Implementing a Back‐to‐Rehab Day

This article discusses the process of planning and implementing an event during which former patients are invited to return to their acute inpatient rehabilitation facility to visit the treating team, provide information about their treatment satisfaction, participate in follow‐up interviews, and measure the functional gains made since discharge. For staff members and former patients and their families, Back‐to‐Rehab Days are rewarding and educational experiences.     

Injectable freeze‐dried chitosan‐platelet‐rich‐plasma implants improve marrow‐stimulated cartilage repair in a chronic‐defect rabbit model

Bone‐marrow stimulation (BMS) improves knee‐joint function but elicits incomplete repair. Liquid chitosan (CS)–glycerol phosphate/blood clots have been shown to improve BMS‐based cartilage repair. Platelet‐rich‐plasma (PRP)—a rich source of growth factors and cytokines—improves recruitment and chondrogenic potential of subchondral mesenchymal stem cells. We hypothesised that repair response in a rabbit chronic‐defect model will improve when freeze‐dried CS/PRP is used to augment BMS. Bilateral trochlear defects created in New Zealand white rabbits were allowed to progress to a chronic stage over 4 weeks. Chronic defects were debrided and treated by BMS in second surgery, then augmented with PRP (BMS + PRP) or freeze‐dried CS/PRP implants (BMS + CS/PRP). The quality of 8‐week repair tissue was assessed by macroscopic, histological, and micro computed tomography (Micro‐CT) analysis. ICRS macroscopic scores indicated fibrocartilaginous or fibrous repair in control defects that were improved in the BMS + CS/PRP group. An overall improvement in repair in BMS + CS/PRP group was further confirmed by higher O'Driscoll scores, %Saf‐O and %Coll‐II values. Micro‐CT analysis of subchondral bone indicated ongoing remodelling with repair still underway. Quality and quantity of cartilage repair was improved when freeze‐dried CS/PRP implants were used to augment BMS in a chronic defect model.     

MRI tumor characterization using Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M™), a protein‐avid contrast agent

The rationale and objectives were to define the MRI tumor‐characterizing potential of a new protein‐avid contrast agent, Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M?; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd kg^?1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N‐ethyl‐N‐nitrosourea (ENU), 45–250 mg kg^?1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two‐compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (K^PS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff–Bloom–Richardson score) and location of necrosis. Eighteen tumor‐bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. K^PS and fEV*, but not fPV obtained from tumors correlated significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56, respectively. Estimates for K^PS and fEV* but not fPV were significantly lower in a group consisting of benign and low‐grade malignant tumors compared with the group of less‐differentiated high‐grade tumors (1.61 ± 0.64 vs 3.37 ± 1.49, p < 0.01; 0.45 ± 0.17 vs 0.78 ± 0.24, p < 0.01; and 0.076 ± 0.048 vs 0.121 ± 0.088, p = 0.24, respectively). It is concluded that the protein‐avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low‐grade malignant lesions from high‐grade cancers. Copyright © 2006 John Wiley & Sons, Ltd.     

Nurses' Perspectives of Encouraging Clients' Care‐of‐Self in a Short‐Term Rehabilitation Unit Within a Long‐Term Care Facility

This article presents a study conducted on a short‐term rehabilitation unit in a long‐term care facility. The purpose of the study was to explore, through qualitative methods, nurses' perspectives of encouraging clients to care for themselves. Although the literature suggested that encouraging self‐care does not occur, the findings of this study showed that nurses have a broader view than what is currently known in nursing as “self‐care.” Potential impediments to nursing practice were overcome by the development of nurse‐client relationships through which the nurses encouraged clients in what is described throughout this study as “care‐of‐self” Rehabilitation nurses play an important role in helping clients to integrate and reclaim the care of their emerging new selves. Care‐of‐self may be critical to clients not only in reaching their outcome goals for discharge but also in maintaining outcomes beyond discharge.     

