Deficient mismatch repair screening of advanced adenomas in the population screening program for colorectal cancer is not effective.

AIM: Currently, screening of colorectal cancers (CRC) by assessing mismatch repair deficiency (dMMR) or microsatellite instability (MSI) is used to identify Lynch syndrome (LS) patients. Advanced adenomas are considered immediate precursor lesions of CRC. In this study we investigate the relevance of screening of advanced adenomas for LS in population screening. METHODS AND RESULTS: Advanced adenomas (n = 1572) were selected from the Dutch colorectal cancer population screening programme, based on one or more of the criteria: tubulovillous (n = 848, 54%) or villous adenoma (n = 118, 7.5%), diameter ≥ 1 cm (n = 1286, 82%) and/or high-grade dysplasia (n = 176, 11%). In 86 cases (5%), all three criteria were fulfilled at the same time. MMR-IHC and/or MSI analyses were performed on all cases. Only five advanced adenomas (0.3%) showed dMMR and MSI, including two cases with hypermethylation. In at least two patients a germline event was suspected based on allelic frequencies. No pathogenic explanation was found in the last case. CONCLUSION: Timely testing of precursor lesions would be preferable to detect new LS patients before CRC development. However, standard assessment of dMMR of advanced adenomas from the population screening is not effective.

Amplified Ca2+ dynamics and accelerated cell proliferation in breast cancer tissue during purinergic stimulation.

Intracellular Ca2+ dynamics shape malignant behaviors of cancer cells. Whereas previous studies focused on cultured cancer cells, we here used breast organoids and colonic crypts freshly isolated from human and murine surgical biopsies. We performed fluorescence microscopy to evaluate intracellular Ca2+ concentrations in breast and colon cancer tissue with preferential focus on intracellular Ca2+ release in response to purinergic and cholinergic stimuli. Inhibition of the sarco-/endoplasmic reticulum Ca2+ ATPase with cyclopiazonic acid elicited larger Ca2+ responses in breast cancer tissue, but not in colon cancer tissue, relative to respective normal tissue. The resting intracellular Ca2+ concentration was elevated, and ATP, UTP and acetylcholine induced strongly augmented intracellular Ca2+ responses in breast cancer tissue compared with normal breast tissue. In contrast, resting intracellular Ca2+ levels and acetylcholine-induced increases in intracellular Ca2+ concentrations were unaffected and ATP- and UTP-induced Ca2+ responses were smaller in colon cancer tissue compared with normal colon tissue. In accordance with the amplified Ca2+ responses, ATP and UTP substantially increased proliferative activity-evaluated by bromodeoxyuridine incorporation-in breast cancer tissue, whereas the effect was minimal in normal breast tissue. ATP caused cell death-identified with ethidium homodimer-1 staining-in breast cancer tissue only at concentrations above the expected pathophysiological range. We conclude that intracellular Ca2+ responses are amplified in breast cancer tissue, but not in colon cancer tissue, and that nucleotide signaling stimulates breast cancer cell proliferation within the extracellular concentration range typical for solid cancer tissue.

Improving preoperative diagnosis in endometrial cancer using systematic morphological assessment and a small immunohistochemical panel.

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2 ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC = 0.92; 95%CI = 0.88-0.95) compared to solely morphological evaluation (AUC = 0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC = 0.93; 95%CI = 0.88-0.98) compared to solely morphological evaluation (AUC = 0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2 ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%).

Incidental morphological findings in colorectal adenomas.

Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are increasingly being observed. These may present diagnostic challenges and cause clinical management issues. Paneth cell metaplasia is a more common occurrence, but the incidence rates of squamous metaplasia, clear cell metaplasia, osseous metaplasia, neuroendocrine differentiation and signet-ring cell-like lesion are low, and they can be seen in <1% of colorectal adenomas. Their histomorphological characteristics are quite unique; ancillary studies are not very helpful and often not needed. In this review, we give an overview and describe the potential clinical consequences of such incidental and special morphological findings in colorectal adenomas.

Quorum sensing-induced phenotypic switching as a regulatory nutritional stress response in a competitive two-species biofilm: An individual-based cellular automata model.

