Neuropathic Form Research Articles

Frequency, characteristics, and correlates of pain in a pilot study of colorectal cancer survivors 1-10 years post-treatment.

The long-term effects of disease and treatment in colorectal cancer (CRC) survivors are poorly understood. This study examined the prevalence and characteristics of pain in a sample of CRC survivors up to 10 years post-treatment. One hundred cancer-free CRC survivors were randomly chosen from an institutional database and completed a telephone survey using the Brief Pain Inventory, Neuropathic Pain Questionnaire-Short Form, Quality of Life Cancer Survivor Summary, Brief Zung Self-Rating Depression Scale, Zung Self-Rating Anxiety Scale, and Fear of Recurrence Questionnaire. Participants were primarily Caucasian (90%) married (69%) males (53.5%) with a mean age of 64.7 years. Chronic pain was reported in 23% of CRC survivors, with a mean moderate intensity rating (mean = 6.05, standard deviation = 2.66) on a 0-10 rating scale. Over one-third (39%) of those with pain attributed it to their cancer or treatment. Chi-square and t-test analyses showed that survivors with pain were more likely to be female, have lower income, be more depressed and more anxious, and show a higher endorsement of suicidal ideation than CRC survivors without chronic pain. On average, pain moderately interfered with daily activity. Chronic pain is likely a burdensome problem for a small but not inconsequential minority of CRC survivors requiring a biopsychosocial treatment approach to improve recognition and treatment. Open dialogue between clinicians and survivors about physical and emotional symptoms in long-term follow-up is highly recommended.

Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases

BackgroundAmyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease that is treated by liver transplantation. The non-neuropathic form includes familial autoinflammatory diseases. As no incidence data on these hereditary diseases are available and as even diagnostic data on non-neuropathic forms are lacking we determined the incidence of these diseases and characterized non-neuropathic conditions.MethodsPatients were identified using data from the Swedish Hospital Discharge Register and from the Outpatient Register for 2001 through 2008. All patients discharged with hereditary amyloidosis diagnoses were included and standardized incidence rates were calculated.ResultsNon-neuropathic disease was diagnosed in 210 patients, with an incidence of 2.83 per million. FAP was diagnosed in 221 patients, with an incidence of 2.02 per million. Two northern provinces that are home to 5% of the Swedish population accounted for 77% of FAP cases; the incidence in one of them, West Bothnia, was 100 times that in the rest of Sweden. Approximately 98% of non-neuropathic disease patients were immigrants, most of whom were from the Eastern Mediterranean area. Young Syrian descendants had the highest incidence rate, which was over 500-fold higher than that in individuals with Swedish parents. Even the early onset of these conditions identified them as familial autoinflammatory diseases.ConclusionsFAP cases were highly concentrated in the two northernmost provinces. Non-neuropathic familial autoinflammatory diseases were of early-onset and immigrant origin most likely related to periodic fever syndromes. Paradoxically, FAP has remained endemic, in spite of population movements within the country, while familial autoinflammatory diseases, with an incidence exceeding that of FAP, were brought into the country as a result of immigration mainly from the Eastern Mediterranean area.

INFLUENCE OF SOME RISK FACTORS ON PREDICTION OF PATIENTS WITH DIABETIC FOOT SYNDROME

Patients with diabetic foot syndrome are characterized by a high mortality which is significantly higher at neuroischemic form of the syndrome in comparison with neuropathy. The probability of fatal outcome in the persons with neuropathic form of diabetic foot syndrome constituted 31%, and in case of ischemia this index reached 51%. Angiopathy was revealed in 77,4 % of persons with high amputations and only in 27% of patients with low amputations, thereby the value of osteohumeral index in these groups constituted 0,7±0,2 and 0,9±0,1 correspondingly. For all that, osteohumeral index is considered to be the main factor that determines probability of high amputation. Treatment of the patients with diabetic ulcers of the feet in an outpatient setting is accompanied with initial epithelization of ulcerous defect in 72,9% of cases.

