Frequency and reporting of complications after Dupuytren's contracture interventions: A systematic review and meta-analysis.

INTRODUCTION: Numerous complications are reported following interventions for Dupuytren's contracture; however, their incidence, management, and outcomes remain poorly reported. The aims of this review were to report the proportions of complications, compare likelihood of complications between interventions, and evaluate reporting of complications, including assessment, grading, management, and subsequent reporting of their impact on patient outcomes. METHODS: Extracted data included patient demographics, intervention details, complications, their management, and final outcomes. Analysis of descriptive data enabled review of complications reporting. Meta-analysis(MA) of non-comparative datasets enabled estimation of proportions of patients experiencing complications. Network meta-analysis(NMA) of comparative studies estimated the relative occurrence of complications between interventions. Risk of bias analysis was performed. RESULTS: 26 studies, comprising 10,831 patients, were included. Interventions included collagenase injection, percutaneous needle fasciotomy(PNF), limited fasciectomy(LF), open fasciotomy(OF), and dermofasciectomy(DF). Overall quality and consistency of outcomes reporting was poor. MA enabled estimates of probabilities for three common complications(infection, nerve injury, complex regional pain syndrome(CRPS)) across all interventions; the reported rates for LF were 4.5% for infection, 3% for nerve injury, and 3.3% for CRPS. As the commonest intervention, LF was used as the reference intervention for comparison of the commonest complications via NMA, including haematoma [OF OR 0.450(0.277, 0.695); PNF OR 0.245(0.114, 0.457)], infection [PNF OR 0.2(0.0287, 0.690); DF OR 2.02(1.02, 3.74)], and neuropraxia [PNF OR 0.0926(0.00553, 0.737)]. We noted that the complication incidence was higher the more invasive the intervention. CONCLUSIONS: There was limited reporting of complication occurrence, management, and outcomes following interventions, contributing to a gap in information for informed patient consent. MA was possible for reporting of proportions for infection, nerve injury, and CRPS across interventions. NMA enabled direct comparison of the six commonest complications between interventions. These findings can guide intervention selection. Improving consistency and quality in complications reporting is essential to aid counselling of patients regarding the true rates and consequences of the risks of interventions. TYPE OF STUDY/LEVEL OF EVIDENCE: 2.

Proximal humerus fractures: A review of current practice.

The management of proximal humeral fractures (PHF) remains controversial. Its incidence is increasing. Patients should be meticulously assessed clinically for co-morbidities and neuro-vascular injuries. Radiological investigation helps provide information on the fracture configuration and dislocations. Enhanced by 3-dimensional CT scanning, these further help in decision making and operative planning. PHF classifications have been demonstrated to have poor intra-observer and inter-observer reliability. Research has identified some radiographic predictive factors for humeral head ischaemia and likely failure of surgical fixation. The range of management options include non-operative treatment, operative fixation, intramedullary nailing and arthroplasty (hemiarthroplasty, reverse shoulder replacement). The majority of PHFs are stable injuries and non-operative management is usually successful. Some degree of malunion is readily tolerated especially by elderly patients. Surgical management of significantly displaced, unstable proximal humerus fractures should aim to stabilise the fracture adequately and provide satisfactory function for the long term. Management of the greater tuberosity is pivotal for the eventual outcome. When fixation may appear to be compromised by poor bone quality, likely poor function, age related rotator cuff degeneration or likely humeral head ischaemia clinicians may opt for arthroplasty. Successful hemiarthroplasty outcomes are dependent on sufficient healing of the tuberosity and recovery of the rotator cuff integrity. Reverse shoulder replacement can predictably deliver good functional outcomes for the shoulder in elderly patients, where rotator cuff dysfunction is suspected or as a revision procedure following failure of other surgical interventions. As opposed to hemiarthroplasty, which has shown a downward trend, there has been an increasing trend towards the use of reverse shoulder replacement in proximal humeral fractures. The management of PHFs should be patient specific, fracture specific and meet the functional demands and needs of the individual patient. The surgeon's skill set and clinical experience also plays an important role in the options of management available.

Intriguing structural and magnetic properties correlation study on Fe3+-substituted calcium-copper-titanate.

