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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 19 recordsLinked to original sources
PubMed2006

Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial.

BACKGROUND: Coronary microvascular dysfunction contributes to infarct extension and poor prognosis after an acute myocardial infarction (AMI). Recently, progenitor cell application has been demonstrated to improve neovascularization and myocardial function after experimental myocardial infarction. Therefore, we investigate coronary blood flow regulation in patients after AMI treated with intracoronary progenitor cell therapy. METHODS AND RESULTS: In the TOPCARE-AMI trial, patients received either bone marrow-derived or circulating progenitor cells into the infarct-related artery 3-7 days after AMI. The present substudy investigates in 40 patients coronary blood flow regulation at the time of progenitor cell therapy and at 4-month follow-up by i.c. Doppler in the infarct artery as well as a reference vessel. At the initial measurement, coronary flow reserve (CFR) was reduced in the infarct artery compared to the reference vessel (median 2.5 vs. 3.4, p<0.001). At 4-month follow-up, intracoronary progenitor cell therapy was associated with a normalization of CFR in the infarct artery (median 3.9 vs. reference vessel 3.8, p=0.15). CFR also improved in the reference vessel, but mechanisms were different: reference vessel increase in CFR was secondary to an increased basal vascular resistance, probably due to reduced need for hypercontractility. In contrast, in the infarct artery, adenosine-induced minimal vascular resistance profoundly decreased, indicating an increased maximal coronary vascular conductance capacity. In addition, in a non-randomized matched control group (n=8), minimal vascular resistance in the infarct artery was significantly elevated compared to progenitor cell treated patients 4 months after AMI (p=0.012). CONCLUSIONS: Intracoronary progenitor cell therapy after AMI is associated with complete restoration of coronary flow reserve due to a substantial improvement of maximal coronary vascular conductance capacity. The clinical importance of improved microcirculation by progenitor cell therapy in patients after AMI has to be established in further randomized trials.

Blood Flow Velocity↗
PubMed2006

Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.

AIMS: Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS: 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. CONCLUSIONS: Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.

Aged↗
PubMed2005

Nitric oxide contributes to cytokine-induced apoptosis in pancreatic beta cells via potentiation of JNK activity and inhibition of Akt.

AIMS/HYPOTHESIS: Pro-inflammatory cytokines cause beta cell secretory dysfunction and apoptosis--a process implicated in the pathogenesis of type 1 diabetes. Cytokines induce the expression of inducible nitric oxide (NO) synthase (iNOS) leading to NO production. NO contributes to cytokine-induced apoptosis, but the underlying mechanisms are unclear. The aim of this study was to investigate whether NO modulates signalling via mitogen-activated protein kinases (MAPKs) and Akt. MATERIALS AND METHODS: MAPK activities in INS-1 cells and isolated islets were determined by immunoblotting and in vitro kinase assay. Apoptosis was determined by ELISA measurement of histone-DNA complexes present in cytoplasm. RESULTS: Apoptosis in INS-1 cells induced by IL-1beta plus IFNgamma was dependent on NO production as demonstrated by the use of the NOS blocker NG-methyl-L-arginine. Accordingly, an NO donor (S-nitroso-N-acetyl-D, L-penicillamine, SNAP) dose-dependently caused apoptosis in INS-1 cells. SNAP activated c-Jun N-terminal kinase (JNK) and p38 MAPK, but suppressed the activity of extracellular signal-regulated kinase MAPK. In rat islets, NOS inhibition decreased JNK and p38 activities induced by a 6-h exposure to IL-1beta. Likewise, IL-1beta-induced JNK and p38 activities were lower in iNOS(-/-) mouse islets than in wild-type islets. In human islets, SNAP potentiated IL-1beta-induced JNK activation. The constitutive level of active, Ser473-phosphorylated Akt in INS-1 cells was suppressed by SNAP. IGF-I activated Akt and protected against SNAP-induced apoptosis. The anti-apoptotic effect of IGF-I was not associated with reduced JNK activation. CONCLUSIONS/INTERPRETATION: We suggest that NO contributes to cytokine-induced apoptosis via potentiation of JNK activity and suppression of Akt.

