A simple new non-invasive sweat indicator test for the diagnosis of diabetic neuropathy.

A simple non-invasive indicator test (Neuropad(®)) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1-100%) and negative predictive value (63-100%), with moderate specificity (32-78.5%) and positive predictive value (23.3-93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1-89%) and negative predictive value (64.7-91%), but low to moderate specificity (27-78%) and positive predictive value (24-48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.

Corneal confocal microscopy: a new technique for early detection of diabetic neuropathy.

Corneal confocal microscopy (CCM) is a noninvasive method for the study of human cornea in vivo. It has increasingly been used to assess the morphology of the sub-basal corneal nerve plexus. CCM has good reproducibility and may contribute to the early diagnosis of diabetic polyneuropathy. It may also be useful to document favorable changes in nerve fiber structure early after therapeutic intervention. Corneal nerve pathology is more pronounced in patients with diabetic polyneuropathy and is associated with its clinical severity. The sensitivity and specificity of CCM for the diagnosis of polyneuropathy is moderate to high. CCM now merits further use in large longitudinal studies to provide more information on the natural history of diabetic neuropathy and effects of treatment. Moreover, there is a need for a larger normative database. Finally, technical progress is expected to enable visualization of larger corneal areas and improve nerve fiber quantification, increasing diagnostic accuracy.

Polyneuropathy in impaired glucose tolerance: is postprandial hyperglycemia the main culprit? A mini-review.

There is accumulating evidence for the mutual relationship between peripheral neuropathy and impaired glucose tolerance (IGT). The key factor in the pathogenesis of neuropathy in IGT is postprandial hyperglycemia, which induces increased oxidative stress, endothelial dysfunction, and activation of both protein kinase C and the polyol pathway, leading to impaired neuronal metabolism and DNA damage. Other pathogenic factors include dyslipidemia and the metabolic syndrome. The cornerstone of management is improved glycemic control, although a long sustainable effect has not been documented yet, calling for further supportive trials. Secondary therapeutic targets encompass hypolipidemic and antihypertensive treatment, smoking cessation and weight loss. The increasing awareness of peripheral neuropathy in IGT is expected to improve healthcare provision in subjects with this condition.

Evaluation of the Neuropad sudomotor function test as a screening tool for polyneuropathy in the elderly population with diabetes and pre-diabetes: the KORA F4 survey.

BACKGROUND: Neuropad is a novel indicator test for sudomotor dysfunction, which has not been validated as a screening tool in a population-based study. This study aimed to evaluate the utility of Neuropad as a screening tool for distal symmetric polyneuropathy among elderly subjects with diabetes and pre-diabetes in the general population. METHODS: Eligible subjects aged 61-82 years (n = 940) from the KORA F4 survey were examined, 201 of whom had diabetes and 231 had pre-diabetes (WHO 1999 criteria). Polyneuropathy was defined by the Michigan Neuropathy Screening Instrument (MNSI) score >3. RESULTS: Polyneuropathy was diagnosed in 60 (29.9%) subjects with diabetes and in 45 (19.5%) subjects with pre-diabetes, respectively (p = 0.013). The sensitivity and negative predictive value of Neuropad (reading time: 10 min) for the diagnosis of polyneuropathy were moderately high, reaching 76.7% and 78.1% in subjects with diabetes and 57.8% and 76.5% in those with pre-diabetes, respectively. Conversely, the specificity and positive predictive value for the diagnosis of polyneuropathy were rather low: 35.5% and 33.6% in diabetic individuals and 33.3% and 17.3% in subjects with pre-diabetes, respectively. Use of the >2 cut-off and MNSI combined with monofilament examination did not improve the diagnostic performance of Neuropad. CONCLUSIONS: In the elderly general population with diabetes and pre-diabetes, Neuropad has reasonable sensitivity but rather low specificity for the diagnosis of polyneuropathy. It is a useful simple and inexpensive tool to screen for and to exclude polyneuropathy as desired, while its low specificity implies that a longer reading time merits consideration.

Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases.

