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עמוד בית
Thu, 18.07.24

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January 2015
Maria A. Martínez-Godínez MSc MD1, Maria P. Cruz-Domínguez DSc, Luis J. Jara MD, Aarón Domínguez-López DSc, Rosa A. Jarillo-Luna DSc, Olga Vera-Lastra MD, Daniel H. Montes-Cortes DSc, Rafael Campos-Rodríguez DSc, Dulce M. López-Sánchez MSc, Cesar M. Mejía-Barradas DSc, Enrique E Castelán-Chávez MSc and Angel Miliar-García DSc

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

August 2014
December 2013
Daniel Silverberg, Tal Yalon, Uri Rimon, Emanuel R. Reinitz, Dmitry Yakubovitch, Jacob Schneiderman and Moshe Halak
 Background: Peripheral arterial occlusive disease is common in patients with chronic renal failure requiring dialysis. Despite the increasing use of endovascular revascularization for lower extremity ischemia, the success rates of treating lower extremity ischemia in this challenging population remain obscure. 

Objectives: To assess the results of endovascular revascularization for lower extremity ischemia in dialysis patients.

Methods: We conducted a retrospective review of all dialysis patients who underwent endovascular treatment for critical limb ischemia (CLI) in our institution between 2007 and 2011. Data collected included comorbidities, clinical presentation, anatomic distribution of vascular lesions, amputation and survival rates.

Results: We identified 50 limbs (41 patients). Indications included: gangrene in 22%, non-healing wounds in 45%, rest pain in 31%, and debilitating claudication in 4%. Mean follow-up was 12 months (1–51 months). Nineteen patients required amputations. Freedom from amputation at 5 years was 40%. Factors associated with amputation included non-healing wounds or gangrene (68% and 36% respectively) and diabetes (P < 0.05). The survival rate was 80% after 5 years.

Conclusions:  Despite improvement in endovascular techniques for lower extremity revascularization, the incidence of limb salvage among dialysis patients remains poor, resulting in a high rate of major amputations. 

August 2013
January 2012
Roberta Onesimo, MD, Valentina Giorgio, MD, Stefania Pili, MD, Serena Monaco, MD and Stefano Miceli Sopo, MD

Fish is a common cause of food allergy. The reactions usually occur after its ingestion. In most immunoglobulin E-mediated reactions, the allergens are gastroresistant and heat-stable proteins of low molecular weight (parvalbumin). On the other hand, isolated contact urticaria following the handling of raw fish but without symptoms after its ingestion was found among cooks and professional fish handlers. In these cases, the fish allergens are gastrosensitive and thermolabile, as demonstrated by the decrease in the diameter of the wheal in the skin-prick test using cooked fish. To the best of our knowledge isolated fish contact urticaria in children has not been previously reported. We analyze the features of three pediatric cases of contact urticaria from cod (one of them was sensitized to parvalbumin), with tolerance after ingestion of this fish on oral food challenge.

 

Mauro Calvani, MD, Iride Dello Iacono, MD, Valentina Giorgio, MD, Stefano Miceli Sopo, Valentina Panetta, MD and Salvatore Tripodi, MD.

Background: The diagnostic gold standard for food allergy is an oral food challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset of mild objective symptoms for fear of severe reactions. However, there is no consensus on this issue.

Objective: To investigate the effectiveness and side effects of a new model of oral milk challenge in order to increase the diagnostic accuracy of cow¡¯s milk protein allergy and reduce the number of many useless elimination diets. This model is characterized by a conservative diagnostic protocol and ¡°step-up cow’s milk administered dosing.¡± The secondary aim was to investigate possible factors influencing severe reactions.   

Methods: Sixty-six children (median age 1 year, range 1¨C18) with suspected immunoglobulin E (IgE)-mediated cow’s milk allergy performed a conservative oral food challenge (OFC), i.e., the OFC was continued even in the presence of subjective, even repeated, or mild local or multiple organ objective symptoms. If the first objective reaction occurred when the quantity of milk was > 10 ml, the investigator would decide whether to continue the OFC or prescribe a gradual increase in milk feeding at home.

Results: Symptoms developed during the OFC in 42.4% of the children. Local, generalized and severe generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children, respectively. Only 14/28 (50%) who developed objective symptoms during the OFC were considered to be affected by cow’s milk allergy. In the remaining 14 both subjective and objective symptoms developed and the OFC was continued without the emergence of additional symptoms. Epinephrine was administered to 6 of the 28 children (21.4%) who developed objective symptoms. All but one had subjective symptoms following the early doses of milk, whereas all children who later tolerated milk had their first subjective or mild symptoms following doses ¡Ý 10 ml.

Conclusions: This new model of oral milk challenge criteria led to frequent severe allergic reactions hence its use in daily practice seems inadvisable. However, our study provides evidence that a severe allergic reaction does not invariably occur if the offending food continues to be administered after the onset of symptoms. If mild symptoms appear at doses higher than 10 ml, continued milk administration, on the same day or in subsequent days, seems to facilitate the development of tolerance and may reduce the number of useless elimination diets.