This communication presents a detailed study on a Fe3+ modified CaCu3Ti4O12 cubic perovskite system (CaCu3-xTi4-xFe2xO12 with x = 0.0-0.7) by performing X-ray powder diffractometry, DC SQUID magnetization and 57Fe Mössbauer spectroscopy. The first ever Mössbauer studies on the system supported the reported peculiarity of the structure. Mössbauer analysis for the compositions x = 0.1, 0.3, and 0.5 suggest Fe3+ ions in two different environments. The site with larger quadrupole splitting corresponds to Fe3+ in the octahedral symmetry, while the site with lower chemical shift and quadrupole splitting belongs to Fe3+ in the square-planar (A'-) configuration. With the increase in Fe-substitution, Fe3+ appears to prefer A'- symmetry. Antiferromagnetic features are retained up to x = 0.3, but weak ferromagnetic characteristics appear with higher Fe3+ substitution. The switching of antiferromagnetic to ferromagnetic behavior was related to the preferential occupation of Fe3+ in square-planar symmetry accommodating Cu2+.

Comparison of Short vs Long Anti-rotation in Treating Trochanteric Fractures.

Introduction: A comparative evaluation of the surgical treatment and outcome of patients with pertrochanteric fractures treated with short versus long proximal femoral nail antirotation. Materials and methods: A retrospective review was conducted of patients with pertrochanteric fractures treated between January 2011 and June 2012. In all 80 patients were enrolled in the study, of which 40 were treated with short PFNA and the remaining with long PFNA. Comparative analyses of demographic data, peri-operative outcome and complications were carried out. Results: There was no significant difference noted in the two groups with regards to Arbeitsgemeinschaft fur Osteosynthesefragen (AO) fracture classification, time from injury to surgery, blood transfusion post surgery and hospital stay. The surgical duration for a short PFNA procedure was significantly less (58 minutes) when compared to that of a long PFNA (87 minutes). Similarly intra-operative blood loss was significantly higher in the long PFNA group as compared to the short PFNA. Conclusions: A relatively quicker surgical time of just under an hour , lesser blood loss and better learning curve with trainee surgeons make short PFNA a better implant choice in the treatment of pertrochanteric fractures.

A case report looking at ACE inhibitors as the cause of angioedema during dental treatment.

Angiotensin converting enzymes, also known as ACE inhibitors are regularly prescribed by doctors in the treatment of congestive heart failure and hypertension. In this case report, we will be looking at the delayed onset of angioedema as a result of ACE inhibitors that occurred during dental treatment. We will discuss other causes of angioedema and its management and aim to raise awareness among clinicians to include this in their differential diagnosis of swellings around the mouth, particularly as it can mimic the initial response or be a prelude to an anaphylactic shock.

Thyroid hormone modulates food intake and glycemia via ghrelin secretion in Zucker fatty rats.

Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones.

Novel oxazole containing phenylpropane derivatives as peroxisome proliferator activated receptor agonists with hypolipidemic activity.

alpha-Alkoxy arylpropanoic acids containing 2-phenyloxazole-4yl-alkyl moiety are found to be potent hypolipidemic agents. These compounds were potent activators of the peroxisome proliferator activated receptor gamma (PPARgamma), with moderate PPARalpha activity and known to cause adverse effects such as weight gain and edema, which are essentially attributed to PPARgamma activation. Although extensive work has been done on the phenylpropanoic acid class of compounds, other phenyl propane derivatives such as alcohols, amines, ethers etc. have not received much attention. In order to develop predominant PPARalpha agonists as hypolipidemic agents with minor chemical modifications on compound III, we have synthesised few (2S)-ethoxyphenylpropane derivatives containing a 2-phenyl-5-methyloxazole-4ylalkoxy moiety of the general formula IV and evaluated by PPARalpha and gamma transactivation assay in conjugation with in vivo studies in male Swiss albino mice model. Compounds 3c and 3d showed the desired predominant PPARalpha activity and excellent tryiglyceride reduction in vivo and were selected as lead compounds for further development as hypolipidemic agents.

A Validated HPTLC Method for Determination of Ondansetron in Combination with Omeprazole or Rabeprazole in Solid Dosage Form.

