Immunochemical similarities between monoclonal antibacterial Waldenstrom's macroglobulins and monoclonal anti-DNA lupus autoantibodies.

Six monoclonal IgM from patients with Waldenstrom's macroglobulinemia that react with Klebsiella polysaccharides were tested for their ability to bind to nucleic acid antigens. One of the macroglobulins bound to the polynucleotide poly(G), and one bound to poly(G), poly(I), and single-stranded DNA. The reaction with the polynucleotides was specifically inhibited by the Klebsiella polysaccharide K30. A monoclonal lupus anti-DNA antibody (16/6) was found to react weakly with the Klebsiella polysaccharides K30 and K21. Five of the Waldenstrom macroglobulins shared an idiotypic determinant with the 16/6 anti-DNA antibody. The reaction between the macroglobulins and the antiidiotype serum was specifically inhibited by Klebsiella polysaccharides, an indication that the idiotypic marker was in the antigen-binding site of the macroglobulins. These results indicate the existence of widely dispersed conserved variable region genes that encode idiotypically related immunoglobulins with the capacity to bind to both bacterial polysaccharides and nucleic acids. Such genes can be expressed by patients with either Waldenstrom's macroglobulinemia or systemic lupus erythematosus.

Evaluating the impact of age and disease on survival of chronic lymphocytic leukaemia patients by a new method.

BACKGROUND: The impact of chronic lymphocytic leukaemia (CLL) on survival may be different in younger patients, but this remains controversial. OBJECTIVES: The aim of the study was to examine the effect of age on survival in CLL using an original method. METHODS: Clinical, laboratory and survival data of 87 CLL patients treated in our institute were analysed. The survival of patients in different age groups was determined and compared, as related to the expected survival of age- and gender-matched general population obtained from national statistical data. RESULTS: The mean age in the younger (< or = 65 years, n = 37) and older (> 65 years) age groups was 56 and 74 years (p < 0.001). The younger group had more unfavourable presentation, with advanced stage (Rai 2-4) in 46% vs. 16% (p = 0.002), and diffuse involvement of bone marrow in 60% vs. 18% (p = 0.03), compared with the older group, and were more likely to require treatment (p = 0.02). The Kaplan-Meyer curve showed a more favourable survival for the younger group. However, the loss of expected survival exposed a reversed pattern: while the older patients lost only 13%, the survival loss in the younger patients was 44% (p < 0.001). CONCLUSIONS: Chronic lymphocytic leukaemia had a more unfavourable presentation and a more severe clinical course in the younger patients. Our method of evaluating the negative impact of disease on expected survival reveals that their survival also is significantly more affected than that of older patients. We suggest calculating the loss of expected survival as a new criterion for assessing disease impact.

Primary stroke prevention: a paradigm shift focusing on silent paroxysmal atrial fibrillation.

We review the prevalence, predictability, prognosis and preventability of atrial fibrillation and associated cardiogenic brain embolism, focusing on 'silent' sub-clinical atrial fibrillation (SCAF) which is very common in the elderly and associated with significantly increased risk of stroke and cardiovascular mortality. The current paradigm treats atrial fibrillation once discovered by its symptoms, complications (stroke) or by chance and screening recommendations are limited to opportunistic pulse palpation. We argue that the marked incidence of SCAF in patients over 65 justifies a much more active approach to identify patients at a particularly high-risk by routine evaluation of readily-available clinical, electrocardiographic, echocardiographic and laboratory markers. Elderly patients at high-risk need further monitoring by suitable devices (occasionally, long-term) and treatment with direct oral anti-coagulants once SCAF is revealed. This approach can already be adopted during clinical encounters at the general practitioner and consultant level, to decrease the substantial SCAF-associated morbidity and mortality.

The unbearable lightness of diagnostic testing: time to contain inappropriate test ordering.

The numbers of tests, imaging and diagnostic procedures ordered by doctors in primary care and hospital settings alike are rising. According to established guidelines, many of these tests may be unnecessary. Various non-clinical factors often underlie test ordering, and multiple prevalent problems associated with tests and their interpretation are often under-appreciated. These include the significant potential for cascades of further testing and patient harm. Multifaceted strategies may improve test-ordering behaviour. Brief reconsideration of several points by the clinician before ordering the test is advisable.

Acute steroid myopathy: a highly overlooked entity.

BACKGROUND: Myopathy in patients being treated with corticosteroids is known primarily among chronically treated patients or in critically ill and mechanically ventilated patients receiving corticosteroids, often in high doses. AIM: To highlight the entity of acute, early onset corticosteroid-treatment-associated myopathy and its characteristics. DESIGN AND METHODS: Reporting our experience with four patients and reviewing all published reports of myopathy developing ≤14 days of initiating corticosteroid-treatment. RESULTS: Acute corticosteroid myopathy (ASM) exists, though the syndrome appears to be rare. It is characterized by unpredictability and heterogeneity, sometimes developing within 1-3 days, after a single dose, which may not be high and administered by varied routes. Proximal limb muscle weakness is the most common form, but distal limb, bulbar and respiratory muscles may be involved. Steroid cessation often leads to improvement/resolution, but irreversibility may occur. CONCLUSIONS: A high index of suspicion for the possibility of ASM is necessary to ensure drug discontinuation and recovery. This is particularly true since the entity is not widely recognized and its symptoms are often erroneously interpreted as due to the patient's underlying disease.

Diabetes, but not the metabolic syndrome, predicts the severity and extent of coronary artery disease in women.

BACKGROUND: Previous studies have suggested that diabetes and metabolic syndrome are significant risk factors for coronary artery disease (CAD). However, in women, their relative importance remains controversial. AIM: To evaluate risk factors for CAD in women and their association with the severity and extent of coronary angiographic findings. METHODS: We clinically evaluated 243 consecutive female patients with chest pain who underwent coronary angiography. The location and extent of coronary artery occlusions were assessed using the modified Gensini index. RESULTS: Compared with women with normal coronary arteries (n = 90), those with CAD (n = 153) reported less physical activity (p = 0.001), and had higher prevalences of diabetes (p = 0.046), hypertension (p = 0.002), and the metabolic syndrome (p = 0.001). They also had lower HDL cholesterol levels (p = 0.017), higher levels of triglycerides (p = 0.005), and higher fasting plasma glucose (FPG) (p < 0.001). Physical activity, FPG, serum triglycerides and HDL-cholesterol, but not the metabolic syndrome, were independent predictors of CAD. A score combining the extent and severity of angiographic findings was significantly higher in women with diabetes (p = 0.007), hypertension (p = 0.010) and FPG >or=100 mg/dl (p = 0.031), but showed no association with the metabolic syndrome. In a multivariate linear regression analysis, diabetes was an independent predictor of the extent and severity of angiographic score (p = 0.013). DISCUSSION: Diabetes, fasting plasma glucose and hypertension, but not the metabolic syndrome, were associated with severity of coronary angiographic findings in these women.