Competition for nutrients in a polymicrobial biofilm may lead to susceptible species being subjected to nutritional stress. The influence of bacterial growth rates and interspecies interactions on their susceptibility and response to nutritional stress is not well understood. Pseudomonas aeruginosa and Staphylococcus aureus are two prevalent causative pathogens that coexist in biofilm-associated infections. Despite being the slower-growing species, P. aeruginosa dominates in a two-species biofilm by inducing phenotypic switching of S. aureus to a metabolicallychallenged small colony variant (SCV) via the release of 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). We hypothesize that P. aeruginosa experiences nutritional stress in competition with S. aureus, and that the release of HQNO is an adaptive response to nutritional stress.We present an individual-based two-species biofilm model in which interactions between entities induce emergent properties. As the biofilm matured, the difference in growth rates of the two species caused a non-uniform distribution of nutrients leading to nutritional stress for P. aeruginosa and a concurrent increase in the proportion of S. aureus subpopulation. The latter resulted in increased release of autoinducer, and subsequently the upregulation of P. aeruginosa cells via quorum sensing. Upregulated P. aeruginosa cells released HQNO at enhanced rates, thereby inducing phenotypic switching of S. aureus to SCVs which consume nutrient at a reduced rate. This shifted the nutrient distribution back in favor of P. aeruginosa, thereby relieving nutritional stress. Increase in nutritional stress potentiated the transformation of S. aureus into SCVs. HQNO production decreased once nutritional stress was relieved, indicating that phenotypic switching acts as a regulatory stress-adaptive response.

Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results.

Purpose: To present the 6-month results of the Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial (ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy.

Microsatellite instability screening in colorectal adenomas to detect Lynch syndrome patients? A systematic review and meta-analysis.

The colorectal cancer spectrum has changed due to population screening programs, with a shift toward adenomas and early cancers. Whether it would be a feasible option to test these adenomas for detection of Lynch syndrome (LS) patients is unclear. Through meta-analysis and systematic review, risk factors for DNA mismatch repair deficiency (dMMR) and microsatellite instability (MSI) in adenomas were identified in LS and unselected patient cohorts. Data were extracted for patient age and MMR variant together with adenoma type, grade, size, and location. A total of 41 studies were included, and contained more than 519 LS patients and 1698 unselected patients with 1142 and 2213 adenomas respectively. dMMR/MSI was present in 69.5% of conventional adenomas in LS patients, compared with 2.8% in unselected patients. In the LS cohort, dMMR/MSI was more frequently present in patients older than 60 years (82% versus 54%). dMMR/MSI was also more common in villous adenomas (84%), adenomas over 1 cm (81%), and adenomas with high grade dysplasia (88%). No significant differences were observed for dMMR/MSI in relation to MMR variants and location of adenomas. In the context of screening, we conclude that detection of dMMR/MSI in conventional adenomas of unselected patients is uncommon and might be considered as indication for LS testing. Within the LS cohort, 69.5% of LS patients could have been detected through dMMR/MSI screening of their conventional adenomas.

Elevated levels of Interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, epidermal growth factor, and ß2-microglobulin levels in gingival crevicular fluid during human Orthodontic tooth movement (OTM).

AIM: The aim of this study was to identify and quantify the various cytokines in human gingival crevicular fluid (GCF), and to investigate the changes in their levels during orthodontic tooth movement (OTM). MATERIALS AND METHODS: A statistically significant no. of subjects (n = 10 and mean age = 15.6 years) were included in the study. A maxillary cuspid of each subject having one treatment for distal orthodontic tooth movement served as the experimental tooth, whereas the contralateral cuspids were used as controls. Gingival crevicular fluid (GCF) around the experimental and the two control teeth was collected from each subject immediately before activation, and at 1, 24, and 168 hours after the initiation of tooth movement. RESULT: ELISAs were used to determine cytokine levels. The concentrations of interleukin (IL)-1lß, IL-6, tumor necrosis factor-α, epidermal growth factor, and ß2-microglobulin were significantly higher in the experimental group than in the controls at 24 hr after the experiment was initiated. All the cytokines remained at baseline levels throughout the experiment for the control groups. CONCLUSION: Since all cytokines in GCF play an important role in the bone remodelling processes in vivo, the present results indicate that the changes in cytokines in GCF are associated with OTM.

Microcosm study of atrazine bioremediation by indigenous microorganisms and cytotoxicity of biodegraded metabolites.

