The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial.

BACKGROUND AND AIMS: Endothelial dysfunction, vascular inflammation and oxidative stress have been integrally linked to the pathogenesis of both type 2 diabetes and cardiovascular disease. Aged Garlic Extract (AGE), a potent antioxidant, has been shown in previous studies to attenuate these novel risk factors in a non-diabetic population. AIMS: This study tested the hypothesis that AGE may improve endothelial function, oxidative stress, vascular inflammation and insulin resistance in high risk cardiovascular subjects with type 2 diabetes. METHODS: A double blind, placebo controlled crossover pilot study was performed in 26 subjects with type 2 diabetes who received 1200 mg of AGE or placebo daily for 4 weeks with a 4 week washout period. Plasma HsCRP was measured as a marker of inflammation. Plasma TAOS, blood GSH/GSSG and plasma LHP were measured as markers of oxidative stress/anti-oxidant defense. Insulin resistance was measured using the HOMA-IR method. Endothelial function was measured using change in the reflective index (RI) post-salbutamol using digital photoplethysmography and urinary albumin/creatinine ratio was measured as a biochemical surrogate. Measurements were taken at baseline and after intervention with AGE or placebo. RESULTS: Of the 26 patients studied (male 17, female 9), age was 61 ± 8 years (mean ± 1 SD), HbA1c 7.2 ± 1.1%, BP 130/75 ± 15.9/9.8 mmHg, total cholesterol 4.2 ± 0.81 mmol/l, triglyceride 2.11 ± 1.51 mmol/l, and HDL cholesterol 1.04 ± 0.29 mmol/l. The majority of patients were being treated with metformin (59%), aspirin (50%) and statin (96%) therapy. 36% were treated with an ACEI. There were no changes in these therapies throughout the study. Treatment with AGE had no significant effect upon the above metabolic parameters including insulin resistance. Treatment with AGE also had no significant effect on markers of endothelial function (plethysmography), oxidative stress (TAOS, GSH/GSSG, LHP) or inflammation (HsCRP). CONCLUSION: In this group of type 2 diabetic patients at high cardiovascular risk, 4 weeks treatment with AGE did not significantly improve endothelial function, vascular inflammation, oxidative stress or insulin resistance.

Enfermedad de Kawasaki / Malaltia de Kawasaki / Kawasaki´s disease

La malaltia de Kawasaki (MK) és una vasculitis sistèmica aguda d'etiologia desconeguda. El diagnòstic es basa en criteris clínics que inclouen febre, exantema, conjuntivitis, canvis en les extremitats, eritema de la mucosa oral i llavis, i adenopaties cervicals. No obstant això, aquests criteris tenen una sensibilitat i una especificitat baixes i, per tant, altres característiques clíniques i de laboratori poden ser útils per establir el diagnòstic, sobretot en els casos d'MK atípica o incompleta. El pronòstic depèn de l'extensió de l'afectació cardíaca; els aneurismes coronaris, que es de-sen volupen en el 20-25% dels pacients no tractats, poden provocar infart de miocardi o mort sobtada en l'edat adulta. El tractament amb altes dosis d'immunoglobulina intrave-nosa és eficaç per reduir el risc d'aneurismes coronaris en la majoria dels casos i és el tractament d'elecció. En aquesta revisió analitzem la clínica, l'epidemiologia i el tractament d'aquesta malaltia típica de l'edat pediàtrica

La enfermedad de Kawasaki (EK) es una vasculitis sistémica aguda de etiología desconocida. El diagnóstico se basa en criterios clínicos que incluyen fiebre, exantema, conjuntivitis, cambios en las extremidades, eritema de la mucosa oral y labios, y adenopatías cervicales. Sin embargo, estos criterios tienen una sensibilidad y una especificidad bajas y, por tanto, otras características clínicas y de laboratorio pueden ser útiles para establecer el diagnóstico, sobre todo en los casos de MK atípica o incompleta. El pronóstico depende de la extensión de la afectación cardiaca; los aneurismas coronarios, que se desarrollan en el 20-25% de los pacientes no tratados, pueden provocar infarto de miocardio o muerte súbita en la edad adulta. El tratamiento con altas dosis de inmunoglobulina intravenosa es eficaz para reducir el riesgo de aneurismas coronarios en la mayoría de los casos y es el tratamiento de elección. En esta revisión analizamos la clínica, la epidemiología y el tratamiento de esta enfermedad típica de la edad pediátrica (AU)

