Gideon Nesher

Valvular dysfunction in antiphospholipid syndrome: prevalence, clinical features, and treatment.

Valvular abnormalities develop in 36% and 35% of patients with primary antiphospholipid syndrome (PAPS) and with systemic lupus erythematosus (SLE) respectively, and in 48% of patients with SLE and antiphospholipid antibodies (aPL). Valvulopathy includes leaflet thickening, vegetations, regurgitation, and stenosis. A literature survey shows that significant morbidity from valvular dysfunction, mostly mitral regurgitation leading to congestive heart failure, occurs in 4% and 6% of SLE and PAPS patients, respectively. The pathogenesis of valvulopathy may involve interaction of aPL with antigens on the valve surface, resulting in valvulitis. Current therapy includes symptomatic measures and valve replacement. A novel approach for symptomatic antiphospholipid syndrome (APS) related valvulopathy involves treatment with systemic corticosteroid. We describe four such patients and their dramatic clinical and hemodynamic response to treatment with prednisone when symptomatic measures failed.

Predicting post-vaccination autoimmunity: Who might be at risk?

Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.).

Alpha-interferon-induced arthritis: clinical presentation, treatment, and prevention

OBJECTIVEnThe therapeutic applications of alpha-interferon (IFN) have expanded greatly to include chronic viral hepatitis and malignant disorders. Autoimmune phenomena occur frequently with IFN therapy, but arthritis is uncommon. We describe the clinical features and treatment of IFN-induced arthritis.nnnMETHODSnA patient with chronic myelogenous leukemia who developed arthritis secondary to IFN therapy is presented. The clinical features and treatment of this condition in 37 additional cases are reviewed.nnnRESULTSnThe most common clinical presentation was symmetric polyarthritis. This was associated with antinuclear antibodies in 72% of patients and rheumatoid factor in 34%. Cessation of IFN, with or without the addition of antiinflammatory or remittive agents, resulted in remission of arthritis in 89% and 71% of the cases, respectively. Restarting IFN therapy resulted in recurrence of arthritis in 63%. In the patient described in this report, recurrence of arthritis was prevented by coadministration of hydroxychloroquine (HCQ) and prednisone.nnnCONCLUSIONnArthritis is an uncommon complication of IFN therapy; but it may lead to cessation of this treatment modality. In such cases, coadministration of a remittive agent such as HCQ may enable reinstitution of IFN therapy without recurrence of arthritis.

Recurrent Ventricular Tachycardia in Hypothyroidism -Report of a Case and Review of the Literature

A 47-year-old woman suffered from recurrent attacks of ventricular tachycardia. Her electrocardiogram showed low voltage, right bundle branch block and prolonged QT interval. Hormonal studies disclosed primary hypothyroidism. The arrhythmia responded to treatment with procainamide and did not recur following thyroid replacement therapy. The QT interval returned to normal. Five similar cases reported in the literature are reviewed, emphasizing the importance of QT prolongation, in the context of hypothyroidism, as a risk factor for the occurrence of ventricular tachycardia.

Trends in the clinical presentation of temporal arteritis in israel: Reflection of increased physician awareness

SummaryWe have noticed significant changes in the clinical presentation in patients diagnosed with temporal arteritis in Israel between 1980–1992 compared to patients diagnosed prior to 1977. At the time of diagnosis 57% of the patients were older than 75 years, compared to only 23% within this age group in the previous period. There was an increase in the number of nonspecific and unusual presenting symptoms such as weakness, respiratory and neurological symptomatology, and a decreased proportion of patients presenting with the “classical” manifestation such as headaches, temporal tenderness and visual symptoms. The time from presentation to diagnosis was shortened significantly. It is suggested that these changes are largely due to the increasing awareness among physicians to the various manifestations of this conditions.

Predictors of mortality of mechanically ventilated patients in internal medicine wards.

PURPOSEnBudget restrictions have led to shortage of intensive care unit (ICU) beds in several countries. Consequently, ventilated patients are often kept on the wards. This study examined survival likelihood among patients ventilated on the wards and the predictive value of commonly used severity-of-illness scores.nnnMETHODSnThis study is a prospective observation and characterization of consecutive, mechanically ventilated patients in 3 internal medicine wards of a single hospital who were denied ICU admission. Outcome measures are as follows: 28-day mortality, survival to hospital discharge, and 3 months postdischarge.nnnRESULTSnEighty-six patients were examined. The patients were 78.9 ± 8.9 years old; 53% were independent preadmission. Respiratory insufficiency due to infection was the main reason for mechanical ventilation (58%). Charlson and acute physiology scores (APS) averaged 4 ± 2.2 and 91.8 ± 26.7, respectively. Twenty-eight-day mortality was 71%, whereas in-hospital mortality was 74% and 3 months postdischarge mortality was 79%. Survivors were significantly younger than nonsurvivors (74.4 ± 8.5 years vs 80.4 ± 8.6 years, P < .01), were more likely to be ventilated for cardiac causes (41% vs 11%, P = .04), and had significantly higher initial mean blood pressure (79.4 mm Hg vs 58.2 mm Hg, P = .02) and blood albumin levels (29.8 g/L vs 25.7 g/L, P = .05). Death rate was 10 times more likely, with an APS greater than 90 on the day of intubation as compared with an APS less than 90.nnnCONCLUSIONnMortality in patients ventilated on the ward was high, especially in the subgroup of patients with an APS score greater than 90. The early calculation of APS may assist in focusing therapeutic efforts on patients with better survival chances.

