Perceived health and physical functioning in postpoliomyelitis syndrome: a 6-year prospective follow-up study

OBJECTIVES: To study prospectively the health status, and especially the physical functioning, of polio survivors with and without postpoliomyelitis syndrome (PPS), and to identify prognostic determinants of change in physical functioning. DESIGN: Prospective cohort study; measurements at baseline and after 1, 2, and 6 years. SETTING: University hospital in the Netherlands. PARTICIPANTS: Seventy-six subjects with PPS and 27 without PPS. INTERVENTIONS: Not applicable.Main Outcome Measure: The Nottingham Health Profile (NHP) physical mobility category. RESULTS: Subjects with PPS had significantly poorer health status than subjects without PPS. No significant differences in mean NHP physical mobility scores between baseline and 6 years were found; both groups had improved after 1 year, after which there was a slow decline over the next 5 years. During the first 2 years, strength measurements showed little decline that was not related to changes in NHP physical mobility score. A physical performance test revealed no mean change in the first 2 years, but the subgroup with a decline above the 75th percentile eventually deteriorated 10.5+/-16.3 points on the NHP physical mobility category (P=.01) at 6 years from baseline. This subgroup had more extensive paresis than the other subjects, although it was not significant (P=.07). The extent of paresis at baseline was the only prognostic determinant for an increase in NHP physical mobility problems after 6 years. CONCLUSIONS: Subjects with and without PPS did not differ with regard to changes in health status in a 6-year period. The fact that the extent of paresis was a prognostic factor for a decline in physical functioning is in accord with a (slow) decline in muscle mass, as a late effect of polio, that may lead to a decline in physical functioning as the reduced muscle capacity becomes less able to meet the demands of daily physical activities.     

The relation between extrapolated risk, expressed as potentially affected fraction, and community effects, expressed as pollution-induced community tolerance

The results of toxicity tests can be used to calculate the potentially affected fraction (PAF) of species in an ecosystem at a given pollutant concentration using statistical extrapolation methods. The PAF curve indicates the fraction of species from the original community that may become inhibited at each elevated pollutant concentration and is a measure of the ecotoxicological risk. Pollution-induced community tolerance (PICT) is a true community response that is measured under controlled conditions in the laboratory, using organisms from contaminated field sites. Microorganisms from experimental field plots with added Zn were exposed to various concentrations of Zn in the laboratory and the mineralization of 14C acetate was monitored. Microorganisms from plots with Zn concentrations above 124 mg/kg showed a significant increase in the effect concentration 10% (EC10) and, therefore, had a significant PICT. The pore-water concentrations of Zn in these field soils were in the same magnitude as the EC10 of the microorganisms from these soils. The PAF curve was calculated from previously reported toxicity tests with five different microbial species using the average and the standard deviation of the logarithmically transformed EC10 values. The average sensitivity of this PAF curve was similar to the EC50 of the acetate mineralization curve from the field plot without added Zn2+, but the PAF curve was less steep. Our experiments indicated that 27 to 84% of the original microbial species were inhibited at Zn concentrations from 334 to 1,858 mg/kg soil, respectively. Our results suggest that the PICT method can now also be used to quantify the fraction of the original species composition that is inhibited at a specific pollutant concentration.     

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

Morphological and functional characteristics of rat steady state peritoneal dendritic cells.

Dendritic cells (DC) are present in lymphoid organs and also in many non-lymphoid tissues. In this study, DC in the steady state peritoneal cavity of rats were identified morphologically and functionally. Approximately 1% of the peritoneal cells are DC. On cytocentrifuge preparations these cells had the same characteristics as lymph node and spleen DC: they had an irregular outline, all were strongly MHC class II positive and had acid phosphatase activity in a spot in a juxtanuclear position. Also ultrastructurally, peritoneal DC were similar to DC isolated from lymph node and spleen. Enrichment of peritoneal DC, using overnight culture and a Nycodenz gradient, resulted in a highly purified DC fraction. Functionally, peritoneal DC appeared to be very potent antigen-presenting cells, far more potent than peritoneal macrophages, which had an inhibitory rather than an accessory function.     

Short dwell times reduce the local defence mechanism of chronic peritoneal dialysis patients

The effect of different intraperitoneal dwell times on the phagocytic capacity of the effluent-derived macrophages in 6 peritoneal dialysis patients was studied. The number of peritoneal cells increased after longer dwell times, and a significant increase in the percentage of macrophages phagocytosing opsonized sheep red blood cells [( IgG]SRBC) and unopsonized latex beads was determined when the dwell time increased from 1.5 to 15 h. Thus, the total phagocytic capacity of the effluent-derived macrophages dramatically increased with prolonged dwell times. In addition, the IgG concentration showed a five-fold increase following long intraperitoneal dwell times. The increasing IgG levels were accompanied by an increase, however not significant (p less than 0.06), in the opsonic activity of the effluents. The increase in local phagocytic and opsonic capacity following longer intraperitoneal dwell times must be taken in consideration by dialysis fluid exchange schedules of peritoneal dialysis patients.     

