacteriosis rose, with an annual adjusted notification rate of 100.4 per 100,000 population; more notifications were received for this disease than for any other in 1996. The number of hepatitis A cases also rose relative to 1995. This is a reversal of the trend observed in recent years when the notification rate fell. The number of cases of salmonellosis and shigellosis remained stable. Notifications for chlamydial infection and gonococcal infection rose relative to 1995, whilst those for syphilis fell.

Alphavirus Infections↗
PubMed1997

National Influenza Surveillance 1996.

In 1996 data from laboratories, general practitioners and a national employer were combined to detect trends in influenza activity in Australia. An epidemic of influenza A (H3N2) was recorded. Little influenza B activity was noted throughout the winter months, however the number of laboratory reports of influenza B rose in the last quarter of the year. Influenza activity was reflected in the consultation rates recorder by sentinel general practitioner reporting schemes. Of particular note was the Tropical Influenza Surveillance in the Northern Territory which demonstrated a bimodal epidemic pattern. There was no apparent trend in national absenteeism rates recorded by a national employer.

Adolescent↗
PubMed1997

HLA-DR antigens associated with major genetic risk for late-onset Alzheimer's disease.

Hla-dr antigen types were determined from DNA isolated from post-mortem brain tissue of age-matched groups of 78 patients with pathologically confirmed late-onset Alzheimer's disease (AD) and 50 controls. The results suggest that for individuals with no apolipoprotein E epsilon 4 alleles the presence of either DR1, 2 or 3 antigens is associated with a significantly increased risk for development of late-onset AD. Conversely the DR4 or 6 antigens are associated with a decreased risk of similar magnitude. This DR effect, rather than prolonged use of non-steroidal anti-inflammatory drugs, could be responsible for the reported lower prevalence of AD in rheumatoid arthritis (a condition associated with an increased frequency of DR-4).

Age of Onset↗