The role of Sudoscan feet asymmetry in the diabetic foot.

The aim of this study was to investigate the role of Sudoscan asymmetry parameters in the diabetic foot. PATIENTS AND METHODS: In this study we included 165 participants: 84 type 2 diabetes patients divided into three HbA1c matched groups - group 1: newly diagnosed diabetics (n = 31), group 2: people with longer diabetes duration and established neuropathy (n = 33), group 3: patients with diabetic foot ulcer (n = 20), and a control group of 81 people with prediabetes. All subjects underwent peripheral sudomotor evaluation using Sudoscan device (Impeto Medical, Paris). RESULTS: Patients with diabetic foot had significantly higher Sudoscan feet asymmetry (19.6%) compared to those with only diabetic neuropathy (7.9%), compared to the group with newly diagnosed diabetes (7.44%), and compared to controls (2.5%). This test has shown a good discriminative value (with a threshold of 9.5%) for diabetic foot with area under the ROC curve of 0.955 (p = 0.001). Additionally, in a regression model feet asymmetry proved its predictive value for participants with diabetic foot. CONCLUSION: In this study Sudoscan feet asymmetry proved to be a novel discriminator and predictor for diabetic foot patients. It might be considered as a marker for early damage in the neuropathy evaluation protocol.

Evaluation of Hepcidin and Atherosclerosis in Dialysis Patients.

BACKGROUND: Chronic kidney disease (CKD) is a condition that involves 10% - 15% of population worldwide, which increases the risk of cardio-vascular diseases (CVD). Chronic kidney disease is one of the main reasons for illness and mortality in the world. Chronic kidney disease is a serious health problem caused by involvement of a large number of patients with kidney injury, especially in industrial countries. Among the main reasons for this are population living longer and the number of diseases in elderly persons, such as diabetes mellitus type 2, hypertension, and cardio-vascular diseases. METHODS: We evaluated 63 patients on chronic dialysis at the Dialysis Centre at University "Aleksandrovska" Hospital; the average age was 49.9 ± 7.8. Their results were compared to 63 age matched controls. Blood samplings were taken before dialysis procedure. In the included groups, we measured CBC, serum iron (by Ferrozine method), ferritin, soluble transferrin receptors and hsCRP (by nephelometric method), hepcidin (by ELISA method), and homocysteine (by CLIA method). IMT was measured by using electronic calipers and evaluated by automated software programs. RESULTS: We established elevated serum hepcidin levels in CKD patients (205.1 ± 29.9 µg/L) compared to the control group (20.8 ± 3.1 µg/L), p < 0.001. Serum homocysteine and hsCRP concentrations were elevated in CKD cases (48.7 ± 6.8 µmol/L; 29.7 ± 4.1 mg/L) compared to controls (7.9 ± 1.8 µmol/L; 1.1 ± 0.4 mg/L), p < 0.005. In patients with CKD we found a strong positive correlation between serum hepcidin and homocysteine concentrations, r = 0.879, p < 0.001. In patients with impaired kidney function soluble transferrin receptors correlated negatively to hepcidin: r = -0.799, p < 0.001. In dialysis, the transferrin concentration correlated highly positive to hepcidin: r = 0.691, p < 0.001. IMT in CKD patients correlated positively to hepcidin and homocysteine levels: r = 0.788 and r = 0.841, respectively, p < 0.005. CONCLUSIONS: Chronic kidney disease is connected to cardio-vascular disease risk factors. CKD might be an independent CVD risk factor. In early kidney injury stages, increased morbidity is found from CVD. The risk of fatal and non-fatal cardio-vascular incidents is connected to kidney injury. For clinical practice, early evaluation of hepcidin and atherosclerosis in chronic kidney disease patients is very important.

Screening for mild cognitive impairment in patients with cardiovascular risk factors.

AIM: Cardiovascular risk factors are also risk factors for cognitive impairment. They have cumulative effect in target organ damage. The precise correlation between cardiovascular risk factors and cognitive impairment, as well as assessing the extent to which they may affect cognitive functioning, is difficult to ascertain in everyday clinical practice. Quick, specific, and sensitive neuropsychological tests may be useful in screening for, and the prophylaxis of, target organ damage in hypertensive patients. METHODS: We gathered full anamnesis, performed physical examination, laboratory screening and echocardiography. These variables were observed at office and home for all patients, For half of the patients, 24-hour ambulatory blood pressure monitoring and neuropsychological testing using Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), Geriatric Depression Scale, and the 4-instrumental activities of daily living scale were undertaken. RESULTS: For a period of 2 years, 931 patients were included after applying the inclusion and exclusion criteria. The mean age was 65.90±10.00 years. Two hundred and sixty three patients (85 [32.32%] males and 178 [67.68%] females) were reevaluated after a mean follow-up period of 12 months (6-20 months). The mean results of MoCA and MMSE were significantly lower (p<0.05) in the group of patients with poorly controlled blood pressure and cardiovascular risk factors. There was mild to intermediate negative correlation between Systematic Coronary Risk Evaluation (SCORE) and the neuropsychological tests' results. CONCLUSION: Cardiovascular risk factors play an important role for the development of cognitive impairment in the eastern European population because of their high frequency and interaction. The use of easily applicable neuropsychological tests in everyday clinical practice of specialties other than neurology may help in stratifying the risk for development and progression of mild cognitive impairment in this high-risk group.

