Polymorphisms in FcgammaRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstr?m's macroglobulinemia.

PURPOSE: Rituximab is an important therapeutic for Waldenstrom's macroglobulinemia (WM). Polymorphisms in FcgammaRIIIA (CD16) receptor expression modulate human immunoglobulin G1 binding and antibody-dependent cell-mediated cytotoxicity, and may therefore influence responses to rituximab. PATIENTS AND METHODS: Sequence analysis of the entire coding region of FcgammaRIIIA was undertaken in 58 patients with WM whose outcomes after rituximab were known. RESULTS: Variations in five codons of FcgammaRIIIA were identified. Two were commonly observed (FcgammaRIIIA-48 and FcgammaRIIIA-158) and predicted for amino acid polymorphisms at FcgammaRIIIA-48: leucine/leucine (L/L), leucine/arginine (L/R), and leucine/histidine (L/H). Polymorphisms at FcgammaRIIIA-158 were phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V), and valine/valine (V/V). A clear linkage between these polymorphisms was detected and all patients with FcgammaRIIIA-158F/F were always FcgammaRIIIA-48L/L, and patients with either FcgammaRIIIA-L/R or -L/H always expressed at least one valine at FcgammaRIIIA-158 (P < or = .001). The response trend was higher for patients with FcgammaRIIIA-48L/H (38.5%) versus -48L/R (25.0%) and LL (22.0%), and was significantly higher for patients with FcgammaRIIIA-158V/V (40.0%) and -V/F (35%) versus -158F/F (9.0%; P = .030). Responses for patients with FcgammaRIIIA-48L/L were higher when at least one valine was present at FcgammaRIIIA-158 (P = .057), thereby supporting a primary role for FcgammaRIIIA-158 polymorphisms in predicting rituximab responses. With a median follow-up of 13 months, no significant differences in the median time to progression and progression-free survival were observed when patients were grouped according to their FcgammaRIIIA-48 and -158 polymorphisms. CONCLUSION: The results of these studies therefore support a predictive role for FcgammaRIIIA-158 polymorphisms and responses to rituximab in WM.     

Shoulder activity level in the preoperative assessment of patients with rotator cuff tears

The purpose of this study was to investigate shoulder activity level in preoperative assessment of shoulder function and health-related quality of life (QoL) for patients with rotator cuff tears. One hundred and six patients with rotator cuff tears were prospectively evaluated using the following outcome instruments: the Shoulder Activity scale, the Constant scale, the Simple Shoulder Test, and the Short Form-36v2 (SF-36v2). Clinical and structural data, including patients’ demographics, comorbidities, duration of symptoms, shoulder contracture, and tear size, were collected and analyzed. We determined that the shoulder activity level was associated with gender, medical comorbidities, and age. Females had lower activity level, worse scores for health-related QoL, and longer duration of symptoms than males. Patients who had severe comorbidities had lower shoulder activity scores and worse SF-36v2 scores compared to patients who did not have such comorbidities. The patient age correlated with the shoulder activity level, but did not have significant correlation with the duration of symptoms and shoulder function. The shoulder activity level was related to patient gender, general health status and age; therefore, further investigation is warranted to determine if the activity level can be used as a prognostic variable relating to outcome in the treatment of rotator cuff tears.     

The Time-Course of Voluntary and Electrically Evoked Muscle Performance During and After Stretch-Shortening Exercise is Different

The aim of the study was to establish the dynamics of maximal voluntary contraction force (MVCF), height of drop jump (DJ) and electrically evoked quadriceps muscle force at different stimulation frequencies during and after 100 DJs (stretch-shortening exercise, SSE). Healthy untrained men (n = 11; age = 21.8 ± 1.7 years) participated in the study. DJs were performed with 30 s intervals between jumps from the height of 0.5 m with counter-movement to 90 degrees angle in the knee and immediate maximal rebound. The force of the quadriceps muscle, evoked by electrical stimulation at 1 Hz (Pt), 20 Hz (P20) and 100 Hz (P100) frequencies (electrically evoked performance, EEP), MVCF and height of DJ (voluntary evoked performance, VEP) were established during SSE (after 10, 50, 100 DJ) as well as at 1, 4, 8, 24, 48 and 72 h after SSE. Time-course of P20 and P100 during and after SSE was time (ANOVA: p < 0.001) and frequency dependent (ANOVA: p < 0.001) The Pt, P20 and P100 decreased significantly (p < 0.01) more than MVCF and H of DJ during SSE. At the beginning of SSE (during 1-10 DJs) P20 and P100 decreased significantly (p < 0.001) more than during 11-50 and 51-100 DJs. There was a significant (p < 0.05) increase in Pt, P20 and P100 from 8 h to 48 h, whereas height of DJ and MVCF significantly decreased at that time. In conclusion, the differences in time course of VEP and EEP are most evident at beginning of SSE, where VEP does not change as EEP decreases, and within 8-48 hours after SSE, where VEP decreases as EEP increases.

Key points

• There was no change in voluntary muscle performance while electrically evoked performance decreased significantly during first 10 drop jumps.
• There was a significant increase in electrically evoked muscle performance from 8 h to 48 h after 100 drop jumps, whereas voluntary contraction force, decreased significantly.
• The secondary decrease in the height of drop jump as well as in maximal voluntary contraction force correlated significantly with muscle soreness within 24-48 h after exercise.

