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1.
Br J Surg ; 105(3): 168-181, 2018 02.
Article in English | MEDLINE | ID: mdl-29405276

ABSTRACT

BACKGROUND: This study aimed to examine the effect of metabolic surgery on pre-existing and future microvascular complications in patients with type 2 diabetes mellitus (T2DM) in comparison with medical treatment. Although metabolic surgery is the most effective treatment for obese patients with T2DM regarding glycaemic control, it is unclear whether the incidence or severity of microvascular complications is reduced. METHODS: A systematic literature search was performed in MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) with no language restrictions, looking for RCTs, case-control trials and cohort studies that assessed the effect of metabolic surgery on the incidence of microvascular diabetic complications compared with medical treatment as control. The study was registered in the International prospective register of systematic reviews (CRD42016042994). RESULTS: The literature search yielded 1559 articles. Ten studies (3 RCTs, 7 controlled clinical trials) investigating 17 532 patients were included. Metabolic surgery reduced the incidence of microvascular complications (odds ratio 0·26, 95 per cent c.i. 0·16 to 0·42; P < 0·001) compared with medical treatment. Pre-existing diabetic nephropathy was strongly improved by metabolic surgery versus medical treatment (odds ratio 15·41, 1·28 to 185·46; P = 0·03). CONCLUSION: In patients with T2DM, metabolic surgery prevented the development of microvascular complications better than medical treatment . Metabolic surgery improved pre-existing diabetic nephropathy compared with medical treatment.


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/prevention & control , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/therapy , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/etiology , Humans , Incidence , Microvessels , Odds Ratio , Treatment Outcome
2.
Arch Orthop Trauma Surg ; 138(4): 527-535, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29372384

ABSTRACT

INTRODUCTION: The Kujala score is the most frequently used questionnaire for patellofemoral disorders like pain, instability or osteoarthritis. Unfortunately, we are not aware of a validated German version of the Kujala score. The aim of our study was the translation and linguistic validation of the Kujala score in German-speaking patients with patella instability and the assessment of its measurement characteristics. MATERIALS AND METHODS: The German Kujala score was developed in several steps of translation. In addition to healthy controls, the Kujala German was assessed in consecutive patients undergoing reconstruction of the medial patellofemoral ligament for recurrent patellar dislocations. Pre-op, 6 and 12 months postop the patients completed the Kujala German score, the KOOS, the Lysholm score, a VAS Pain, and the SF-12v2 scores. In addition, there was a Kujala German Score retest preop after a 1-week interval. RESULTS: We found high reliability in terms of internal consistency for the Kujala score (Cronbach's alpha = 0.87). Convergent validity with the KOOS (symptom r = 0.65, pain r = 0.78, ADL r = 0.74, sports/recreation r = 0.84, quality of life r = 0.70), the Lysholm score (r = 0.88) and the SF-12 physical component summary score (r = 0.79) and VAS pain (r = - 0.71) was also very high. Discriminant validity in terms of correlation with the SF-12 mental component summary Score was satisfactory (r = 0.14). CONCLUSIONS: In conclusion, the German version of the Kujala score proved to be a reliable and valid instrument in the setting of a typical patellofemoral disease treated with a standard patellofemoral procedure.


Subject(s)
Arthralgia/physiopathology , Joint Instability , Knee Joint/physiopathology , Ligaments, Articular/physiopathology , Patellofemoral Joint/physiopathology , Humans , Joint Instability/diagnosis , Joint Instability/physiopathology , Severity of Illness Index , Surveys and Questionnaires
3.
Neuroscience ; 387: 28-37, 2018 09 01.
Article in English | MEDLINE | ID: mdl-28942323

ABSTRACT

A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.


Subject(s)
Biomedical Research , Diabetic Neuropathies/complications , Pain/complications , Animals , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/drug therapy , Disease Progression , Humans
4.
Joints ; 5(2): 59-69, 2017 Jun.
Article in English | MEDLINE | ID: mdl-29114633

ABSTRACT

Purpose A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. Methods A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. Results The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. Discussion The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. Level of Evidence I.