Intestinal pseudo-obstruction due to small bowel α-actin deficiency in a child with Ehlers–Danlos syndrome

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by signs and symptoms of intestinal obstruction without a mechanical cause. In children, two main subtypes, the neuropathic and myopathic forms, are found [1]. A variety of pathological findings of the smooth muscle can result in clinical syndromes involving a motility disorder of the small or large intestine. Moreover, abnormalities of enteric innervation or intestinal muscle defects may be diffuse or involve limited tracts [1]. Deficiency of one of the isoforms of the cytoskeletal smooth muscle protein actin, aactin, involving the circular muscle of the jejunum, is known to induce CIPO both in adults and in children [2]. We report a unique case of a-actin deficiency associated with Ehlers– Danlos syndrome. A 14-year-old girl was urgently admitted because of shock with abdominal distension and severe dehydration. On plain abdominal X-rays, severe small and large bowel dilatation was noted. The patient’s history was negative for any previous medical or surgical condition. She had mandibular prognathism causing aerophagia and affecting speech and mastication. An urgent exploratory laparoscopy was carried out; dilatation of the ascending colon and terminal ileum were found. No perforation or necrosis was detected on inspection of the whole intestine. Two weeks later, persistent bowel dilatation necessitated ileostomy. The patient developed intestinal obstruction following ileostomy closure. Subsequently, several surgical intestinal deviation procedures were performed and after every attempt at reversal immediate reoperation was required. Ten months later, a definitive end ileostomy had to be fashioned 10 months later. Full-thickness biopsies of the ileum and colon were obtained. Histological examination with conventional (hematoxylin and eosin, H&E) staining appeared basically normal (Fig. 1a). Immunohistochemical assessment (NSE, S100, CD117) showed normal features of the enteric nervous system in both the small intestine and the colon, whereas immunohistochemistry for a-actin revealed decreased expression in the circular layer of the small bowel (Fig. 1b– d) and normal features in the colon. Skin biopsy performed after abdominal surgery, revealed hallmarks of disturbed fibrillogenesis and led to the diagnosis of Ehlers–Danlos syndrome, classical type (old type I) [3]. Abnormal intestinal findings often leading to intestinal perforation, especially in the colon, are observed in Ehlers– Danlos syndrome, although almost exclusively in patients with subtype IV [4]. As far as we know, no previous association has been described between Ehlers–Danlos syndrome and a-actin deficiency. The latter was probably the cause of CIPO in our patient (since the enteric nervous system appeared normal), causing impaired propulsion in the small bowel and pseudo-obstructive symptoms. The diagnosis of CIPO, in both adults and children, is often delayed, due a low index of suspicion and the fact G. Pelizzo ! G. Nakib ! V. Calcaterra Pediatric Surgery Unit, Department of Mother and Child Health, IRCSS Polyclinic S. Matteo Foundation, University of Pavia, Pavia, Italy

Molecular Basis and Clinical Management of Gaucher Disease

Gaucher disease (GD) type I is an autosomal recessive disease caused by a genetic deficiency of lysosomal β-glucocerebrosidase that leads to accumulation of undergraded substrate glucocerebroside and other glycolipids, thus causing damage in different organs. GBA is the only gene in which mutations are known to cause GD. Nearly 300 mutations have been identified in GD patients, including frame-shift mutations, point mutations, deletions, insertions, splice site mutations and recombinants. The variety of phenotypes associated to GD shows imperfect correlation with mutations. GD encompasses a spectrum of clinical findings from a perinatal lethal form to an asymptomatic form. However the classification of GD by clinical subtype is still useful in describing the wide range of clinical findings and broad variability in presentation. Three major clinical types are delineated: type I (chronic nonneuropathic), type II (acute neuropathic), and type III (chronic neuropathic). Patients with type I GD present with visceromegaly, hematological complications, and bone disease. Cardiac and pulmonary complications are rare. Type I GD adult patients have elevated risk of malignancies, Parkinson’s disease or Parkinsonism. Neuropathic forms of GD are rare and clinically ranging from lethal perinatal form to very mild form limited to abnormalities of horizontal ocular saccades. Diagnosis of acid β-glucosylceramidase relies on enzyme activity in peripheral blood leukocytes or skin fibroblasts and/or identification of GBA mutations. Enzyme replacement therapy is an effective treatment for non-neuropathic GD. Substrate inhibitor is the alternative therapy for some patients with GD is miglustat, iminosugar inhibitor of glucocerebroside synthase.

