Objective: Screening for diabetic peripheral neuropathy (DPN) is essential for early detection and timely intervention. Quantitative assessment of small nerve fiber damage is key to the early diagnosis and assessment of its progression. Corneal confocal microscopy (CCM) is a non-invasive, in-vivo diagnostic technique that provides an accurate surrogate biomarker for small-fiber neuropathy. In this novel study for the first time, we introduced CCM to primary care as a screening tool for DPN alongside retinopathy screening to assess the level of neuropathy in this novel cohort. Research design and methods: 450 consecutive subjects with type 1 or type 2 diabetes attending for annual eye screening in primary care optometry settings underwent assessment with CCM to establish the prevalence of sub-clinical diabetic peripheral neuropathy. Subjects underwent assessment for neurological and ocular symptoms of diabetes and a history of diabetic foot disease, neuropathy and diabetic retinopathy (DR). Results: CCM examination was completed successfully in 427 (94.9%) subjects, 22% of whom had neuropathy according to Diabetic Neuropathy Symptom (DNS) score. The prevalence of sub-clinical neuropathy as defined by abnormal corneal nerve fiber length (CNFL) was 12.9%. In the subjects with a short duration of type 2 diabetes, 9.2% had abnormal CNFL. CCM showed significant abnormalities in corneal nerve parameters in this cohort of subjects with reduction of corneal nerve fiber density (CNFD, p

Objectives: Neck roots lesions are among the etiologies of cervical and arm pain. A detailed patient evaluation could assist the diagnosis, reduce imaging requests, and promote the treatment of cervical pain. We tried to estimate the value of pronator teres reflex in C6 and C7 roots irritation. Methods: the present study comprises 118 participants, including 56 patients with C6 and C7 lesions and 62 normal controls. The reliability and usefulness of this reflex in C6 and C7 roots lesions were compared to positive electromyography and imaging with magnetic resonance. Results: the sensitivity, specificity, positive predictive value, and negative predictive value for pronator teres reflex were 36.4%, 13.6%, 64.8%, and 4.6%, respectively. Discussion: This reflex can be considered an additional reflex during the physical examination for C6 and C7 nerve roots injury, but its diagnostic value for C6 and C7 radiculopathy is unreliable to be used for screening purposes

Objective Recently, ozone injection has been used to treat various musculoskeletal diseases. This study was performed to compare ultrasound-guided corticosteroid versus ozone injections in the treatment of carpal tunnel syndrome. Design Forty patients with mild to moderate carpal tunnel syndrome were enrolled and randomly placed in one of the two groups of receiving a corticosteroid or ozone injection under ultrasound guidance. To determine the effectiveness of both injection techniques and compare their outcomes, visual analog scale and scores of Boston Carpal Tunnel Questionnaire, as well as ultrasound and electrodiagnostic criteria, were followed at 0, 6, and 12 wks after the injection. Results Both groups showed improvement in visual analog scale and Boston Carpal Tunnel Questionnaire at week 6, and this improvement continued until the 12th week after the injections. However, electrodiagnostic values of sensory nerve action potentials and compound motor action potentials latency, and ultrasound carpal tunnel syndrome criteria showed significant improvement only among the subjects in the corticosteroid group at 6 and 12 wks after the injection (P < 0.05). Conclusions Ozone might be as effective as corticosteroid injection in reducing pain and improving the function. Objective improvements in electrodiagnostic and ultrasound criteria of carpal tunnel syndrome were shown only among patients after corticosteroid injection.

Introduction: Ozone has been recently used as a safe alternative treatment in musculoskeletal disorders with fewer adverse effects than corticosteroids. The aim of this study was to compare the efficacy of a single injection of ozone with that of a corticosteroid in the treatment of shoulder impingement. Design: Thirty patients with shoulder pain and clinical signs and symptoms of impingement were randomly assigned into two groups: ultrasound-guided injection with ozone or corticosteroid. Patients’ symptoms were evaluated by visual analog scale, constant score, shoulder pain and disability scale, shoulder range of motion, and ultrasonographic measures before treatment, 2 wks, and 2 mos after injections. Results: Patients’ visual analog scale, shoulder pain and disability scale and constant score improved significantly in both groups (P < 0.001), but the benefits were in favor of corticosteroid group (P < 0.001). At intervals between the two follow-ups, an improvement was observed in the visual analog scale score among patients receiving ozone, whereas during the same interval, patients’ pain slightly worsened in the corticosteroid group. The range of motion and ultrasonographic measures did not show statistical differences between the two groups. Conclusions: Corticosteroid injection improves the pain and disability scores more significantly than a one-time ozone injection. Ozone may serve as an alternative modality in treating shoulder impingement when the use of steroids is contraindicated.