BACKGROUND: Macrolides have long been recognised to exert immunomodulary and anti-inflammatory actions. They are able to suppress the "cytokine storm" of inflammation and to confer an additional clinical benefit through their immunomodulatory properties. METHODS: A search of electronic journal articles was performed using combinations of the following keywords: macrolides, COPD, asthma, bronchitis, bronchiolitis obliterans, cystic fibrosis, immunomodulation, anti-inflammatory effect, diabetes, side effects and systemic diseases. RESULTS: Macrolide effects are time- and dose-dependent, and the mechanisms underlying these effects remain incompletely understood. Both in vitro and in vivo studies have provided ample evidence of their immunomodulary and anti-inflammatory actions. Importantly, this class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia. Macrolides have also been reported to reduce airway hyper-responsiveness and improve pulmonary function. CONCLUSION: This review provides an overview on the properties of macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin), their efficacy in various respiratory diseases and their adverse effects.

Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with obstructive sleep apnoea syndrome: new indices of severity?

UNLABELLED: To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. MATERIALS AND METHODS: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n=148) with AHI<5/h; Group B (n=121) with AHI: 5-14.9/h; Group C (n=85) with AHI: 15-29.9/h and Group D (n=256) with AHI ≥ 30/h. MPV and PDW were measured using an automated blood cell counter. RESULTS: MPV was significantly higher in group D (mean value 12.1 ± 1.3 fl) than in groups A (9.8 ± 1.1 fl), B (9.8 ± 1.6 fl), and C (11.5 ± 1.3 fl) (p<0.001). The same pattern was observed in PDW values (15.9 ± 2.2 fl for group D and 13.2 ± 2.2 fl for group A, 14.1 ± 2.8 fl for group B, and 15 ± 2.2 fl for group C, p<0.001). Significant correlations were seen between MPV and AHI (p<0.001), average pulse oxygen saturation (SpO(2)) (p<0.001), minimum SpO(2) (p<0.001) and percent of the total sleep time with SpO(2) lower than 90% (t<90%) (p<0.001) during sleep, Arousal Index (p<0.001) and Epworth sleepiness scale (ESS) (p=0.028). Similarly, PDW was correlated with AHI (p<0.001), average SpO(2) (p=0.001), minimum SpO(2) (p<0.001), t<90% (p=0.002), and Arousal Index (p<0.001). CONCLUSIONS: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep.

Neuropad: evaluation of three cut-off points of sudomotor dysfunction for early detection of polyneuropathy in recently diagnosed diabetes.

AIMS: To examine the sensitivity and specificity of three cut-off points of Neuropad for the diagnosis of distal symmetric polyneuropathy and small-fibre dysfunction in patients within the first year after diagnosis of diabetes. METHODS: Neuropad results were read at 10, 15 and 20 min and evaluated for diagnostic utility in distal symmetric polyneuropathy confirmed by electrophysiology and small-fibre dysfunction in 52 patients with Type 1 diabetes and 99 patients with Type 2 diabetes. RESULTS: The prevalence of distal symmetric polyneuropathy was 15.4% in Type 1 diabetes and 43.4% in Type 2 diabetes, while that of small-fibre dysfunction was 9.6 and 31.3%, respectively. Sensitivity of Neuropad for the diagnosis of distal symmetric polyneuropathy and small-fibre dysfunction was highest in Type 1 diabetes for the 10-min threshold reaching 87.5 and 80.0%, respectively, while it was modestly high in Type 2 diabetes at 65.1 and 67.7%, respectively. Specificity in both diabetes types was modest for the 10-min threshold (44.7-48.2%). It was highest for the 20-min threshold (83.8-89.3%) at the cost of poor sensitivity at 12.5-34.9%. Negative predictive values were relatively high for all three cut-off points in both types of diabetes (64.1-97.1%) at the cost of poor positive predictive values at 12.5-71.4%. CONCLUSIONS: In patients within the first year after diagnosis of diabetes, the 10-min cut-off for Neuropad provides a relatively high sensitivity and modest specificity for distal symmetric polyneuropathy and small-fibre dysfunction, rendering the test more suitable as a screening tool than the 15- and 20-min cut-offs.

