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Biomedical subjects

P Hardy

Publications and source records attributed to P Hardy.

At least 19 recordsLinked to original sources

Overweight, obesity and girth of Australian preschoolers: prevalence and socio-economic correlates.

OBJECTIVE: (1) To determine the prevalence of overweight and obesity in Australian 4-5-year-old children. (2) To investigate associations between socio-economic characteristics and (a) overweight/obesity and (b) waist circumference. DESIGN: Cross-sectional population survey. SETTING: Wave 1 (2004) of the Longitudinal Study of Australian Children. PARTICIPANTS: Nationally representative sample of 4983 4-5-year-old children (2537 boys and 2446 girls; mean age 56.9 months (s.d. 2.64 months; range 51-67 months)). MAIN OUTCOME MEASURES: Prevalence of overweight and obesity (International Obesity TaskForce definitions) and waist circumference (cm). ANALYSIS: Prevalence estimates were obtained as weighted percentages. Uni- and multivariable ordinal logistic regression (using the proportional odds model) were used to assess associations between potential predictors and the risk of higher child body mass index status and a multivariable linear regression model to assess relationships between the same potential predictors and waist circumference. RESULTS: 15.2% of Australian preschoolers are estimated to be overweight and 5.5% obese. In univariate analyses, seven of the 12 variables were associated with higher odds of being in a heavier body mass index category. In a multivariable regression model, speaking a language other than English (particularly for boys), indigenous status and lower disadvantage quintile were the clearest independent predictors of higher body mass index status, with children in the lowest quintile of social disadvantage having 47% higher odds (95% CI 14, 92%) of being in a heavier body mass index category compared to those in the highest quintile. Waist circumference was not related to any socio-economic variable. CONCLUSIONS: This nationally representative survey confirms high rates of overweight and obesity in preschoolers throughout Australia. The recent emergence of a substantial socio-economic gradient should bring new urgency to public health measures to combat the obesity epidemic.

Abdomen↗

Randomized controlled trial of tacrolimus versus microemulsified cyclosporin (TMC) in liver transplantation: poststudy surveillance to 3 years.

The 1-year results of the tacrolimus versus microemulsified cyclosporin (TMC) study found a benefit with tacrolimus immunosuppression after primary liver transplants in adults with respect to freedom from graft loss and immunological failure. The integrity of the randomization process was preserved for a further 2 years for poststudy surveillance. The data after 3 years confirms the significant difference between tacrolimus and cyclosporin with tacrolimus less likely to meet the composite primary endpoint (log rank p = 0.01; relative risk 0.75; 95% CI 0.60-0.95; p = 0.016). However, freedom from death or retransplantation no longer achieves statistical significance (relative risk 0.79; 95% CI 0.62-1.02; p = 0.065). A total of 62.1% of patients randomized to tacrolimus were alive at 3 years with their original graft and still on their allocated study medication, as compared with only 41.6% in the cyclosporin limb (p < 0.001). No difference was detected between tacrolimus and cyclosporin in hepatitis-C-positive patients with the available data. The TMC study confirms after 3 years of follow-up the benefits of tacrolimus-based immunosuppression over cyclosporin using C(0) monitoring.

Adult↗

Exaggerated vasomotor response to ANG II in rats with fetal programming of hypertension associated with exposure to a low-protein diet during gestation.