Objective. Plantar fasciitis (PF) is one of the most common causes of heel pain. The affected area is often close to the attachment of plantar fascia to calcaneus bone. The purpose of this study was to compare the effects of ozone (O2-O3) injection to corticosteroid injection under ultrasound guidance for the treatment of chronic PF. Design. Randomized clinical trial. Setting. Academic University and Neuromusculoskeletal Research Center. Subjects. Thirty patients with chronic PF. Methods. The patients were randomly divided into two groups receiving methylpredniso-lone (15 subjects) vs ozone (O2-O3; 15 subjects). The following outcome measures were assessed before injection and then two weeks and 12 weeks after the injection in each group; morning and daily pain via visual analog scale, daily life and exercise activities via the Foot and Ankle Ability Measure, and plantar fascia thickness at insertion and 1 cm distal to its insertion into the calcaneus via ultrasound imaging. Results. Intragroup changes showed significant improvement in pain, functional parameters, and sonographic findings in both groups (P < 0.05). Pain reduction (both daily and morning) and daily activity improvement were better in the corticosteroid group two weeks after injection; however, at 12 weeks, the ozone (O2-O3) group had significantly more improvement (P ¼ 0.003, P ¼ 0.001, and P ¼ 0.017, respectively). Conclusions. Both methods were effective in the treatment of chronic PF. Steroid injection provided a more rapid and short-term therapeutic effect. However, ozone (O2-O3) injection led to a slow and longer-lasting treatment outcome. Ozone (O2-O3) injection can be an effective treatment, with slow onset and a longer durability in the treatment of chronic PF.

Objective in this study, the clinical effectiveness of ultrasound-guided corticosteroid injection "above" versus "below" the median nerve for treatment of patients with mild to moderate carpal tunnel syndrome was compared. Design This prospective randomized double-blind clinical trial included 44 patients with mild to moderate carpal tunnel syndrome. The subjects were randomly assigned to two groups to receive ultrasound-guided injection of 40 mg of triamcinolone either "above" or "below" the involved median nerve. Outcome measures were the Boston Carpal Tunnel Questionnaire, visual analog scale, electrophysiological tests, and ultrasonographic measurement of the median nerve cross-sectional area at baseline, 6, and 12 wks after the injection. Results all outcome measures improved significantly in both groups at 6 wks after intervention, and these improvements were persevered up to 12 wks of follow-up (all P values

BACKGROUND: Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans. METHODS: in a cross-sectional, population-based study, age- and sex-matched South Asians (n = 77) and Europeans (n = 78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage. RESULTS: Corneal nerve fibre length (22.0 ± 7.9 vs. 19.3 ± 6.3 mm/mm2 ; P = 0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7-246.2) vs. 46.0 (3.1-129.2) no./mm2 ; P = 0.021) and heart rate variability (geometric mean (range): 7.9 (1.4-27.7) vs. 6.5 (1.5-22.0); P = 0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3-43.0) vs. 7.2 (1.0-30.0); P = 0.006). Variables with the greatest impact on attenuating the P value for age- and HbA1C -adjusted ethnic difference in corneal nerve fibre length (P = 0.032) were pack-years smoked (P = 0.13), BMI (P = 0.062) and triglyceride levels (P = 0.062). CONCLUSIONS: South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers.

Osteoarthritis (OA) is a chronic multifactorial disease characterized by progressive joint degeneration. The purpose of this study was to compare the effects of ultrasound-guided corticosteroid injection with oxygen–ozone injection in patients with knee OA. This double-blind randomized clinical trial was performed on 62 patients with knee OA. The patients were randomly divided into two groups. In the first group 40 mg triamcinolone (1 cc) and in the second group 10 cc (15 μg/ml) oxygen–ozone (O2–O3) were injected into the knee joint under ultrasound guidance. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC), knee flexion range of motion (ROM), effusion in ultrasound images of the suprapatellar recess, and visual analog scale (VAS), which were evaluated before injection, 1 week, 1 month, and 3 months after the treatment. Sixty-two patients (10 men and 52 women) were enrolled with mean age of 57.9 years. VAS improved in both groups (steroid P value = 0.001, oxygen–ozone P value > 0.001). The improvements seen in VAS and WOMAC scores 3 months after treatment were in favor of the oxygen–ozone group when compared to the steroid group (P = 0.041 vs P = 0.19). There was no significant difference between the two groups in ROM and joint effusion seen under ultrasound (ROM p = 0.880, effusion p = 0.362). However, in the oxygen–ozone-receiving group, joint effusion was decreased significantly (p < 0.001). Both steroid and oxygen–ozone injections are effective in patients with knee osteoarthritis. Our study showed that the effects of oxygen–ozone injection last longer than those of steroid injection to the knee joint.

