Similar humoral immunity parameters in chronic lymphocytic leukemia patients independent of VH gene mutation status

Chronic lymphocytic leukemia (CLL) is a clonal B-cell disorder, which has recently been divided into 2 subtypes based on the somatic hypermutation status of the immunoglobulin heavy chain (IgVH) genes. In patients with unmutated tumor cells the survival time is approximately half of that in mutated cases, but the reason for this difference is poorly understood. Since infections are the major cause of mortality in CLL, we investigated the effect of the mutation status on host immunity and proneness to infections in patients with CLL. As expected, the disease progression seemed to be faster and the disease more advanced (Binet B and C) among unmutated patients than in the mutated ones. Surprisingly, no differences in humoral immunity [immunoglobulin G (IgG), IgM, IgA, IgG subclasses, anti-ABO blood group antibodies and mannan-binding lectin (MBL)] or immune responses (Haemophilus influenzae serotype b conjugate vaccination) were detected between these 2 patient groups. Furthermore, UM-patients were not more prone to infections compared to M-patients, and therapy had no impact on the incidence and pattern of infections in either of the patient groups. The current findings within this patient cohort reveal that the worse outcome in the unmutated subgroup is not caused by more severe defects in immunity and increased susceptibility to infections when compared with the hypermutated group. It is thus conceivable that active immunization procedures such as vaccination can successfully be applied on patients with unmutated IgVH gene and advanced disease stage.     

Infections preceding early arthritis in southern Sweden: a prospective population-based study

OBJECTIVE: To detect evidence of infections preceding early arthritis in Southern Sweden and to compare the clinical outcome of remission during a 6-month followup for patients with and without signs of prior infection. METHODS: Adult patients with arthritis of less than 3 months' duration were referred from primary health care centers to rheumatologists. All patients were systematically screened for infections caused by Salmonella typhimurium and Salmonella enteritidis, Yersinia enterocolitica, Campylobacter jejuni, Borrelia burgdorferi, Chlamydia trachomatis, Chlamydia pneumoniae, and parvovirus B19. RESULTS: Seventy-one patients were included in this study. Twenty-seven (38%) patients had reactive arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other diagnoses. Of all the patients, 45% had evidence of a recent infection preceding the arthritis, as indicated by laboratory tests and/or disease history. C. jejuni dominated the ReA group. The occurrence of recent C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections was low. Overall, 58% of the patients went into remission during the 6-month followup. Of the patients with a preceding infection, 69% went into remission as compared to 38% of the patients without a preceding infection (p = 0.011). Thirty-three percent of the patients with RA were in remission after 6 months. CONCLUSION: In this population-based cohort, 45% of the patients presenting with a new-onset arthritis had had a prior infection. Campylobacter ReA dominated the ReA group. There were only a few cases preceded by infections by C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections. Remission during the first 6 months was especially frequent in the group of patients with a prior infection, but the remission rate was relatively high even for arthritis without prior infection.     

Articulatory error in a group of children with neonatal risk factors

The present study is a part of a multidisciplinary research project in order to follow up a group of infants who neonatally had been at risk. It studies reports on the articulatory errors in children born in 1971 and 1972 and investigated at the age of five years at the Children's Hospital, University of Helsinki. The results show that children with neonatal risk factors had more articulatory errors than a control group. The articulatory errors were more common in children with neurodevelopmental disturbances.     

Geographical variation in the incidence of acute myocardial infarction in eastern Finland--a Bayesian perspective

BACKGROUND: Large geographical variation in the incidence and mortality of cardiovascular disease (CHD) has been repeatedly reported in Finland with persistent difference between east and west. We undertook this study to estimate the geographical distribution of Acute Myocardial Infarction (AMI) incidence in the high-risk province of North Karelia and in the province of Kuopio. METHODS: Data on men aged 25-64 years with first event of acute myocardial infarction (AMI) were obtained from the FINMONICA AMI register, which recorded detailed information of AMI events during the period 1983 to 1992. The geographical pattern of AMI incidence was studied in two five-year periods 1983 to 1987 and 1988 to 1992 separately in 10 km x 10 km grid cells employing the Geographical Information System (GIS) and a Bayesian hierarchical approach. RESULTS: In both periods Bayesian modeling revealed a geographical pattern of AMI incidence and high risk (probability that incidence exceeds the observed mean incidence) in the remote rural areas. CONCLUSIONS: Detection of high-risk areas in both provinces showed that underlying environmental and/or genetic risk factors of AMI are not evenly distributed within the province but enriched in certain geographical non-administratively defined locations in eastern Finland.     

Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression

BACKGROUND: In adults, pravastatin reduces the development and progression of transplant vasculopathy, the main long-term risk after cardiac transplantation. The pharmacokinetics of pravastatin is not known in children taking calcineurin inhibitors. Our aim was to determine the single-dose pharmacokinetics and short-term safety of pravastatin in children undergoing regular triple-drug immunosuppressive therapy after cardiac transplantation. METHODS: Nineteen pediatric cardiac transplant recipients (aged 4.4 to 18.9 years) receiving triple immunosuppression therapy consisting of methylprednisolone (19 patients), cyclosporine (INN, cyclosporin) (17 patients) or tacrolimus (2 patients), and azathioprine (18 patients) or mycophenolate mofetil (1 patient) ingested a single 10-mg dose of pravastatin, and plasma pravastatin concentrations were measured up to 24 hours. Subsequently, the patients took 10 mg pravastatin orally once daily for 8 weeks. The lipid-lowering effect and the safety of pravastatin therapy were studied. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 122.2 +/- 88.2 ng/mL (range, 11.4-305.0 ng/mL), and the area under the plasma concentration-time curve of pravastatin from 0 to 10 hours [AUC(0-10)] was 264.1 +/- 192.4 ng.h/mL (range, 30.8-701.6 ng.h/mL). These C(max) and AUC(0-10) values are nearly 10-fold higher than the corresponding values reported in hypercholesterolemic children in the absence of immunosuppressive therapy. The time of peak concentration (t(max)) of pravastatin was 1.1 +/- 0.4 hours (range, 0.5-2 hours), and the mean elimination half-life (t(1/2)) was 1.2 +/- 0.3 hours (range, 0.7-2.2 hours); these parameters were similar to those in the hypercholesterolemic children. By 8 weeks of treatment, the concentration of serum total cholesterol decreased by 13% (P =.005), low-density lipoprotein cholesterol by 27% (P <.0001), and triglycerides by 6% (not significant, P =.28); the concentration of high-density lipoprotein cholesterol increased by 7% (not significant, P =.30). No clinically significant increases in serum ALT, creatine kinase, or creatinine levels were observed. CONCLUSIONS: The plasma concentrations of pravastatin in pediatric cardiac recipients receiving triple immunosuppressive medication are nearly 10-fold higher than in hypercholesterolemic children after the same pravastatin dose. However, the short-term therapy of pravastatin was well tolerated and effective in lowering serum cholesterol levels in cardiac recipients.     

Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.     

Diet does not explain the high prevalence of dyslipidaemia in paediatric renal transplant recipients

Dyslipidaemia exists frequently after renal transplantation (RTx) and promotes atherosclerosis. In this study, we examined the association between daily intake of nutrients and serum lipids after paediatric RTx. We studied 45 children with acceptably functioning kidney grafts and adequately completed food records at a median age of 10.6 years (range 4.3–17.2 years), a median 5.2 years (range 1.0–11.0) after RTx, and 178 healthy controls at a median age of 9.0 years (range 3.2–18.7 years). Serum total cholesterol (TC), triglyceride, and apolipoprotein B concentrations were higher in the RTx patients than in the controls (P < 0.001), despite similar dietary intakes of saturated and polyunsaturated fats, and cholesterol. Both the RTx patients and controls ingested a low amount of polyunsaturated fats [mean (SD) percent of total calories (E%) 4.8 (1.3) and 4.6 (1.5), respectively] and an excessive amount of saturated fats [mean (SD) E% 14.4 (2.4) and 14.1 (2.8), respectively]. In multiple regression analyses, dietary fibre was negatively associated with serum TC concentration. The standard deviation score for body mass index was negatively associated with serum concentration of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein diameter, and positively with serum triglyceride concentration. In addition, dietary total fat intake was positively associated with serum HDL-C. In conclusion, the higher prevalence of dyslipidaemia in our paediatric RTx patients than in the controls was not explained by the diet. However, the type of fat consumed implicates the counselling for a healthier dietary lifestyle, with an increase in the ingestion of polyunsaturated fats and a decrease in that of saturated fats.     

The holistic approach to rehabilitation: A commentary

Abstract

Maria Pachalska's approach to aphasia rehabilitation is from a holistic perspective. Traditionally, aphasia therapists have tried to promote communicative ability using several methods. Pachalska has combined the most important approaches and created a model which she calls the Complex Aphasia Rehabilitation Model (CARM). She offers this model as an example of a holistic approach to aphasia rehabilitation. It stresses the importance of taking into account both psychological and social factors in aphasia rehabilitation.