The renin-angiotensin system plays a key role in the initiation and maintenance of elevated blood pressure associated with altered intrauterine milieu. The current studies were undertaken to verify whether vascular response to ANG II is increased in adult offspring of low-protein fed dams (LP) compared with control (CTRL) and if so, to examine underlying mechanism(s). ANG II-induced contraction of carotid rings was increased in LP (E(max), the maximum asymptote of the curve, relative to maximal response to KCl 80 mM: 230 +/- 3% LP vs. 201 +/- 2% CTRL, P < 0.05). In both groups, contraction to ANG II was mediated solely by AT1R. Responses to thromboxane A2 analog U-46619 and to KCl 80 mM under step increases in tension were similar between groups. Endothelium depletion enhanced contraction to ANG II in both groups, more so in LP. Blockade of endothelin formation had no effect on response to ANG II, and ANG-(1-7) did not elicit vasomotor response in either group. Superoxide dismutase (SOD) analog Tempol normalized LP without modifying CTRL response to ANG II. Basal levels of superoxide (aortic segments, lucigenin-enhanced chemiluminescence and fluorescent dye hydroethidine) were higher in LP. ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex). AT1R expression in carotid arteries was increased in LP, whereas SOD expression was unchanged. In conclusion, vasoconstriction to ANG II is exaggerated in this model of developmental programming of hypertension, secondary to enhanced vascular production of superoxide anion by NADPH oxidase with concomitant increase of AT1R expression.

Age Factors↗

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.

Administration, Inhalation↗

[Adult lateral meniscus].

Meniscal lesion does not mean meniscectomy and this is particularly true for the lateral meniscus. The reputation of mildness of the meniscectomy is usurped. The rate of joint space narrowing after lateral meniscectomy is of 40% at a follow-up of 13 years compared to 28% for the medial meniscus (symposium SFA 1996). Several arguments explain those results: biomechanical: the lateral meniscus contributes to the congruence; particularly the lateral meniscus is the zone where antero-posterior translational during knee flexion is 12 mm. The pejorative effects of lateral meniscectomy have conducted, more though to the medial meniscus, to the concept of meniscal economy. Lateral meniscectomy must be as partial as possible. Particularly, a discoid meniscus presenting a complete tear should be treated by a meniscoplasty in order to shape the meniscus in a more anatomic form than a total meniscectomy. Lateral meniscectomy is indicated in complex or horizontal cleavage, symptomatic, on stable knees. A particular case is the cyst of the lateral meniscus. It is a cystic subcutaneous formation, usual consequence of a horizontal cleaved meniscus of which the particularity is that it opens besides the articulation. The strategy must not consist in the isolated treatment of the cyst. This pathology should be addressed by an arthroscopic meniscectomy reaching the meniscosynovial junction at the level of the cyst. Meniscal repair must be proposed every time if possible. Criteria of reparability are better studied on MRI. Preoperatively MRI is the first choice radiological exam. Two essential indications can be held back: the vertical peripheral longitudinal lesion is on the non-vascularized area, and the horizontal cleaving of the junior athlete (if the cleaving remains purely intra meniscal). Meniscal repair is highly performed when the meniscal tear is associated to a rupture of the ACL (simultaneous reconstruction of the LCA). Postoperative outcome is different of that of a "simple" arthroscopic meniscectomy. The healing process being slow, it suits to protect the suture by a splint in the first month, and with an exclusion of sports with knee torsion during 6 months. Functional results (absence of secondary meniscectomy) and anatomical results (reality of the cicatrisation) are good in 77% of cases (symposium of the French Society of Arthroscopy 2003) at a follow-up of 55 months. Survivorship analysis indicates that majority of the failures occur within two years: this testifies a default of primary cicatrisation. At the studied follow-up, meniscal repair was efficient to protect the cartilage. Lateral meniscus results are better that medial meniscus one. Those data support indications: All suspicion of meniscal lesion must have an MRI preoperatively to confirm the lesion, to localize her and to search criteria of reparability; All vertical longitudinal peripheral lesions can and must be repaired especially in young patients and children; All horizontal cleaving of the junior athletes should be treated by open repair; surgical abstention must be proposed when the lesion is non symptomatic, or when lesion is limited and associated to an ACL tear (in that case isolated ACL reconstruction is proposed), or when clinical symptoms are minimal; Meniscectomy, always arthroscopic, is proposed for a symptomatic lesion in the avascular zone or for a deep horizontal cleavage or a complex tear; Tear of the discoid meniscus should be treated by meniscoplasty. A painful knee after lateral meniscectomy might be due to a too limited initial meniscectomy: an iterative meniscectomy may be indicated or lateral femorotibial arthritis, especially after subtotal or total meniscectomy. In this last case and after failure of usual medical treatment such as viscosupplementation surgery may be indicated. Osteotomy in order to unload the lateral femorotibial compartment gives a partial response as the shearing forces remain. This osteotomy is indicated only if the lower limb axis is normal or in valgus. Meniscal allograft is an option in young patients in grade I or II arthritis. Results are promising. Rene Verdonk's series show a survivorship analysis of 75% at 7 years. Early diagnosis of a postmeniscectomy syndrome before cartilaginous lesions occur is essential for an adapted treatment. In conclusion, lateral meniscectomy are less frequent than those of the medial meniscus but their prognosis is less favorable. They should be early diagnosed (MRI). Treatment options are various: abstention, meniscectomy, and repair. Painful post lateral meniscectomy syndrome may be treated by a new surgical option: meniscal allograft.