Neuropathic pain needs systematic classification

Neuropathic pain needs systematic classification

Possibilities of three phase scintigraphy in the diagnosis of diabetic osteoarthropathy

Establishing informative of 3-phase scintigraphy in the evaluation of blood flow and identify pyo-inflammatory process in patients with neuropathic, ischemic, and mixed forms of diabetic foot. This study includes the results of three-phase scintigraphy of 76 patients with diabetes mellitus and with suspicion of osteomyelitis in diabetic foot. Results were verified with morphological study in 39 patient. In patients with diabetic foot the depression of the main vessels blood flow and blood flow prevalence the changes intraos­seous blood flow. Comparison of scintigraphy and morphological studies confirmed the highly informative three-phase scintigraphy in the evaluation of main and peripheral blood flow. 3-phase scintigraphy revealed a lower specificity (66.7%) in the diagnosis of osteomyelitis in patients with diabetes mellitus at the sensitivity (94.7%) and accuracy (73.7%). Three-phase scintigraphy is high-performance method in revealing the arterial and peripheral blood flow disorder in patients with diabetes mellitus. The low specificity of the three-phase scintigraphy with high sensitivity indicate the limited possibilities of the method in the identification of pyo-inflammatory process in patients with diabetes mellitus. The observed preservation of blood flow makes it possible to expand the employment of methods of nuclear medicines and apply scintigraphy with labeled leukocytes for indicating purulent infection in patients with complicated course.

Differential, size-dependent sensory neuron involvement in the painful and ataxic forms of primary Sjögren's syndrome-associated neuropathy

Primary Sjögren's syndrome (pSS)-associated neuropathy manifests a wide variety of peripheral neuropathies that may show overlap among the neuropathic forms. In this report, we describe histopathological findings of two autopsy cases with pSS-associated neuropathy; one of them manifested the painful form and another showed ataxic form. The population of dorsal root ganglion (DRG) neurons and the density of myelinated fibers in the dorsal spinal root were variably reduced among spinal segments in both forms. In the painful form, there was a prominent reduction of small neurons, while in the ataxic form, large neurons were predominately lost. In accordance with the degree of the DRG cell loss, the modality of nerve fiber loss in the dorsal spinal roots and sural nerve correlated well with the corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was present in the DRG, sympathetic ganglion, epineurial and perineurial space throughout the peripheral nerve trunks, and visceral organs, including the submandibular gland of both forms.Although the size of affected DRG neurons is different, these two forms share a similar causal mechanism, namely, cytotoxic autoimmunity to ganglion neurons, which may be one of a continuum of etiological factors. This hypothesis may have an impact on therapeutic approach.

Effects of Nicotine on Spinal Cord Injury Pain: A Randomized, Double-Blind, Placebo Controlled Crossover Trial

One factor affecting spinal cord injury (SCI)-related pain may be nicotine. Case reports have described a worsening of neuropathic pain from smoking and relief from abstinence. Neurobiological correlates also implicate the potential effect of nicotine on SCI-related pain. The current study employed a randomized, placebo-controlled crossover design to examine the effect of nicotine exposure on subtypes of SCI-related pain among smokers and nonsmokers. Whereas nonsmokers with SCI showed a reduction in mixed forms of pain following nicotine exposure, smokers with SCI showed a converse increase in pain with regard to both mixed and neuropathic forms of pain. The exacerbation of pain in chronic nicotine or tobacco users may not only elucidate possible pain mechanisms but may also be of use in smoking cessation counseling among those with SCI.

A newly described mutation of the CLCN7 gene causes neuropathic autosomal recessive osteopetrosis in an Arab family

Neurologic manifestations in osteopetrosis are usually secondary to sclerosis of the skull bones. However, a rare neuropathic subtype of osteopetrosis exists that resembles neurodegenerative storage disorders. Unlike other forms of osteopetrosis, this latter form does not respond to hematopoietic stem cell transplantation. Preliminary studies suggest that this neuropathic form is more likely to be caused by mutations in the CLCN7 gene in an autosomal recessive manner. This study provides further evidence for this phenotype-genotype correlation by presenting a previously unreported mutation in the CLCN7 gene in a Yemeni family with the neuropathic form. This is also the first study of any mutation in patients with osteopetrosis of Arabic ethnicity. As literature review suggests that this type may be more common in Arabs, cascade genetic screening of early onset of autosomal recessive-osteopetrosis in patients of Arabic ancestry may preferably start with the CLCN7 gene rather than the TCIRG gene as is routinely done in clinical laboratories. Identifying a mutation in the CLCN7 gene in a patient with early onset of autosomal recessive-osteopetrosis may also guide therapeutic decisions including the option of hematopoietic stem cell transplantation.

