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1.  Noise from total hip replacements 
Bone & Joint Research  2014;3(6):183-186.
Our study aimed to examine not only the incidence but also the impact of noise from two types of total hip replacement articulations: ceramic-on-ceramic and ceramic-on-polyethylene.
We performed a case-controlled study comparing subjective and objective questionnaire scores of patients receiving a ceramic-on-ceramic or a ceramic-on-polyethylene total hip replacement by a single surgeon.
There was a threefold higher incidence of noise from patients in the ceramic-on-ceramic group compared with the control group. The impact of this noise was significant for patients both subjectively and objectively.
This study reports a high patient impact of noise from ceramic-on-ceramic total hip replacements. This has led to a change in practice by the principal author.
Cite this article: Bone Joint Res 2014;3:183–6.
PMCID: PMC4054012  PMID: 24920252
Noise; Total hip replacement; Ceramic
2.  Mobile- versus fixed-bearing modern total knee replacements – which is the more patella-friendly design? 
Bone & Joint Research  2013;2(7):129-131.
Our study aimed to examine if a mobile-bearing total knee replacement (TKR) offered an advantage over fixed-bearing designs with respect to rates of secondary resurfacing of the patella in knees in which it was initially left unresurfaced.
We examined the 11-year report of the New Zealand Joint Registry and identified all primary TKR designs that had been implanted in > 500 knees without primary resurfacing of the patella. We examined how many of these were mobile-bearing, fixed-bearing cruciate-retaining and fixed-bearing posterior-stabilised designs. We assessed the rates of secondary resurfacing of the patella for each group and constructed Kaplan-Meier survival curves.
Our study showed a significantly higher rate of revision for secondary resurfacing of the patella in the fixed-bearing posterior-stabilised TKR designs compared with either fixed-bearing cruciate-retaining or mobile-bearing designs (p = 0.001 and p = 0.036, respectively).
This New Zealand Registry study shows that during the last 11 years, revision procedures to resurface an unresurfaced patella in primary TKR occurred at a higher rate in fixed-bearing posterior-stabilised designs.
PMCID: PMC3728649  PMID: 23836478
Total knee replacement; Patellar resurfacing; Knee revision; Patella pain; Anterior knee pain; 
3.  Should a Patients BMI Status be Used to Restrict Access to Total Hip and Knee Arthroplasty? Functional Outcomes of Arthroplasty Relative to BMI - Single Centre Retrospective Review 
We reviewed the experience of a dedicated orthopaedic elective service to determine whether we could establish a BMI group where arthroplasty was no longer effective as assessed by the patient’s functional outcome. This was a prospective observational study with retrospective analysis of data collected on 1439 total hip arthroplasty, 934 total knee arthroplasty and 326 unicompartment knee arthroplasty patients. Functional scores (WOMAC, Oxford hip and knee scores and HAAS) were obtained preoperatively and at 12 months post op. Patients had their BMI recorded at the preoperative assessment and were divided into BMI groups (BMI<25, BMI 25-30, BMI 30-35 and BMI > 35).
Patients with a BMI of ≤ 30 had significantly better functional scores at 12 months post op compared to those with a BMI of > 35. The absolute gain in functional scores from pre op to 12 months post op did not differ significantly between BMI groups, the only significant difference we found for absolute gain showed patients with a BMI of > 35 have a greater increase in HAAS scores following total hip arthroplasty compared to patients with a BMI of 30 or less (p = 0.0435).
Our patients with higher BMI’s had worse preoperative and post operative functional scores but their benefit from surgery measured by the change in functional scores showed no difference compared to patients with lower BMI. We could find no reason on the basis of the 12-month results to limit surgery to obese patients because of an expected poorer functional outcome.
PMCID: PMC3805982  PMID: 24155808
Arthroplasty; BMI; Functional scores; Oxford scores; WOMAC scores; HAAS scores.
4.  MSNA during prolonged post-faint hypotension 
Clinical Autonomic Research  2012;22(4):167-173.
Following tilt-induced syncope, blood pressure usually recovers rapidly after tilt back to the horizontal position. However, in some patients, hemodynamic recovery is delayed, a condition recently termed “prolonged post-faint hypotension” (PPFH). The mechanism is thought to be mediated by increased vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have been reported in this condition, so we aimed to confirm that neither vasodilatation nor MSNA withdrawal was responsible.