5.
Orthopade ; 46(10): 805-807, 2017 10.
Article in German | MEDLINE | ID: mdl-29149367
6.
Orthopade ; 46(10): 831-838, 2017 Oct.
Article in German | MEDLINE | ID: mdl-28887704

ABSTRACT

BACKGROUND: Meniscal lesions are among the most important musculoskeletal disorders and are the most common indication for knee joint arthroplasty. However, the structural integrity and function is rarely retained, and a loss of tissue results. Thus, there is a huge demand for meniscal replacement options. CURRENT PROCEDURES: Autografts were used in the past but did not fulfill expectations. Meniscus allografts have been developed to be a viable treatment option. However, availability is limited and evidence of a long-term chondroprotective effect scarce. Artificial scaffolds made from either collagen or PCU foam are available, which aid the regeneration of meniscal tissue and are rather intended as a partial replacement with an intact peripheral rim. Those implants thus have a limited spectrum of indication. While they seem to be symptomatically effective, it remains unclear whether they can reduce secondary cartilage damage. Newer developments aim at a permanent replacement of lost meniscal tissue. LIMITATIONS: In summary, there is currently no meniscal replacement available for a broad range of indications and with a solid scientific foundation. Prophylactic use should be limited to cases with a high chance of progression to osteoarthritis, like a lateral total meniscectomy. Otherwise meniscal replacement should be considered in younger, symptomatic patients with mild to moderate secondary changes. Potential causes of the initial meniscal injury like instability or deformities should be carefully assessed and addressed. In many cases, osteotomy might be a viable alternative to meniscus replacement.


Subject(s)
Meniscectomy , Prostheses and Implants , Tibial Meniscus Injuries/surgery , Allografts , Autografts , Collagen , Follow-Up Studies , Humans , Polycarboxylate Cement , Tissue Scaffolds , Urethane
7.
Orthopade ; 46(10): 808-821, 2017 Oct.
Article in German | MEDLINE | ID: mdl-28875226

ABSTRACT

BACKGROUND: The treatment of degenerative meniscal lesions has received increased attention since the publication of several Level 1 studies over the last few years. The following review of literature including the consensus statement given by ESSKA reports on the management of patients with degenerative meniscal lesions. MATERIAL AND METHODS: The analysis includes the literature of Level 1 to 4 studies and the statement of the consensus group of ESSKA concerning the surgical or conservative management of these patients. RESULTS: Meniscal lesions cause progression in osteoarthritis. Patients presenting a combination of degenerative meniscal lesion and osteoarthritis show inferior clinical outcome. The average clinical outcome after surgical treatment was 70 points based on the Lysholm score. Level 1 studies show no difference in clinical outcome. However, over 30% of these patients require arthroscopy at the second stage after an interval of 3 to 6 months. Patients presenting a flap tear or complaining about mechanical symptoms show poor outcome after conservative treatment. DISCUSSION: Level 1 studies have focused on very selected patients. These patients do not represent the daily practice of orthopaedic surgeons. The findings of the level 1 studies should, therefore, not be generalized. According to the consensus statement of ESSKA, the treatment of degenerative meniscal lesions should start with conservative management. In the case of persistent symptoms, surgery should be considered after 3 months. In the case of mechanical symptoms, arthroscopy might be indicated earlier. Arthroscopy in advanced osteoarthritic knees is not indicated due to inferior clinical outcome.


