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D Holden

Publications and source records attributed to D Holden.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of ambulance use in patients with acute myocardial infarction in Australia.

AIMS: To determine ambulance transport rates and investigate predictors for ambulance use by patients with acute myocardial infarction (AMI) in Australia. METHODS: A prospective, cross-sectional descriptive survey using structured interviews. It included patients who were admitted to two hospitals (Western, Bendigo, Melbourne, Victoria, Australia) with AMI between 1 October 2004 and 31 March 2005, and data were collected by semistructured interview and medical record review. Data were analysed by descriptive statistics, univariate and multivariate analysis using SPSS. RESULTS: 105 patients were interviewed. 48 (46%) participants called for an ambulance as their initial medical contact. Participants who called for an ambulance had a shorter interval between symptom onset and presentation to hospital than those who did not (non-ambulance participants)(median 2.1 v 7.8 h; p = 0.001). Predictors of ambulance transport were older age (p = 0.008), symptom onset on the weekend (p = 0.022), presence of sharp chest pain (p = 0.011), self-administered anginine (p = 0.007), symptom onset at home (p = 0.027) and having a lower income (<dollarsA20 000; p = 0.022). After multivariate analysis, self-administered anginine, sharp chest pain and occurrence of symptom onset at home remained as independent predictors of ambulance use. CONCLUSION: A substantial number of patients do not call for an ambulance as their first medical contact after the onset of AMI symptoms. Public education on the benefits of ambulance transport and early treatment, as well as recognition of AMI symptoms, is required.

Adult↗
PubMed2004

Sex-specific antenatal reference growth charts for uncomplicated singleton pregnancies at 15-40 weeks of gestation.

OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.

Embryonic and Fetal Development↗
PubMed2003

Sterile nodular panniculitis and pansteatitis in three weimaraners.

The clinical and pathological findings in three unrelated weimaraners with pyrexia and multiple subcutaneous nodules are reported. Abdominal pain was an additional feature in two of the dogs and clinical investigations revealed inflammation of subcutaneous, mesenteric and falciform fat. Histopathological findings were consistent with pansteatitis. In the third dog, lesions were apparently limited to the subcutis and, hence, a diagnosis of nodular panniculitis was made. Microbiological examination of tissues was negative in all dogs, and there was no evidence of pancreatic disease. This report thus describes a presumed sterile and idiopathic panniculitis/pansteatitis complex in weimaraner dogs. Although the aetiology is unknown, this may represent an immune-mediated disorder.

Animals↗
PubMed2002

Differential effect of oestrogen on post-exercise cardiac muscle myeloperoxidase and calpain activities in female rats.

The effects of oestrogen administration on 1 h post-exercise cardiac muscle myeloperoxidase (MPO) and calpain activities were determined in female rats. Rats were ovariectomized and implanted for 2 weeks with either oestrogen (25 mg 17-oestradiol) or placebo pellets or left with ovaries intact. Rats were then run for 1 h at 21 m min-1, 12% grade, killed 1 h post-exercise and cardiac muscle and blood samples were removed. Control animals from each group were killed without prior exercise. Serum oestrogen levels in the order of the highest to lowest were; ovariectomized oestrogen replaced rats > intact ovaries rats > ovariectomized placebo rats. Oestrogen induced significant (P < 0.05) elevations in cardiac MPO activity at rest and at 1 h post-exercise in ovariectomized rats. No significant elevations in cardiac MPO activity were evident in placebo ovariectomized or normal ovary rats at rest or post-exercise. Cardiac calpain activities were similar in all unexercised groups. Ovariectomized placebo and intact ovary rats had significantly (P < 0.05) elevated cardiac calpain activities 1 h post-exercise while calpain activity was not significantly elevated in hearts from ovariectomized oestrogen rats. These results demonstrate that oestrogen supplementation in ovariectomized rats induces elevations in cardiac muscle MPO activities at rest and at 1 h post-exercise. This is opposite to the effect of oestrogen in post-exercise skeletal muscle and implies a greater neutrophil infiltration into cardiac muscle caused by oestrogen. This effect cannot be explained by changes in 1 h post-exercise cardiac muscle calpain activity, the elevation of which was suppressed by oestrogen administration. Oestrogen influences cardiac calpain activity similarly to its effect in skeletal muscle. Thus, oestrogen administration to ovariectomized rats induces elevations in cardiac MPO activity while suppressing cardiac calpain activity.

Animals↗
PubMed2001

Intraobserver and interobserver variability of transabdominal Doppler velocimetry measurements of the fetal ductus venosus between 10 and 14 weeks of gestation.

