Israel Medical Association Journal

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition associated with inflammatory bowel disease. PG[1] occurs rarely in IBD[2] patients and there are insufficient data on the clinical manifestations of this disease with IBD.

Objective: To determine the incidence, clinical manifestations and treatment of PG in patients with IBD and the connection to IBD, its activity and extent.

Methods: All patients hospitalized with IBD at a university hospital during a 20 year period were evaluated for the occurrence of PG.

Results: Of 986 patients hospitalized for IBD 6 suffered from PG (0.6% incidence). Their average age was 37 with equal sex distribution and equal distribution of Crohn’s disease and ulcerative colitis. PG appeared 6.5 years on average after diagnosis of IBD in all patients. The development of PG correlated with significant clinical exacerbation of IBD, the majority having active colitis at the onset of the PG. Extra-intestinal manifestations of IBD occurred in half the patients (sacroiliitis, peripheral arthritis and erythema nodosum). Pathergy was not elicited in any patients. Four patients had multiple skin lesions, frequently on the lower extremities. Diagnosis was made by skin biopsy in four patients. There was little correlation between amelioration of IBD and the skin lesions. Treatment consisted of high dose steroids and immunomodulatory drugs (cyclosporine, azathioprine and dapsone) in conjunction with topical treatment.

Conclusions: PG is a rare extra-intestinal manifestation of IBD that coincides with the exacerbation of the intestinal disease but does not always respond to treatment of the bowel disease.

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30–50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC[1]. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.

Sepsis is an inflammatory syndrome caused by infection. Consequently, anti-inflammatory therapies in sepsis have been a subject of extensive research and corticosteroids have been used for years in the therapy of severe infections. However, studies conducted in the 1980s failed to demonstrate any beneficial effects of high dose, short-term steroid therapy in sepsis and this therapy was therefore abandoned during the last decade. Recently, a new concept has emerged with more promising results - low dose, long-term hydrocortisone therapy – and this approach is now being evaluated in the treatment of septic shock. It is supported by the observation that many sepsis patients have relative adrenal insufficiency. Moreover, the anti-inflammatory effects of steroids and their ability to improve reactivity to catecholamines further contribute to their effects in sepsis. Large randomized clinical trials will be required to determine the exact role of corticosteroids in septic shock.