Intensive use of atrazine in agriculture to increase crop productivity has resulted in pollution and consequently deteriorated the environment. Three isolated bacteria, Rhodococcus sp. BCH2 (RB), Bacillus sp. PDK1 (BP1) and Bacillus sp. PDK2 (BP2) possessing capability to degrade atrazine were used in different combinations (RB + BP1, RB + BP2, BP1 + BP2, RB + BP1 + BP2) to prepare a highly effective bacterial consortium which can significantly reduce the toxicity of atrazine. Cytotoxicity tests evaluated by MTT assay on HepG2 indicated significant decrease in the toxicity of atrazine by the consortium RB + BP1 + BP2 due to its effective degradation and formation of simpler and less/nontoxic metabolites compared to other combinations of consortia. A microcosm study was conducted to check the survivability of this consortium (RB + BP1 + BP2) in the presence of atrazine and indigenous soil microflora for four weeks. LC-Q-TOF/MS analysis revealed that RB + BP1 + BP2 could degrade atrazine to various simple metabolites in the microcosm. The cluster analysis of the DGGE patterns of the microcosm of control-soil, soil exposed to atrazine and soil augmented with consortium in the presence of atrazine (1000 mg kg-1) revealed a shift in microbial community of soil. The microbial dynamics studies suggested that the augmented bacteria were well-thrived with natural microflora during four weeks of exposure to atrazine.

SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial.

The efficacy of biologic therapies in critical limb ischemia (CLI) remains elusive, in part, due to limitations in trial design and patient selection. Using a novel design, we examined the impact of complementing revascularization therapy with intramuscular JVS-100 - a non-viral gene therapy that activates endogenous regenerative repair pathways. In this double-blind, placebo-controlled, Phase 2B trial, we randomized 109 patients with CLI (Rutherford class V or VI) to 8 mg or 16 mg intramuscular injections of placebo versus JVS-100. Patients were eligible if they persistently had reduced forefoot perfusion, by toe-brachial index (TBI) or skin perfusion pressure (SPP), following successful revascularization with angiographic demonstration of tibial arterial flow to the ankle. The primary efficacy end point was a 3-month wound healing score assessed by an independent wound core laboratory. The primary safety end point was major adverse limb events (MALE). Patients' mean age was 71 years, 33% were women, 79% had diabetes, and 8% had end-stage renal disease. TBI after revascularization was 0.26, 0.27, and 0.26 among the three groups (placebo, 8 mg, and 16 mg injections, respectively). Only 26% of wounds completely healed at 3 months, without any differences between the three groups (26.5%, 26.5%, and 25%, respectively). Similarly, there were no significant changes in TBI at 3 months. Three (2.8%) patients died and two (1.8%) had major amputations. Rates of MALE at 3 months were 8.8%, 20%, and 8.3%, respectively. While safe, JVS-100 failed to improve wound healing or hemodynamic measures at 3 months. Only one-quarter of CLI wounds healed at 3 months despite successful revascularization, highlighting the need for additional research in therapies that can improve microcirculation in these patients. ClinicalTrials.gov Identifier: NCT02544204.

Asparagus densiflorus in a vertical subsurface flow phytoreactor for treatment of real textile effluent: A lab to land approach for in situ soil remediation.

This study explores the potential of Asparagus densiflorus to treat disperse Rubin GFL (RGFL) dye and a real textile effluent in constructed vertical subsurface flow (VSbF) phytoreactor; its field cultivation for soil remediation offers a real green and economic way of environmental management. A. densiflorus decolorized RGFL (40 gm L-1) up to 91% within 48 h. VSbF phytoreactor successfully reduced American dye manufacture institute (ADMI), BOD, COD, Total Dissolved Solids (TDS) and Total Suspended Solids (TSS) of real textile effluent by 65%, 61%, 66%, 48% and 66%, respectively within 6 d. Oxidoreductive enzymes such as laccase (138%), lignin peroxidase (129%), riboflavin reductase (111%) were significantly expressed during RGFL degradation in A. densiflorus roots, while effluent transformation caused noteworthy induction of enzymes like, tyrosinase (205%), laccase (178%), veratryl oxidase (52%). Based on enzyme activities, UV-vis spectroscopy, FTIR and GC-MS results; RGFL was proposed to be transformed to 4-amino-3- methylphenyl (hydroxy) oxoammonium and N, N-diethyl aniline. Anatomical study of the advanced root tissue of A. densiflorus exhibited the progressive dye accumulation and removal during phytoremediation. HepG2 cell line and phytotoxicity study demonstrated reduced toxicity of biotransformed RGFL and treated effluent by A. densiflorus, respectively. On field remediation study revealed a noteworthy removal (67%) from polluted soil within 30 d.

Influence of Nutrient Availability and Quorum Sensing on the Formation of Metabolically Inactive Microcolonies Within Structurally Heterogeneous Bacterial Biofilms: An Individual-Based 3D Cellular Automata Model.