Subject(s)
Menisci, Tibial , Osteoarthritis, Knee/therapy , Osteoarthritis/therapy , Consensus Development Conferences as Topic , Europe , Evidence-Based Medicine , Guideline Adherence , Osteoarthritis/diagnosis , Osteoarthritis, Knee/diagnosis , Societies, Medical , Sports Medicine
8.
Orthopade ; 46(10): 839-845, 2017 Oct.
Article in German | MEDLINE | ID: mdl-28831524

ABSTRACT

Meniscal roots play an important role in load distribution of the tibiofemoral knee joint. Thus, meniscal root tears are severe injuries of the knee, which significantly expose cartilage to increased stress. Two entities are distinguished: (i) acute root tears that mainly affect the posterolateral root and often occur with ruptures of the anterior cruciate ligament; and (ii) chronic, degenerative root tears that mainly affect the posteromedial root. For diagnosis of both entities, the patient's medical history, a knee examination and especially MRI play key roles. The treatment of choice is in general transtibial fixation of the torn root, which leads to an increased clinical improvement and a decrease of the progression of arthritis.


Subject(s)
Osteoarthritis, Knee/surgery , Tibial Meniscus Injuries/surgery , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/diagnosis , Anterior Cruciate Ligament Injuries/physiopathology , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction , Disease Progression , Humans , Magnetic Resonance Imaging , Menisci, Tibial/surgery , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/physiopathology , Risk Factors , Tibial Meniscus Injuries/diagnosis , Tibial Meniscus Injuries/physiopathology , Weight-Bearing/physiology
10.
Knee Surg Sports Traumatol Arthrosc ; 25(2): 335-346, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28210788

ABSTRACT

PURPOSE: A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. METHODS: A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. RESULTS: The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. DISCUSSION: The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. LEVEL OF EVIDENCE: I.


Subject(s)
Algorithms , Arthroscopy/methods , Cartilage Diseases/surgery , Menisci, Tibial/surgery , Aged , Bone Neoplasms/diagnostic imaging , Cartilage Diseases/diagnostic imaging , Conservative Treatment , Europe , Fractures, Bone/diagnostic imaging , Humans , Magnetic Resonance Imaging , Menisci, Tibial/diagnostic imaging , Middle Aged , Osteoarthritis, Knee/diagnostic imaging , Practice Guidelines as Topic , Radiography , Research Design
11.
Bone Joint J ; 98-B(9): 1185-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27587518

ABSTRACT

AIMS: It is widely held that most Baker's cysts resolve after treatment of the intra-articular knee pathology. The present study aimed to evaluate the fate of Baker's cysts and their associated symptoms after total knee arthroplasty (TKA). PATIENTS AND METHODS: In this prospective cohort study, 102 patients with (105 were included, however three were lost to follow-up) an MRI-verified Baker's cyst, primary osteoarthritis and scheduled for TKA were included. Ultrasound was performed to evaluate the existence and the gross size of the cyst before and at one year after TKA. Additionally, associated symptoms of Baker's cyst were recorded pre- and post-operatively. RESULTS: After one year, a Baker's cyst was still present in 87 patients (85%). There was a significant reduction in associated symptoms arising from the Baker's cyst before (71%) to after surgery (31%). No patients developed a new Baker's cyst associated symptoms. However, of the 72 patients who had reported Baker's cyst associated symptoms pre-operatively, 32 patients (44%) still complained of such symptoms one year after surgery. CONCLUSION: Baker's cysts had resolved in only a small number of patients (15%) one year after TKA and symptoms from the cysts persisted in 31%. Cite this article: Bone Joint J 2016;98-B:1185-8.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Popliteal Cyst/surgery , Adult , Aged , Arthroscopy/methods , Cohort Studies , Confidence Intervals , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/diagnosis , Pain Measurement , Popliteal Cyst/complications , Popliteal Cyst/diagnosis , Prospective Studies , Severity of Illness Index , Statistics, Nonparametric , Time Factors , Treatment Outcome , Ultrasonography, Doppler
12.
Exp Clin Endocrinol Diabetes ; 123(10): 617-21, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26240957