Carotid endarterectomy in patients with foetal-type posterior circle of Willis: is there an indication for local anaesthesia?

Foetal-type posterior circle of Willis is a common anatomical variation with a variable degree of vessel asymmetry. In patients with this abnormality, carotid endarterectomy (CEA) may create cerebral hypo-perfusion intraoperatively, and this may be underestimated under general anaesthesia. There is currently no evidence that anatomical variations in the circle of Willis represent an independent risk factor for stroke. Moreover, there is a paucity of data on treating patients with such anatomical variations and co-existing ICA stenosis. We present a case of CEA under local anaesthesia (LA) in a 52-year-old female patient with symptomatic stenosis of the right ICA and coexistent foetal-type posterior circle of Willis. There were no post-operative complications and she was discharged free from symptoms. She was seen again 3 months later and was free from complications. This case higlights that LA should be strongly considered to enable better intra-operative neurological monitoring in the event of foetal-type posterior circle of Willis.

Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnoea Syndrome and Overlap Syndrome.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea syndrome (OSAS) are among the most prevalent chronic respiratory disorders. Accumulating data suggest that there is a significant burden of cardiovascular disease (CVD) in patients with COPD and OSAS, affecting negatively patients' quality of life and survival. Overlap syndrome (OS), i.e. the co-existence of both COPD and OSAS in the same patient, has an additional impact on the cardiovascular system multiplying the risk of morbidity and mortality. The underlying mechanisms for the development of CVD in patients with either OSAS or COPD and OS are not entirely elucidated. Several mechanisms, in addition to smoking and obesity, may be implicated, including systemic inflammation, increased sympathetic activity, oxidative stress and endothelial dysfunction. Early diagnosis and proper management of these patients might reduce cardiovascular risk and improve patients' survival. In this review, we summarize the current knowledge regarding epidemiological aspects, pathophysiological mechanisms and present point-to-point specific associations between COPD, OSAS, OS and components of CVD, namely, pulmonary hypertension, coronary artery disease, peripheral arterial disease and stroke.

Peripheral vascular changes in the lower limbs following cocaine abuse.

Background: Worldwide, substance use disorder is on the rise, especially amongst the young generation. Although cocaine-induced cardiovascular and cerebrovascular events are well documented, knowledge about the relationship of cocaine use and its effect on arterial perfusion in the lower limbs is scarce.Objective: This study sought to investigate the relationship between cocaine use and peripheral arterial disease.Methods: The study population comprised 30 subjects' dependent on cocaine, smoking and alcohol [Group A] and another 30 subjects dependent on smoking and alcohol only [Group B]. A comprehensive lower limb vascular assessment was conducted utilizing pulse palpation, Doppler spectral waveform analysis, Ankle brachial pressure index (ABPI) and Toe brachial pressure index (TBPI) to determine the arterial perfusion status in the lower limbs.Results: Group A had lower ABPIs and TBPIs than Group B suggesting poorer vascular perfusion in lower limbs. Furthermore, a larger percentage of Group A had monophasic/continuous waveforms of all three pedal pulses compared to Group B. Conversely there was a higher percentage in Group B with biphasic/triphasic waveforms compared to Group A implying better vascular perfusion.Conclusion: In this study, cocaine use was associated with diminished arterial perfusion of the lower limbs suggesting that cocaine use has the potential to increase the risk of peripheral arterial disease. Regular vascular foot screening is warranted if foot complications are to be avoided.

Letters to the editor: definitely not children of a lesser god.

Letters to the editor are brief texts that are published in a special section of medical journals. There are two types of letters to the editor: the observation and the comment. The former presents original work, while the latter constitutes criticism on work already published in the same journal. Although short, letters to the editor require as much effort and discipline in writing as, indeed, any other manuscript. Clarity and brevity should be their principal values. It is also important to comply with the journals' instructions for correspondence. Thus, eloquent letters to the editor may promote knowledge and enable fruitful exchange of ideas.

Risk factors for ipsilateral reamputation in patients with diabetic foot lesions.