Animals↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2005

Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human beta-cells from hyperglycemia-induced apoptosis.

Studies in vivo indicate that IRS2 plays an important role in maintaining functional beta-cell mass. To investigate if IRS2 autonomously affects beta-cells, we have studied proliferation, apoptosis, and beta-cell function in isolated rat and human islets after overexpression of IRS2 or IRS1. We found that beta-cell proliferation was significantly increased in rat islets overexpressing IRS2 while IRS1 was less effective. Moreover, proliferation of a beta-cell line, INS-1, was decreased after repression of Irs2 expression using RNA oligonucleotides. Overexpression of IRS2 in human islets significantly decreased apoptosis of beta-cells, induced by 33.3 mM D-glucose. However, IRS2 did not protect cultured rat islets against apoptosis in the presence of 0.5 mM palmitic acid. Overexpression of IRS2 in isolated rat islets significantly increased basal and D-glucose-stimulated insulin secretion as determined in perifusion experiments. Therefore, IRS2 is sufficient to induce proliferation in rat islets and to protect human beta-cells from D-glucose-induced apoptosis. In addition, IRS2 can improve beta-cell function. Our results indicate that IRS2 acts autonomously in beta-cells in maintenance and expansion of functional beta-cell mass in vivo.

Animals↗
PubMed2005

[Islet transplantation in type I diabetes mellitus].

Type 1 diabetes mellitus results from autoimmune destruction of the insulin-secreting cells in the pancreas. The dramatic breakthrough in 2000 with the "Edmonton protocol" for successful solitary islet transplantation has restored optimism for the application of islet transplantation as a treatment for type I diabetes. Due to the recent successes, islet transplantation has evolved from a theoretical concept to its current status as a therapeutic option for patients with type 1 diabetes. Islet transplantation has shown to normalize metabolic control in a way that has been virtually impossible to achieve with exogenous insulin. The less invasive procedure of islet transplantation as compared to whole pancreas transplantation in patients with type 1 diabetes mellitus would be expected to be safer and much less costly. However, this procedure also requires lifetime immunosuppression with drugs. The limited availability of donor organs and the necessity of transplantation of several pancreata in order to achieve insulin independence limit this procedure to a small minority of patients. Unlike the North American centers, the European centers concentrated their efforts on islet after kidney and simultaneous islet kidney transplantation. The two Swiss islet transplantation programs have been pioneers in applying the steroid-free "Edmonton protocol" to simultaneous islet-kidney and islet after kidney transplantation. The long term follow-up showed that islet function decreases over time. In order to maintain insulin independence repeated islet transplants would have to be given to the patients. Therefore, there has been a change in paradigm over time. The major goal of islet transplantation focuses now on achieving a good blood glucose control and avoidance of severe hypoglycaemic episodes rather than only insulin-independence. Thus, due to the limited supply of donor organs, more patients can benefit from islet transplantation. Small insulin doses of exogenous insulin prevent stress on the islet in particular after meals and might help to maintain the transplanted islet mass over time. Due to the severe limitations of immunosuppression solitary islet transplantation is limited to a very small number of patients with type 1 diabetes. The most common indication for islet transplantation in Switzerland is terminal kidney failure in patients with type I diabetes. A simultaneous islet-kidney or pancreas-kidney transplantation should be offered to these patients. The choice between islet or pancreas transplantation is a matter of age and diabetic complications because the perioperative risk is considerably higher in pancreas transplantation.

Diabetes Mellitus, Type 1↗
PubMed2004

Comparative analysis of the Borrelia garinii genome.