Reduced Incidence of Hyperkalemia and Azotemia in Patients Receiving Sulindac Compared with Indomethacin

The incidence and severity of hyperkalemia and azotemia was investigated in a prospective randomized study involving 74 patients receiving either sulindac 200 mg p.o. b.i.d. or indomethacin 25 mg p.o. t.i.d. and 100 mg p.r. The mean +/- SE posttreatment increment in serum potassium was 0.8 +/- 0.1 mmol/l in patients treated by indomethacin compared to 0.5 +/- 0.1 in those receiving sulindac (p less than 0.025). The mean +/- SE posttreatment increment in blood urea nitrogen (BUN) was 3.1 +/- 0.4 mmol/l in patients on indomethacin compared to only 0.9 +/- 0.3 in patients on sulindac (p less than 0.001). In 5 patients who developed hyperkalemia while on indomethacin, changing to sulindac resulted in a sharp reduction of serum potassium in 3, and normalization of BUN in all patients. These data support the claim of a reduced risk of impaired renal function associated with the use of sulindac.

Dual‐energy computed tomography as a diagnostic tool for gout during intercritical periods

The aim of this study is to evaluate the diagnostic yield of dual‐energy computed tomography (DECT) in detection of uric acid accumulation in joints or periarticular structures in patients suspected of having gout, in their intercritical period.

Dolichol-Mediated Enhanced Protein N-Glycosylation in Experimental Diabetes— A Possible Additional Deleterious Effect of Hyperglycemia

In liver cells from diabetic rats, an increased incorporation of labeled glucosamine into cellular and secretory proteins was found, when related to the incorporation of labeled leucine. This increased N-glycosylation was present in the face of decreased synthesis of hepatic cellular and secretory proteins evident from reduced leucine incorporation and diminished glycosyltransferase activity. To elucidate the mechanisms involved we incubated isolated hepatocytes with two N-glycosylation inhibitors: tunicamycin and 2-deoxyglucose. Tunicamycin exerted a marked inhibitory effect on the incorporation rate of labeled glucosamine into proteins in liver cells from diabetic rats, while 2-deoxyglucose had a negligible effect on this process in these cells. These diverse effects might be explained by the fact that tunicamycin acts through strong association with the enzyme catalyzing the first step in glycoprotein synthesis, namely, the transfer of UDP-GlcNAc to dolichol-P (indicating noncompetitive inhibition). This enzyme is reduced in liver cells from diabetic animals. On the other hand, 2-deoxyglucose exerts its effect by being attached to dolichol-P, preventing further elongation of oligosaccharide chain on the protein backbone. This latter effect might be eliminated by excess dolichol-P (indicating competitive inhibition). The dolichol content in liver extract from diabetic rats was about 2.5-fold higher compared with nondiabetic rats (51.6 micrograms/g versus 20.6 micrograms/g wet liver weight). These two lines of evidence confirm the notion that the enhanced enzymatic glycosylation in liver from diabetic animals is maintained by an increased hepatic dolichol concentration, which is most probably related to the hyperglycemia. Thus, the dolichol-N-glycosylation pathway may represent another detrimental aspect of hyperglycemia and may operate by dolichol mass action rather than through glycosylating enzyme activity.

The Incidence of Primary Systemic Vasculitis in Jerusalem: A 20-year Hospital-based Retrospective Study

Objective. The incidence of primary systemic vasculitides varies among different geographic regions and ethnic origins. The aim of this study was to examine the incidence rates of vasculitides in the Jerusalem Jewish population, and to examine possible trends in incidence rates over a 20-year period. Methods. The clinical databases of inpatients at the 2 medical centers in Jerusalem were searched for patients with vasculitis diagnosed between 1990–2009. Individual records were then reviewed by one of the authors. The significance of trends in incidence rates throughout the study period was evaluated by Pearson correlation coefficient. Results. The average annual incidence rate of polyarteritis nodosa was 3.6/million adults (95% CI 1.6–4.7). Incidence rates did not change significantly during this period (r = 0.39, p = 0.088). The incidence of granulomatosis with polyangiitis (GPA) was 4.1 (2.2–5.9) for the whole period, during which it increased significantly (r = 0.53, p < 0.05). The incidence of microscopic polyangiitis (MPA) was lower: 2.3 (1.2–3.5)/million. It also increased significantly (r = 0.55, p < 0.05). The incidence of eosinophilic granulomatosis with polyangiitis was 1.2 (0.4–1.9), which remained stable throughout the study period. The incidence of Takayasu arteritis was 2.1/million (95% CI 1.2–2.9), and it also remained stable. Giant cell arteritis (GCA) incidence was 8.1 (5.7–10.6)/100,000 population aged 50 years or older. In sharp contrast with other vasculitides, its incidence decreased significantly throughout the study period (r = −0.61, p < 0.01). Conclusion. The incidence rates of vasculitides in the Jewish population of Jerusalem are in the lower range of global incidence rates. While GPA and MPA incidence are increasing, GCA incidence is decreasing.