Kawasaki disease (MK) is an acute systemic vasculitis of unknown etiology. The diagnosis is based on clinical criteria that includes fever, rash, conjunctivitis, changes in the limbs, erythema of the oral mucosa and lips, and cervical lymphadenopathy. However, these criteria have a low sensitivity and specificity and, therefore, other clinical and laboratory features may be helpful in establishing the diagnosis, especially in cases of atypical or incomplete MK. The prognosis depends on the extent of heart involvement; coronary aneurysms, which develop in 20-25% of untreated patients can cause a heart attack or sudden death in adulthood. Treatment with high doses of intravenous immunoglobulin is effective to reduce the risk of coronary aneurysms in most cases and is the treatment of choice. In this review we analyze the symptoms, epidemiology and treatment of this disease, typical of paediatric patients (AU)

Ameliorative potential of montelukast on ischemia-reperfusion injury induced vasculitic neuropathic pain in rat.

AIMS: Ischemia-reperfusion (I/R) event in vascular and nervous system has been documented to rising ischemic and vasculitic neuropathic pain, clinically resembles the complex regional pain syndrome (CRPS). The present study evaluated the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC(4) and Cys-LTD(4)) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic pain in rats. MAIN METHODS: Behavioral parameters were assessed at different time intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic nerve tissue samples were also performed along with histopathological studies. KEY FINDINGS: Behavioral pain assessment has shown increase in paw and tail withdrawal threshold in montelukast treated groups against thermal and mechanical stimuli as compared to I/R control group. We observed a decrease in the total calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO) activity levels, whereas there is rise in reduced glutathione level in montelukast treated groups as compared to I/R control group. However, significant behavioral and biochemical results were observed only in medium and high dose of treated groups which were comparable to normal control group. Moreover, histopathological study has revealed the reduction of I/R induced neuronal edema and axonal degeneration due to montelukast. SIGNIFICANCE: Montelukast has ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to inhibition of lipid peroxidation, reduction of oxidative stress, release of inflammatory mediators and neuroprotective actions. Hence, it could be used as a novel therapeutic agent for the management of vasculitic inflammation related neuropathic pain.

Spinal cord stimulation in the treatment of acute and chronic vasculitis: clinical discussion and synopsis of the literature.

OBJECTIVES: Spinal cord stimulation (SCS) has been widely noted as a treatment for ischemic pain secondary to peripheral vascular disease, but evidence in the vasculitis disease state is lacking. In this paper we present two cases that exemplify the potential of SCS in this unique population. MATERIAL AND METHODS: Two case studies involving patients with the conditions noted including initial findings, treatment protocol, and results documented throughout the treatment regimen. A comprehensive review of the critical literature also was performed. RESULTS: Both patients showed marked improvement with SCS. Pain scores improved dramatically, with a major improvement in disease symptom and quality of life. CONCLUSIONS: Based on literature and our results, SCS is an effective and safe therapy for patients with therapeutically refractory vasculitis.

Large leg ulcers due to autoimmune diseases.

BACKGROUND: Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. CASE REPORT: Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU's with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU's due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU's healed. CONCLUSIONS: LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases.

Refractory vasculitic ulcer of the toe in an adolescent suffering from systemic lupus erythematosus treated successfully with hyperbaric oxygen therapy.

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.

Eosinophilic vasculitis: an inhabitual and resistant manifestation of a vasculitis.

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosuppressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.

Thalamic pain syndrome due to cytomegalovirus vasculitis in an HIV-positive child.

Dejerine-Roussy syndrome, also known as the thalamic pain syndrome is a condition in which the body becomes hypersensitive to pain as a result of damage to the thalamus, a part of the brain that affects sensation. Association of this syndrome with HIV is rare with few case reports described in adults. We report a 10 year old male child who was HIV positive and had developed this syndrome due to cytomegalovirus vasculitis.

Homeopathic treatment in resistant livedoid vasculopathy: case report.

