The acquisition of cytokine responsiveness by murine B cells: a role for antigen and IL-5 in the induction of IL-2 receptors.

The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose-coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface expression of IL-2R alpha. The level of expression induced by IL-5 was equivalent to that on anti-Ig-activated B cells. Neither stimulus induced detectable expression of IL-2R beta, and neither induced B cells to respond to IL-2. IL-2R alpha expression was strongly enhanced, and low levels of IL-2R beta staining and mRNA were induced by the combination of LPS plus IL-5. LPS+IL-5-treated B cells responded to IL-2 by Ig secretion. This indicates that B cells regulate their responsiveness to IL-2 similarly to T cells, via the combined level of expression of IL-2R beta and IL-2R alpha. The synergy between IL-5 and LPS for B-cell responses shows a requirement for complementary stimuli such as would be provided by cytokines, and either cellular interaction or antigen recognition in regulation of B-cell responsiveness to IL-2.     

Sirolimus allows renal recovery in lung and heart transplant recipients with chronic renal impairment.

BACKGROUND: Until recently, there has been no practical alternative to the use of calcineurin inhibitors (CIs) as primary immunosuppressants in lung transplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is a novel powerful immunosuppressant without renal toxicity, a common post-transplant problem associated with CI therapy. METHODS: SRL was used in 20 LTx and 5 HTx recipients >90 days post-transplant, where serious renal impairment was limiting CI dosing. Patients started on 2 to 5 mg/day orally at a median of 1,185 days post-transplant. Dosage adjustments were made according to trough levels, toxicity and perceived efficacy. With SRL initiation, 48% ceased CI therapy and the remainder decreased their dose substantively. RESULTS: After 30 days, 4 of 5 dialyzed patients ceased dialysis and 15 of 20 patients with an elevated serum creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. The direction of change in Cr at 30 days predicted longer term Cr. The starting Cr did not predict the 30-day or long-term value. There were two bouts of acute and one bout of chronic rejection. There were 35 infectious complications in 16 patients and 24 episodes of potential SRL-related toxicity in 17 patients. These events generally responded to dose reduction or temporary cessation and were level-related. Fifteen recipients presently remain on the drug. None of the 7 deaths could be directly related to toxicity. CONCLUSION: SRL is a useful alternative immunosuppressant, allowing significant CI withdrawal in transplant recipients with renal impairment. Whether the resulting improvement in Cr can be maintained in the long term probably depends on the balance between the extent of acute and chronic renal damage.     

Mini dental implants: an adjunct for retention, stability, and comfort for the edentulous patient.

OBJECTIVE: This article examines the success of mini-dental implants (MDI'S) by assessing four subjective measures of patient satisfaction for MDI's in the edentulous maxilla and mandible: comfort, retention, chewing ability and speaking ability. Success rates, surgical techniques, and financial advantages of the MDI's are reviewed. STUDY DESIGN: Thirty consecutive patients received four MDI's between the mental foramen of the mandible from 9/18/2003 to 10/22/2004. Questionnaires were sent to all thirty patients an average of 5 months postoperatively. The patients ranked comfort, retention, chewing ability, and speaking ability from 1 to 10 (1=poor and 10=excellent). RESULTS: A total of 116 MDI's were placed in 13 months and 113 remain stable for a 97.4% implant success rate. Pre-operatively patients rated their retention at 1.7+/-0.42 and post-operatively at 9.6+/-0.37, for a difference of 7.9 (p=3.6-19). Comfort was the next greatest improvement, with a pre-operative rating of 2.2+/-0.63 and a post-operative rating of 9.4+/-0.45, for a difference of 7.2 (p=3.5-15). Chewing ability also improved, with a difference of 7.0 (p=2.9e-16). In the final category of speaking ability, the pre-operative to post-operative difference was 3.2 (p=1.1e-5). CONCLUSION: MDI's are a highly successful implant option for patients with poor tolerance to maxillary and mandibular prosthesis. The implants are relatively affordable and overall patient satisfaction is excellent.     

Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans.

Prospective studies suggest that tea may protect against cardiovascular disease. A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea. Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation. Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2)-isoprostane excretion. Study 1: The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a randomized 3-period (7 d each) crossover design. Study 2: The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a randomized 2-period (4 wk each) crossover design. F(2)-isoprostane excretion was not altered after regular ingestion of green tea (273 +/- 48 pmol/mmol creatinine) or black tea (274 +/- 39 pmol/mmol creatinine) in comparison with hot water (263 +/- 47 pmol/mmol creatinine; Study 1), or by regular ingestion of black tea (334 +/- 71 pmol/mmol creatinine) in comparison with hot water (355 +/- 75 pmol/mmol creatinine; Study 2). These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation.     