To retrospectively select patients with satisfactory recordings of continuous BP and MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in patients with PPFH to patients with normal recovery (NR) after tilt-back.
All patients were studied in Christchurch, New Zealand, between 1998 and 2008 using continuous arterial BP monitoring, and microneurographic recordings of MSNA from the right leg. Only patients with satisfactory BP and MSNA data throughout baseline, head-up tilt and presyncope were selected. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived using Modelflow. After baseline measurements, patients were tilted to the head-up 60° position and given GTN spray if asymptomatic after 20 min. Following the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH was defined as systolic BP <85 mmHg for at least 2 min after tilt-back. Measurements were averaged at baseline, early tilt, presyncope, early and late recovery. Within-group comparisons were made between baseline and all other time points. Between-group comparisons were made over all time points.
Patients with PPFH (7 males, age 46 ± 5 years, n = 8) and with NR (8 males, age 47 ± 6 years, n = 8) were selected. Presyncope was provoked by GTN in 4/8 patients in each group. In both groups, MAP remained below baseline during early and late recovery: PPFH 84 ± 5 versus 51 ± 5 and 64 ± 5 mmHg (p = 0.001, p = 0.001); NR 104 ± 5 versus 83 ± 5 and 93 ± 5 mmHg (p = 0.001, p = 0.03). However, MAP and HR were lower in the PPFH group (p = 0.004, p = 0.023). During early recovery, CO remained below baseline only in the PPFH group (p = 0.001), whereas TPR remained constant in both groups. In both groups, all MSNA indices tended to remain above baseline levels during early and late recovery. PPFH 25 ± 2 increased to 31 ± 6 and 29 ± 4 bursts/min (p = 0.09, 0.02); NR 23 ± 3 increased to 33 ± 3 and 34 ± 3 bursts/min (p = 0.06, 0.01).
PPFH does not appear to be mediated by exaggerated vasodilatation or sympathetic withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a more likely mechanism.
PMCID: PMC3412950  PMID: 22415156
Prolonged post faint hypotension (PPFH); Muscle sympathetic nerve activity (MSNA); Total peripheral resistance (TPR); Cardiac output (CO); Sympathetic withdrawal; Vagal outflow
5.  Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial 
Acetaminophen is often used with a non-steriodal anti-inflammatory drug for acute pain. Hitherto, these drugs have had to be given separately, typically at different time intervals. Maxigesic® tablets combine acetaminophen and ibuprofen in clinically appropriate doses to simplify administration and dosage regimen. We compared this combination with each of the constituent drugs for the relief of pain after extraction of third molar teeth.
Adults (more than 16 yr) having one or more wisdom teeth removed under general or local anaesthesia were instructed to take two tablets before operation, then two tablets every 6 h for up to 48 h of: (i) a combination of acetaminophen 500 mg and ibuprofen 150 mg per tablet (Maxigesic®); (ii) acetaminophen 500 mg per tablet alone; or (iii) ibuprofen 150 mg per tablet alone. The primary outcome measure was the area under the curve (AUC) of the 100 mm visual analogue scale pain measurements taken for up to 48 h after surgery, divided by time, at rest and on activity. Pharmacokinetic data were collected in a subset of patients.
The mean (sem) time-corrected AUC on rest and activity, respectively, were: combination group 22.3 (3.2) and 28.4 (3.4); acetaminophen group 33.0 (3.1) and 40.4 (3.3); and ibuprofen group 34.8 (3.2) and 40.2 (3.4); P<0.01 for each of the four comparisons of combination vs constituent drug. There was no pharmacokinetic interaction between acetaminophen and ibuprofen administered together.
Maxigesic® tablets provide superior pain relief after oral surgery to acetaminophen or ibuprofen alone.
PMCID: PMC2791549  PMID: 20007794
anaesthesia, dental; analgesia, postoperative; analgesics non-opioid, acetaminophen; analgesics non-opioid, ibuprofen; non-steroidal anti-inflammatory drugs
6.  Short‐term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non‐ischaemic heart failure 
Heart  2006;92(11):1603-1609.
To investigate the effect of short‐term statin treatment on impaired endothelium‐dependent vasodilatation and haemodynamic abnormalities typically occurring in chronic heart failure (CHF).