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed for the simultaneous estimation of ondansetron combinations in solid dosage form with omeprazole and rabeprazole, respectively. The method involved separation of components by TLC on a precoated silica gel 60 F(254) using a mixture of dichloromethane:methanol (9:1) as a mobile phase. Detection of spots was carried out at 309 nm and 294 nm for ondansetron with omeprazole and ondansetron with rabeprazole combinations, respectively. The mean retardation factor for ondansetron and omeprazole were found to be 0.42+/-0.02, 0.54+/-0.03, respectively while for ondansetron and rabeprazole, 0.41+/- 0.02 and 0.51+/-0.02, respectively. The linearity and range was 0.1 to 0.5 mug/spot for three drugs. The method was validated for precision, accuracy and reproducibility.

Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.

1. The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in the anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine following intraduodenal administration. 2. There were no effects on resting blood pressure, heart rate, carotid blood flow or carotid vascular resistance for any compound evaluated. 3. Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressure (< 10%) and no effect on heart rate. Intravenous infusion of tonabersat or carabersat (both 3.4 micromol h(-1)) produced time related reductions in stimulation-induced responses with a maximal inhibition (relative to control) of 30 +/- 7% (n=4), at 240 min for tonabersat and 33+/-4% (n=3) at 180 min for carabersat. Tonabersat (11.5 micromol h(-1)) produced a similar inhibitory effect (32 +/- 9%, n=4) after 120 min of infusion. 4. Following intraduodenal administration of tonabersat, the maximal inhibition of nerve stimulation-induced responses was 55 +/- 4% at 120 min (n=4) for tonabersat 10 mg kg(-1), and 24+/-2% after 180 min for 1 mg kg(-1) (n=4). 5. Intraduodenal administration of sodium valproate (10 or 100 mg kg(-1) n=4/group) had no effect on neurovascular reflexes. Maximal inhibition of nerve ganglion-stimulated reductions in carotid vascular resistance were observed at 150 min for lamotrigine (50 mg kg(-1), 52+/-12%, n=4) and gabapentin (100 mg kg(-1), 17+/-13%, n=3). Lamotrigine 10 mg kg(-1) produced 22+/-11% (n=3) inhibition after 180 min. 6. These data demonstrate blockade of trigeminal parasympathetic reflexes with tonabersat, carabersat and other anticonvulsants. These agents may therefore have therapeutic benefit in conditions where this type of reflex is evident.

Inhibition of inflammation-induced thermal hypersensitivity by sumatriptan through activation of 5-HT(1B/1D) receptors.

Migraine is effectively treated by drugs acting via 5-HT(1B/1D) receptors; however, the antinociceptive effects of such agents have not been fully investigated, particularly in models in which sensitization may be present. The aim of these studies was to evaluate the effects of the 5-HT(1B/1D) receptor agonist sumatriptan in specific models of pain states: a mouse model of inflammation-induced thermal hyperalgesia and a rat model of nerve injury-induced thermal hyperalgesia. In female mice, following intraplantar injection of carrageenan 225 min earlier, sumatriptan (300 microg/kg intraperitoneally; i.p.) increased paw withdrawal latency (PWL) from 3.1 +/- 0.4 s in the saline group to 5.6 +/- 0.9 s, measured 240 min postcarrageenan (P < 0.05 ANOVA followed by post hoc Dunnett's test). A similar effect was seen in male mice. Sumatriptan was also effective in male mice when given i.p. and subcutaneously 15 min precarrageenan, with a maximum effect at 30 microg/kg (i.p. latency 7.4 +/- 1.3 s compared to saline group, 2.6 +/- 0.7 s; i.v. latency 5.9 +/- 0.8 s compared to saline group, 2.9 +/- 0.3 s; P < 0.05 ANOVA followed by post hoc Dunnett's test). The number of mice required to give a response that could be reliably attributed to sumatriptan (number needed to treat) was calculated using discriminant analysis and found to be 2.6. The ability of sumatriptan to attenuate the carrageenan-induced reduction in PWL was blocked by the mixed 5-HT(1B/1D) receptor antagonist GR-127935 (3 mg/kg i.p.) but not by the 5-HT(1B) receptor antagonist SB-224289 (10 mg/kg i.p.). Sumatriptan had no effect on thermal hyperalgesia induced by sciatic nerve ligation in the rat at any time point. These data demonstrate that sumatriptan attenuates the hypersensitivity to noxious thermal stimuli induced by intraplantar carrageenan.