Drug‐induced aseptic meningitis: a mini‐review

Aseptic meningitis associates a typical clinical picture of meningitis with the absence of bacterial or fungal material in the cerebrospinal fluid. Drug‐induced aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal irritation caused by the intrathecal administration of drugs and (ii) an immunologic hypersensitivity reaction to a systemic administration. If the direct meningeal irritation allows a rather easy recognition, the immunologic hypersensitivity reaction is a source of challenging diagnostics. DIAM linked to a systemic treatment exerts typically an early onset, usually within a week. This period can be shortened to a few hours in case of drug rechallenge. The fast and spontaneous regression of clinical symptoms is usual after stopping the suspected drug. Apart from these chronological aspects, no specific clinical or biological parameters are pathognomonic. CSF analysis usually shows pleiocytosis. The proteinorachia is increased while glycorachia remains normal. Underlying pathologies can stimulate the occurrence of DIAM. Thus, systemic lupus erythematosus appears to promote DIAM during NSAID therapy, especially ibuprofen‐based one. Similarly, some patients with chronic migraine are prone to intravenous immunoglobulin‐induced aseptic meningitis. DIAM will be mainly evoked on chronological criteria such as rapid occurrence after initiation, rapid regression after discontinuation, and recurrence after rechallenge of the suspected drug. When occurring, positive rechallenge may be very useful in the absence of initial diagnosis. Finally, DIAM remains a diagnosis of elimination. It should be suggested only after all infectious causes have been ruled out.     

Concentration‐independent MRI of pH with a dendrimer‐based pH‐responsive nanoprobe

The measurement of extracellular pH (pH_e) has significant clinical value for pathological diagnoses and for monitoring the effects of pH‐altering therapies. One of the major problems of measuring pH_e with a relaxation‐based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH‐unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation‐based dendritic MRI contrast agent in a concentration‐independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA‐4AmP)₄₄‐G5, a G5–PAMAM dendrimer‐based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r₁) increased from 7.91 to 9.65 mM^?1 s^?1 (on a per Gd³⁺ basis) on changing pH from 8.84 to 6.35. At 7 T, r₁ relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r₂) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA‐4AmP)₄₄‐G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R₂/R₁ also showed a linear relationship in a pH‐responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA‐4AmP)₄₄‐G5 agent. Importantly, the nanoprobe (GdDOTA‐4AmP)₄₄‐G5 shows pH response in the range commonly found in the microenvironment of solid tumors. Copyright © 2015 John Wiley & Sons, Ltd.     

Bone marrow‐on‐a‐chip: Long‐term culture of human haematopoietic stem cells in a three‐dimensional microfluidic environment

Multipotent haematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to date, no in vitro model exists that accurately mimics the aspects of the bone marrow niche and simultaneously allows the long‐term culture of HSPCs. In this study, a novel three‐dimensional coculture model is presented, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic multiorgan chip. The HSPCs were found to stay in their primitive state (CD34⁺CD38^?) and capable of granulocyte, erythrocyte, macrophage, megakaryocyte colony formation. Furthermore, a microenvironment was formed bearing molecular and structural similarity to the in vivo bone marrow niche containing extracellular matrix and signalling molecules known to play an important role in HSPC homeostasis. Here, a novel human in vitro bone marrow model is presented for the first time, capable of long‐term culture of primitive HSPCs in a microfluidic environment.     

Beta‐lactam‐induced severe neutropaenia: a descriptive study

The objectives of this study were to describe the characteristics and natural history of beta‐lactam‐induced severe neutropaenia and to evaluate the risk of recurrences after another beta‐lactam readministration. Reports of pure agranulocytosis associated with a beta‐lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome. Sixty‐two cases were included (median age: 65 years). The median duration of treatment before neutropaenia was 16 days. In 47% of cases, the diagnosis was made on a systematic blood cell count. The median neutrophil count at nadir was 0.125 × 10⁹/L, and bone marrow examination evidenced features of neutrophilic maturation arrest or aplasia in 21 patients, hyperplasia of granulopoietic cells in three and normal findings in five. Three patients developed severe sepsis. All but one recovered a normal blood cell count within 2–56 days after beta‐lactam discontinuation. The last patient died from recurrent severe septic shock. No significant effect of granulocyte colony stimulating factor on the mean duration of haematological recovery was found. Among the 21 patients who later received another beta‐lactam, two experienced recurrence of the neutropaenia after receiving a beta‐lactam from another subfamily. Beta‐lactam‐induced agranulocytosis was usually observed after prolonged treatment, and severe complications are uncommon. In most patients, a subsequent treatment with another beta‐lactam was well tolerated.