Three members of the genus Borrelia (B.burgdorferi, B.garinii, B.afzelii) cause tick-borne borreliosis. Depending on the Borrelia species involved, the borreliosis differs in its clinical symptoms. Comparative genomics opens up a way to elucidate the underlying differences in Borrelia species. We analysed a low redundancy whole-genome shotgun (WGS) assembly of a B.garinii strain isolated from a patient with neuroborreliosis in comparison to the B.burgdorferi genome. This analysis reveals that most of the chromosome is conserved (92.7% identity on DNA as well as on amino acid level) in the two species, and no chromosomal rearrangement or larger insertions/deletions could be observed. Furthermore, two collinear plasmids (lp54 and cp26) seem to belong to the basic genome inventory of Borrelia species. These three collinear parts of the Borrelia genome encode 861 genes, which are orthologous in the two species examined. The majority of the genetic information of the other plasmids of B.burgdorferii is also present in B.garinii although orthology is not easy to define due to a high redundancy of the plasmid fraction. Yet, we did not find counterparts of the B.burgdorferi plasmids lp36 and lp38 or their respective gene repertoire in the B.garinii genome. Thus, phenotypic differences between the two species could be attributable to the presence or absence of these two plasmids as well as to the potentially positively selected genes.

Borrelia burgdorferi↗
PubMed2004

Soma-germ line competition for lipid phosphate uptake regulates germ cell migration and survival.

Lipid phosphates can act as signaling molecules to influence cell division, apoptosis, and migration. wunen and wunen2 encode Drosophila lipid phosphate phosphohydrolases, integral membrane enzymes that dephosphorylate extracellular lipid phosphates. wun and wun2 act redundantly in somatic tissues to repel migrating germ cells, although the mechanism by which germ cells respond is unclear. Here, we report that wun2 also functions in germ cells, enabling them to perceive the wun/wun2-related signal from the soma. Upon Wun2 expression, cultured insect cells dephosphorylate and internalize exogenously supplied lipid phosphate. We propose that Drosophila germ cell migration and survival are controlled by competition for hydrolysis of a lipid phosphate between germ cells and soma.

Animals↗
PubMed2003

Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging.

BACKGROUND: Experimental and initial clinical studies suggest that transplantation of circulating blood- (CPC) or bone marrow-derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion. METHODS AND RESULTS: In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7+/-1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44+/-10% to 49+/-10%; P=0.003), a decrease in end-systolic volume (from 69+/-26 to 60+/-28 mL; P=0.003), and unchanged end-diastolic volumes (122+/-34 versus 117+/-37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46+/-32 to 37+/-28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling. CONCLUSIONS: Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.

Cell Movement↗
PubMed2003

Impact of elevated ambient temperatures on the acute immune response to intensive endurance exercise.

To date, there has been little research examining how elevated ambient temperatures exert an additional effect on the acute immune response to endurance exercise. Seven endurance-trained, non-heat-acclimated men [mean (95% confidence interval): 29.7 (25.9-33.5) years, .VO(2max) 66.3 (61.3-71.3) ml.kg(-1).min(-1)] performed two 60-min treadmill runs (75% .VO(2max)) in two different environments (EX1: 18 degrees C/50% room temperature/relative humidity and EX2: 28 degrees C/50% room temperature/relative humidity) with a 7-day interval between the runs. Blood samples were drawn at rest and 0, 0.5, 3, 24, and 48 h after exercise. Compared to EX1, exercise-induced increases in core temperature, sweating rate, heart rate, plasma norepinephrine, cortisol, human growth hormone, and neutrophil and monocyte counts were significantly (5% level) more pronounced after EX2. In contrast, responses of plasma epinephrine, myeloperoxidase, interleukin (IL)-6 as well as lymphocyte counts were similar in EX1 and EX2. Plasma concentrations of IL-8 and C-reactive protein were affected by neither exercise nor by additional heat exposure. Our results suggest that the additional impact of elevated ambient temperatures on stress responses to endurance exercise in trained subjects seems to affect primarily the cardiocirculatory and hormonal systems, and resulting changes in neutrophil and monocyte cell-trafficking. In contrast, heat stress does not seem to exert large additional effects on the acute immune response to endurance exercise as performed in the present study.