ABSTRACT

Comprehensive diabetes treatment has been shown to reduce quality of life in diabetic patients. However, there is evidence to suggest that group singing can have positive effects on quality of life in various clinical settings. In this randomized controlled pilot study, the effect of singing as a therapy to reduce stress and improve quality of life was investigated in insulin-dependent diabetic patients, undergoing a lifestyle intervention program. Patients from the singing group felt less discontented following treatment. This effect, however, was lost after 3 months. No effect on serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels could be seen when comparing the singing group with the control group, although reduced levels of ACTH and cortisol 3 days after treatment could be found and were still present after 3 months within the group of patients who undertook singing as a therapy. Singing led to an increase in bodyweight, which interestingly had no effect on glucose control or methylglyoxal levels. Therefore, singing during a lifestyle intervention program for insulin-dependent diabetic patients had a short lasting and weak effect on patients' mood without affecting glucose control, but no significant effect on stress related hormones.


Subject(s)
Diabetes Mellitus, Type 1/therapy , Singing , Stress, Psychological/therapy , Adult , Aged , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Stress, Psychological/blood , Stress, Psychological/physiopathology , Time Factors
13.
J Fish Biol ; 84(6): 1820-41, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24814314

ABSTRACT

Critical (<30 min) and prolonged (>60 min) swimming speeds in laboratory chambers were determined for larvae of six species of Australian freshwater fishes: trout cod Maccullochella macquariensis, Murray cod Maccullochella peelii, golden perch Macquaria ambigua, silver perch Bidyanus bidyanus, carp gudgeon Hypseleotris spp. and Murray River rainbowfish Melanotaenia fluviatilis. Developmental stage (preflexion, flexion, postflexion and metalarva) better explained swimming ability than did length, size or age (days after hatch). Critical speed increased with larval development, and metalarvae were the fastest swimmers for all species. Maccullochella macquariensis larvae had the highest critical [maximum absolute 46.4 cm s(-1) and 44.6 relative body lengths (L(B)) s(-1)] and prolonged (maximum 15.4 cm s(-1), 15.6 L(B) s(-1)) swimming speeds and B. bidyanus larvae the lowest critical (minimum 0.1 cm s(-1), 0.3 L(B) s(-1)) and prolonged swimming speeds (minimum 1.1 cm s(-1), 1.0 L(B) s(-1)). Prolonged swimming trials determined that the larvae of some species could not swim for 60 min at any speed, whereas the larvae of the best swimming species, M. macquariensis, could swim for 60 min at 44% of the critical speed. The swimming performance of species with precocial life-history strategies, with well-developed larvae at hatch, was comparatively better and potentially had greater ability to influence their dispersal by actively swimming than species with altricial life-history strategies, with poorly developed larvae at hatch.


Subject(s)
Perciformes/physiology , Swimming , Animals , Australia , Fresh Water , Larva/physiology , Linear Models , Species Specificity
14.
Exp Clin Endocrinol Diabetes ; 122(6): 341-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24798861

ABSTRACT

Current guidelines for the treatment of type 2 diabetes focus on pharmacological treatment of glucose and cardio-vascular risk factors. The aim of this prospective randomized controlled intervention study was to examine the effects of a psychosocial intervention on clinical endpoints and risk factors in patients with type 2 diabetes and early diabetic kidney disease.110 patients were randomized to receive an 8-week mindfulness-based stress reduction (MBSR) training (n = 53) compared to standard care (n = 57). The study was carried out open-labelled and randomization was performed computer-generated in a 1:1 ratio. Primary outcome of the study was the change in urinary albumin excretion (albumin-creatinine-ratio, ACR); secondary outcomes were metabolic parameters, intima media thickness (IMT), psychosocial parameters and cardiovascular events.89 patients (42 in control group and 47 in intervention group) were analysed after 3 years of follow-up. After 1 year, the intervention group showed a reduction of ACR from 44 [16/80] to 39 [20/71] mg/g, while controls increased from 47 [16/120] to 59 [19/128] mg/g (p = 0.05). Parallel to the reduction of stress levels after 1 year, the intervention-group additionally showed reduced catecholamine levels (p < 0.05), improved 24 h-mean arterial (p < 0.05) and maximum systolic blood pressure (p < 0.01), as well as a reduction in IMT (p < 0.01). However, these effects were lost after 2 and 3 years of follow-up.This is the first study to show that a psychosocial intervention improves cardiovascular risk factors in high risk type 2 diabetes patients. Trial-Registration: NCT00263419 http://clinicaltrials.gov/ct2/show/NCT00263419 TRIAL REGISTRATION: clinicaltrials.gov-Identifier: NCT00263419.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Stress, Psychological , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/psychology , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/therapy , Diabetic Nephropathies/psychology , Diabetic Nephropathies/therapy , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Stress, Psychological/psychology , Stress, Psychological/therapy
15.
Exp Clin Endocrinol Diabetes ; 122(5): 316-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24710646