In a double‐blind, crossover study endothelium‐dependent vasodilatation was measured in conduit and resistance vessels of 23 patients with non‐ischaemic CHF after 6 weeks of placebo and 40 mg atorvastatin. The haemodynamic impact was assessed by cardioendocrine hormones, echocardiography and clinical indicators of CHF.
Cholesterol concentrations were population average (low density lipoprotein 3.56 (SEM 0.16) mmol/l, triglycerides 1.70 (0.20) mmol/l and high density lipoprotein 1.17 (0.07) mmol/l). In resistance vessels, the area under the curve ratio during acetylcholine infusion increased from 9.2 (1.9) with placebo to 12.2 (2.1) with statin (p < 0.01). This improvement was reversed during co‐infusion with the nitric oxide antagonist NG‐monomethyl‐l‐arginine. In conduit arteries, flow‐mediated dilatation increased from 5.64 (SEM 0.88)% with placebo to 6.83 (0.97)% with statin (p < 0.05). Endothelium‐independent vasodilatation did not change (p  =  0.68 for conduit and p  =  0.45 for resistance vessels). Endothelin 1 and atrial natriuretic peptide (ANP) decreased from 1.57 (0.08) and 51.3 (1.0) with placebo to 1.42 (0.09) pg/ml (p < 0.05) and 42.1 (7.5) pmol/l (p < 0.05), respectively, with statin.
In patients with non‐ischaemic CHF and population‐average cholesterol concentrations, short‐term statin treatment improves endothelial function in conduit and resistance vessels and lowers plasma endothelin 1 and ANP concentrations.
PMCID: PMC1861248  PMID: 16709697
7.  Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1α) and the HIF-1α target gene DEC1, but not lymph node metastasis in primary human breast carcinomas 
Journal of Clinical Pathology  2004;57(8):829-834.
Background: Vascular endothelial growth factor D (VEGF-D) induces angiogenesis and lymphangiogenesis. Nodal metastasis is recognised as a powerful prognostic marker in breast carcinoma, but the molecular mechanisms underlying this process are unknown. Although it has been suggested that VEGF-D may regulate nodal metastasis, this is based largely on animal models, its role in human disease being unclear.
Aims: To measure the pattern and degree of VEGF-D protein expression in normal and neoplastic human breast tissues.
Methods: The pattern and degree of VEGF-D expression was measured in normal tissue and invasive carcinomas, and expression was correlated with clinicopathological parameters, hypoxia markers, and survival. Because other VEGF family members are affected by oestrogen, whether VEGF-D is regulated by oestrogen in breast cancer cell lines was also assessed.
Results: VEGF-D was significantly positively associated with hypoxia inducible factor (HIF-1α) (p = 0.03) and the HIF-1α regulated gene DEC1 (p = 0.001), but not lymph node status, the number of involved lymph nodes, patient age, tumour size, tumour grade, lymphovascular invasion, oestrogen receptor, progesterone receptor, c-erb-B2, or tumour histology (all p>0.05). There was no significant relation between tumour VEGF-D expression and relapse free (p = 0.78) or overall (p = 0.94) survival. VEGF-D expression was enhanced by oestrogen in MCF-7 and T47D breast cancer cells, and was blocked by hydroxytamoxifen.
Conclusion: These findings support a role for hypoxia and oestrogen induced VEGF-D in human breast cancer and also suggest that tamoxifen and related oestrogen antagonists may exert some of their antitumour effects through the abrogation of VEGF-D induced function.
PMCID: PMC1770393  PMID: 15280403
metastasis; hypoxia; lymphangiogenesis; angiogenesis; vascular endothelial growth factor D
8.  Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction 
Heart  1999;81(2):114-120.
Objective—To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction.
Design—Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1-4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3-5 months after infarction. Clinical events were recorded over a mean period of 14 months.
Results—Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = −0.60, n = 220, p < 0.001; and r = −0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death.
Conclusions—Plasma BNP measured within 1-4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

 Keywords: cardiac natriuretic peptides; noradrenaline; myocardial infarction; heart failure
PMCID: PMC1728940  PMID: 9922344
9.  The significance of haemochromatosis gene mutations in the general population: implications for screening 
Gut  1998;43(6):830-836.
Background—Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. 
Aims—To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. 
Methods—Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. 