This paper describes the successful outcome of homeopathic treatment in a case of resistant livedoid vasculopathy (LV). LV is a rare disease characterized by chronic recurrent and painful ulceration of the lower limbs, frequently associated to atrophie blanche (AB), probably due to procoagulant conditions. Most literature reports single or very few cases; response to treatment is difficult, even resistant. This patient suffered LV for 7 years before seeking homeopathic treatment; ulcers recurred frequently, at intervals less than 3 months, in spite of continual use of pentoxyfilline. Configuration of signs and symptoms strongly pointed out to the prescription of homeopathic remedy Sepia succus that promptly elicited significant improvement of LV and the patient's overall state (non suppressive treatment). Considerations are made on the value of single case reports and the reliability of prescriptions grounded on consistent signs and coherence among the manifold features of individual disease.

A case of refractory vasculitic ulcers in a systemic lupus erythematosus patient responding to rituximab and hyperbaric oxygen therapy.

Large refractory vasculitic ulcers are not commonly seen in systemic lupus erythematosus (SLE) patients. We report a case of refractory vasculitic ulcers responding to rituximab, a monoclonal antibody directed against CD20 cells leading to prolonged B cell depletion. This treatment was initiated after treatment with high-dose steroids and other immunosuppressants were ineffective/associated with significant side-effects. Following treatment with rituximab, there was sustained clinical improvement and subsequent reduction of prednisolone dose. Rituximab was well-tolerated. Concomitant methotrexate therapy and hyperbaric oxygen therapy (HBOT) may have aided the recovery of the patient's vasculitic ulcers. This case and anecdotal reports have illustrated the efficacy and safety of rituximab in the treatment of refractory SLE-related vasculitic ulcers. Further studies to determine the long-term efficacy and side-effects would be useful.

AA amyloidosis due to chronic oxalate arthritis and vasculitis in a patient with secondary oxalosis after jejunoileal bypass surgery.

We report a case of a woman with secondary oxalosis after jejunoileal bypass surgery for obesity, who presented with oxalate stone disease and renal insufficiency requiring dialysis. Thirty years after surgery, longstanding osteoarticular symptoms were recognized as oxalate arthritis. Eventually, she also developed oxalate vasculitis, which improved with corticoid treatment and intensification of dialysis. Work-up for kidney transplantation revealed AA amyloidosis on gastric and colonic biopsies. Since no other cause of chronic inflammation could be identified, it was concluded that the amyloidosis was secondary to oxalate arthritis and vasculitis. To our knowledge, this is the first report on this association.

Ketamine: an introduction for the pain and palliative medicine physician.

A history of an escalating chronic intractable pain in a patient with cryoglobulinemia, vasculitis, and severe cutaneous ulcerations is presented. A strategy of progressive, multi-agent, N-methyl-D-aspartate-receptor (NMDA-R) blockade that resulted in adequate pain control and a three-fold reduction in opioid consumption is described. Diagnostic process of neuropathic pain and the role of NMDA-R in the development of hyperalgesia are briefly reviewed. Thereafter, existing clinical literature describing the use of Ketamine, a major NMDA-R antagonist for management of malignant pain, is reviewed. Lastly, evidence-based original protocol for intravenous adjuvant Ketamine analgesia for severe cancer pain is presented.

Indications for biotherapy in systemic vasculitides.

Biotherapy now holds a specific place in the therapeutic armamentarium for systemic vasculitides. Such therapy includes cytokines, such as (pegylated) alpha-interferon for hepatitis B virus-related polyarteritis nodosa and hepatitis C virus-related cryoglobulinemic vasculitis, and polyvalent immunoglobulin (IVIg), with well-defined indications and pending positive results. More specifically targeted monoclonal antibodies include antitumor necrosis factor-alpha or anti-CD20 for antineutrophil cytoplasmic antibody-associated vasculitides or anti-interleukin-5 and anti-IgE for Churg-Strauss syndrome. However, the exact indications of these latter new agents, as well as their optimal dosage and duration, are not defined. Therefore, they are prescribed mainly for patients with disease refractory to conventional therapy, in whom results are promising. Results of international ongoing trials will determine whether the agents may also have a place as first-line treatment.

[Microscopic polyangiitis]. / Polyangéite microscopique.