OBJECTIVES: Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against a range of established measures of nerve damage in patients with diabetic neuropathy. METHODS: in this cross sectional study, thirty subjects with Type 1 diabetes without neuropathy (T1DM), thirty one T1DM subjects with neuropathy (DSPN) and twenty seven non-diabetic healthy control subjects underwent detailed assessment of neuropathic symptoms and neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy and corneal confocal microscopy (CCM). RESULTS: Subjects with DSPN were older (C vs T1DM vs DSPN: 41.0±14.9 vs 38.8±12.5 vs 53.3±11.9, P = 0.0002), had a longer duration of diabetes (P

AIMS/HYPOTHESIS: the aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus. METHODS: a total of 70 participants (29 without and 41 with erectile dysfunction) with type 1 diabetes and 34 age-matched control participants underwent a comprehensive assessment of large- and small-fibre neuropathy. RESULTS: the prevalence of erectile dysfunction in participants with type 1 diabetes was 58.6%. After adjusting for age, participants with type 1 diabetes and erectile dysfunction had a significantly higher score on the Neuropathy Symptom Profile (mean ± SEM 5.3 ± 0.9 vs 1.8 ± 1.2, p = 0.03), a higher vibration perception threshold (18.3 ± 1.9 vs 10.7 ± 2.4 V, p = 0.02), and a lower sural nerve amplitude (5.0 ± 1.1 vs 11.7 ± 1.5 mV, p = 0.002), peroneal nerve amplitude (2.1 ± 0.4 vs 4.7 ± 0.5 mV, p 

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type a receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.

BACKGROUND: Accurate and economic detection of nerve damage in diabetes is key to more widespread diagnosis of patients with diabetic peripheral neuropathy (DPN) and painful diabetic neuropathy. This study examined the diagnostic performance of NerveCheck, an inexpensive ($500) quantitative sensory testing (QST) device. METHODS: One hundred forty-four subjects (74 with and 70 without diabetes) underwent assessment with NerveCheck, neuropathy disability score (NDS), nerve conduction studies (NCS), intraepidermal and corneal nerve fiber density (IENFD and CNFD), and McGill questionnaire for neuropathic pain. RESULTS: of the 74 subjects with diabetes, 41 were diagnosed with DPN based on the NDS. The NerveCheck scores for vibration perception threshold (VPT), cold perception threshold (CPT), and warm perception threshold (WPT) were significantly lower (P ≤ 0.0001) in diabetic patients with DPN compared to patients without DPN. The diagnostic accuracy of VPT was high with reference to NCS (area under the curve [AUC]: 82%-84%) and moderate for IENFD, CNFD, and neuropathic pain (AUC: 60%-76%). The diagnostic accuracy of CPT and WPT was moderate with reference to NCS, IENFD, and CNFD (AUC: 69%-78%) and low for neuropathic pain (AUC: 63%-65%). CONCLUSIONS: NerveCheck is a low-cost QST device with good diagnostic utility for identifying sensory deficits, comparable to established tests of large and small fiber neuropathy and for the severity of neuropathic pain.

Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%,P=0.0003) and CNFD (AUC: 82%,P=0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.