OBJECTIVE: To assess the intraobserver repeatability and interobserver reproducibility of transabdominal Doppler ultrasound measurements of ductus venosus blood flow in fetuses between 10 and 14 weeks of gestation. DESIGN: A prospective study with the following end-points: coefficient of variation, intraclass correlation coefficients within and between observers, repeatability coefficient and Cohen's kappa coefficient. SUBJECTS AND METHODS: Doppler velocimetry indices (maximum peak systolic velocity during ventricular systole, end-diastolic velocity during atrial contraction, peak systolic velocity/end-diastolic velocity ratio and pulsatility index for veins) were successfully measured three times by the same trained observer in 67 fetuses. Of these, in 24 fetuses, the measurements were then repeated by a second trained observer. In addition, both observers classified qualitatively the blood flow as being normal or abnormal with regard to the presence or absence/reversal of flow during atrial contraction. RESULTS: The intraobserver repeatability of the pulsatility index for veins measurements was considered good with a coefficient of variation of 8.9% and an intraclass correlation coefficient value of 0.62. However, inconsistencies occurred in maximum peak systolic velocity, end-diastolic velocity and systolic/diastolic ratio measurements, which had coefficients of variation of 19%, 28.5%, and 25.4%, respectively. The corresponding intraclass correlation coefficient values were 0.70, 0.69 and 0.60. Interobserver reproducibility of these indices was unsatisfactory, the coefficient of variation varying between 11.5% and 47.2% and the intraclass correlation coefficient between 0.18 and 0.44. Agreement between the repeated observations with regard to interpretation of normal or abnormal blood flow varied from moderate (interobserver) to very good (intraobserver). CONCLUSIONS: There was considerable variability in all Doppler indices except for the intraobserver repeatability of the pulsatility index for veins measurement. This makes the implementation of the semiquantitative Doppler indices in a screening setting difficult. On the contrary, qualitative classification of the flow velocity waveforms seemed to be a reproducible method.

Adolescent↗
PubMed2001

Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity.

We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise. Ovariectomized female rats were implanted with either an estogen pellet (25 mg beta-estradiol) or a placebo pellet. Two weeks postimplant, animals were killed either at rest or 1 h after running exercise (60 min at 21 m x min(-1), 12% grade). The 4 experimental groups (n = 12) used were: unexercised placebo (UP), unexercised estrogen (UE), exercised placebo (EP), and exercised estrogen (EE). Blood samples were analyzed for creatine kinase (CK) activity and estradiol content. Plantaris and gastrocnemius muscles were removed and histochemical determination of neutrophil content or biochemical determination of myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G6PD), and calpain-like activity determined. Estrogen supplemented animals had 10-20-fold higher circulating estradiol levels than placebo animals. EP animals had significantly higher (P < 0.05) circulating CK activities than EE or unexercised animals. Muscle neutrophil concentrations were significantly (P < 0.01) elevated in EP and EE groups compared with unexercised controls, with EP muscle neutrophil levels also being over 60% greater (P < 0.05) than in EE animals. EP animals also had higher (P < 0.05) muscle MPO activities than unexercised or EE animals. Muscle G6PD activities were not significantly different between any groups. Muscle caplain-like activities were 80% higher (P < 0.01) in EP animals than EE animals with calpain-like activities in EE animals similar to unexercised groups. These results indicate that estrogen supplementation in ovariectomized rats attenuated 1-h post-exercise serum CK activities, muscle neutrophil infiltration, MPO activities, and calpain-like activities when compared with exercised, unsupplemented animals. This supports the possibility of a relationship between estrogen, calpain dependent production of neutrophil chemo-attractant peptides, and 1-h post-exercise skeletal muscle neutrophil infiltration.

Animals↗
PubMed1999

Feasibility of the second-trimester fetal ultrasound examination in an unselected population at 18, 20 or 22 weeks of pregnancy: a randomized trial.