ABSTRACT

The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/analogs & derivatives , Pyruvaldehyde/blood , Adult , Female , Humans , Lactoylglutathione Lyase/metabolism , Male , Middle Aged , Prospective Studies
16.
Exp Clin Endocrinol Diabetes ; 121(10): 601-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24057510

ABSTRACT

The established marker for tubular damage, urinary n-acetyl-beta-d-glucosaminidase is significantly increased in type 1 and 2 diabetes patients and is related to albuminuria and other diabetic complications. In this cross sectional study of type 2 diabetes patients with a history of albuminuria, we studied the relationship between excretion of n-acetyl-beta-d-glucosaminidase in urine and diabetic neuropathy.160 type 2 diabetes patients were screened for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy. N-acetyl-beta-d-glucosaminidase excretion was detected in 24 h urine samples.Urinary excretion of n-acetyl-beta-d-glucosaminidase correlated significantly with -glucose control (fasting glucose r=0.18; p=0.04; HbA1c r=0.20; p=0.02) and urine albumin excretion (r=0.22; p=0.01). Binary regression analyses showed that increased urinary n-acetyl-beta-d-glucosaminidase concentration is an independent predictor for presence of clinical symptoms of peripheral neuropathy (OR 1.8 [95%CI 1.2-2.74] and vibration deficiency [OR 1.7; 95% CI 1.2-2.66]. There was also a significant negative association between urinary n-acetyl-beta-d-glucosaminidase and E/I-Ratio (r=-0.21, p<0.02) as well as the 30:15-Ratio (r=-0.24; p<0.01) of heart rate variability. Furthermore, increased n-acetyl-beta-d-glucosaminidase excretion independently predicted cardiovascular autonomic diabetic neuropathy with an OR for decreased E/I-Ratio of 1.7 [95%CI 1.1-2.75]; (p<0.02) and 30:15-Ratio:OR 2.4 [95% CI 1.26-4.45]; (p<0.01).Urinary n-acetyl-beta-d-glucosami-nidase excretion is an independent marker for diabetic peripheral and cardiovascular autonomic neuropathy in type 2 diabetic patients.


Subject(s)
Acetylglucosaminidase/urine , Diabetes Mellitus, Type 2/urine , Diabetic Neuropathies/urine , Aged , Albuminuria/urine , Female , Humans , Male , Middle Aged
17.
Br J Cancer ; 108(3): 570-8, 2013 Feb 19.
Article in English | MEDLINE | ID: mdl-23299527

