Anterior cruciate ligament injury about 20 years post‐treatment: A kinematic analysis of one‐leg hop

Reduced dynamic knee stability, often evaluated with one‐leg hops (OLHs), is reported after anterior cruciate ligament (ACL) injury. This may lead to long‐standing altered movement patterns, which are less investigated. 3D kinematics during OLH were explored in 70 persons 23 ± 2 years after ACL injury; 33 were treated with physiotherapy in combination with ACL reconstruction (ACL_R) and 37 with physiotherapy alone (ACL_PT). Comparisons were made to 33 matched controls. We analyzed (a) maximal knee joint angles and range of motion (flexion, abduction, rotation); (b) medio‐lateral position of the center of mass (COM) in relation to knee and ankle joint centers, during take‐off and landing phases. Unlike controls, ACL‐injured displayed leg asymmetries: less knee flexion and less internal rotation at take‐off and landing and more lateral COM related to knee and ankle joint of the injured leg at landing. Compared to controls, ACL_R had larger external rotation of the injured leg at landing. ACL_PT showed less knee flexion and larger external rotation at take‐off and landing, and larger knee abduction at Landing. COM was more medial in relation to the knee at take‐off and less laterally placed relative to the ankle at landing. ACL injury results in long‐term kinematic alterations during OLH, which are less evident for ACL_R.     

Improving postoperative pain management in subpectoral tissue expander implant reconstruction of the breast using an elastomeric pump

IntroductionPostoperative pain after breast surgery is one of the major factors contributing to delay in mobilisation and prolonged hospital stay. A retrospective analysis was performed of patients undergoing skin sparing mastectomy and insertion of a subpectoral implant. The aim was to determine whether the use of an elastomeric local anaesthetic pump improved pain control and length of stay.MethodsTwenty-five consecutive patients undergoing the above procedure were sited with an elastomeric local anaesthetic infusion pump intraoperatively, in addition to standard regular and pro re nata analgesia. The control group comprised 25 patients undergoing the same procedure in the same year who received standard analgesia alone. Visual analogue scale scores were recorded for the duration of inpatient stay, as was any further analgesic requirement.ResultsThe median age was 51 years (range: 26–75 years) in the intervention group and 50 years (range: 28–70 years) in the control group. The mean visual analogue scale score was 0.28 (standard deviation [SD]: 0.61) at 24 hours for the intervention group and 1.84 (SD: 0.37) for the control group (p<0.0001). The mean length of stay was 1.8 days (SD: 0.71 days) for the intervention group and 2.28 days (SD: 0.94 days) for the control group (p=0.15). There were no complications involving catheter placement, leakage or toxicity relating to use of the local anaesthetic.ConclusionsThere was significantly reduced pain with the use of the local anaesthetic infusion pump. The elastomeric pump is a step towards enhanced patient recovery after breast surgery in the case of skin sparing mastectomy and subpectoral tissue expander reconstruction.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.     

Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.

AIMS: We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.     

Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide

Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.