Key words: Drop jump, muscle damage, electrical stimulation, low frequency fatigue     

Do nurses feel stressed? A perspective from primary health care

This study describes nurses' experiences of stress in primary healthcare settings, and examines correlations between stress and personal factors. There were 187 nurses from 18 public primary care centers participating, drawn from one county of Lithuania. The Expanded Nursing Stress Scale was used to evaluate the study data. The study indicates that in primary healthcare centers, nurses working with adult patients experienced less stress than those working with younger patients. The most frequently reported stressors were those related to death and dying, and conflicts with physicians and patients and their families. In particular, older nurses more frequently experienced stress related to death and dying. The intensity of nurses' stress in conflict situations with physicians was related to age, however, the depth of work experience in the healthcare setting was more influential. Findings indicate that more detailed research is needed regarding stress experiences in primary health care, and especially the related impact of the social contexts involved in the setting.     

Expression of matrix metalloproteinases, their tissue inhibitors, and osteopontin in the wall of thoracic and abdominal aortas with dilatative pathology

Matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of aortic aneurysms. We studied 2 groups of patients: 15 with dilatative pathology of the ascending thoracic aorta and 17 with aneurysm of the abdominal aortic wall (AAA). We compared the expression of MMPs, tissue inhibitors of matrix metalloproteinases (TIMPs), and osteopontin in the wall of thoracic and abdominal aneurysms. In AAA, MMP-9 and TIMP-1 expression in inflammatory cells was higher than in smooth muscle cells (SMCs) (median score: 3.5 versus 1, P < .0001; 2 versus 1, P < .04, respectively), whereas MMP-2 demonstrated higher expression in SMCs than in inflammatory cells (median score: 0 versus 4, P < .0001). In ATA, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3, and osteopontin expression in SMCs was higher than in inflammatory cells (median score: 3 versus 0, P < .0001; 4 versus 1, P < .0005; 2 versus 0, P < .001; 5 versus 2, P < .0001; 2 versus 0, P < .005; and 5 versus 1.5, P < .0001, respectively), when both inflammatory cells of the media and the adventitia were considered together. The cellular expression of MMP-9 and their tissue inhibitors TIMP-1, TIMP-2, and TIMP-3 differs in the dilatative pathology of abdominal and thoracic aortas, so the hypothetical model of morphogenesis of AAA cannot completely explain the formation of dilatative pathology of the ascending thoracic aorta.     

Leg Immersion in Warm Water,Stretch-Shortening Exercise,and Exercise-Induced Muscle Damage

Context:

Whether muscle warming protects against exercise-induced muscle damage is unknown.

Objective:

To determine the effect of leg immersion in warm water before stretch-shortening exercise on the time course of indirect markers of exercise-induced muscle damage.

Design:

Crossover trial.

Setting:

Human kinetics laboratory.

Patients or Other Participants:

Eleven healthy, untrained men (age  =  21.5 ± 1.7 years).

Intervention(s):

Participants'' legs were immersed in a water bath at 44 ± 1°C for 45 minutes.

Main Outcome Measure(s):

Creatine kinase changes in the blood, muscle soreness, prolonged (within 72 hours) impairment in maximal voluntary contraction force and height of drop jump, and electrically evoked muscle force at low and high stimulation frequencies at short and long muscle lengths.

Results:

Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage, including creatine kinase activity in the blood, muscle soreness, maximal voluntary contraction force, and jump height. The values for maximal voluntary contraction force and jump height, however, were higher during prewarming than for the control condition at 48 hours after stretch-shortening exercise, but this difference was only minor at other time points. Muscle prewarming did not bring about any changes in the dynamics of low-frequency fatigue, registered at either short or long muscle length, within 72 hours of stretch-shortening exercise.

Conclusions:

Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage. However, the clinical application of muscle prewarming may be limited, because decreasing muscle damage did not necessarily lead to improved voluntary performance.     

The repeated bout effect of eccentric exercise is not associated with changes in voluntary activation

The aim of this study was to compare the possible changes in muscle activation level between a first and second bout of damaging eccentric exercise performed at 2 weeks interval (i.e. repeated bout effect). To that purpose, ten physically active males took part in this study. The eccentric exercise consisted of 10 sets of 12 maximal voluntary contractions (MVC) produced by the knee extensors during movements performed at a constant speed of 160°s⁻¹. Changes in voluntary and electrically evoked torque in concentric and/or isometric conditions were assessed at the following time points: pre-exercise, and 2 min, 1 and 24 h after each eccentric exercise. At the same time points, voluntary activation was quantified by the superimposed electrical stimulation technique. Muscle soreness and plasma CK activity were measured within 48 h after the eccentric exercise. The results showed that the decrease in eccentric peak torque was linear throughout the exercise protocol. At the end of bouts 1 and 2, torque was significantly reduced by 27.7 ± 9.1 and 23.4 ± 11.2, respectively, with no difference between bouts (P > 0.05). At 24 h post-exercise, a lower reduction (P < 0.05) in MVC (17.8 ± 5.4%) and electrically evoked (16.7 ± 4.6%) isometric torque was observed for bout 2. In contrast, no statistical difference was found in the deficit in voluntary activation between the two bouts. In conclusion, our results indicate that the repeated bout effect of eccentric exercise appears to reduce muscle damage, but does not influence the level of voluntary activation.