ABSTRACT

BACKGROUND: As metastasis is the prime cause of death from malignancies, there is vibrant interest to discover options for the management of the different mechanistic steps of tumour spreading. Some approved pharmaceuticals exhibit activities against diseases they have not been developed for. In order to discover such activities that might attenuate lymph node metastasis, we investigated 225 drugs, which are approved by the US Food and Drug Administration. METHODS: A three-dimensional cell co-culture assay was utilised measuring tumour cell-induced disintegrations of the lymphendothelial wall through which tumour emboli can intravasate as a limiting step in lymph node metastasis of ductal breast cancer. The disintegrated areas in the lymphendothelial cell (LEC) monolayers were induced by 12(S)-HETE, which is secreted by MCF-7 tumour cell spheroids, and are called 'circular chemorepellent induced defects' (CCIDs). The putative mechanisms by which active drugs prevented the formation of entry gates were investigated by western blotting, NF-κB activity assay and by the determination of 12(S)-HETE synthesis. RESULTS: Acetohexamide, nifedipin, isoxsuprine and proadifen dose dependently inhibited the formation of CCIDs in LEC monolayers and inhibited markers of epithelial-to-mesenchymal-transition and migration. The migration of LECs is a prerequisite of CCID formation, and these drugs either repressed paxillin levels or the activities of myosin light chain 2, or myosin-binding subunit of myosin phosphatase. Isoxsuprine inhibited all three migration markers, and isoxsuprine and acetohexamide suppressed the synthesis of 12(S)-HETE, whereas proadifen and nifedipin inhibited NF-κB activation. Both the signalling pathways independently cause CCID formation. CONCLUSION: The targeting of different mechanisms was most likely the reason for synergistic effects of different drug combinations on the inhibition of CCID formation. Furthermore, the treatment with drug combinations allowed also a several-fold reduction in drug concentrations. These results encourage further screening of approved drugs and their in vivo testing.


Subject(s)
Acetohexamide/pharmacology , Breast Neoplasms/drug therapy , Endothelium, Lymphatic/drug effects , Isoxsuprine/pharmacology , Lymphatic Vessels/drug effects , Nifedipine/pharmacology , Proadifen/pharmacology , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/metabolism , Antineoplastic Combined Chemotherapy Protocols , Blotting, Western , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Cell Adhesion/drug effects , Cell Movement , Chemotaxis/drug effects , Coculture Techniques , Drug Synergism , Endothelium, Lymphatic/cytology , Endothelium, Lymphatic/metabolism , Enzyme Inhibitors/pharmacology , Female , Humans , Hypoglycemic Agents/pharmacology , Lymphatic Metastasis , Lymphatic Vessels/blood supply , Lymphatic Vessels/pathology , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Spheroids, Cellular/metabolism , Tumor Cells, Cultured , Vasodilator Agents/pharmacology
18.
Br J Cancer ; 108(3): 564-9, 2013 Feb 19.
Article in English | MEDLINE | ID: mdl-23093227

ABSTRACT

BACKGROUND: Many cancers spread through lymphatic routes, and mechanistic insights of tumour intravasation into the lymphatic vasculature and targets for intervention are limited. The major emphasis of research focuses currently on the molecular biology of tumour cells, while still little is known regarding the contribution of lymphatics. METHODS: Breast cancer cell spheroids attached to lymphendothelial cell (LEC) monolayers were used to investigate the process of intravasation by measuring the areas of 'circular chemorepellent-induced defects' (CCID), which can be considered as entry gates for bulky tumour intravasation. Aspects of tumour cell intravasation were furthermore studied by adhesion assay, and siRNA-mediated knockdown of intracellular adhesion molecule-1 (ICAM-1). Replacing cancer spheroids with the CCID-triggering compound 12(S)-hydroxyeicosatetraenoic acid (HETE) facilitated western blot analyses of Bay11-7082- and baicalein-treated LECs. RESULTS: Binding of LECs to MCF-7 spheroids, which is a prerequisite for CCID formation, was mediated by ICAM-1 expression, and this depended on NF-κB and correlated with the expression of the prometastatic factor S100A4. Simultaneous inhibition of NF-κB with Bay11-7082 and of arachidonate lipoxygenase (ALOX)-15 with baicalein prevented CCID formation additively. CONCLUSION: Two mechanisms contribute to CCID formation: ALOX15 via the generation of 12(S)-HETE by MCF-7 cells, which induces directional migration of LECs, and ICAM-1 in LECs under control of NF-κB, which facilitates adhesion of MCF-7 cells to LECs.