Carrageenan-induced thermal hyperalgesia in the mouse: role of nerve growth factor and the mitogen-activated protein kinase pathway.

NGF is an important link between inflammation and hyperalgesia and interacts with many different mediators of inflammation, including the MAPK signaling pathway. In these studies, carrageenan-induced thermal hyperalgesia was evaluated in the mouse and the role of NGF and the MAPK pathway investigated. Carrageenan induced a time-dependent inflammation and thermal hyperalgesia, which was maximal 4 h post administration. Both indomethacin (0.3, 1.0 and 10 mg/kg s.c., 30 min pre-carrageenan) and morphine (0.4, 1.2, 4.0 mg/kg; s.c., 30 min pre-hyperalgesia measurement) significantly inhibited carrageenan-induced thermal hyperalgesia and indomethicin inhibited paw inflammation, demonstrating the model as suitable for the assessment of anti-hyperalgesic and anti-inflammatory agents. Anti-NGF (0.67 mg/kg sc, 60 min pre-carrageenan) produced a significant inhibition of thermal hyperalgesia, but not inflammation. NGF itself produced a time-dependent hyperalgesia, but not inflammation, following intraplantar injection. The specific MAPK pathway inhibitor, PD98059 (0.1, 0.3 and 1 mg/kg sc, 30 min pre-carrageenan) significantly inhibited carrageenan-induced hyperalgesia, but not inflammation. These data demonstrate a role for both NGF and the MAPK signaling pathway in the production of thermal hyperalgesia, but not inflammation, in the mouse.

Identification of differentially expressed genes in dorsal root ganglia following partial sciatic nerve injury.

Partial sciatic nerve injury, a model of neuropathic pain, elicits a variety of neurochemical, electrophysiological and neuroanatomical changes in primary sensory neurons. We have used the technique of messenger RNA differential display to identify genes with altered expression in these neurons which may contribute to the development of aberrant sensation following such peripheral nerve damage. This approach identified 14 distinct complementary DNA clones, representing transcripts with increased ipsilateral expression in L4/5 dorsal root ganglia, two weeks after unilateral partial ligation of the rat sciatic nerve. Both Zucker diabetic fatty rats and their lean counterparts were used in this study but none of the transcripts identified showed an induction that was confined to one of the two groups. The majority of the clones did not show significant sequence similarity to previously reported genes and therefore may represent novel messenger RNA sequences or, alternatively, unknown regions of partially characterised messenger RNAs. Two of the clones represented transcripts for the known proteins muscle LIM protein and acidic epididymal glycoprotein, neither of which had previously been associated with expression in the nervous system. Reverse transcriptase-polymerase chain reaction analysis and in situ hybridization confirmed that the messenger RNA expression of both muscle LIM protein and acidic epididymal glycoprotein was induced in an ipsilateral-specific manner. Their localisations, examined with in situ hybridization in L5 dorsal root ganglia, were limited in each case to a sub-population of neuronal profiles. Those neuronal profiles that demonstrated muscle LIM protein hybridization were distributed across the profile size range, whereas the distribution of acidic epididymal glycoprotein-positive profiles appeared to be skewed towards smaller profiles. The induction of muscle LIM protein and acidic epididymal glycoprotein in dorsal root ganglia may play an important functional role in the adaptive response of primary sensory neurons following partial sciatic nerve injury.

Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation.

1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases in carotid blood flow, reductions in carotid vascular resistance and non-frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (max. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3) and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.

Effects of the novel antimigraine agent, frovatriptan, on coronary and cardiac function in dogs.