OBJECTIVE: To date, there have been no studies on the optimal timing of second-trimester ultrasound screening for fetal abnormalities. The purpose of this study was to investigate whether, of three gestational ages (18, 20 and 22 weeks), any one was associated with a significant advantage in terms of identification of abnormalities or need for further ultrasound assessment. DESIGN: Prospective, randomized study of second-trimester unselected pregnant women, who had had an ultrasound examination with normal results at 10-14 weeks. SUBJECTS AND METHODS: A total of 1206 women were randomized into three mutually exclusive groups relating to their second-trimester appointment for a screening ultrasound examination for fetal abnormalities in the second trimester of pregnancy: Group 1 at 18-18 + 6 weeks, Group 2 at 20-20 + 6 weeks and Group 3 at 22-22 + 6 weeks. The anomaly scans were carried out according to a standardized protocol. The fetuses were examined for structural and developmental abnormalities. Uterine artery Doppler measurements, including waveform recordings, were performed in all cases. The main end-points were the need for rescanning of all or part of the fetal anatomy, fetal outcome, placental localization, and incidence of notches in the uterine artery waveform. RESULTS: The baseline demographic characteristics and risk factors in the three groups were similar and gestational age-related fetal measurements were comparable. There were significantly higher percentages of completed scans in Group 2 (90%) and Group 3 (88%) than in Group 1 (76%; p < 0.001), but no significant difference between those scanned at 20 and at 22 weeks. This was associated with a higher incidence of non-cephalic presentation in Group 1 (46%) than in the other two groups (36%, p < 0.001). Significant differences in completing the assessment of the thorax, heart, spine and skeleton were also observed. There was no significant difference in maternal body habitus, fetal movements or the occurrence of uterine fibroids between the study groups. The incidences of low-lying placenta and of abnormal uterine artery Doppler screening were also higher at 18 weeks than at 20 and 22 weeks (p < 0.001 for both variables), with no difference seen between Groups 2 and 3. The numbers of fetal anomalies detected in the three groups were three, two and two, respectively; these did not differ significantly between the groups. CONCLUSIONS: This study suggests that, in an unselected pregnant population, second-trimester ultrasound screening is easier to perform and less likely to require an additional scan at 20-22 weeks than at 18 weeks.

Adult↗
PubMed1999

Decision training: the effects of complex instruction, variable practice and reduced delayed feedback on the acquisition and transfer of a motor skill.

Novice, intermediate and advanced baseball hitters followed a 7-week training programme, in which they received either behavioural training or decision training. Participants in the behavioural training group received simple-to-complex instruction, variable practice and an abundance of feedback throughout the acquisition period; the decision training group received complex instruction, variable practice and reduced delayed feedback. As predicted, the intermediate and advanced hitters who received decision training hit at a lower level (%) during acquisition but at a higher level during a transfer test in week 7. Novices in the behavioural training group were better than novices in the decision training group over both acquisition and transfer trials.

Adolescent↗
PubMed1999

The conservative management of first trimester miscarriages and the use of colour Doppler sonography for patient selection.

This study of patients with first trimester miscarriage evaluates whether conservative management is a feasible strategy and assesses the value of colour Doppler ultrasonography for patient selection. After confirmation of the diagnosis by transvaginal sonography all patients were offered the choice of immediate dilatation and curettage or conservative management. The presence of a gestational sac, the occurrence of spontaneous complete miscarriage within 28 days, detectable pulsatile blood flow within the placenta in the presumed region of the intervillous space and post-treatment complications were the main end-points. Out of a total of 108 women recruited, 23 (21.3%) elected to undergo immediate dilatation and curettage and 85 (78.7%) chose conservative management. The treatment groups were similar in age, gestational age, gestational sac diameter, serum concentrations of human chorionic gonadotrophin (HCG) and progesterone, and proportion of patients who had post-treatment complications (12-13%). Of patients in the conservative management group, 71 out of 85 (84%) had a spontaneous, complete abortion, while 37 out of 46 cases (80%) with detectable presumed intervillous pulsatile blood flow had a complete, spontaneous abortion within 1 week; this occurred in 23% of cases with no detectable flow. This suggests that conservative management is a successful approach for many patients with first trimester miscarriage; colour Doppler ultrasonography can be used to select the most suitable patients for this strategy, and thus reduce the need for hospital admission and surgery.

Abortion, Spontaneous↗
PubMed1999

Evaluation of Salmonella typhimurium mutants in a model of experimental gastroenteritis.

Salmonella typhimurium strains harboring independent, defined mutations in aroA, invA, ssrA, or msbB were assessed for their ability to induce fluid accumulation, tissue damage, and local inflammation in rabbit ileal loops. Three wild-type strains of S. typhimurium, TML, HWSH, and SL1344, and two mutant strains, S. typhimurium SL1344 ssrA and S. typhimurium SL1344 msbB, consistently induced fluid accumulation in the lumen of loops and inflammation of loop-associated tissues. In contrast, three different S. typhimurium aroA strains and an invA mutant of SL1344 did not induce significant fluid accumulation in the rabbit ileal loops. However, the S. typhimurium aroA strains did induce an inflammatory infiltrate and some local villus-associated damage, but the invA mutant did not. Histologically, wild-type S. typhimurium, S. typhimurium SL1344 ssrA, and S. typhimurium SL1344 msbB demonstrated more severe effects on villus architecture than S. typhimurium aroA strains, whereas S. typhimurium invA-infected loops showed no detectable damage. This suggests that villus damage most likely contributes to fluid accumulation within the loop.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1999

Pathogen virulence genes--implications for vaccines and drug therapy.