Subject(s)
Breast Neoplasms/drug therapy , Cell Adhesion/drug effects , Endothelium, Lymphatic/drug effects , Intercellular Adhesion Molecule-1/chemistry , NF-kappa B/antagonists & inhibitors , Nitriles/pharmacology , Spheroids, Cellular/drug effects , Sulfones/pharmacology , Blotting, Western , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Movement , Chemotaxis/drug effects , Endothelium, Lymphatic/cytology , Endothelium, Lymphatic/metabolism , Female , Humans , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
19.
Knee Surg Sports Traumatol Arthrosc ; 20(4): 718-23, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22323098

ABSTRACT

PURPOSE: The purposes of the study were to evaluate and to quantify the pivot shift phenomenon by using a small and easy to handle measuring device for pivot shift quantification. METHODS: Twenty patients (forty knees) with primary torn anterior cruciate ligaments (ACL) were tested under anesthesia, graded by the examiner and by the device according to the IKDC classification [normal (0), glide (1), clunk (2), and gross (3)]. For the grading by the device, a femoral and a tibial miniature inertial sensor measured the acceleration and the angular velocities. Three parameters were used for pivot shift identification and quantification: (1) difference between the positive and negative acceleration peak value (a(diff)), (2) the maximum jerk (j(max)), and (3) the standard deviation (SD(a)) of the acceleration. The ratio between the ACL-deficient and the intact knees was calculated in order to normalize the data. RESULTS: The pivot shift phenomenon could be identified, and all three parameters showed significant higher values in the ACL-deficient knees compared to the intact knees (p < 0.05). The grading by examiner did not significantly correlate with a(diff) (p = 0.38; r = 0.21), j(max) (p = 0.36; r = -0.22), SD(a) (p = 0.65; r = 0.11), and grading by the device (p = 0.62; r = 0.12). CONCLUSIONS: The present study has shown that the quantification of the pivot shift test is practicable when inertial sensors are used. The results have shown that the subjective grading of the pivot shift test does not correlate well with objective quantification.


Subject(s)
Anterior Cruciate Ligament Injuries , Arthrometry, Articular/methods , Joint Instability/diagnosis , Range of Motion, Articular/physiology , Acceleration , Adult , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament Reconstruction/methods , Cohort Studies , Equipment Design , Evaluation Studies as Topic , Female , Humans , Joint Instability/surgery , Knee Injuries/diagnosis , Knee Injuries/surgery , Male , Physical Examination/methods , Preoperative Care/methods , Prospective Studies , Reproducibility of Results , Severity of Illness Index , Young Adult
20.
Geobiology ; 10(3): 216-22, 2012 May.
Article in English | MEDLINE | ID: mdl-22212713

ABSTRACT

This study investigates the role iron oxidation plays in the purple non-sulfur bacterium Rhodobacter capsulatus SB1003. This organism is unable to grow photoautotrophically on unchelated ferrous iron [Fe(II)] despite its ability to oxidize chelated Fe(II). This apparent paradox was partly resolved by the discovery that SB1003 can grow photoheterotrophically on the photochemical breakdown products of certain ferric iron-ligand complexes, yet whether it could concomitantly benefit from the oxidation of Fe(II) to fix CO(2) was unknown. Here, we examine carbon fixation by stable isotope labeling of the inorganic carbon pool in cultures growing phototrophically on acetate with and without Fe(II). We show that R. capsulatus SB1003, an organism formally thought incapable of phototrophic growth on Fe(II), can actually harness the reducing power of this substrate and grow photomixotrophically, deriving carbon both from organic sources and from fixation of inorganic carbon. This suggests the possibility of a wider occurrence of photoferrotrophy than previously assumed.


Subject(s)
Ferrous Compounds/metabolism , Rhodobacter capsulatus/growth & development , Rhodobacter capsulatus/metabolism , Carbon Dioxide/metabolism , Heterotrophic Processes , Oxidation-Reduction , Phototrophic Processes
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