Silvia Sanchez-Garcia, MD, Pablo Rodriguez del Rio, MD, Carmelo Escudero, MD, Cristina Garcia-Fernandez, MD, Antonio Ramirez, MD and M.D. Ibanez, MD, PhD

Background: In the last two decades milk oral immunotherapy has gained interest as an effective treatment option for milk-allergic patients.

Objectives: To report on the efficacy of a milk oral immunotherapy.

Methods: Children with immunoglobulin E-mediated cow’s milk allergy were included in the protocol. The treatment consisted of an induction phase in which milk doses were increased weekly in the hospital, while the tolerated dose was continued daily at home. The goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance phase, patients ingested at least 200 ml of milk in a single dose every day.

Results: The protocol was applied to 105 milk-allergic children diagnosed by specific IgE to milk and controlled oral food challenge. The mean duration of the induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully complied with the protocol and 19 (19.1%) failed. Causes of failure were moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7 (6.66%). A total of 182 adverse reactions occurred during the induction phase, most of them mild. Baseline specific IgE to milk and casein were significantly lower (P < 0.05) in the successfully treated group compared to the group in which the treatment failed.

Conclusions: Milk oral immunotherapy is a safe and effective treatment for milk-allergic children, although adverse reactions may occur. Baseline milk and casein-specific IgE may be useful to predict a good response to milk oral immunotherapy.

______

[1] IgE = immunoglobulin E

Giuseppe Crisafulli, PhD, Lucia Caminiti, MD and Giovanni B. Pajno, MD
March 2011
G. Kerekes, P. Soltész, G. Szűcs, S. Szamosi, H. Dér, Z. Szabó, L. Csáthy, A. Váncsa, P. Szodoray, G. Szegedi and Z. Szekanecz

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFα) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA.

Objectives: To assess the effects of adalimumab treatment on FMD[1], ccIMT[2] and PWV[3] in early RA[4].

Methods: Eight RA patients with a disease duration ≤ 1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reacive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint Disease Activity Score (DAS28).

Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP[5] levels (P = 0.04) and DAS28[6] (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF[7] levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P = 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038).

Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.






[1] FMD = flow-mediated vasodilation



[2] ccIMT = common carotid intima-media thickness



[3] PWV = pulse-wave velocity



[4] RA = rheumatoid arthritis



[5] CRP = C-reactive protein



[6] DAS28 = 28-joint Disease Activity Score



[7] vWF = vonWillebrand factor


May 2009
S. Heller, I. Fenichel, M. Salai, T Luria and S. Velkes

Background: Unicompartmental knee replacement has become a surgical alternative for treating isolated medial or lateral osteoarthritis of the knee or avascular necrosis of the femoral condyls.

Objectives: To evaluate the short-term results of the Oxford Phase 3® unicompartmental knee replacement for unicompartmental knee arthrosis or avascular necrosis of the medial

femoral condyle.

Methods: During the period 2003–2005 a total of 59 patients (59 knees) underwent medial Oxford Phase 3® unicompartmental knee replacement in our unit. The patients were interviewed and examined, and standing anteroposterior and lateral X-rays were taken. All patients completed the Western Ontario and McMaster Universities Index of Osteoarthritis and the Short Form 12 questionnaire, and the International Knee Society score was evaluated. The data were collected and statistical analysis was performed.

Results: X-rays were performed and scores for the WOMAC[1] and IKS[2] were assessed for 42 patients (31 females, 11 males). At an average of 32 months after surgery, the total WOMAC score was 30. The mean SF[3]12 physical score was 38 and the mean SF12 mental score was 51. The mean IKS score was 166. Ninety-one percent of the patients had active flexion of 120 degrees or more. Of 59 knees 7 were converted to total knee arthroplasty – all of them within the first 2 years of starting the procedure and all of them in relatively young patients.

Conclusions: Despite the higher revision rate to TKR[4] in this study, our findings confirm the short-term results reported in other studies of the Oxford medial unicompartmental knee and our early failure rate could be explained by a performance learning curve. This study confirms that this bone-preserving procedure should be considered in end-stage isolated unicompartmental osteoarthritis or avascular necrosis by surgeons who have the adequate training and experience.






[1] WOMAC = Western Ontario and McMaster Universities Index of Osteoarthritis

[2] IKS = International Knee Society

[3] SF = short form

[4] TKR = total knee arthroplasty

 


A. Blum

Experimental and clinical data suggest a causal relationship between immunological and inflammatory processes and heart failure. Inflammatory processes may be involved in the pathogenesis of heart failure and may play a role in the progression of ventricular dysfunction. In the last decade several immunological methods were developed that tried to address these questions and overcome the inflammatory and immunological insults. We hope that the present review will increase awareness of new treatment options and encourage researchers and physicians to investigate this novel approach to treat patients with heart failure.
 

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