This study aimed to examine the rates and risk factors for ipsilateral re-amputation in 121 patients with diabetic foot and prior amputation. Twenty-six (21.5%) patients required re-amputation during a mean follow-up of 18 months. Most re-amputations were performed within the first 6 months of the initial amputation. Re-amputation was more common among patients in whom the initial amputation had only affected one or two toes. Age (hazard ratio: 1.06) and heel lesions (hazard ratio: 2.69) were significantly associated with re-amputation. There is a high risk of re-amputation in the diabetic foot, especially within the first 6 months of the initial amputation, mainly due to poor selection of the original amputation level in an effort to save a greater part of the lower extremity. Patients 70 years and those with heel lesions are at greatest risk of re-amputation.

Correlation of cardiac autonomic neuropathy with small and large peripheral nerve function in type 2 diabetes mellitus.

AIMS: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). METHODS: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. RESULTS: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). CONCLUSIONS: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.

Post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure: the role of cytokines.

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure. PATIENTS AND METHODS: The study included 42 patients (group A: 20 men, mean age of 54.5+/-6.8 years) with NYHA I or II heart failure and 54 patients (group B: 25 men, mean age of 52.9+/-7.1 years) without heart failure. All patients had undergone total thyroidectomy and were euthyroid on a stable thyroxine replacement dose. Serum Interleukin-1b (IL-1b), Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6), TSH, T3, T4, fT3 and fT4 were measured. RESULTS: Both groups exhibited a significant positive correlation between IL-6 and levothyroxine replacement dosage (group A: r=0.708, p<0.001; group B: r=0.345, p=0.012) and a negative correlation between IL-6 and T3 (group A: r=-0.342, p=0.023, group B: r=-0.294, p=0.035). Significant independent predictors of levothyroxine replacement dosage were IL-6 (p<0.001) and TNF-alpha (p=0.007) in group A (58.3% of dosage variation) and only IL-6 (p=0.012) in group B (10.1% of dosage variation). CONCLUSIONS: In both groups, a significant positive correlation was observed between IL-6 and levothyroxine replacement dosage, but this correlation was stronger in group A. In the same group, there was evidence for a more pronounced influence of cytokines on levothyroxine dosage.

A comparison of the new indicator test for sudomotor function (Neuropad) with the vibration perception threshold and the clinical examination in the diagnosis of peripheral neuropathy in subjects with type 2 diabetes.

UNLABELLED: Peripheral neuropathy remains a major cause of morbidity and is a cardinal factor in the pathogenesis of diabetic foot ulceration. The aim of the present study was to compare the new indicator test for sudomotor function (Neuropad) with the vibration perception threshold (VPT) and the clinical examination in the diagnosis of peripheral neuropathy in subjects with type 2 diabetes. This study included 154 type 2 diabetic patients (76 men) with a mean age of 64.3+/-7.3 years and a mean diabetes duration of 12.8+/-4.3 years. Neuropathy was diagnosed clinically using the Neuropathy Disability Score (NDS). The VPT was measured with a neurothesiometer, values > 25Volts being classified as abnormal. Sudomotor function was evaluated by the indicator test. Sensitivity of the indicator test for neuropathy was 97.8% and specificity was 67.2%. Sensitivity and specificity of VPT for neuropathy were 78.9% and 85.9% respectively. A significant correlation was shown between time to colour change of the indicator test and VPT (rs=0.889, p<0.001). CONCLUSIONS: Both the indicator test and the VPT have a high sensitivity for neuropathy. Sensitivity is higher with the indicator test, but specificity is higher with VPT. Time until complete colour change of the indicator test shows a positive correlation with VPT. Thus, the indicator test appears to be a useful additional diagnostic tool of neuropathy, particularly suitable for screening and self-examination, in type 2 diabetes. The correlation between time to colour change of the indicator test and VPT is interesting and merits investigation in a prospective study.

Writing a case report: polishing a gem?