The new Gaucher-Pass: A key tool in management of shortage

Aims: Gaucher disease is an autosomal recessive inherited lysosomal storage disease which manifests as a non-neuropathic type (type I) or in a neuropathic form (type II+III). There are about 250 Gaucher patients in Germany and an estimated 4000 cases worldwide. Gaucher disease has been treated successfully for the last 20 years with regular intravenous enzyme replacement therapy (ERT). One of the goals is to retain mobility in patients with the neuropathic form of Gaucher disease. A concise tool for documentation of the management a supervision of the therapy would be a valuable asset.

Velaglucerase alfa as a therapeutic option for Gaucher disease

Gaucher disease (GD) is an inherited disorder characterized by deficiency of the lysosomal enzyme glucocerebrosidase and the accumulation of an incompletely metabolized substrate (glucocerebroside) in cells of monocyte lineage. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly and bone disease; in a subset of patients with the neuropathic form, additional problems related to primary CNS involvement develop, resulting in a shortened lifespan. Velaglucerase alfa is a human recombinant formulation of glucocerebrosidase; in clinical trials it has been shown to be safe and effective in reversing the cardinal systemic features of GD. Prior to the introduction of velaglucerase alfa, enzyme replacement therapy with imiglucerase for GD type 1 (the non-neuronopathic form) had been established as the standard of care. Problems with imiglucerase supply have resulted in the increased use of velaglucerase alfa, through an expanded access program prior to regulatory approval (which was obtained in February 2010 in the USA and more recently in countries of the EU). Thus far, the therapeutic profile for velaglucerase alfa appears comparable to the historical data set for imiglucerase, although the reported rate of antibody formation against velaglucerase alfa is lower (1 vs 15%). In addition, in vitrostudies involving human macrophages have demonstrated a more rapid internalization of velaglucerase alfa. The long-term implications of these observations need to be established. Moreover, factors that will influence the choice of treatment agent in GD patients will need to be determined.

Chronic wounds and diabetes mellitus: modern concept and prospects for conservative treatment

Current trends in conservative therapy of chronic wounds associated with diabetes mellitus are discussed along with results of original studies aimedto assess efficacy of different methods for unloading the affected leg in patients with the neuropathic form of diabetic foot syndrome and diabeticnephropathy. Effects of collagen-containing dressings on the wound-related factors (matrix metalloproteinases 2 and 9, collagenolytic activity) andwound epithelization rate are described.

The use of dressing materials based on the lipid-colloid technology for the local treatment of diabetic foot syndrome

Aim. Clinical assessment of the use of dressing materials based on the lipid-colloid technology for the local treatment of diabetic foot syndrome (DFS). Materials and methods. The study included 24 patients with DM1 and DM2 and neuropathic or neuroischemic forms of DFS in the absence of pronounced leg ischemia (ankle-brachial index >0.7). Duration of the observation period was 8 weeks, the patients were examined once in 2 weeks. The dressing materials used in the study were based on the Cellosorb NA, Cellosorb Ag, Urgotul S Ag. technology (Laboratories Urgo). Efficacy and safety of the dressing materials were estimated from the wound size, degree of exudation, characteristics of the wound bed and the surrounding tissues. The data obtained were treated using Statistica v. 7.0 software (StatSoft Inc.). Results. Efficacy of local therapy was assessed based on the Pressure Ulcer Scale of Healing (PUSH). Neither local nor systemic adverse events related to the use of the above dressing materials were registered during the follow-up. Cellosorb NA and Cellosrb Ag hydrocellular dressings showed high absorption activity and atraumatic properties. Most patients especially those using Cellosorb Ag were free from local infection. Conclusion. Dressing materials based on the lipid-colloid technology are safe and meet all requirements for the means of local treatment of chronic wounds.

