Pollen-derived low-molecular weight factors inhibit 6-sulfo LacNAc+ dendritic cells' capacity to induce T-helper type 1 responses.

BACKGROUND: Evidence is accumulating that the pollen exsudate contains an array of non-allergenic, pro-inflammatory and immunomodulatory substances acting on the innate and adaptive immune system. In this context, pollen-associated E(1)-phytoprostanes (PPE(1)) were shown to licence human monocyte-derived dendritic cells for T-helper type 2 (Th2) polarization of naïve T cells. OBJECTIVE: This study aims at analysing the impact of pollen-associated lipid mediators on cytokine secretion and maturation of 6-sulfo LacNAc(+) dendritic cells (slanDCs), the most abundant native dendritic cell (DC) in human peripheral blood, and further dissecting the biologically active substance(s) within aqueous pollen extracts. RESULTS: Aqueous birch pollen extracts dose-dependently inhibited the lipopolysaccharide (LPS)-induced IL-12 p70 production, while the levels of IL-6 remained unaffected. PPE(1) inhibited secretion of both IL-12 p70 and IL-6. Aqueous pollen extracts, but not PPE(1) or F(1)-phytoprostanes significantly reduced the LPS-induced surface expression of the maturation markers CD80, CD83, CD40 and CCR-7, an effect that was independent of proteins and that was still present in a 3 kDa cut-off fraction of the pollen extract. These effects were observed irrespective of the atopy status of the donors. Finally, slanDCs exposed to aqueous pollen extracts were impaired in eliciting an IFN-gamma response in naïve CD4(+) T cells. CONCLUSION: Our data show that slanDCs, a subset of human blood DCs with constitutively high potency to induce Th1 responses, are susceptible to the Th2 polarizing effect of low molecular weight, non-protein factors derived from pollen.

Response of neutron detectors to high-energy mixed radiation fields.

Radiation protection around CERN's high-energy accelerators represents a major challenge due to the presence of complex, mixed radiation fields. Behind thick shielding neutrons dominate and their energy ranges from fractions of eV to about 1 GeV. In this work the response of various portable detectors sensitive to neutrons was studied at CERN's High-Energy Reference Field Facility (CERF). The measurements were carried out with conventional rem counters, which usually cover neutron energies up to 20 MeV, the Thermo WENDI-2, which is specified to measure neutrons up to several GeV, and a tissue-equivalent proportional counter. The experimentally determined neutron dose equivalent results were compared with Monte Carlo (MC) simulations. Based on these studies field calibration factors can be determined, which result in a more reliable estimate of H*(10) in an unknown, but presumably similar high-energy field around an accelerator than a calibration factor determined in a radiation field of a reference neutron source.

Radically novel prostaglandins in animals and plants: the isoprostanes.

Animal prostaglandins and plant jasmonates are well-known enzymatically formed cyclopentanoic lipids that have regulatory functions and serve as inducible mediators of host defense reactions. A novel group of prostaglandin-like compounds, the isoprostanes, generated in animals and plants by a nonenzymatic, free radical-catalyzed process, are now suspected to be mediators of oxidant injury in vivo.

Therapeutic footwear can reduce plantar pressures in patients with diabetes and transmetatarsal amputation.

OBJECTIVE: To compare how footwear (full-length shoe or short shoe), a total contact insert, a rigid rocker-bottom (RRB) sole, and an ankle-foot orthosis (AFO) affect peak plantar pressure (PPP) on the distal residuum and contralateral extremity of patients with diabetes and transmetatarsal amputation (TMA). RESEARCH DESIGN AND METHODS: Thirty patients with diabetes and TMA participated (mean age 62 +/- 4 years). In-shoe plantar pressures during walking were measured in six types of footwear. Each measurement occurred after a 1-month adjustment period. Repeated measure analysis of variance (ANOVA) was used to compare treatments. RESULTS: All five types of therapeutic footwear reduced plantar pressures compared with regular shoes with a toe-filler (P < 0.05). A full-length shoe, total contact insert, and RRB sole resulted in lower pressures on the distal residuum (222 vs. 284 kPa) and forefoot of the contralateral extremity (197 vs. 239 kPa), compared with a regular shoe and toe-filler. Footwear with an AFO showed reduced PPP on the residuum, but most patients complained of reduced ankle motion during walking. A short shoe reduced pressures on the residuum, but not on the contralateral extremity, and many patients had complaints regarding cosmesis of the shoe. CONCLUSIONS: The full-length shoe, total contact insert, and an RRB sole provided the best pressure reduction for the residuum and contralateral foot, with the optimal compromise for cosmetic acceptance and function.

Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial.

This study compared the treatment of total contact casting (TCC) with traditional dressing treatment (TDT) in the management of diabetic plantar ulcers. Forty patients with diabetes mellitus and a plantar ulcer but with no gross infection, osteomyelitis, or gangrene were randomly assigned to the TCC group (n = 21) or TDT group (n = 19). Age, sex, ratio of insulin-dependent diabetes mellitus to non-insulin-dependent diabetes mellitus, duration of diabetes mellitus, vascular status, size and duration of ulcer, and sensation were not significantly different between groups (P greater than .05). In the experimental group, TCC was applied on the initial visit, and subjects were instructed to limit ambulation to approximately 33% of their usual activity. Subjects in the control group were prescribed dressing changes and accommodative footwear and were instructed to avoid bearing weight on the involved extremity. Ulcers were considered healed if they showed complete skin closure with no drainage. Ulcers were considered not healed if they showed no decrease in size by 6 wk or if infection developed that required hospitalization. In the TCC group, 19 of 21 ulcers healed in 42 +/- 29 days; in the TDT group, 6 of 19 ulcers healed in 65 +/- 29 days. Significantly more ulcers healed (chi 2 = 12.4, P less than .05) and fewer infections developed (chi 2 = 4.1, P less than .05) in the TCC group. We conclude TCC is a successful method of treating diabetic plantar ulcers but requires careful application, close follow-up, and patient compliance with scheduled appointments to minimize complications.

Upper extremity impairments, pain and disability in patients with diabetes mellitus.

OBJECTIVES: To determine the severity of, and relationships between, upper extremity impairments, pain and disability in patients with diabetes mellitus, and to compare upper extremity impairments in patients with diabetes with non-diabetic controls. DESIGN: Case-control, cross-sectional design. SETTING: University-based, outpatient diabetes centre and physical therapy research clinic. PARTICIPANTS: Two hundred and thirty-six patients with diabetes attending an outpatient diabetes clinic completed the Shoulder Pain and Disability Index (SPADI) questionnaire. A detailed shoulder and hand examination was conducted on a subgroup of 29 volunteers with type 2 diabetes, and 27 controls matched for age, sex and body mass index. INTERVENTIONS: None. MAIN OUTCOME MEASURES: SPADI score, passive shoulder range of motion (ROM) and strength, grip strength, hand sensation, dexterity and limited joint mobility of the hand. RESULTS: Sixty-three percent (149/236) of patients with diabetes reported shoulder pain and/or disability [median SPADI score 10.0 (interquartile range 0.0 to 39.6)]. Compared with the control group, the subgroup of patients with diabetes had substantial reductions in shoulder ROM, shoulder muscle strength, grip and key pinch strength (P<0.05). Patients with diabetes had a greater prevalence of decreased sensation (26/27 vs 14/27) and limited joint mobility of the hand (17/27 vs 4/27) compared with the control group. Total SPADI score was negatively correlated (P<0.05) with shoulder ROM (r=-0.42 to -0.74) and strength measures (r=-0.44 to -0.63) in patients with diabetes. CONCLUSIONS: Upper extremity impairments in this sample of patients with diabetes were common, severe and related to complaints of pain and disability. Additional research is needed to understand the unique reasons for upper extremity problems in patients with diabetes, and to identify preventative treatments.

Formation of isoprostane F(2)-like compounds (phytoprostanes F(1)) from alpha-linolenic acid in plants.

Isoprostanes F(2) are biologically active prostaglandin F(2)-like compounds formed by free radical-catalyzed oxidation of arachidonic acid (C20:4). Here, we show that a series of dinor isoprostanes F(1), which we term phytoprostanes F(1) (PPF(1)s), are formed by nonenzymatic oxidation of linolenate (C18:3) in plants. Identification and quantification of PPF(1)s were achieved by a negative ion chemical ionization gas chromatography-mass spectrometry method using oxygen 18-labeled PPF(1)s as internal standards. PPF(1)s were found in leaves, flowers, and roots of taxonomically distinct plant species at concentrations ranging from 43 to 1380 ng/g of dry weight. In addition, esterified PPF(1)s were found at 10- to 150-fold higher concentrations. During the drying and storage of various plant organs, endogenous PPF(1) levels increased dramatically by 15- to 263-fold. Because the structurally related prostaglandin F(2alpha) and isoprostanes F(2) exert potent biological activities (i.e., broncho- and vasoconstriction) in the nanomolar range, PPF(1)s could potentially exert similar biological activities. Notably, fresh birch pollen, which can easily be inhaled, contains exceedingly high concentrations (32,440 ng/g) of free PPF(1)s.