Microscopic polyangiitis was initially considered a "microscopic" form of polyarteritis nodosa and was not definitively distinguished from it until the Chapel Hill nomenclature (1994). Microscopic polyangiitis is a systemic necrotizing vasculitis of small vessels. Its typical clinical manifestations are rapidly progressive glomerulonephritis and alveolar hemorrhage. Other possible symptoms resemble those encountered in polyarteritis nodosa. Microscopic polyangiitis belongs to the group of ANCA-associated vasculitides, and 75-80% of patients have pANCA to myeloperoxidase (MPO). Anti-MPO ANCA pathogenicity has been established in animal models, and a recent report describes transplacental transfer of these antibodies in humans, resulting in pulmonary hemorrhage and renal involvement in the newborn. Patients with no poor prognostic factors, as defined by a five-factor score, can be treated with corticosteroids alone, with immunosuppressants added only in case of treatment failure. Patients with one or more poor prognostic factors must receive a combination of corticosteroids and immunosuppressants, mainly intravenous pulsed cyclophosphamide, with plasma exchange as an adjuvant therapy for those with severe renal involvement. Once remission is achieved, maintenance therapy can replace cyclophosphamide by azathioprine or methotrexate. Biological therapies are under evaluation. The remission rate is above 80% with these regimens, and the relapse rate is around 30% at 5 years, lower than for Wegener's granulomatosis.

Hyperbaric oxygen therapy for nonhealing vasculitic ulcers.

BACKGROUND: Cutaneous nonhealing ulceration is a threatening manifestation of vasculitis. Hyperbaric oxygen (HBO), frequently used as adjuvant therapy for patients with ischaemic ulcers, exerts additional beneficial effects on the vascular inflammatory response. AIM: To evaluate the effect of HBO on vasculitis-induced nonhealing skin ulcers. METHODS: The study population comprised 35 patients aged >or= 18 years with severe, nonhealing, vasculitis-induced ulcers that had not improved following immunosuppressive therapy. Baseline ulcer tissue oxygenation was evaluated at room air concentration (21% O2), at 1 atmosphere absolute (ATA) breathing 100% O2, and at 2 ATA breathing 100% O2. The baseline treatment protocol consisted of a 4-week course of 100% O2 for 90 min at 2 ATA, five times/week. RESULTS: The mean baseline ulcer tissue oxygenation (3.1 +/- 2.4 kPa at room air concentration), was significantly increased to 13.9 +/- 11.9 kPa at 1 ATA breathing 100% O2 (P < 0.001), and subsequently increased further to 59.1 +/- 29.8 kPa at 2 ATA breathing 100% O2 (P < 0.001). At the end of the hyperbaric therapy, 28 patients (80%) demonstrated complete healing, 4 (11.4%) had partial healing and 3 (8.6%) had no improvement. None of the patients had any side-effects related to the HBO therapy. CONCLUSION: HBO therapy may serve as an effective safe treatment for patients with vasculitis having nonhealing skin ulcers. Further studies are needed to evaluate its role as primary therapy for this group of patients.

S18886, a selective TP receptor antagonist, inhibits development of atherosclerosis in rabbits.

OBJECTIVE: To investigate the effect of S18886, a novel TP (thromboxane A2 and prostaglandin endoperoxide) receptor antagonist, on the development of aortic fatty streaks and advanced lesions in a rabbit model of atherosclerosis and restenosis. METHODS AND RESULTS: The right iliac artery of 96 rabbits (8 groups, n=12/group) was balloon injured, then the animals were fed a cholesterol-enriched diet for 6 weeks. In Groups 1-4, concomitant oral administration of S18886 at 5 mg/kg/day over the 6-week-period reduced the intima to media ratio of lesions in the uninjured aorta and injured iliac artery, the accumulation of macrophages and the expression of ICAM-1 compared with 1 mg/kg/day S18886, 30 mg/kg/day aspirin and placebo, with no effect on body weight or plasma cholesterol levels. In Groups 5-8, 2 weeks of treatment with 5 mg/kg/day S18886 reduced the intima to media ratio of restenosing lesions when pre-formed iliac artery lesions underwent a second balloon injury at week 6. The smaller lesions resulting from S18886 treatment correlated with a significant decrease in the neointimal area occupied by macrophages, as well as in ICAM-1 expression, with no effect on the smooth muscle component. Aspirin treatment had no significant effect on the neointimal smooth muscle component, but partially inhibited macrophage infiltration, without inhibiting ICAM-1 expression. CONCLUSION: Inhibition of the TP receptor using S18886 causes a significant decrease in the recruitment of monocyte/macrophages within fatty streaks in the uninjured aorta and within primary and restenosing atherosclerotic lesions in the iliac artery of rabbits. Since TP receptor agonists, such as thromboxane A2, prostanoid endoperoxides and isoprostanes participate in vessel wall inflammation and are localized and increased in atherosclerotic plaques, treatment with S18886 may enhance atherosclerotic lesion stability by attenuating inflammatory processes that ultimately lead to plaque rupture.