Editorial overview: lysosomal storage disorders with primary neurological involvement

The focus of this issue of the Journal of Inherited Metabolic Disease is on lysosomal storage diseases (LSD) subtypes associated with primary neurological involvement. Conceptual advances that have had practical applications will be highlighted in this review issue. Although rare, LSDs are a global problem and represent life-limiting or threatening disorders that can have a significant impact on patients’ wellbeing. We have chosen experts from around the world, whose experience reflect the forefront in medical genetics devoted to progress in the LSDs. In the course of soliciting articles on the topic, it became apparent that use of certain terms required clarification. Although several publications have described LSD variants with primary neurological involvement as neuropathic or neuronopathic forms of the disease, strictly speaking this choice of terms is misplaced. In our copy of Pryse-Phillips’ Companion to Clinical Neurology (1995), neuropathy is defined as a disorder of one or more peripheral nerves, whereas neuronopathy is used to refer to a disease of the peripheral nervous system in which primary neuropathological changes appear in the nerve cell body rather than the axon of the myelin sheath. As peripheral nerve pathology is seen in only a subset of LSDs, the term neurodegenerative was suggested as a more appropriate descriptor, which may be acceptable but perhaps not for all entities (e.g., mucolipidosis IV). In the end, and for the sake of brevity, it was decided the term neuropathic would be retained, but discussion of disorders would not cover topics relating to secondary neurologic complications (e.g., radiculopathy secondary to vertebral compression in osteoporotic patients with Gaucher disease). Over the past few decades, we have witnessed remarkable progress in our understanding of LSD; a group of inborn errors of metabolism characterized by a disruption in the degradation, processing and/or transport of various molecules that represent by-products of cellular turnover. The article by Jardim and colleagues, presented in two formats—a review in print and a detailed description of individual clinical entities in an electronic version as supplementary material—describes the various modes of clinical presentation. It is evident that, historically, examination of the phenotype has not included systematic analysis of disease course in ways that enable quantitative assignment of disease severity or rate of progression. Furthermore, studies that have attempted to correlate clinical expression with the genotype have repeatedly pointed to the lack of perfect concordance, except in a few cases, and there remain limited investigations of the factors that influence age of onset or specific patterns of neuronal vulnerability. Recent interest in the neurological problems noted in patients with Gaucher disease type 1 (GD1, conventionally viewed as the non-neuronopathic form) has prompted re-evaluation of the phenotype and investigations of putative causal links, if any, and in particular, the relationship between GD1 and risk for Parkinsonism and/or peripheral neuropathy. Along these lines, the paper by Cherin and co-workers describe observations garnered from a national (French) cross-sectional observational survey. G. M. Pastores (*) Departments of Neurology and Pediatrics, New York University School of Medicine, New York, USA e-mail: Gregory.Pastores@nyumc.org

Pneumoperitoneum without intestinal perforation in an adolescent girl

Pneumoperitoneum without intestinal perforation in an adolescent girl

Quantification of the Thermodynamically Linked Quaternary and Tertiary Structural Stabilities of Transthyretin and Its Disease-Associated Variants: The Relationship between Stability and Amyloidosis

Urea denaturation studies were carried out as a function of transthyretin (TTR) concentration to quantify the thermodynamically linked quaternary and tertiary structural stability and to improve our understanding of the relationship between mutant folding energetics and amyloid disease phenotype. Urea denaturation of TTR involves at least two equilibria: dissociation of tetramers into folded monomers and monomer unfolding. To deal with the thermodynamic linkage of these equilibria, we analyzed concentration-dependent denaturation data by globally fitting them to an equation that simultaneously accounts for the two-step denaturation process. Using this method, the quaternary and tertiary structural stabilities of well-behaved TTR sequences, wild-type (WT) TTR and the disease-associated variant V122I, were scrutinized. The V122I variant is linked to late onset familial amyloid cardiomyopathy, the most common familial TTR amyloid disease. V122I TTR exhibits a destabilized quaternary structure and a stable tertiary structure relative to those of WT TTR. Three other variants of TTR were also examined, L55P, V30M, and A25T TTR. The L55P mutation is associated with the most aggressive familial TTR amyloid disease. L55P TTR has a complicated denaturation pathway that includes dimers and trimers, so globally fitting its concentration-dependent urea denaturation data yielded error-laden estimates of stability parameters. Nevertheless, it is clear that L55P TTR is substantially less stable than WT TTR, primarily because its tertiary structure is unstable, although its quaternary structure is destabilized as well. V30M is the most common mutation associated with neuropathic forms of TTR amyloid disease. V30M TTR is certainly destabilized relative to WT TTR, but like L55P TTR, it has a complex denaturation pathway that cannot be fit to the aforementioned two-step denaturation model. Literature data suggest that V30M TTR has stable quaternary structure but unstable tertiary structure. The A25T mutant, associated with central nervous system amyloidosis, is highly aggregation-prone and exhibits drastically reduced quaternary and tertiary structural stabilities. The observed differences in stability among the disease-associated TTR variants highlight the complexity and heterogeneity of TTR amyloid disease, an observation that has important implications for the treatment of these maladies.