Analyses of prostaglandin D2 metabolites in urine: comparison between enzyme immunoassay and negative ion chemical ionisation gas chromatography-mass spectrometry.

Measurements of the prostaglandin (PGD2) metabolite 9 alpha, 11 beta-PGF2 in unextracted urine performed by enzyme immunoassay (EIA) were compared with values obtained by negative chemical ionisation gas chromatography-mass spectrometry (NCI GC-MS). Values determined by NCI GC-MS were in the same range but consistently lower than those obtained by EIA, suggesting that other endogenous compounds could be contributing to the immunoreactivity. Isoprostanes were generated by autoxidation of arachidonic acid and the 9 alpha, 11 beta-PGF2 antibody demonstrated less than 0.7% crossreactivity to the mix, making it unlikely that isoprostanes in urine interfere with quantification of 9 alpha, 11 beta-PGF2 by EIA. This was further supported by the 70% reduction in immunoreactive material measured in urine after three days treatment in a healthy volunteer with the cyclooxygenase inhibitor ibuprofen. Purification of urine samples by reverse phase high-performance liquid chromatography (HPLC) revealed the presence of two immunoreactive compounds in addition to 9 alpha, 11 beta-PGF2. The compounds were identified as dinor compounds by NCI GC-MS. One of the compounds was identical to 9 alpha, 11 beta-2,3-dinor-PGF2 which was generated by beta-oxidation of 9 alpha, 11 beta-PGF2 and identified by electron impact (EI)-GC-MS. In conclusion, urinary 9 alpha, 11 beta-PGF2 concentrations measured by EIA represent the sum of 9 alpha, 11 beta-PGF2 and two isomers of its dinor metabolite. Thus, the direct EIA is fast, sensitive and sufficiently specific to monitor activation of the PGD2 pathway, thereby providing a valuable clinical tool to assess the status of mast cell activation in vivo.

Accuracy and reliability testing of a portable soft tissue indentor.

We have designed, built, and tested a portable indentor device that allows us to determine force/displacement (F/D) measurements on soft tissue in a clinical or research setting. The indentor system consists of a load cell mounted on a three-dimensional measurement device (Metrecom). The output of the load cell and the Metrecom are recorded and analyzed by software running on a notebook computer. The displacement calibration of the Metrecom gave an average error = 0.005 mm [standard deviation (SD) = 0.062)]. The force calibration of the load cell resulted in an average error = 0.022 N (SD = 0.049) and a linearity of 1.0062 (R2 = 0.9998). The indentor device was tested on six different human soft tissues by two different investigators. The interreliabilities and intrareliabilities were 0.99 [interclass correlation (ICC)] indicating that the results were repeatable by more than one investigator. F/D measurements from indentor testing on two materials were comparable to values measured using an Instron device (5.34 versus. 5.52 N/mm, and 0.98 versus 1.04 N/mm). The device was used to measure the soft tissue characteristics on the plantar surface of the foot of one subject. These data were used to calculate the effective Young's modulus for the tissue using equations derived by Zheng et al. [1] and indicated a wide range of values dependent upon the portion of the F/D curve used. All results indicate data from this portable indentor device are reliable, accurate, and sensitive enough to identify mechanical properties of human tissues.

Tendon Achilles lengthening for the treatment of neuropathic ulcers causes a temporary reduction in forefoot pressure associated with changes in plantar flexor power rather than ankle motion during gait.

The purposes of this study were to determine the effects of tendon Achilles lengthening (TAL) on ambulatory plantar pressures and ankle range of motion, moment, and power, and to determine whether changes in forefoot pressure after treatment of a neuropathic ulcer are related to changes in ankle dorsiflexion range of motion (DFROM) or plantar flexor (PF) power during gait. Pressure and gait tests were performed before treatment, and at 3 weeks and 8 months after treatment in two randomly assigned groups of subjects with diabetes, equinus deformity, and a neuropathic forefoot ulcer treated with TAL and total contact casting (TAL group, n=14), or total contact casting alone (TCC group, n=14). The TAL group had an initial decrease in forefoot peak pressure (PP) (27%), forefoot pressure-time integral (PTI) (42%), PF moment (53%), and PF power (65%), along with an initial increase in rear foot PP (34%), rear foot PTI (48%), and DFROM (74%). Post-surgical changes in rear foot pressure and DFROM were maintained up to 8 months after treatment with TAL, whereas forefoot pressure and PF moment and power increased significantly. Changes in forefoot pressure after treatment in either group were correlated with changes in PF power (r=0.45-0.60), but not with changes in DFROM during gait (r=-0.02-0.08). Results suggest TAL causes a temporary reduction in forefoot pressure primarily by reducing PF power during gait. The initial decrease in forefoot pressure, followed by progressive reloading of forefoot tissues as PF muscles regain strength after TAL, may help reduce the risk of ulcer recurrence in patients with diabetes.