The effects of frovatriptan (VML 251/SB-209509) on coronary artery function were investigated in isolated coronary arteries from beagle dogs. Low concentrations of frovatriptan produced contraction with -logEC50 7.55 +/- 0.08 (n = 11). The maximal observed contraction attained was 56 +/- 7% of the control 5-hydroxytryptamine (5-HT; 10 microM) response. At high concentrations of frovatriptan (>6 microM), reversal of sumatriptan (10 microM)-induced contractions was noted. In arteries precontracted with the thromboxane mimetic, U46619, frovatriptan produced a bell-shaped concentration-response relation with a maximal response at 600 nM. Concentrations of frovatriptan >2 microM produced marked reversal of tone, with full relaxation of precontracted tissues at 200 microM. In anesthetized, open-chest mongrel dogs, intravenous (n = 5) or intracoronary (n = 5) artery administration of frovatriptan (0.0001-1 mg/kg) had no consistent effect on left ventricular end-diastolic pressure, left end-systolic pressure, cardiac contractility, aortic blood flow, systemic peripheral resistance, coronary blood flow, coronary vascular resistance, mean arterial blood pressure, or heart rate when compared with vehicle (n = 3). Intravenous sumatriptan produced minor effects on blood pressure and heart rate. Intracoronary artery administration of sumatriptan (0.0003 mg/kg) produced an increase in systemic peripheral resistance to 120.5 +/- 8.2% compared with vehicle (97.8 +/- 5.4%; p < 0.05). This dose of sumatriptan also produced a significant increase in coronary blood flow and decrease in coronary vascular resistance. Intravenous administration of sumatriptan produced a dose-related reduction in left ventricular diastolic pressure with a reduction to 58.3 +/- 8.3% and 41.7 +/- 25% of control values observed at 0.3 and 1 mg/kg, respectively; however, administration of sumatriptan by an intracoronary route had no effect. In a model of myocardial infarction, comparable doses of sumatriptan (1.0 mg/kg) or frovatriptan (0.1 mg/kg), in terms of their effect on carotid vascular resistance, had no significant effect on infarct size. Frovatriptan had no effect on coronary blood flow after reperfusion; however, sumatriptan produced a significant reduction in coronary blood flow for < or =3 h. These studies show that frovatriptan has the capability of relaxing coronary arteries in vitro, has no overall effect on cardiac function at rest with no effect on coronary hemodynamics after myocardial infarction, and has a profile superior to that of sumatriptan.

Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries.

The contractile actions of the novel high-affinity 5-hydroxytryptamine (5-HT(1B/1D)) ligand, frovatriptan (formerly VML 251/SB-209509) were investigated in human isolated basilar and coronary arteries in which the endothelium had been removed. Basilar arteries were obtained post mortem, and coronary arteries were obtained from patients undergoing heart transplant (recipient) or from donor hearts that were not suitable for transplant. Frovatriptan was a potent contractile agent in isolated basilar artery with a -log mean effective concentration (EC50) value of 7.86 +/- 0.07 and intrinsic activity of 1.25 +/- 0.10 relative to 5-HT (n = 4). Frovatriptan was 8.5-fold more potent than sumatriptan, which produced a -log EC50 value of 6.93 +/- 0.09 and intrinsic activity 11.1 +/- 0.08 relative to 5-HT (n = 4). In coronary arteries, frovatriptan produced contraction with -log EC50 values of 7.38 +/- 0.12 and 7.81 +/- 0.2 in recipient (n = 7) and donor (n = 3) arteries, respectively. The relative degree of contraction of frovatriptan was lower than that of 5-HT, with relative intrinsic activities of 0.42 +/- 0.06 and 0.40 +/- 0.09, respectively. Sumatriptan produced contraction of human recipient and donor arteries with -log EC50 values (intrinsic activity) of 6.57 +/- 0.13 (0.79 +/- 0.27; n = 6) and 7.35 (1.41; n = 2), respectively. Furthermore, marked bell-shaped responses were apparent for frovatriptan in coronary arteries, with relaxation occurring at concentrations >6 microM in some tissues. In contrast, no bell-shaped concentration-response curves were apparent for sumatriptan or 5-HT. Threshold concentrations for frovatriptan-induced contractions were also different between basilar (>2 nM) and coronary arteries (>20 nM). No separation of threshold activity was observed with sumatriptan or 5-HT. These data show that frovatriptan produces constriction of human isolated basilar and coronary arteries. However, frovatriptan produces a complex pharmacologic response in the coronary artery, with threshold contractile activity requiring approximately 10-fold greater concentrations of agonist than in the basilar artery. Frovatriptan also shows a differential pharmacologic profile compared with sumatriptan in coronary arteries, with reversal of tone predominating at high concentration.