Comparison of Central, Ambulatory, Home and Office Blood Pressure Measurement as Risk Markers for Mild Cognitive Impairment in Hypertensive Patients.

AIMS: We compared the role of central blood pressure (BP), ambulatory BP monitoring (ABPM), home-measured BP (HMBP) and office BP measurement as risk markers for the development of mild cognitive impairment (MCI). METHODS: 70 hypertensive patients on combination medical therapy were studied. Their mean age was 64.97 ± 8.88 years. Eighteen (25.71%) were males and 52 (74.28%) females. All of the patients underwent full physical examination, laboratory screening, echocardiography, and office, ambulatory, home and central BP measurement. The neuropsychological tests used were: Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). SPSS 19 was used for the statistical analysis with a level of significance of 0.05. RESULTS: The mean central pulse pressure values of patients with MCI were significantly (p = 0.016) higher than those of the patients without MCI. There was a weak negative correlation between central pulse pressure and the results from the MoCA and MMSE (r = -0.283, p = 0.017 and r = -0.241, p = 0.044, respectively). There was a correlation between ABPM and MCI as well as between HMBP and MCI. CONCLUSIONS: The correlation of central BP with target organ damage (MCI) is as good as for the other types of measurements of BP (home and ambulatory). Office BP seems to be the poorest marker for the assessment of target organ damage.

8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients.

BACKGROUND: Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown. AIM: To determine whether oxidative stress (urinary 8-isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients. METHODS: A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8-isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA. RESULTS: In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4·62% ±1·9) and (7·1% ±2·8), respectively (P: 0·013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 µm versus. 666 µm); (ABI -1·06 versus 1·20). Urinary isoprostanes were higher in OSA patients (0·091 versus 0·078) and correlated negatively to FMD (r: -0·825, P: 0·00), IMT (r: -0·324, P: 0·003) and ABI (r: -0·226, P: 0·043). No association between resistin and the degree of vascular injury was found. CONCLUSIONS: In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8-isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI.

Plasma Selenium Levels in Chronic Cocaine Abuse.

BACKGROUND: Cocaine abuse is a significant health problem worldwide. We aim to evaluate the role of selenium in oxidative stress in patients with cocaine related cardio- and cerebrovascular diseases. Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways. METHODS: We included 26 patients with chronic cocaine abuse separated into two groups according to duration of intake--from six months up to one year and more than a year, with and without only vascular incidents (TIA, stroke, myocardial infarction), or presence of hypertension. All included groups were analyzed for laboratory parameters: CBC, CRP, AST, ALT, γ-GT, serum creatinine, urea, K, Na, and Ca. Main risk factors were evaluated: total cholesterol, LDL and HDL-cholesterol, triglycerides, glucose, and selenium. RESULTS: Our result shows that in the first group only 20% have cardiovascular problems. In the group with cocaine abuse more than a year, number of vascular incidents has increased (58.3%). Patients from the group cocaine abuse up to 1 year showed no changes in lipid profile, but cocaine abuse more than a year showed interesting changes in the lipid profile. We found a high positive correlation between the two cocaine groups for plasma selenium concentrations. This means that after the first six months oxidative stress has occured. It increases with duration of cocaine abuse. CRP correlated positively between these two groups, showing an endothelial function disorder. CONCLUSIONS: Development of oxidative stress increased with cocaine abuse, which leads to lower plasma selenium levels in patients with different duration of intake--less and more than a year. It is possible to supplement selenium during the early period of cocaine dependence to prevent hard vascular accidents, which are common after more than one year of cocaine abuse.

Is There a Link Between Changes in Levels of Hepcidin and Stroke?