In-shoe multisensory data acquisition system.

Patients with diabetes and peripheral neuropathy are susceptible to unnoticed trauma on the foot that can cause skin breakdown. We have designed an electronic system in a shoe that monitors temperature, pressure, and humidity, storing the data in a battery-powered device for later uploading to a host computer for data analysis. The pressure sensors are located at the heel, and under three metatarsal heads. Temperature sensors are located under the medial metatarsal head and under the heel. The humidity sensor is located in the toe of the shoe. Correlations of data from pressure sensors with known values were high (r > 0.85), even after extended use. Although data currently are being collected for descriptive purposes, the design potentially can be used to provide feedback to patients.

Effect of plantar flexor muscle stiffness on selected gait characteristics.

Although plantar flexor muscle strength is known to affect gait characteristics, the effect of plantar flexor (PF) muscle stiffness on gait is unknown. The purpose of this study was to determine the effect of PF muscle stiffness, in addition to PF strength, on the gait characteristics of subjects with diabetes and peripheral neuropathy (DM & PN) and age-matched controls. Thirty-four subjects were tested (17 DM & PN, 17 controls), 10 males and seven females in each group. PF muscle strength (concentric peak torque) explained a significant amount of variance in all gait variables (20-37%). Passive stiffness added a unique contribution to plantar flexor peak moment and walking speed (10-11%). Plantar flexor stiffness, in addition to strength, may be an important factor contributing to gait characteristics. Treatment techniques designed to preserve or increase stiffness may be indicated for patients with limited PF strength.

Identifying patients with diabetes mellitus who are at risk for lower-extremity complications: use of Semmes-Weinstein monofilaments.

Research indicates that the SW monofilament is an inexpensive, reliable, valid, and easy-to-use clinical indicator for identifying patients who are at risk for developing foot ulcers and subsequent amputations. Those patients unable to sense the 5.07 SW monofilament on any part of their foot should be provided preventive care, including patient education and prescription of appropriate therapeutic footwear.

Comparison of removable rigid dressings and elastic bandages in preprosthetic management of patients with below-knee amputations.

The purpose of this study was to determine if the removable rigid dressing is more effective in preprosthetic management than the conventional support dressing with elastic bandages. Residual limb circumference, independent application of the dressing, tendency of the dressing to remain secure, development of pressure areas, and presence of pain were evaluated in two groups of below-knee amputees. Subjects were randomly assigned to use either removable rigid dressings or conventional elastic bandages. Residual limb circumference was measured three times a week, and the other variables were measured weekly. The results indicated that the removable rigid dressing is more effective in preprosthetic management than the elastic bandage.

Biomechanical treatment approach to diabetic plantar ulcers. A case report.

The purpose of this case report is to describe a physical therapy approach designed to reduce the mechanical pressure at the site of a diabetic plantar ulcer. The patient was a 69-year-old man with diabetes mellitus for 24 years, insensitive feet, and a right plantar ulcer at the first metatarsal head for 21 months. He had a fixed equinus and rear-foot varus deformity, which seemed to place increased pressure on his forefoot. The patient was treated with total contact casting and showed progressive healing until he refused additional casting. One week later, the ulcer was considerably larger. He consented to resume casting, and the ulcer was completely healed in 85 days from the initial treatment. We provided the patient with extra-depth shoes with rigid rocker-bottom soles and a polyethylene-lined ankle-foot orthosis. The ulcer remained healed at one-week and six-month follow-up visits. The primary cause of diabetic plantar ulcers is often excessive pressure on an insensitive foot, and physical therapists should utilize biomechanical principles to reduce these excessive plantar pressures.

Selective criteria for successful long-term prosthetic use.