A study on soluble intercellular adhesion molecule-1 and selenium in patients with rheumatoid arthritis complicated by vasculitis.

Clinical manifestations of vasculitis, as a complication of rheumatoid arthritis (RA), can be postulated as a consequence of immune response abnormalities and endothelial cell dysfunction. In this study we searched for the relationship between the extent of vascular involvement and either serum sICAM-1 or selenium concentrations. We also explored the possible interaction of serum selenium with sICAM-1 to provide a greater understanding of their role in rheumatoid vasculitis (RV). For the study, we measured the serum titers of sICAM-1 using an ELISA assay and the serum selenium concentrations using the ETAAS method in 37 women suffering from RA and 18 normal women serving as controls. All the RA patients were evaluated by extensive clinical, laboratory and capillaroscopic studies. In all patients with extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum sICAM-1 titers in RA patients with mild vasculitis on nailfold capillaroscopy did not differ significantly from those of the healthy subjects, whereas a higher sICAM-1 level seemed to reflect the more intensive vascular changes in capillaroscopy. These data suggest that sICAM-1 serum levels may reflect the extent of the microvascular involvement in RA patients. Compared with controls, all the RA patients had markedly lower serum selenium concentrations, irrespective of the degree of the capillaroscopic vascular changes. A significant inverse correlation between sICAM-1 and selenium was found in the controls (r = -0.54; P<0.02). By contrast, no correlation was noted in RA patients (r=0.10, P not significant). This suggests that the sICAM-1 shedding in RV does not appear to be influenced by selenium, presumably owing to its low serum concentration.

Inflammation, arteriosclerosis, and cardiovascular therapy in hemodialysis patients.

BACKGROUND: Aortic stiffness and left ventricular hypertrophy (LVH) are predictors of mortality in hemodialysis (HD) patients. Attenuation of arterial stiffness and regression of LVH had a favorable effect on survival in these patients, but this favorable effect was observed in less than 50% of patients, the rest being resistant to therapeutical interventions. The aim of this study was to analyze the factors associated with this resistance to treatment. METHODS: 138 patients on HD were studied during a follow-up survey. From entry until the end of follow up, the changes of aortic pulse wave velocity (PWV) and of LV mass were measured in response to treatment with antihypertensive drugs and erythropoietin, together with measurements of blood chemistry, including high-sensitive C-reactive protein (CRP). Patients with decreased aortic PWV were considered to be responders (N = 68), the others to be nonresponders (N = 70). RESULTS: Nonresponders were older (P < 0.05) and had persistently higher systolic blood pressure (BP) and pulse pressure. Responders were treated more frequently with an ACE inhibitor (P < 0.001), and had lower serum CRP (P < 0.01). The baseline PWV, as well as the changes of PWV and LV mass during the follow-up were significantly and independently correlated with serum CRP level (P < 0.001). According to logistic regression after adjustment for age, gender, diabetes, history of CVD, and the nonspecific cardiovascular risk factors, the improvement of aortic stiffness and LV hypertrophy was positively associated with prescription of ACE inhibitor (P < 0.0001), and negatively with the serum CRP level (P < 0.01). CONCLUSION: These results indicate that in HD patients, the presence of low-grade inflammation decreases the efficiency of cardiovascular therapeutic interventions and participates in the persistence of cardiovascular hemodynamic overload.

Severe diaphragmatic necrosis in 4 horses with degenerative myopathy.

Severe diaphragmatic necrosis occurred in horses with degenerative myopathy due to polysaccharide storage myopathy (n = 2), nutritional myopathy (n = 1), and vasculitis (n = 1). Blood gas analysis performed in 1 horse indicated development of respiratory acidosis. Respiratory muscle necrosis can be severe in horses with degenerative myopathy and can lead to respiratory failure.