The emergence and spread of bacteria resistant to antimicrobial drugs is a major public health problem with a growing number of infections becoming virtually untreatable. There is a need to develop interventions both to prevent and to treat diseases caused by multi-resistant microbes. We review some recently developed methods (including whole genome nucleotide sequencing projects) to study bacterial pathogenesis, and discuss how knowledge gained from understanding the molecular mechanisms of disease can be applied to combat the threat of infectious diseases.

Animals↗
PubMed1998

Regulatory volume increase in rat pancreatic beta-cells.

This study investigated regulatory volume increase (RVI) in rat pancreatic beta-cells. Volume changes in isolated beta-cells were measured by a video-imaging method. Cell shrinkage was induced by exposure to solutions made hypertonic by the addition of 100 mM mannitol. In HEPES-buffered solutions, beta-cells exhibited an RVI which was almost completely abolished by 10 microM bumetanide. These data indicate that Na+-2Cl--K+ cotransporters make a major contribution to RVI in beta-cells. In HCO3--buffered solutions, however, an RVI was observed in the presence of 10 microM bumetanide. This bumetanide-insensitive component of RVI was inhibited by 100 microM amiloride or 100 microM 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). These data suggest that, in addition to the Na+-2Cl--K+ cotransporter, functionally coupled Na+-H+ exchangers and Cl--HCO3- exchangers may also contribute to RVI in pancreatic beta-cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Structure solution of C-reactive proteins: molecular replacement with a twist.

The pentameric structure of C-reactive proteins (CRP) has been derived by a combination of automated and manual molecular-replacement techniques. The method is generally applicable to other multimeric assemblies. The highly homologous human serum amyloid P component (hSAP) structure fails to provide a pentameric molecular-replacement solution for CRP. In the absence of a significant signal from an individual protomer, the hSAP structure has been manually modified in terms of protomer assembly to provide the true pentameric model of CRP. The CRP protomers are rotated or twisted by 14 degrees about an axis, through the protomer centre, which is approximately perpendicular to the pentamer radius and the molecular fivefold axis. The results demonstrate clearly that protomers with very similar folds arising from high sequence homology need not necessarily be assembled together in the same way although the symmetry of the resulting oligomer may be maintained. In a curious twist the CRP structure which provided the general CRP model remains unsolved, while the model itself has so far provided the solution of two other CRP structures.

Journal Article↗
PubMed1996

Use of recombinant human follicle-stimulating hormone for in vitro fertilization-embryo transfer after severe systemic immunoglobulin E-mediated reaction to urofollitropin.

OBJECTIVE: To report the successful use of recombinant human FSH in a patient with a history of a severe systemic immunoglobulin E (IgE)-mediated reaction to urofollitropin. SETTING: University hospital. PATIENT: A 38-year-old infertility patient who had experienced a whole-body rash with hives, tachycardia, fever, and other symptoms after urofollitropin administration, with confirmation of IgE-mediated sensitivity to urofollitropin by intradermal skin testing. INTERVENTION: In vitro fertilization-ET after the use of recombinant human FSH to stimulate ovarian follicular development. RESULTS: Establishment of a clinical pregnancy. CONCLUSIONS: Our case provides evidence for the involvement of nongonadotropin proteins as the direct cause of some adverse reactions from conventional urine-derived human FSH preparations.

Adult↗
PubMed1996

Three dimensional structure of human C-reactive protein.

The structure of the classical acute phase reactant human C-reactive protein provides evidence that phosphocholine binding is mediated through calcium and a hydrophobic pocket centred on Phe 66. The residue Glu 81 is suitably positioned to interact with the choline group. A cleft on the pentameric face opposite to that containing the calcium site may have an important functional role. The structure provides insights into the molecular mechanisms by which this highly conserved plasma protein, for which no polymorphism or deficiency state is known, may exert its biological role.

Amino Acid Sequence↗
PubMed1996

Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.

PURPOSE: A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS: Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS: Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION: This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.

Adult↗