Properties of the mantle cell and mantle cell lymphoma.

The major lymphoid inhabitant of the follicular mantle is the mantle cell, an immunologically na?ve B cell. It is the putative cell of origin of mantle cell lymphoma (MCL), the cells of which have similar morphologic, immunophenotypic, and molecular characteristics to the normal B lymphocytes of the mantle zone. In the past year a number of advances have been made in the biology of the normal mantle cell, its interactions with the other constituents of the follicular and mantle zone microenvironments, and the development of neoplasia in this cell population. In addition, new developments in diagnostic molecular pathology have been used to more readily identify cases of MCL. The authors summarize these new advances in the understanding of the biology of the mantle cell and newer ancillary techniques in the diagnosis of lymphomas arising from this cell type.     

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.     

Sudden cardiac death during nighttime hours

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Lack of benefit of a primary care-based nurse-led education programme for people with osteoarthritis of the knee

Osteoarthritis (OA) is the commonest cause of locomotor disability and forms a major element of the workload of the primary care team. There is evidence that patient education may improve quality of life, physical functioning, mental health and coping as well as reducing health service use. The aim of this study was to evaluate the effectiveness of a primary care-based patient education programme (PEP) using a randomised controlled trial. A cluster randomised controlled trial, involving 22 practices, was used to determine the efficacy of a nurse-led education programme. The programme consisted of a home visit and four 1-h teaching sessions. Patients were assessed at baseline and then 1, 3, 6 and 12 months post intervention using 36-item Short Form (SF-36), Western Ontario and McMaster Universities Arthritis Index (WOMAC), arthritis helplessness index and a patient knowledge questionnaire. Direct interviews were used at baseline and at the 12-month follow-up. There were no differences in depression, OA knowledge, pain or physical ability at either 1 month or 1 year between the two groups. Control practices (65 patients from 12 practices) recruited significantly fewer patients than intervention practices (105 patients from ten practices, p=0.02). Control practices had more doctors (p=0.02), more non-white patients (p=0.007), fewer patients living alone (p=0.005) and lower levels of disability (p=0.008). We detected a lack of benefit of PEP for people with OA of the knee. This was thought to be due in part to the short intervention time employed and the heterogeneous nature of the disease and the population studied.     

Health economic evaluation of controlled and maintained physical exercise in the prevention of cardiovascular and other prosperity diseases.

OBJECTIVES: Several studies and reports support the health benefits of frequent physical exercise, on the condition that this exercise is controlled and maintained. Given the scarce resources that can be spent on health and health care, the objective of this study was to evaluate the long-term health and economic outcomes of controlled and maintained physical exercise in a fitness setting. METHODS: A 25-year Markov model with a 12-month cycle-length and states representing diabetes, coronary heart disease, stroke, colon cancer and breast cancer was developed to predict cumulative costs and QALYs (quality adjusted life years) for three defined population cohorts, of different risk levels. Physical exercise was thereby compared with no intervention. Reduced risks associated with physical exercise, cost of diseases and loss of quality of life in case of disease were obtained from published literature. Costs were taken from a societal perspective; Belgium was selected as the setting. One way and probabilistic sensitivity analyses were carried out. RESULTS: For each of the cohorts, physical exercise is predicted to increase the QALYs and to offset a large part of the initial investment. The cost per QALY varies from 2000 to 15,000 Euro per QALY depending on the risk levels, which is better compared with a majority of secondary preventions that are currently publicly financed. CONCLUSION: Controlled and maintained physical exercise is projected to be cost-effective, which is likely to be explained by its simultaneous effect on several diseases and the associated weight loss, which affects quality of life positively.     

Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model

The Cardiovascular Risk Identification and Treatment Center was established in 1997, adopting a collaborative-care clinic model for the purpose of improving the management of high-risk patients with dyslipidemia. This was a retrospective analysis of 417 high-risk patients with ≥1 year of follow-up laboratory data. Analysis included changes in total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, triglycerides, and total cholesterol to HDL ratio; lipoprotein goal achievement; Framingham risk score; liver function; and cardiovascular events. At baseline, 66% of patients had coronary heart disease (CHD) or equivalent risk, 45% were not receiving dyslipidemia therapy, and 29% were on statin monotherapy. After 3 years in the program, 56% were receiving combination therapy, 41% were on monotherapy, and 2% were not on therapy. The 3 most common treatment regimens were statin plus niacin (36%), statin alone (22%), and niacin alone (14%). All lipoproteins improved from baseline (p <0.001). Overall, 62% to 74% of patients reached singular lipid goals and 35% achieved combined lipid goals. Patients with Framingham 10-year CHD risk of >20% were reduced from 6% to <1%. Only 29 patients (7.0%) had a cardiovascular event, including 5 (1.0%) who experienced a myocardial infarction. Aspartate aminotransferase/alanine transferase elevation >3 times normal occurred in 1% of patients. In conclusion, a collaborative-care practice model adopting individualized, aggressive pharmacologic and nonpharmacologic treatment strategies is highly effective in achieving lipid goals, is sustainable, and is safe. Furthermore, this approach yields reduced projected 10-year CHD risk. A low rate of cardiovascular events was observed.     

Transforming growth factor beta contributes to lung leak in rats given interleukin-1 intratracheally

Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1alpha (rhIL-1alpha) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor beta (TGFbeta) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGFbeta (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGFbeta contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.     

A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down-regulates β-catenin but its zygotic expression is not essential for the regulation of Armadillo

Mutations in the adenomatous polyposis coli gene (which encodes a protein called APC) are associated with the formation of intestinal polyps and colon cancers. To facilitate the functional study of APC we have isolated its Drosophila homolog (D-APC) by screening an expression library with an antibody against human APC. The isolated cDNA encodes a predicted 2416-amino acid protein containing significant homology to multiple domains of mammalian APCs. D-APC has seven complete armadillo repeats with 60% identity to its human homolog, one β-catenin binding site, and up to 7 copies of a 20-amino acid repeat with the average of 50% identity to human APC at amino acid level. D-APC, like its human counterpart, also contains a basic domain. Expression of the domain of D-APC homologous to the region required for β-catenin down-regulation resulted in down-regulation of intracellular β-catenin in a mammalian cell line. This same region bound to the Armadillo (Arm) protein, in vitro, the Drosophila homolog of β-catenin. D-APC RNA and protein expression is very low, if detectable at all, during stages when Arm protein accumulates in a striped pattern in the epidermis of the Drosophila embryos. Removing zygotic D-APC expression did not alter Arm protein distribution, and the final cuticle pattern was not affected significantly. As observed in the rodent, high levels of D-APC expression have been detected in the central nervous system, suggesting a role for D-APC in central nervous system formation.     

Comparative Effectiveness of Usual Care With or Without Chiropractic Care in Patients with Recurrent Musculoskeletal Back and Neck Pain

Background

Chiropractic care is a popular alternative for back and neck pain, with efficacy comparable to usual care in randomized trials. However, the effectiveness of chiropractic care as delivered through conventional care settings remains largely unexplored.

Objective

To evaluate the comparative effectiveness of usual care with or without chiropractic care for patients with chronic recurrent musculoskeletal back and neck pain.

Study design

Prospective cohort study using propensity score-matched controls.

Participants

Using retrospective electronic health record data, we developed a propensity score model predicting likelihood of chiropractic referral. Eligible patients with back or neck pain were then contacted upon referral for chiropractic care and enrolled in a prospective study. For each referred patient, two propensity score-matched non-referred patients were contacted and enrolled. We followed the participants prospectively for 6 months.

Main measures

Main outcomes included pain severity, interference, and symptom bothersomeness. Secondary outcomes included expenditures for pain-related health care.

Key results

Both groups’ (N?=?70 referred, 139 non-referred) pain scores improved significantly over the first 3 months, with less change between months 3 and 6. No significant between-group difference was observed. (severity ??0.10 (95% CI ??0.30, 0.10), interference ??0.07 (??0.31, 0.16), bothersomeness ??0.1 (??0.39, 0.19)). After controlling for variances in baseline costs, total costs during the 6-month post-enrollment follow-up were significantly higher on average in the non-referred versus referred group ($1996 [SD?=?3874] vs $1086 [SD?=?1212], p?=?.034). Adjusting for differences in age, gender, and Charlson comorbidity index attenuated this finding, which was no longer statistically significant (p?=?.072).

Conclusions

We found no statistically significant difference between the two groups in either patient-reported or economic outcomes. As clinical outcomes were similar, and the provision of chiropractic care did not increase costs, making chiropractic services available provided an additional viable option for patients who prefer this type of care, at no additional expense.