Results—Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. 
Conclusions—HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis. 

Keywords: haemochromatosis; iron overload; HFE gene; screening
PMCID: PMC1727339  PMID: 9824612
10.  Community acquired pneumonia: aetiology and usefulness of severity criteria on admission. 
Thorax  1996;51(10):1010-1016.
BACKGROUND: Community acquired pneumonia remains an important cause of hospital admission and carries an appreciable mortality. Criteria for the assessment of severity during admission have been developed by the British Thoracic Society (BTS). A study was performed to determine the sensitivity and specificity of a severity rule based on a modification of the BTS prognostic rules applied on admission, to compare severity as assessed by medical staff with the modified rule, and to determine the microbiological cause of community acquired pneumonia in Christchurch. METHODS: A 12 month study of all adults admitted to Christchurch Hospital with community acquired pneumonia was undertaken. Three hundred and sixteen consecutive patients with suspected community acquired pneumonia were screened for inclusion. Variables obtained from the history, examination, investigations, and initial treatment were examined for association with mortality. RESULTS: Two hundred and fifty five patients met the inclusion criteria. Their mean age was 58 years (range 18-97). A microbiological diagnosis was made in 181 cases (71%), Streptococcus pneumonia (39%), Mycoplasma pneumoniae (16%), Legionella species (11%), and Haemophilus influenzae (11%) being the most commonly identified organisms. Patients had a 36-fold increased risk of death if any two of the following were present on admission: respiratory rate > or = 30/min, diastolic BP < or = 60 mm Hg, urea > 7 mmol/l, or confusion. The severity rule identified 19 of the 20 patients who died and six of eight patients admitted to the intensive care unit as having life threatening community acquired pneumonia. The sensitivity of the modified rule for predicting death was 0.95 and the specificity 0.71. In 47 cases (21%) the clinical team appeared to underestimate the severity of the illness. CONCLUSIONS: The organisms responsible for community acquired pneumonia in Christchurch are similar to those reported from other centres except for Legionella species which were more common than in most studies. The modification of the BTS prognostic rules applied as a severity indicator at admission performed well and could be incorporated into management guidelines.
PMCID: PMC472650  PMID: 8977602
11.  Effect on lipoprotein profile of replacing butter with margarine in a low fat diet: randomised crossover study with hypercholesterolaemic subjects. 
BMJ : British Medical Journal  1996;312(7036):931-934.
OBJECTIVE--To examine the effect on lipid and lipoprotein concentrations when butter or an unsaturated margarine is used for cooking or spreading in a reduced fat diet. DESIGN--Randomised crossover study with two intervention periods of six weeks' duration separated by a five week washout. SETTING--Community setting in New Zealand. SUBJECTS--49 volunteers with polygenic hypercholesterolaemia and baseline total cholesterol concentration in the range 5.5-7.9 mmol/l. MAIN OUTCOME MEASURES--Concentrations of total and low density lipoprotein, Lp(a) lipoprotein, high density lipoprotein, apolipoprotein B 100, and apolipoprotein A I. RESULTS--Concentrations of low density lipoprotein cholesterol and apolipoprotein B were about 10% lower with margarine than with butter. Lp(a) lipoprotein and high density lipoprotein cholesterol concentrations were similar with the two diets. CONCLUSION--Despite concerns about adverse effects on lipoproteins of trans fatty acids in margarines, the use of unsaturated margarine rather than butter by hypercholesterolaemic people is associated with a lipoprotein profile that would be expected to reduce cardiovascular risk.
PMCID: PMC2350773  PMID: 8616303
12.  Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline. 
Nine healthy male volunteers were studied to assess the interaction between theophylline and ciprofloxacin and to assess whether a similar interaction occurred with lomefloxacin, using a randomised, crossover design. Subjects received theophylline 125 mg 8 hourly with and without lomefloxacin 400 mg 12 hourly or ciprofloxacin 500 mg 12 hourly for 7 days. Ciprofloxacin treatment lowered total theophylline clearance by 27%, owing to a decreased clearance via 1-, 3-demethylation and 8-hydroxylation. Lomefloxacin treatment did not alter theophylline clearance. Ciprofloxacin, at usual clinical doses, could cause a clinically significant interaction when co-administered with theophylline.
PMCID: PMC1380121  PMID: 2328197

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