Surgery for Pediatric Patients With Chronic Intestinal Pseudo‐Obstruction Syndrome

Surgery for Pediatric Patients With Chronic Intestinal Pseudo‐Obstruction Syndrome

The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy

We assessed the clinicopathological features of 92 patients with primary Sjögren's syndrome-associated neuropathy (76 women, 16 men, 54.7 years, age at onset). The majority of patients (93%) were diagnosed with Sjögren's syndrome after neuropathic symptoms appeared. We classified these patients into seven forms of neuropathy: sensory ataxic neuropathy (n = 36), painful sensory neuropathy without sensory ataxia (n = 18), multiple mononeuropathy (n = 11), multiple cranial neuropathy (n = 5), trigeminal neuropathy (n = 15), autonomic neuropathy (n = 3) and radiculoneuropathy (n = 4), based on the predominant neuropathic symptoms. Acute or subacute onset was seen more frequently in multiple mononeuropathy and multiple cranial neuropathy, whereas chronic progression was predominant in other forms of neuropathy. Sensory symptoms without substantial motor involvement were seen predominantly in sensory ataxic, painful sensory, trigeminal and autonomic neuropathy, although the affected sensory modalities and distribution pattern varied. In contrast, motor weakness and muscle atrophy were observed in multiple mononeuropathy, multiple cranial neuropathy and radiculoneuropathy. Autonomic symptoms were often seen in all forms of neuropathy. Abnormal pupils and orthostatic hypotension were particularly frequent in sensory ataxic, painful, trigeminal and autonomic neuropathy. Unelicited somatosensory evoked potentials and spinal cord posterior column abnormalities in MRI were observed in sensory ataxic, painful and autonomic neuropathy. Sural nerve biopsy specimens (n = 55) revealed variable degrees of axon loss. Predominantly large fibre loss was observed in sensory ataxic neuropathy, whereas predominantly small fibre loss occurred in painful sensory neuropathy. Angiitis and perivascular cell invasion were seen most frequently in multiple mononeuropathy, followed by sensory ataxic neuropathy. The autopsy findings of one patient with sensory ataxic neuropathy showed severe large sensory neuron loss paralleling to dorsal root and posterior column involvement of the spinal cord, and severe sympathetic neuron loss. Degrees of neuron loss in the dorsal and sympathetic ganglion corresponded to segmental distribution of sensory and sweating impairment. Multifocal T-cell invasion was seen in the dorsal root and sympathetic ganglion, perineurial space and vessel walls in the nerve trunks. Differential therapeutic responses for corticosteroids and IVIg were seen among the neuropathic forms. These clinicopathological observations suggest that sensory ataxic, painful and perhaps trigeminal neuropathy are related to ganglioneuronopathic process, whereas multiple mononeuropathy and multiple cranial neuropathy would be more closely associated with vasculitic process.

Current techniques for diagnosis of diabetic macroangiopathy

The present paper deals with the epidemiology, pathogenesis, and diagnosis of peripheral diabetic macroangiopathy. A total of 102 patients (51 males and 51 females) aged 45 to 74 years (mean 63.4 ± 4.0years) who had type 2 diabetes mellitus (DM) and clinical manifestations of coronary heart disease (CHD) were examined to study endothelial function and the degree and extent ofocclusive lesions in the lower extremity arteries in the neuropathic and neuroischemic forms of the diabetic foot. The study of endothelial function in the reactive hyperemia test demonstrated a significant reduction inflow-dependent vasodilatation in all the examined patients with type 2 DM and CHD as compared with gender- and age-matched CHD patients without carbohydrate metabolic disorders. This is mostly characteristic for patients with type 2 DM, CHD, and femoropopliteal atherosclerosis who showed a 2-fold decrease in flow-dependent vasodilatation as compared with the control patients. Endothelial function more significantly impaired as the severity and extent of diabetic macroangiopathy increased.