Cysts↗

Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero.

In hypertension, increased peripheral vascular resistance results from vascular dysfunction with or without structural changes (vessel wall remodeling and/or microvascular rarefaction). Humans with lower birth weight exhibit evidence of vascular dysfunction. The current studies were undertaken to investigate whether in utero programming of hypertension is associated with in vivo altered response and/or abnormal vascular structure. Offspring of Wistar dams fed a normal (CTRL) or low (LP)-protein diet during gestation were studied. Mean arterial blood pressure response to ANG II was significantly increased, and depressor response to sodium nitroprusside (SNP) infusions significantly decreased in male LP adult offspring relative to CTRL. No arterial remodeling was observed in male LP compared with CTRL offspring. Capillary and arteriolar density was significantly decreased in striated muscles from LP offspring at 7 and 28 days of life but was not different in late fetal life [day 21 of gestation (E21)]. Angiogenic potential of aortic rings from LP newborn (day of birth, P0) was significantly decreased. Striated muscle expressions (Western blots) of ANG II AT(1) receptor subtype, endothelial nitric oxide synthase, angiopoietin 1 and 2, Tie 2 receptor, vascular endothelial growth factor and receptor, and platelet-derived growth factor C at E21 and P7 were unaltered by antenatal diet exposure. In conclusion, blood pressure responses to ANG II and SNP are altered, and microvascular structural changes prevail in this model of fetal programming of hypertension. The capillary rarefaction is absent in the fetus and appears in the neonatal period, in association with decreased angiogenic potential. The study suggests that intrauterine protein restriction increases susceptibility to postnatal factors resulting in microvascular rarefaction, which could represent a primary event in the genesis of hypertension.

Animals↗

Antibiotic prophylaxis and third molar surgery.

The issue of prophylactic antibiotic therapy in third molar surgery is highly controversial. The current evidence questions the benefits of routine prophylactic antibiotic therapy which does not appear to overcome the risk of undesirable outcomes after third molar removal. In our opinion there is no justification for routine antibiotic prophylaxis for third molar surgery.

Antibiotic Prophylaxis↗

[Prospective study assessing quality-of-life after hemiarthroplasty for hip fracture].