The purpose of this study was to identify criteria contributing to successful long-term prosthetic use in patients with an amputation secondary to vascular disease. All elderly patients with a unilateral below-knee amputation or an above-knee amputation, secondary to vascular disease, seen in our clinic between 1977 and 1982 were included in this telephone survey. Of those contacted, 37 of 38 below-knee amputees (BKAs) and 7 of 18 above-knee amputees (AKAs) still wore their prostheses at least part of every day (success). We used a two-tailed chi-square to compare the success of the BKAs with the success of the AKAs. The BKAs were successful more often (X2 = 24.81, df = 1, p less than .001). All AKAs also were characterized according to age, time from prescription, obesity, ambulatory status, strength, range of motion, sex, general compliance, and medical problems after prosthetic prescription. Of these criteria, only compliance and medical problems after prescription showed a significant difference between successful and nonsuccessful long-term AKA prosthetic users (X2 = 5.76, df = 1, p less than .05 for each criterion). As the demands of quality assurance and diagnostic related groupings increase, these results can assist the physical therapy clinician in setting realistic goals for the geriatric amputee and help predict if the patient will be a successful prosthetic user.

Rehabilitation factors following transmetatarsal amputation.

Despite the occurrence of approximately 10,000 transmetatarsal amputations (TMAs) a year in the United States, there are few reports describing rehabilitation for this patient group. The purposes of this clinical perspective are (1) to identify common problems encountered during rehabilitation of patients with TMA, (2) to identify factors that may contribute to these problems, and (3) to propose methods to manage these problems. A review of the literature and biomechanical models of the residuum, footwear, and orthotic devices are provided to help accomplish these purposes. Common problems encountered during rehabilitation of patients with TMA are skin breakdown and instability during functional activities. Decreased foot length and peripheral neuropathies appear to contribute to these problems. Solutions focus on attempting to provide a substitute for the plantar-flexor lever arm and protection of the insensitive residual foot. Suggestions for additional research are presented.

Physical therapy director as professional value setter. A special communication.

The purpose of this special communication is to emphasize the importance of balancing the physical therapy director's dual roles as fiscal manager and professional value setter. We will discuss the need for balancing these roles and our perception that professional values are underemphasized in many hospital-based physical therapy departments. The physical therapy director's professional values of commitment to high standards of patient care, professional growth, and self-discipline are presented, in addition to specific methods of conveying these values to others. These specific methods include providing a clear focus for the department, being active in patient care, and providing specific mechanisms to allow professional growth of staff members in a directed, but flexible, environment. Our contention is that these dual roles are required to maximize fiscal productivity and professional growth of the staff.

Reliability of kinematic measurements of rear-foot motion.

The purpose of this study was to examine the ability of a video-based, computer-interfaced motion analysis system to provide reliable data. Ten subjects with no significant orthopedic or neurological dysfunction and ranging in age from 22 to 45 years (mean = 29.6, SD = 7.8) were tested. Retroreflective markers were placed on the posterior shank and foot of each subject. Footswitches were attached to the plantar forefoot and rear foot. A video camera was placed behind the subject, and video data were collected while the subject walked on a treadmill. One representative gait cycle for each subject was selected and processed 10 times with a video processor and analysis software. Three intraclass correlation coefficients (ICCs) were calculated for variables generated by the analysis software, one for two individual measures and one each for the mean of three and five repeated measures. Except for temporal variables, processing data introduced additional variability into the measurement process, particularly for angular velocity data. Measurement of all variables was highly reliable (ICC values greater than or equal to .95) when based on the mean of at least three repeated measures. Although a single measure of temporal and angular position variables may be considered reliable, we recommend using a mean of three trials for angular velocity variables. Additional research is needed to determine tester and subject variability and validity of the measures.

Effect of total contact cast immobilization on subtalar and talocrural joint motion in patients with diabetes mellitus.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of total contact casting (TCC) on dorsiflexion at the talocrural joint (TCJ) and motion (inversion/eversion) at the subtalar joint (STJ). SUBJECTS: Thirty-seven patients (29 men, 8 women), ranging in age from 32 to 79 years (mean = 54, SD = 11), with diabetes mellitus and a unilateral plantar ulceration participated in the study. METHODS: The subjects were measured with a goniometer for dorsiflexion and STJ range of motion (ROM). The ROMs for each subject's casted and noncasted legs were compared before and after treatment with TCC for neuropathic plantar ulcers by use of a 2 x 2 repeated-measures analysis of variance design. RESULTS: Mean time of immobilization in TCC (healing time) was 42 days (SD = 43, range = 8-119). The results indicated (1) ROM was unchanged at the STJ, but dorsiflexion decreased slightly (1 degree) on both the casted and noncasted sides following the last cast removal, and (2) ROM was less on the ulcerated side prior to casting compared with the nonulcerated side. CONCLUSION AND DISCUSSION: We believe the beneficial effects (healing of wounds) outweigh the minimal detrimental effects (decreased dorsiflexion) of treatment with TCC.