Sezary cell morphology induced in peripheral blood lymphocytes: re- evaluation

In this study we examined the effect of mitogens and epidermal cells in inducing a Sezary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sezary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen- stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sezary cells in normal peripheral blood lymphocytes.     

Echocardiography in chronic aortic insufficiency. Prediction of the reversibility of left ventricular dysfunction following surgical correction

The long term outcome of patients undergoing aortic valve replacement (AVR) for chronic aortic regurgitation (AR) is mainly determined by the reversibility or permanence of left ventricular dysfunction. We analysed the echocardiogram of 49 patients before and after surgery to identify the patients whose left ventricular dysfunction regressed completely after AVR. The patients were divided into 2 groups according to the results of the last postoperative echocardiogram: Group I: 25 patients whose left ventricular dimensions and wall motion reverted to normal; Group II: 24 patients with dilated and/or hypokinetic left ventricles. The two groups of patients were comparable for sex (Group I: 19 men, 6 women; Group II: 20 men, 4 women), age (Group I: 50,8 years, Group II: 53,9 years) and length of postoperative follow-up (Group I: 32 months, Group II: 34 months). The following parameters were measured and compared: diastolic and systolic left ventricular dimensions, myocardial mass and ventricular wall motion. Results: Patients in Group I had less left ventricular dilatation than those in Group II (+35% vs +60%, p less than 0,001) and left ventricular contraction was better (FE: 62% vs 45%, p less than 0,001; %FS: 35% vs 23%, p less than 0,001). This study establishes that patients with chronic AR and % delta Dd less than 60%, an EF greater than 50% or %FS greater than 25%, have about a 90% probability of normalisation of LV function after AVR. If one of the indices exceeds these threshold values, the probability of permanent LV dilatation and/or hypokinesia after AVR is also about 90%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Identifying Range-of-Motion Deficits and Talocrural Joint Laxity After an Acute Lateral Ankle Sprain

ContextApproximately 72% of patients with an ankle sprain report residual symptoms 6 to 18 months later. Although 44% of patients return to activity in less than 24 hours after experiencing a sprain, residual symptoms should be evaluated in the long term to determine if deficits exist. These residual symptoms may be due to the quality of ligament tissue and motion after injury.ObjectiveTo compare mechanical laxity of the talocrural joint and dorsiflexion range of motion (DFROM) over time (24 to 72 hours, 2 to 4 weeks, and 6 months) after an acute lateral ankle sprain (LAS).DesignCross-sectional study.SettingAthletic training research laboratory.Patients or Other ParticipantsA total of 108 volunteers were recruited. Fifty-five participants had an acute LAS and 53 participants were control individuals without a history of LAS.Main Outcome Measure(s)Mechanical laxity (talofibular interval and anterior talofibular ligament length) was measured in inversion (INV) and via the anterior drawer test. The weight-bearing lunge test was conducted and DFROM was measured. The data were analyzed using repeated-measures analysis of variance, independent-samples t tests, and 1-way analysis of variance.ResultsOf the 55 LASs, 21 (38%) were grade I, 27 (49%) were grade II, and 7 (13%) were grade III. Increases were noted in DFROM over time, between 24 and 72 hours, at 2 to 4 weeks, and at 6 months (P < .05). The DFROM was less in participants with grade III than grade I LASs (P = .004) at 24 to 72 hours; INV length was greater at 24 to 72 hours than at 2 to 4 weeks (P = .023) and at 6 months (P = .035) than at 24 to 72 hours. The anterior drawer length (P = .001) and INV talofibular interval (P = .004) were greater in the LAS group than in the control group at 6 months.ConclusionsDifferences in range of motion and laxity were evident among grades at various time points and may indicate different clinical responses after an LAS.     

An acoustic startle alters knee joint stiffness and neuromuscular control

Growing evidence suggests that the nervous system contributes to non‐contact knee ligament injury, but limited evidence has measured the effect of extrinsic events on joint stability. Following unanticipated events, the startle reflex leads to universal stiffening of the limbs, but no studies have investigated how an acoustic startle influences knee stiffness and muscle activation during a dynamic knee perturbation. Thirty‐six individuals were tested for knee stiffness and muscle activation of the quadriceps and hamstrings. Subjects were seated and instructed to resist a 40‐degree knee flexion perturbation from a relaxed state. During some trials, an acoustic startle (50 ms, 1000 Hz, 100 dB) was applied 100 ms prior to the perturbation. Knee stiffness, muscle amplitude, and timing were quantified across time, muscle, and startle conditions. The acoustic startle increased short‐range (no startle: 0.044 ± 0.011 N·m/deg/kg; average startle: 0.047 ± 0.01 N·m/deg/kg) and total knee stiffness (no startle: 0.036 ± 0.01 N·m/deg/kg; first startle 0.027 ± 0.02 N·m/deg/kg). Additionally, the startle contributed to decreased [vastus medialis (VM): 13.76 ± 33.6%; vastus lateralis (VL): 6.72 ± 37.4%] but earlier (VM: 0.133 ± 0.17 s; VL: 0.124 ± 0.17 s) activation of the quadriceps muscles. The results of this study indicate that the startle response can significantly disrupt knee stiffness regulation required to maintain joint stability. Further studies should explore the role of unanticipated events on unintentional injury.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.