. OBJECTIVE
. Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management.
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. RESEARCH DESIGN AND METHODS
. Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years.
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. RESULTS
. Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P &amp;lt; 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years.
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. CONCLUSIONS
. CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.
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. OBJECTIVE
. Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard.
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. RESEARCH DESIGN AND METHODS
. Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy.
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. RESULTS
. Manual and automated corneal nerve fiber density (CNFD) (P &amp;lt; 0.0001), branch density (CNBD) (P &amp;lt; 0.0001) and length (CNFL) (P &amp;lt; 0.0001), and IENFD (P &amp;lt; 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14).
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. CONCLUSIONS
. This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.
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. OBJECTIVE
. Impaired glucose tolerance (IGT) represents one of the earliest stages of glucose dysregulation and is associated with macrovascular disease, retinopathy, and microalbuminuria, but whether IGT causes neuropathy is unclear.
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. RESEARCH DESIGN AND METHODS
. Thirty-seven subjects with IGT and 20 age-matched control subjects underwent a comprehensive evaluation of neuropathy by assessing symptoms, neurological deficits, nerve conduction studies, quantitative sensory testing, heart rate variability deep breathing (HRVdb), skin biopsy, and corneal confocal microscopy (CCM).
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. RESULTS
. Subjects with IGT had a significantly increased neuropathy symptom profile (P &amp;lt; 0.001), McGill pain index (P &amp;lt; 0.001), neuropathy disability score (P = 0.001), vibration perception threshold (P = 0.002), warm threshold (P = 0.006), and cool threshold (P = 0.03), with a reduction in intraepidermal nerve fiber density (P = 0.03), corneal nerve fiber density (P &amp;lt; 0.001), corneal nerve branch density (P = 0.002), and corneal nerve fiber length (P = 0.05). No significant difference was found in sensory and motor nerve amplitude and conduction velocity or HRVdb.
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. CONCLUSIONS
. Subjects with IGT have evidence of neuropathy, particularly small-fiber damage, which can be detected using skin biopsy and CCM.
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. OBJECTIVE
. To establish if corneal nerve loss, detected using in vivo corneal confocal microscopy (IVCCM), is symmetrical between right and left eyes and relates to the severity of diabetic neuropathy.
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. RESEARCH DESIGN AND METHODS
. Patients (n = 111) with type 1 and type 2 diabetes and 47 age-matched healthy control subjects underwent detailed assessment and stratification into no (n = 50), mild (n = 26), moderate (n = 17), and severe (n = 18) neuropathy. IVCCM was performed in both eyes and corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) and the tortuosity coefficient were quantified.
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. RESULTS
. All corneal nerve parameters differed significantly between diabetic patients and control subjects and progressively worsened with increasing severity of neuropathy. The reduction in CNFD, CNBD, and CNFL was symmetrical in all groups except in patients with severe neuropathy.
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. CONCLUSIONS
. IVCCM noninvasively detects corneal nerve loss, which relates to the severity of neuropathy, and is symmetrical, except in those with severe diabetic neuropathy.
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Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas–kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

The use of diagnostic and therapeutic methods for assessing pulmonary vein due to its status as a main source of ectopic beats for the initiation of atrial dysrrythmias is strongly recommended. We report the case of a 13-year-old girl who was admitted to our hospital with the electrocardiogram manifestation of an ectopic atrial tachycardia. The focus of arrhythmia was inside the right upper pulmonary vein. The patient underwent successful ablation with a conventional electrophysiology catheter via the retrograde aortic approach. We showed that when the origin of atrial tachycardia is in the right upper pulmonary vein, it is possible to advance the catheter into this vein via the retrograde aortic approach and find the focus of arrhythmia. This case demonstrates that right upper pulmonary vein mapping is feasible through the retrograde aortic approach and it is also possible to ablate the arrhythmia using the same catheter and approach.

Diabetic neuropathy is common, under- or misdiagnosed, and causes not only substantial morbidity but also increased mortality. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, although a number of pathogenetic pathways remain under active study. Focal and multifocal neuropathies are not common but can be extremely debilitating with few proven therapies. Autonomic dysfunction is more common, but significant deficits, although severe, are relatively rare, with limited therapeutic options. Painful diabetic neuropathy is a cause of considerable morbidity and many pharmacological as well as non-pharmacological interventions have been used. The recent NICE (2010) guidance provides an evidence-based rationale for the management of neuropathic pain in primary care. © John Wiley and Sons 2008.

Diabetic neuropathy is common, under or misdiagnosed, and causes substantial morbidity with increased mortality. Defining and developing sensitive diagnostic tests for diabetic neuropathy is not only key to implementing earlier interventions but also to ensure that the most appropriate endpoints are employed in clinical intervention trials. This is critical as many potentially effective therapies may never progress to the clinic, not due to a lack of therapeutic effect, but because the endpoints were not sufficiently sensitive or robust to identify benefit. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, however, a number of pathogenetic pathways remain under active study. Painful diabetic neuropathy is a cause of considerable morbidity and whilst many pharmacological and nonpharmacological interventions are currently used, only two are approved by the US Food and Drug Administration. We address the important issue of the ‘placebo effect’ and also consider potential new pharmacological therapies as well as nonpharmacological interventions in the treatment of painful diabetic neuropathy.