PURPOSE OF THE STUDY: We conducted a prospective multicentric study of 203 consecutive patients who underwent hemi-arthroplasty for femoral neck fracture between May 1999 and August 2001. The purpose of the study was to assess quality-of-life among these patients one year after their surgery. MATERIAL AND METHODS: Mean patient age was 79.6 +/- 8.6 years; 71.2% were women. Most fractures were Garden type III and IV (87.4%) and 90.9% were recent (< 21 d). The hemiarthroplasty was performed with the Intermedia implant via a posterolateral approach in 73.9% of patients with acetabular reaming for 13.7%; a skirted head was used in only 20.8%. The Robinson score (19/26 < or = 6.89) for joint motion, lifestyle, degree of osteoporosis (Singh score), and history (ASA score), as well as a psychomotor indicator (Hodkinson score) were noted preoperatively. Quality-of-life was measured at one year in the same patients using the Postel Merle d'Aubigne (PMA) score and a quality-of-life score. RESULTS: Among the 203 patients, 38 (18.7%) were lost to follow-up and 37 died (18.2%). Eleven posterior dislocations (5.4%) were noted and four were reduced orthopedically. The PMA score was 84.7% satisfactory results (excellent, very good, good). Preoperatively 58.8% of the patients were independent and 7% were in nursing homes; one year postoperatively, these proportions were 54% and 4.8%. There was a significant difference in the PMA score between two populations defined by the preoperative Robinson score less than or greater than 20. Outcome was better for patients with a Robinson score > 20 pre-operatively. For these two populations, change in lifestyle was highly significant one year postoperatively. However, for the overall population, changes in lifestyle and joint motion were not significantly different between the pre- and postoperative evaluations. Paradoxically, 29.1% of the patients who were dependent preoperatively were not one year after surgery, which indicates that certain patients also had a better quality-of-life after their hemiarthroplasty. CONCLUSION: Mortality after fracture of the femoral neck remains high (18.2% at one year). There were no infections requiring revision in this series, but there were eleven cases of dislocation (5.4%). The difference in joint motion and quality-of-life between the pre- and postoperative assessment was not significant for the whole population, but one third of the patients who were independent preoperatively were not at last follow-up.

Aged↗

Team-based occupational stress reduction: a European overview from the perspective of the OSCAR Project.

Work-related stress is a significant impediment to job satisfaction and healthy psycho-social functioning. It can alter the behaviour of the person involved and impair the quality of their life. In the European Union (EU), over the last decade, work-related stress has been consistently identified as one of the major workplace concerns--a challenge not only to the health of working people but also to the healthiness of their organizations. The study reported below attempted to address the issue of work-related stress through whole team training programmes, on a background of largely ineffective stress reduction training programmes offered to individuals within the workplace. This EU 'framework 5 Quality of Life' project focused instead on tackling the organizational level through training of mental health teams in five countries. The findings have significant implications to the conceptual, methodological and everyday organizational practice levels of tackling this central issue to the health of the workplace.

Adult↗

Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: the INNOVO multicentre randomised controlled trial (ISRCTN 17821339).

BACKGROUND: Although inhaled nitric oxide (iNO) may be a promising treatment for newborn infants with severe respiratory failure, the results from 3 previous small trials were inconclusive. METHODS: Infants of <34 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomized to receive or not receive iNO. The study was not blinded. FINDINGS: Recruited were 108 infants (55 allocated to receive iNO and 53 not allocated to receive iNO) from 15 neonatal units in the United Kingdom and Republic of Ireland. Fifty-nine percent (64 of 108) died, and 84% of the survivors (37 of 44) had signs of some impairment or disability, 9 (20%) of them classified as severely disabled. There was no evidence of an effect of iNO on the primary outcomes: death or severe disability at 1 year corrected age (relative risk [RR]: 0.99; 95% confidence interval [CI]: 0.76 to 1.29); death or supplemental oxygen on expected date of delivery (RR: 0.84; 95% CI: 0.68 to 1.02); or death or supplemental oxygen at 36 weeks' postmenstrual age (RR: 0.98; 95% CI: 0.87 to 1.12). There was a trend for infants allocated to the iNO group to spend more time on the ventilator (log rank: 3.6), on supplemental oxygen (log rank: 1.4), and in hospital (log rank: 3.5) than those allocated to receive no iNO. This pattern predominantly reflected the infants who died. Mean total costs at 1 year corrected age were significantly higher in the iNO group, partly because of the costs of the gas but mainly because of the difference in initial hospitalization costs. INTERPRETATION: Evidence of prolongation of intensive care and increased costs of such care, without clear beneficial effects, implies that iNO cannot be recommended for preterm infants with severe hypoxic respiratory failure.

Administration, Inhalation↗

Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment.