Sensory re-education after nerve injury of the upper limb: a systematic review

OBJECTIVE: To systematically review the available evidence for the effectiveness of sensory re-education to improve the sensibility of the hand in patients with a peripheral nerve injury of the upper limb. DATA SOURCES: Studies were identified by an electronic search in the databases MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), and the database of the Dutch National Institute of Allied Health Professions (Doconline) and by screening the reference lists of relevant articles. REVIEW METHODS: Two reviewers selected studies that met the following inclusion criteria: all designs except case reports, adults with impaired sensibility of the hand due to a peripheral nerve injury of the upper limb, and sensibility and functional sensibility as outcome measures. The methodological quality of the included studies was independently assessed by two reviewers. A best-evidence synthesis was performed, based on design, methodological quality and significant findings on outcome measures. RESULTS: Seven studies, with sample sizes ranging from 11 to 49, were included in the systematic review and appraised for content. Five of these studies were of poor methodological quality. One uncontrolled study (N = 1 3 ) was considered to be of sufficient methodological quality, and one randomized controlled trial (N = 49) was of high methodological quality. Best-evidence synthesis showed that there is limited evidence for the effectiveness of sensory re-education, provided by a statistically significant improvement in sensibility found in one high-quality randomized controlled trial. CONCLUSION: There is a need for further well-defined clinical trials to assess the effectiveness of sensory re-education of patients with impaired sensibility of the hand due to a peripheral nerve injury.     

Disability and functional assessment in former polio patients with and without postpolio syndrome

OBJECTIVES: To compare perceived health problems and disability in former polio subjects with postpolio syndrome (PPS) and those without postpolio syndrome (non-PPS), and to evaluate perceived health problems, disability, physical performance, and muscle strength. DESIGN: Cross-sectional survey; partially blinded data collection. SUBJECTS: One hundred three former polio subjects, aged 32 to 60yrs. This volunteer sample came from referrals and patient contacts. Criterion for PPS: new muscle weakness among symptoms. MAIN OUTCOME MEASURES: Nottingham Health Profile (NHP), adapted D-code of the International Classification of Impairments, Disabilities and Handicaps, performance test, and muscle strength assessment. RESULTS: PPS subjects (n = 76) showed higher scores (p < .001) than non-PPS subjects (n = 27) within the NHP categories of physical mobility, energy, and pain. On a 16-item Polio Problems List, 78% of PPS subjects selected fatigue as their major problem, followed by walking outdoors (46%) and climbing stairs (41%). The disabilities of PPS subjects were mainly seen in physical and social functioning. No differences in manually tested strength were found between patient groups. PPS subjects needed significantly more time for the performance test than non-PPS subjects and their perceived exertion was higher. Perceived health problems (NHP-PhysMobility) correlated significantly with physical disability (r = .66), performance-time (r = .54), and muscle strength (r = .38). With linear regression analysis, 54% of the NHP-PhysMobility score could be explained by the performance test (time and exertion), presence of PPS, and muscle strength, whereas strength itself explained only 14% of the NHP-PhysMobility score. CONCLUSIONS: PPS subjects are more prone to fatigue and have more physical mobility problems than non-PPS subjects. In former polio patients, measurements of perceived health problems and performance tests are the most appropriate instruments for functional evaluation.     

Single exposure of mesothelial cells to glucose degradation products (GDPs) yields early advanced glycation end-products (AGEs) and a proinflammatory response.

BACKGROUND: Fluids commonly used for peritoneal dialysis (PD) have a low pH and a high glucose content. Furthermore, heat sterilization of dialysis fluids degrades some of the glucose into glucose degradation products (GDPs), such as methylglyoxal (MGO) and 3-deoxyglucosone (3-DG). Mesothelial cells (MCs) form the first line in the peritoneal cavity and are constantly exposed to these nonphysiological conditions. Since MCs play an important role in the regulation of inflammatory responses in the peritoneal cavity, we studied the kinetics of MC uptake of highly purified GDP species, along with their effect on various cellular biological and immunological parameters. METHODS: Methylglyoxal and 3-DG were purified and added to MC cultures. Complexing to medium components or uptake by MCs was analyzed over time by HPLC of the culture supernatant and by immunocytochemistry of MCs for MGO-modified proteins. Furthermore, MCs were exposed to a single dose of MGO or 3-DG and analyzed for apoptosis, proliferation by MTT assay, and [3H]-thymidine incorporation. Incorporation of [35S]-methionine was determined in order to analyze de novo protein synthesis. Expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), CD44, and vascular cell adhesion molecule-1 (VCAM-1) was analyzed by cell-bound ELISA. Effects of MGO and 3-DG on cytokine production were also analyzed. RESULTS: Substitution of MGO and 3-DG in culture medium resulted in a spontaneous decrease in MGO over time, whereas 3-DG levels decreased minimally. The concentration of these GDPs was more reduced in the presence of MCs, indicating binding to and/or uptake by MCs of these GDPs. Mesothelial cells that had been cultured in the presence of MGO showed positive staining with a monoclonal that specifically recognizes MGO-modified proteins, demonstrating complexing to mesothelial cellular proteins. Cell-bound ELISA showed a two- to three-fold induction of expression of VCAM-1 by MGO and 3-DG; the expression of ICAM-1 and CD44 was not changed. Mesothelial cells showed a twofold increase in interleukin (IL)-6 and IL-8 production after exposure to 3-DG. Furthermore, incubation with MGO and 3-DG induced apoptosis and reduced the proliferation of cells, but did not influence protein synthesis. CONCLUSIONS: In the current report we demonstrate that MCs take up MGO and 3-DG and form early advanced glycation end-products. Upon short exposure to a single GDP, MCs react with enhanced cytotoxic damage and a proinflammatory response, evidenced by increased VCAM-1 expression and elevated production of IL-6 and IL-8.     

Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n?=?28; viral, n?=?26; bacterial, n?=?18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n?=?16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n?=?6; Mucorales-PCR, n?=?1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P?=?.049) and inferior ICU survival (6% versus 37%, P?<?.01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.