The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity. Cell death occurred preferentially in layers in close proximity to the substratum, resulting in increased heterogeneity in this section of the biofilm; the thickness and heterogeneity of this lowermost layer increased with time, ultimately leading to sloughing. The model predicted the formation of metabolically dormant cellular microniches embedded within faster-growing cell clusters. Biofilms utilizing quorum sensing were more heterogeneous compared to their non-quorum sensing counterparts, and resisted sloughing, featuring a cell-devoid layer of EPS atop the substratum upon which the remainder of the biofilm developed. Overall, our study provides a computational framework to analyze metabolic diversity and heterogeneity of biofilm-associated microorganisms and may pave the way toward gaining further insights into the biophysical mechanisms of antibiotic resistance.

Biodegradation of atrazine by Rhodococcus sp. BCH2 to N-isopropylammelide with subsequent assessment of toxicity of biodegraded metabolites.

Atrazine is a persistent organic pollutant in the environment which affects not only terrestrial and aquatic biota but also human health. Since its removal from the environment is needed, atrazine biodegradation is achieved in the present study using the bacterium Rhodococcus sp. BCH2 isolated from soil, long-term treated with atrazine. The bacterium was capable of degrading about 75 % atrazine in liquid medium having pH 7 under aerobic and dark condition within 7 days. The degradation ability of the bacterium at various temperatures (20-60 °C), pH (range 3-11), carbon (glucose, fructose, sucrose, starch, lactose, and maltose), and nitrogen (ammonium molybdate, sodium nitrate, potassium nitrate, and urea) sources were studied for triumph optimum atrazine degradation. The results indicate that atrazine degradation at higher concentrations (100 ppm) was pH and temperature dependent. However, glucose and potassium nitrate were optimum carbon and nitrogen source, respectively. Atrazine biodegradation analysis was carried out by using high-performance thin-layer chromatography (HPTLC), Fourier transform infrared spectroscopy (FTIR), and liquid chromatography quadrupole time-of-flight (LC/Q-TOF-MS) techniques. LC/Q-TOF-MS analysis revealed formation of various intermediate metabolites including hydroxyatrazine, N-isopropylammelide, deisopropylhydroxyatrazine, deethylatrazine, deisopropylatrazine, and deisopropyldeethylatrazine which was helpful to propose biochemical degradation pathway of atrazine. Furthermore, the toxicological studies of atrazine and its biodegraded metabolites were executed on earthworm Eisenia foetida as a model organism with respect to enzymatic (SOD and Catalase) antioxidant defense mechanism and lipid peroxidation studies. These results suggest innocuous degradation of atrazine by Rhodococcus sp. BCH2 in nontoxic form. Therefore the Rhodococcus sp.BCH2 could prove a valuable source for the eco-friendly biodegradation of atrazine pesticide.

Ophthalmic complications following treatment of paranasal sinus rhabdomyosarcoma in comparison to orbital disease.

PURPOSE: To identify the type and frequency of ocular and orbital complications observed following treatment for primary rhabdomyosarcoma of the paranasal sinuses or the orbit. METHODS: An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective chart review was conducted to identify all patients treated at one institution from 1966 to 2005 with biopsy-proven primary paranasal sinus or orbital rhabdomyosarcoma. Pretreatment, treatment, and follow-up data were collected. RESULTS: Forty-four patients (25 male) of a median age of 7.8 years (range 1.0-18.0 years) with primary paranasal sinus (17) or orbital (27) rhabdomyosarcoma were treated and followed for a median period of 5.3 years (range 0.6-32.0 years). The three most frequently observed ophthalmic complications were persistent eyelid erythema or cellulitis (12), epithelial keratitis (7), and conjunctival injection (6) in the paranasal sinus and epithelial keratitis (18), conjunctival injection (11), and cataract (10) in the orbit. Overall survival after treatment trended higher for the orbital rhabdomyosarcoma group (23 of 27) than the paranasal sinus group (9 of 17). CONCLUSIONS: The most frequently observed treatment-induced ophthalmic complications in the paranasal sinus group were manageable with minimal patient morbidity, as in the patients with orbital disease. Vision-threatening complications were infrequently encountered. Despite maximal therapy, the mortality rate was higher in the paranasal sinus rhabdomyosarcoma group than in the orbital rhabdomyosarcoma group.

Levofloxacin-induced torsades de pointes.

A 91-year-old woman, presenting with flu-like symptoms, developed a brief episode of polymorphic ventricular tachycardia in the emergency department. The arrhythmia resolved spontaneously, and a subsequent electrocardiogram revealed Q waves and ST-segment elevation in the anterior precordial leads, along with a prolonged QT interval. The presumed diagnosis was ST-segment-elevation myocardial infarction with ischemia-induced ventricular tachycardia. Emergent coronary artery angiography revealed only minimal luminal irregularities. It was discovered that the patient had been taking levofloxacin and, apparently as a result, developed drug-induced torsades de pointes. The case of this patient is an example of the difficulties that are occasionally encountered in differentiating ST-segment-elevation myocardial infarction from nonischemic ST elevation.