Case reports describe patient cases which are of particular interest due to their novelty and their potential message for clinical practice. While there are several types of case reports, originality and clinical implications constitute the main virtues by which case reports are judged. Defining the educational message and choosing the right audience are vital steps in the process of writing. Generally, a case report is structured, its main components being the abstract, the introduction, the case description and the discussion. Guidelines and tips for writing case reports are not enough for making a successful author, but they help, especially less experienced doctors, to exercise and improve their writing. If properly prepared, case reports can still communicate new observations in an interesting and pleasant way, thereby enriching our knowledge, even in the era of evidence-based medicine.

Double gall-bladder--two pathologies: a case report.

True gall-bladder duplication is a rare biliary anomaly, which is usually discovered as an incidental finding. There are reports of double gall-bladders missed during the first operation. We present the case of a double gall-bladder which, albeit suspected during the operation, was confirmed post-operatively. The patient underwent successful laparoscopic cholecystectomy and the examination of the resected gall-bladder revealed two chambers, only one containing stones. Predisposing factors for the development of gall-stones in one gall-bladder only, as well as surgical options, are briefly discussed.

Vitamin D Levels in Middle-Aged Patients with Obstructive Sleep Apnoea Syndrome.

BACKGROUND: Vitamin D (Vit D) insufficiency has been implicated in the pathophysiology of numerous diseases. Obstructive sleep apnoea syndrome (OSAS), a disorder associated with increased cardiovascular and cerebrovascular morbidity, has been associated with decreased Vit D levels, but reports are inconclusive. AIM: To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of Vit D status, with anthropometric and sleep characteristics of OSAS patients and to compare those levels between OSAS patients and non-apnoeic controls. METHOD: Consecutive subjects who had undergone polysomnography and pulmonary function testing were divided into controls (apnoea-hypopnea index, AHI <5/h) and OSAS group (AHI ≥5/h). RESULTS: A total of 169 subjects (135 men) were included. OSAS patients (n=139) significantly differed from non-apnoeic controls in terms of age (53.9±12.8 vs. 44.9±12.8 years, p=0.002) and body mass index (BMI) (35.9±6.9 vs. 29.9±6.8 kg/m2, p<0.001). Serum 25(OH)D levels were lower in OSAS patients (17.8±7.8 vs. 23.9±12.4 ng/ml, p=0.019). In OSAS patients, levels of serum 25(OH)D were negatively correlated with sleep stage transitions (r=-0.205, p=0.028), AHI (r=-0.187, p=0.045), oxygen desaturation index (r=-0.234, p=0.011) and percentage of time with oxyhaemoglobin saturation <90% (r=-0.172, p=0.041). In contrast, they were positively correlated with average oxyhaemoglobin saturation during sleep (r=0.179, p=0.033), forced expiratory volume in 1 sec (r=0.207, p=0.037) and oxygen partial pressure (r=0.197, p=0.029). CONCLUSION: Vit D levels were lower in OSAS patients compared with non-apnoeic controls. Several indices of OSAS severity also correlated with Vit D levels.

An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

UNLABELLED: Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions in humans. An insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on chromosome 2 has been described. The aim of the present study was to investigate the potential association between alpha2B gene I/D polymorphism and peripheral neuropathy in Greek patients with type 2 diabetes mellitus. The study included 130 patients (70 men) with diabetic neuropathy (group A) and 60 patients (34 men) without diabetic neuropathy (group B). There was no difference in age, gender and diabetes duration between the groups. Diabetic neuropathy was diagnosed by clinical examination using the Diabetic Neuropathy Index (DNI). Genotyping of I/D polymorphism was performed by PCR. Frequency of the D allele was significantly higher (p=0.001) in group A (26.9%) as compared to group B (11.7%). DNI score differed significantly (p=0.001) between the three genotype groups (I/I, I/D, D/D). It was significantly higher (p=0.04) in patients with I/D (3.7+/-1) than in those with I/I (2.5+/-0.9) and significantly higher (p=0.001) in patients with D/D (5.6+/-1.3) than in those with I/D (3.7+/-1). CONCLUSIONS: Patients with neuropathy exhibit a significantly higher frequency of the D allele in comparison to those without neuropathy. Presence of the D allele is also associated with a higher neuropathic score. These results provide evidence for an association of the D allele with both presence and severity of neuropathy in patients with type 2 diabetes mellitus.