Meta-analysis of metabolic surgery versus medical treatment for microvascular complications in patients with type 2 diabetes mellitus.

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.

Validation of the German version of the Kujala score in patients with patellofemoral instability: a prospective multi-centre study.

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.

Surgical management of degenerative meniscus lesions: the 2016 ESSKA meniscus consensus.

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.

[Meniscal root lesions: clinical relevance and treatment]. / Meniskuswurzelläsionen: Klinische Relevanz und Therapie.

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.

[Indication and limitations of meniscus replacement]. / Indikation und Grenzen des Meniskusersatzes.

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.

[Treatment of degenerative meniscal lesions : From eminence to evidence-based medicine]. / Therapie degenerativer Meniskusläsionen : Von der eminenz- zur evidenzbasierten Medizin.

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.

Ontogeny of critical and prolonged swimming performance for the larvae of six Australian freshwater fish species.

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.

Bay11-7082 inhibits the disintegration of the lymphendothelial barrier triggered by MCF-7 breast cancer spheroids; the role of ICAM-1 and adhesion.

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.

In vitro inhibition of breast cancer spheroid-induced lymphendothelial defects resembling intravasation into the lymphatic vasculature by acetohexamide, isoxsuprine, nifedipin and proadifen.

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.

A new quantitative method for pivot shift grading.

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.

Transient hyperthyroidism after surgery for secondary hyperparathyroidism: a common problem.

BACKGROUND: Postoperative hyperthyroidism occurs in approximately one third of patients following parathyroidectomy due to primary hyperparathyroidism (PHP), but has only rarely been described in secondary hyperparathyroidism (SHP). The frequency, course, and laboratory markers of postoperative hyperthyroidism in SHP remain unknown. Our purpose was to evaluate the frequency and the clinical course of postoperative hyperthyroidism following surgery of SHP and to determine the diagnostic value of thyroglobulin in this setting. MATERIAL AND METHODS: A total of 40 patients undergoing parathyroidectomy because of SHP were included in this study. Thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroglobulin (Tg) were determined one day before and on day 1, 3, 5, 10, and 40 after surgery. At each of these visits patients were clinically evaluated for signs or symptoms of hyperthyroidism. RESULTS: Biochemical evidence of hyperthyroidism was evident in 77% of patients postoperatively despite of preoperatively normal serum levels. TSH dropped from 1.18 ± 0.06mU/L to 0.15 ± 0.07mU/L (p = 0.0015). Free triiodothyronine (fT3) and fT4 levels increased from 2.86 ± 0.02ng/L and 10.32 ± 0.13ng/L, respectively, to their maximum of 4.83 ± 0.17ng/L and 19.35 ± 0.58ng/L, respectively. Thyroglobulin levels rose from 3.8 ± 0.8ng/mL to 111.8 ± 45.3ng/mL (p<0.001). At day 40 all thyroid related laboratory values were within normal range. Correlation analysis of postoperative values revealed significant correlations for lowest TSH (r = -0.32; p = 0.038), and highest fT3 (r = 0.55; p<0.001) and fT4 levels (r = 0.67; p<0.001) with Tg. CONCLUSION: Transient hyperthyroidism is frequent after parathyroidectomy for SHP with Tg being a suitable marker. Awareness of this self-limiting disorder is important to avoid inappropriate and potentially harmful treatment.

No bone tunnel enlargement in patients with open growth plates after transphyseal ACL reconstruction.

Bone tunnel enlargement after ACL reconstruction has been described extensively in adults. However, little is known about this phenomenon in patients with open growth plates. Thus, the goals of the current study were to evaluate changes in bone tunnel size in patients with open growth plates after transphyseal ACL reconstruction with suspensory fixation and to correlate tunnel size with clinical outcome after medium-term follow-up. Fourteen patients with open growth plates were included that underwent primary transphyseal ACL reconstruction using hamstrings autografts and suspensory fixation. Mean follow-up time was 7 years. At the time of follow-up, MRIs of the operated knee were performed, and outcome was assessed using KOS-ADLS, Lysholm score, IKDC Subjective Knee Form score, Knee Examination Form score, and KT-1000 measurements. On MRI, the cross-sectional area of the bone tunnels was assessed using special axial cuts perpendicular to the axes of the tunnels. Two orthopaedic surgeons and two radiologists analysed the MRIs. Change in bone tunnel size from surgery to follow-up was calculated. No significant changes in bone tunnel size from surgery to follow-up were found. Regarding outcome measures, KOS-ADLS averaged 95%, Lysholm Score averaged 96 points, IKDC Subjective Knee Form averaged 95%, IKDC Knee Examination Form scores were 8A, 5B, 1C, and KT-1000 measurements averaged 1.8 ± 1.4 mm. No significant correlations were found between tunnel size at follow-up and outcome measures. Based on our study, bone tunnel enlargement does not occur in patients who have open growth plates and undergo ACL reconstruction using suspensory fixation.

The Quest for more Research on Painful Diabetic Neuropathy.

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.

Surgical Management of Degenerative Meniscus Lesions: The 2016 ESSKA Meniscus Consensus.

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.

The fate of Baker's cyst after total knee arthroplasty.

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.

Role of unstirred layer in intestinal absorption of phenylalanine in vivo.

The appearance rate of L- and D-phenylalanine in the venous blood of rat jejunal loops in vivo is increased up to 60% if the intraluminal solution is mixed more efficiently by the simultaneous perfusion of air. The effect decreases as the luminal concentration is increased to 100 mmol/l. Thus, the apparent Michaelis constants are by 50% lower in the case of the reduced unstirred layer (26 to 17 for L- and 9 to 6 mmol/l for D-phenylalanine). The enhancement of the absorption and the reduction of the Michaelis constants can be attributed to the reduction of the effective unstirred layer thickness by about 400--500 micrometer.

Group Singing as a Therapy during Diabetes Training--A Randomized Controlled Pilot Study.

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.

Selective muscarinic antagonists differentially affect in vivo acetylcholine release and memory performances of young and aged rats.

Brain acetylcholine release and memory performance were investigated in young (three- to six-months) and old (20- to 24-months) rats. Acetylcholine release was measured in vivo in the cortex and hippocampus of freely-moving animals, under basal conditions and in the presence of the following muscarinic antagonists: scopolamine, (+/-)-5,11-dihydro-11-[[(2-[2-[(dipropylamino) methyl]-1-piperidinyl]ethyl) amino] carbonyl]-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one (AFDX 384) and pirenzepine. The amount of acetylcholine released from the cortex and hippocampus of old rats was significantly reduced. In the presence of scopolamine and AFDX 384 but not of pirenzepine, the acetylcholine release was significantly higher in the old than the young rats, suggesting that changes in presynaptic M2/M4 muscarinic receptor function occur with ageing in the two brain regions. Cognitive capacities were evaluated using two different behavioural tasks: object recognition and passive avoidance response. Old rats were unable to discriminate between familiar and novel objects and had impaired performance in the passive avoidance test. AFDX 384 restored the performance in both tests. Furthermore, in young rats AFDX 384 reversed the impairment of both object recognition and passive avoidance response induced by scopolamine. The effect of AFDX 384 on acetylcholine release and behaviour in the old rats offers further support to a relationship between the age-related cholinergic hypofunction and cognitive impairment and indicates the blockade of presynaptic muscarinic receptors as a possible selective target for therapeutic strategies aimed at improving age-associated memory deficits.