Specialist training

Specialist training must be reshaped to meet the challenges of new systems for the delivery of health care and rapid expansion in biomedical knowledge. An adequate and affordable supply of trained specialists and generalists able to deal with the health problems of populations served, is the responsibility of governments and policymakers that fund and those who deliver graduate education. Clearly defined objectives for specialist training are needed, linked to planning for the medical workforce size. A balance between numbers of specialists and generalists is essential, although flexibility in programmes should allow individuals to change. Curricula for all specialties should be published. Strategies and methods for delivery of graduate education and training must be coherent with those of medical schools. Training should be planned and sequenced to meet the identified needs of individuals. Those who teach should themselves learn how to train and assess trainees. The location for training should reflect present and future clinical practice if disfunction between medical education and the health of populations served and their need is to be avoided. Specialist training should form the basis for continuing education by encouraging lifelong, evidence-based learning. Any reshaping of specialist training must be consistent with the continuum of medical education. Instruments for assessment of specialists in training have to be refined, based on action research. Ensuring mastery in the competencies of each component of the curriculum is essential. Those competencies will change in consequence of altered societal needs plus advances in technology and biomedical knowledge.     

Pathways of lymph flow through intestinal lymph nodes in the horse

In the horse, several thousand lymph nodes receive lymph from the intestine, part of which is very large and contains microorganisms that enable the animal to utilize refractory dietary constituents such as cellulose. The aim of this study was to describe the pathways by which lymph is delivered into, traverses, and is drained from these lymph nodes. These pathways were studied with either Microfil or methacrylate casting materials and with light and electron microscopy. The afferent lymphatic vessel delivering lymph into one of the nodes divides over the capsular surface and within trabeculae into terminal branches, and these are continuous with the subcapsular and trabecular sinuses through rounded holes up to 30 μm across. Lymph is conveyed from the subcapsular and trabecular sinuses through the cortex by four types of sinuses: trabecular sinuses, cortical tubular sinuses, tubulelike sinuses with a network of stellate cell processes, and sinuses between cortical cords. It is conveyed through the medulla by sinuses both within and between medullary cords. Lymph is drained from these sinuses by initial efferent lymphatics of three types: those between medullary cords, those within the subcapsular sinus overlying medullary or cortical cords, and those within trabeculae. All three types are continuous with surrounding sinuses through holes 5–30 μm across. These three alternative routes for lymph drainage may ensure adequate lymph flow during different intranodal conditions that may exist when the node is responding to microcrganisms or other foreign materials.     

Comparison of ultrasonic cleaning schemes: a pilot study.

OBJECTIVE: Ultrasonic cleaning is an effective method for cleaning dental instruments prior to sterilisation. However, there are few studies that directly compare precleaning and ultrasonic cleaning solutions. This study evaluated the efficacy of different ultrasonic cleaning schemes. METHOD AND MATERIALS: Twenty representative dental instruments, five of which were soiled with a mixture of blood and hydroxyapatite, were used in a series of cleaning runs. Cleaning employed a presoaking agent, ultrasonic cleaning, or a combination of both. Two presoaking agents (Non-ionic Ultrasonic Cleaning Solution and ProEZ Foaming Enzymatic Spray) plus five ultrasonic cleaners (UltraDose, General Purpose Cleaner, Co-enzyme Concentrate, Enzol Enzymatic Detergent, and Non-ionic Ultrasonic Cleaning Solution) were compared, with tap water serving as a control. There were two cleaning times: seven and 15 minutes. After rinsing, the working ends of the instruments underwent scrubbing for 20 seconds using a dental polishing brush held in a haemostat. After scrubbing, the brush and instrument were placed in a tube containing sterile saline. Vortexing of the tube lasted 30 seconds. Testing for the post-cleaning presence of blood involved Hemastix dipsticks. These sticks measure minute amounts of blood in urine and can detect as few as 35 red blood cells per ml. Comparisons of colour change were made to a standard scale followed by assignment of numeric values. RESULTS: Tap water was the poorest cleaning solution, while UltraDose was the most effective. Blood removal improved when cleaning time was increased from seven to 15 minutes. The combined effect of a presoak immersion followed by ultrasonic cleaning was the most effective cleaning scheme overall. Cleaning by either ultrasound or presoaking only was less effective. Some instruments were more difficult to clean than others. CONCLUSION: Within the constraints of the small number of test runs performed, it was concluded that application of a presoak agent before ultrasonic cleaning produced the most effective instrument-cleaning regimen.