BACKGROUND: Iron is an essential element for the living body. It is well known that iron homeostasis disorders are important in two ways--its deficiency and its overload lead to several pathologies. METHODS: We measured 17 patients with iron deficiency anemia (IDA); 19 with anemia of chronic diseases (ACD); 15 with ischemic stroke (IS). The results were compared to a previously selected control group. For evaluation of iron metabolism status, we measured serum iron levels, ferritin, and soluble transferrin receptors. For inflammation, serum interleukin-6 and hsCRP were measured. Serum hepcidin quantification was performed using a previously validated immunosorbent method. Ferritin was measured by an ECLIA method; serum iron on AAS; hsCRP using a nephelometric analysis. RESULTS: We found statistically significant elevated serum hepcidin levels in patients with ACD and IS compared to the control group (p < 0.001). Patients with IDA had statistically significant lower hepcidin levels compared to the control group (p < 0.001). Serum ferritin levels in the IS group was higher compared to the control and other groups (p < 0.001). The lowest ferritin concentrations were established in the IDA group compared to the control (p < 0.001). We found a strong correlation between serum hepcidin and ferritin levels in the IS group (r = 0.583; p < 0.001). CONCLUSIONS: Quantification of serum hepcidin levels might be used as a link for prediction of acute ischemic stroke and future therapeutic influences.

ADMA--a Possible Marker for Early Therapeutic Outcome in Acute Stroke.

BACKGROUND: Ischemic acute stroke is a leading cause for mortality and invalidity in recent years. Clinical trials show the role of ADMA as endogenous inhibitor of nitric oxide synthase and its connection to acute stroke. An early decrease of serum ADMA levels might help in recovery of the blood stream in patients with acute stroke and non-affective changes in the brain. METHODS: We compared 18 patients with acute stroke before and after thrombolysis and 21 patients (without history of cardiovascular disease, diabetes, kidney and liver injury, non-smokers) before and after thrombolysis. All results were compared to 30 healthy persons. Patients were evaluated by NIHSS, with ultrasound, CT and laboratory methods (traditional risk factors and CRP, D-dimmer, homocysteine, and ADMA). RESULTS: Classic vascular factors showed statistical significance in patients with acute stroke. Serum hsCRP levels and D-dimer in our study showed no connection to acute stroke. We found a statistically significant correlation in patients with stroke between ADMA and homocysteine levels (r = 0.469, p < 0.001). We found no significant difference between basic serum ADMA concentrations in groups with stroke who underwent different treatment (r = -0.449, p < 0.001). In patients with thrombolysis ADMA concentrations are reduced earlier, which also shows that earlier clinical recovery leads to no brain damaging effects. CONCLUSIONS: Through its pathophysiological changes, ADMA might be a predictor for acute stroke (along with already known risk factors) and can be a marker for the outcome of stroke, depending on the treatment.

Early clinical and electrophysiologic features of the two most common autosomal recessive forms of Charcot-Marie-Tooth disease in the Roma (Gypsies).

Our recent studies of the genetic epidemiology of neuromuscular disorders in Gypsies in Bulgaria have revealed that two private disorders, hereditary motor and sensory neuropathy type Lom and hereditary motor and sensory neuropathy type Russe, account for most cases of Charcot-Marie-Tooth disease in this population. In this study, we examined the clinical and electrophysiologic manifestations of the two disorders in childhood, aiming to identify the distinctive features that allow early differential diagnosis. The study included 13 patients, aged between 2 and 15 years. The childhood clinical manifestations of both neuropathies were similar, although they tended to be more severe in hereditary motor and sensory neuropathy type Lom. The nerve conduction velocities in hereditary motor and sensory neuropathy type Lom were lower than in hereditary motor and sensory neuropathy type Russe. Brainstem auditory evoked potentials were abnormal in hereditary motor and sensory neuropathy type Lom, even at an early age, and normal in hereditary motor and sensory neuropathy type Russe. Although electrophysiologic data provide a more reliable differentiation than clinical data, the definitive diagnosis should rely on genetic testing. (J Child Neurol 2006;21:20-25).

Recurrent somatic mosaicism for D4Z4 contractions in a family with facioscapulohumeral muscular dystrophy.

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of the D4Z4 repeat on 4q35. We describe a FSHD family of unusual genetic complexity presenting with two independent mitotic contractions of D4Z4 in two successive generations. In addition, a non-pathogenic FSHD-sized allele of approximately the same size is interfering with the DNA diagnosis in this family. Interestingly, this allele is not recognized by the probes 4qA and 4qB representing two distal variants of 4qter, suggesting the presence of yet another, infrequent variant of 4qter.

Genetic confirmation of facioscapulohumeral muscular dystrophy in a case with complex D4Z4 rearrangments.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of the D4Z4 repeat on chromosome 4q. Genetic confirmation of the clinical diagnosis of FSHD is complicated by the presence of a homologous repeat on chromosome 10q and the frequent repeat exchanges between both chromosomes. Here, we describe the genetic evaluation of an FSHD patient with a complex D4Z4 allele constitution in which the potentially pathogenic allele seemingly resides on chromosome 10, despite FSHD being exclusively linked to chromosome 4. Complementary allele typing and segregation analysis confirmed the clinical diagnosis of FSHD by revealing the chromosome 4 origin of the pathogenic allele in the presence of two exchanged repeat arrays, one on chromosome 4 and one on chromosome 10, an allele constitution that cannot be identified by conventional DNA diagnosis.