OBJECTIVE: The objective of this study was to determine the effect of multiple impairments in drug elimination on the pharmacokinetics and pharmacodynamics (effect on QTc interval), using clarithromycin as a comparator. METHODS: Thirty-two subjects aged > or = 60 years with renal impairment who were otherwise medically stable were recruited into this parallel-group study. Following stratification according to creatinine clearance (CL(CR)), subjects were randomized to a five-day treatment with ketoconazole (400 mg once daily) alone, or a five-day treatment with ketoconazole (400 mg once daily) and telithromycin (800 mg once daily) given concomitantly or a five-day treatment with ketoconazole (400 mg once daily) and clarithromycin (500 mg twice daily) given concomitantly. Steady-state pharmacokinetics and safety, including serial electrocardiograms, were assessed. RESULTS: In subjects with CL(CR) 30 - 80 ml/min, the mean maximal telithromycin concentration at steady state (C(max),ss) was 3.6 mg/l and the steady state area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24 h) ss) was 33.4 mg x h/l. The mean C(max), ss and AUC(0-12 h)ss for clarithromycin were 6.2 mg/l and 56.1 mg x h/l, respectively. The increases in telithromycin C(max) ss and AUC(0-24 h) ss compared to corresponding data for healthy young subjects were 1.6- and 2.7-fold, respectively, whereas corresponding increases for clarithromycin were 2.2- and 3.3-fold, respectively. In the telithromycin plus ketoconazole group deltaQTc values were equal or < 60 ms. All QTc values were equal or < 450 ms in males and equal or < 470 ms in females. CONCLUSIONS: The increase in telithromycin plasma concentrations during ketoconazole-mediated inhibition of CYP3A4 in subjects aged 60 years or older with renal impairment was similar to that for clarithromycin under the same conditions. Telithromycin was well tolerated and produced no clinically significant prolongations in the QTc interval.

Aged↗

Drop foot after high tibial osteotomy: a prospective study of aetiological factors.

Drop foot is not uncommon after high tibial osteotomy for genu varum. The authors report their results of a prospective study of 16 patients operated on between May 1990 and May 1991. All patients had medial femoro-tibial osteoarthritis with a constitutional genu varum. They all had a subtraction valgus high tibial osteotomy fixed by a blade plate. The experimental protocol included clinical review, antero-lateral compartment pressure measurements, intra- and post-operative electromyography, assessment of the post-operative drainage, serum estimation of muscle enzymes and post-operative arteriography. From their own results and a literature review, the authors consider successively the different aetiological factors for post-operative drop foot. Certain deficits occur due to direct trauma on the nerve during high osteotomy of the fibula, by local high pressure due to poor haemostasis or ineffective drainage. In addition, there are several related phenomena. The pneumatic tourniquet sensitises the nerve to trauma, and stretching of the nerve during correction of the deformation depends on the local anatomical factors and their marked variation. In order to diminish the frequency of these post-operative complications, the authors suggest limiting the surgical approach, and limiting as far as possible the traumatic manoeuvres on the nerve by using a tibial resection jig, which allows correction without forced manoeuvres. Finally, the authors discuss the benefits of using a pneumatic tourniquet.

Action Potentials↗

Differences in enquiries to CancerBACUP information service by living arrangements.

The study's aim was to ascertain whether living alone is associated with the use of an independent cancer information service. An Enquirer Record Form is completed for every fifth enquirer to the service; two questions asking whether enquirers, patients, relatives/friends were living alone or with others where asked in association with the routine questions. A total of 552 callers were asked in a 5-week period, 77% of all callers in these categories. The main findings were: (1) the proportion of enquirers living alone was similar to the general population; (2) among enquirers, patients were more likely to live alone than relatives/friends; (3) requests differed by whether living alone and by type of enquirer, for example, significantly more people living with others requested emotional support than those living alone, and this contrast was most marked for patients than relatives/friends. This study, notwithstanding its limitations, highlights some of the differences in the use of a service and demonstrates the complexity of information and support seeking.

Family↗