Acute-Phase Reaction↗
PubMed2003

[Primary malignant melanoma of the uterine cervix. Report of two cases and review of the literature].

The manifestation of a malignant melanoma in the uterus is very rare, more often it is the result of metastasis rather than a primary tumor. A malignant melanoma at this site can originate either from melanocytic elements within the cervical epithelium or from the cervical stroma. We report on two cases of primary malignant melanoma of the uterine cervix and compare them with other cases from the literature.

Adult↗
PubMed2003

[Langerhans cell histiocytosis: petrosal remodelling after chemotherapy--case report and review of the literature].

We report the case of a child presented by her parents to the ENT outpatient service for swelling of the right temporal bone. The child had a history of recurrent bilateral inflammation of the middle ear. Tympanometry revealed a reduced compliance. Due to conductive hearing loss it was impossible to measure otoacustic emissions. Otherwise a normal ENT status was found. Imaging (MRI/CT) demonstrated bitemporal soft-tissue changes with extensive osseous destruction, but no typical imaging signs of an inflammatory, dysplastic or expansive process. The tentative diagnosis of Langerhans' cell histiocytosis (LCH) made on the basis of the clinical and imaging findings was confirmed by biopsy. After exclusion of disseminated LCH, chemotherapy was initiated, and the child underwent follow-up imaging after 3 months. CT showed clear signs of bitemporal reossification. The case reported here illustrates the problems encountered in diagnosing LCH which may present with unspecific clinical symptoms despite advanced osseous destruction. ENT specialists should be familiar with this very heterogeneous entity and think of LCH especially in children presenting with therapy-refractory otitis media, otitis externa, or mastoiditis in order to ensure a timely diagnosis and to thus improve the chances of successful therapy. Imaging modalities (CT, MRI) have a role in the early diagnosis and follow-up of this disorder.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Quantitative perfusion imaging by multi-slice CT in stroke patients].

OBJECTIVES: Evaluation of a parametric deconvolution algorithm (DA) in the diagnostic assessment of stroke patients by multi- slice spiral computed tomography (MS-CT). MATERIAL AND METHODS: 52 patients (age range 34 - 89 years) with clinically suspected acute ischemia of one hemisphere and no infarct demarcation on plain cerebral CT underwent CT perfusion (CTP), performed on average 3.4 hours after the onset of symptoms by using MS-CT (4 x 8 mm scan volume). Using a DA-based software module, perfusion images of the cerebral blood perfusion (CBP), cerebral blood volume (CBV) and mean transit time (MTT) were calculated and assessed by two readers for visually apparent perfusion abnormalities. Amount and extension of perfusion disturbances were measured and correlated with the outcome. RESULTS: Of 44 patients, in whom perfusion maps could be generated, territorial infarction was confirmed by follow-up in 22 subjects. With a sensitivity of 95 % ischemia could be detected on MTT-maps (CBP 91 %, CBV 77 %). Specificity was highest (100 %) for CBV-maps. Patients with infarction showed significant (p < 0.001) reduction of CBP (10.7 vs. 38.3 ml/100 ml/min), CBV (1.3 vs. 2.3 ml/100 ml) and prolongation of MTT (12.3 vs. 4.3 s) compared to the contralateral hemisphere, whereas in patients without infarction no significant changes were found. Extension of CBV reduction showed the best correlation (r = 0.82) with final infarct volume. CONCLUSION: The DA-based CTP protocol evaluated in this study is a suitable tool for the early identification and quantification of acute cerebral ischemia.

Adult↗
PubMed2003

Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.

Adult↗
PubMed2003

Individual differences in self-reported heat tolerance. Is there a link to the cardiocirculatory, thermoregulatory and hormonal response to endurance exercise in heat?