Transblepharoplasty approach to sequestered disease of the lateral frontal sinus with ophthalmologic manifestations.

BACKGROUND: Sequestered disease within the lateral extent of the frontal sinus that has eroded into the orbit through the frontal sinus floor may be difficult to address with standard ESS techniques. We describe an approach to this problem using a transblepharoplasty incision concealed in the upper eyelid crease. METHODS: Five consecutive patients with lateral frontal sinus disease involving the orbit were treated with combined ESS/transblepharoplasty approach. This used an upper lid incision and elevation of a myocutaneous flap. The preexisting dehiscence in the sinus floor was exposed, permitting extraction of fungal debris and marsupialization of the mucocele. Frontal sinusotomy was performed via combined above/below technique RESULTS: The study group included 5 patients with mean age of 50 years. Two patients had post-traumatic mucopyocele, two had allergic fungal sinusitis, and one exhibited both entities. All patients had signs of ophthalmopathy: proptosis with increased IOP (5/5), gaze restriction (5/5), and decrease in visual acuity (2/5). Ophthalmologic symptoms improved postoperatively in 5/5, but 2 patients eventually required revision endoscopic surgery. No complications occurred, and incision healing was excellent in all patients. CONCLUSION: In patients with sequestered disease of the lateral frontal sinus and ophthalmologic manifestations, the transblepharoplasty approach in combination with ESS affords excellent access while preserving cosmesis.

Role of all-trans retinoic acid in neurite outgrowth and axonal elongation.

The vitamin A metabolite, all-trans retinoic acid (atRA) plays essential roles in nervous system development, including neuronal patterning, survival, and neurite outgrowth. Our understanding of how the vitamin A acid functions in neurite outgrowth comes largely from cultured embryonic neurons and model neuronal cell systems including human neuroblastoma cells. Specifically, atRA has been shown to increase neurite outgrowth from embryonic DRG, sympathetic, spinal cord, and olfactory receptor neurons, as well as dissociated cerebra and retina explants. A role for atRA in axonal elongation is also supported by a limited number of studies in vivo, in which a deficiency in retinoid signaling produced either by dietary or genetic means has been shown to alter neurite outgrowth from the spinal cord and hindbrain regions. Human neuroblastoma cells also show enhanced numbers of neurites and longer processes in response to atRA. The mechanism whereby retinoids regulate neurite outgrowth includes, but is not limited to, the regulation of the transcription of neurotrophin receptors. More recent evidence supports a role for atRA in regulating components of other signaling pathways or candidate neurite-regulating factors. Some of these effects, such as that on neuron navigator 2 (NAV2), may be direct, whereas others may be secondary to other atRA-induced changes in the cell. This review focuses on what is currently known about neurite initiation and growth, with emphasis on the manner in which atRA may influence these events.

[Local ice application in therapy of kinetic limb ataxia. Clinical assessment of positive treatment effects in patients with multiple sclerosis]. / Lokale Eisapplikation in der Therapie der gliedkinetischen Ataxie. Klinischer Nachweis positiver Behandlungseffekte bei Patienten mit multipler Sklerose.

Upper limb ataxia is one of the most disabling symptoms of patients with multiple sclerosis (MS). There are some clinically tested therapeutic strategies, especially with regard to cerebellar tremor. But most of the methods used for treatment of limb ataxia in physiotherapy and occupational therapy are not systematically evaluated, e.g. the effect of local ice applications, as reported by MS patients and therapists, respectively. We investigated 21 MS patients before and in several steps 1 up to 45 min after cooling the most affected forearm. We used a series of 6 tests, including parts of neurological status and activities of daily living as well. At each step skin temperature and nerve conduction velocity were recorded. All tests were documented by video for later offline analysis. Standardized evaluation was done by the investigators and separately by an independent second team, both of them using numeric scales for quality of performance. After local cooling all patients showed a positive effect, especially a reduction of intentional tremor. In most cases this effect lasted 45 min, in some patients even longer. We presume that a decrease in the proprioceptive afferent inflow-induced by cooling-may be the probable cause of this reduction of cerebellar tremor. Patients can use ice applications as a method of treating themselves when a short-time reduction of intention tremor is required, e.g. for typing, signing or self-catheterization.