AIM: Tolerance to exercise in heat exhibits great interindividual variability. We questioned whether individual differences in self-reported heat tolerance within a group of endurance trained athletes are linked to the cardiocirculatory, thermoregulatory and hormonal response to endurance exercise in heat. METHODS: Using a rating scale to assess the individual degree of tolerance to exercise in heat we allocated 12 non-heat-acclimated trained runners into two groups of 5 highly heat tolerant (HHT) and 7 less heat tolerant (LHT) athletes. Both groups performed a 60-min treadmill run (velocity 90% of individual anaerobic threshold, room temperature and humidity 28 inverted exclamation mark C and 50%, respectively). RESULTS: Sweating rate did not differ between HHT (mean +/- SEM: 0.44+/-0.02) and LHT (0.40+/-0.02 ml x kg(-1) x min(-1)). Compared to LHT, exercise-induced rises in core temperature (39.3+/-0.2/40.0+/-0.2 inverted exclamation mark C), heart rate, plasma norepinephrine and cortisol were significantly lower in HHT, while epinephrine did not exhibit differences between the groups. In contrast, response of human growth hormone (hGH) was significantly more pronounced in HHT. CONCLUSION: Our initial results, obtained in a small group of endurance-trained runners, show that self-reported tolerance to exercise in heat is associated with an attenuated rise in body core temperature during prolonged exercise under elevated ambient temperatures. This finding in heat tolerant athletes is paralleled by a lower stress response as reflected by lower rises in heart rate and stress hormones such as norepinephrine and cortisol. The functional significance (i.e. with respect to sweating function) of the more pronounced response of hGH in heat tolerant athletes warrants further research.

Body Temperature↗
PubMed2002

[Using multislice spiral CT in neuroradiologic imaging].

Multislice computed tomography (MS-CT) was introduced into clinical radiology in 1999 and has shown a significant effect on various indications for computed tomography (CT) imaging in neuroradiology. Technical highlights of this new scanner type are the simultaneous data acquisition by up to four detector rows at present, an accelerated rotation time, and a reduction of the slice thickness to as low as 0.5 mm. These features account for an extended scan area, such as head and neck imaging in polytraumatized patients, detailed contrast-enhanced studies of the cervicocerebral vascular system from the carotid bifurcation to the vertex, as well as cerebral perfusion studies of a larger brain volume with an improved time resolution compared to established CT procedures. In addition, the diagnostic yield of the CT is increased with respect to several applications by reducing common image artefacts at the level of the cervicothoracic junction as well as those caused by metallic implants. Apart from improving the image quality of the primary cross-sectional slices, MS-CT significantly enhances two- and three-dimensional image reconstructions. Radiation protection is an important issue with MS-CT, especially when skull base imaging is considered.

Artifacts↗
PubMed2002

[Practical management of diabetic foot].

Prevention and the correct treatment of the diabetic foot have important social and economic consequences. Risk stratification is essential for choosing the appropriate treatment strategy. History and careful clinical examination identify the risk in each individual patient with diabetes. Peripheral neuropathy (PNP), foot deformation, peripheral arterial disease (PAD) and a history of previous ulcer or amputation are the most important risk factors. PAD must be diagnosed and treated by percutan transluminal angioplasty or bypass surgery where necessary. Primary foot deformation or secondary due to PNP require shoe modifications. Good metabolic control of diabetes and treatment of other cardiovascular risk factors (dyslipidemia, hypertension) delay or prevent the development of PNP and PAD. Therefore an early multidisciplinary approach is essential for each patient with diabetes and foot problems. In the presence of a foot ulcer, it's important to diagnose osteomyelitis by clinical or radiological examination. The choice and duration of antibiotic treatment and surgical intervention depends on the localisation and extension of infection around the ulcer and the presence of osteomyelitis. In case of limb threatening infection, the patient should be referred to a specialized treatment facility immediately.

Arthropathy, Neurogenic↗