[The German Cartilage Registry (KnorpelRegister DGOU) for evaluation of surgical treatment for cartilage defects: experience after six months including first demographic data]. / Das KnorpelRegister DGOU zur Erfassung von Behandlungsergebnissen nach Knorpeloperationen: Erfahrungen nach 6 Monaten und erste epidemiologische Daten.

The German Cartilage Registry (KnorpelRegister DGOU) has been introduced in October 2013 and aims on the evaluation of patients who underwent cartilage repair for symptomatic cartilage defects. It represents a nation-wide cohort study which has been introduced by the working group "Tissue Regeneration" of the Germany Society of Orthopaedic Surgery and Traumatology and is technically based upon a web-based remote data entry (RDE) system. The present article describes first experiences with the registry including patient and treatment characteristics. Between October 2013 and April 2014, a total of 230 patients who had undergone surgical cartilage repair for symptomatic full-thickness cartilage defects of the knee has been included in the German Cartilage Registry from 23 cartilage repair centres. Mean age was 37.11 years (SD 13.61) and mean defect size was 3.68 cm(2) (SD 0.23). Since the introduction of the KnorpelRegister DGOU the total number of registered patients has increased steadily up to the most recent figure of 72 patients within one month. Patients were treated mainly according to the recommended therapies. The highest percentage in therapy is represented by the bone marrow stimulation techniques (55.02 %) as well as by the autologous chondrocyte transplantation (34.92 %). Unlike the patient collective in the majority of prospective randomised controlled trials, the patient population within the registry shows a high proportion of patients with accompanying pathologies, with an age of more than 50 years at the time of treatment and with unfavourably assessed accompanying pathologies such as an affection of the opposite cartilage surface or a previously resected meniscus. In summary, the technical platform and forms of documentation of the KnorpelRegister DGOU have proved to be very promising within the first six months. Unlike data from other clinical trials, the previous analysis of the patients' data and therapies reflects successfully the actual medical care situation of patients with cartilage defects of the knee joint. This analysis also provides new information on subgroups of patients that have not yet been recorded in the scientific literature. This will be part of the first analysis of clinical treatment data. An expansion of the KnorpelRegister DGOU to patients with cartilage defects of the ankle and hip joints is already decided upon and initialised.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

[Effects of physical stimulation of spontaneous arteriolar vasomotion on microcirculation and the immune system in diabetes and impaired wound healing]. / Wirkungen einer physikalischen Stimulierung der spontanen arteriolären Vasomotion auf Mikrozirkulation und Immunsystem bei Diabetes und Wundheilungsstörungen.

BACKGROUND: Whether and to what extent the complementary use of a biorhythm-defined physical stimulation of insufficient spontaneous arteriolar vasomotion contributes to increasing the therapeutic success of established treatment concepts were examined. MATERIALS AND METHODS: In a placebo-controlled study on a biometrically defined sample of older diabetes patients with impaired wound healing, measurements of representative features of the functional status of the microcirculation and the immune system were investigated using high-resolution methods (intravital microscopy, reflective spectrometry, white light spectroscopy combined with laser Doppler microflow measurements). The stimulation signal corresponding to physiological spontaneous arteriolar vasomotion was transmitted using an electromagnetic alternating field of low magnetic flux density. RESULTS: During the 27-day treatment and observation period, a complementary treatment effect of the applied biorhythm-defined physical vasomotion stimulation could be detected.

Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy.

OBJECTIVE: To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy. RESEARCH DESIGN AND METHODS: In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168). Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS). Data analysis was based on the intention to treat. RESULTS: No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline. The TSS in the feet decreased from baseline to day 19 (median [range]) by -3.7 (-12.6 to 5.0) points in the group given alpha-lipoic acid intravenously and by -3.0 (-12.3 to 8.0) points in the placebo group (P = 0.447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (85.6 [0-219] vs. 95.9 [5.5-220]); P = 0.033). After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial. The NIS decreased after 19 days by -4.34+/-0.35 points (mean +/- SEM) in A-A and A-P and -3.49+/-0.58 points in P-P (P = 0.02 for alpha-lipoic acid versus placebo) and after 7 months by -5.82+/-0.73 points in A-A, -5.76+/-0.69 points in A-P, and -4.37+/-0.83 points in P-P (P = 0.09 for A-A vs. P-P). The rates of adverse events were not different between the groups throughout the study. CONCLUSIONS: These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study. However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions. Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy.

Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy.

AIMS: To evaluate the efficacy and safety of short-term oral treatment with the antioxidant thioctic acid (TA) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: Patients were randomly assigned to oral treatment with 600 mg of TA t.i.d. (n = 12) or placebo (n = 12) for 3 weeks. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) in the feet were scored at weekly intervals and summarized as a Total Symptom Score (TSS). The Hamburg Pain Adjective List (HPAL) and the Neuropathy Disability Score (NDS) were assessed at baseline and day 19. RESULTS: At baseline the TSS, HPAL, and NDS were not significantly different between the groups. The TSS in the foot decreased from baseline to day 19 by -3.75 +/- 1.88 points (-47%) in the TA group and by -1.94 +/- 1.50 points (-24%) in the placebo group (P= 0.021 for TA vs. placebo). The total HPAL score decreased from baseline to day 19 by -2.20 +/- 1.65 points (-60%) in the TA group and by -0.96 +/- 1.32 points (-29%) in the placebo group (P = 0.072 for TA vs. placebo). The NDS decreased by -0.27 +/- 0.47 points in the TA group, whereas it slightly increased by +0.18 +/- 0.4 points in the placebo group (P = 0.025 for TA vs. placebo). No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These preliminary findings indicate that oral treatment with 600 mg of TA t.i.d. for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions.

Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study).

Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.

Experiments on the possible role of leeches as vectors of animal and human pathogens: a light and electron microscopy study.

The presence and survival of pathogens inside the gut of leeches were studied by means of light and electron microscopy. In African leeches from Cameroon, blood was serologically positive for human immunodeficiency virus (HIV) and hepatitis B; blood of Hirudo medicinalis bought in German pharmacies contained up to 11 different species of bacteria. In experiments done at low (3 degrees C) and high (22 degrees, 32 degrees C) temperatures, it was shown that ingested red and white blood cells survive for long periods. The time was prolonged to at least 6 months in cases in which the leeches were stored at 3 degrees C. The same effect occurred with pathogens. Bacteriophages (viruses of bacteria) and bacteria persisted in large numbers for at least 6 months in the gut of experimentally infected leeches. Protozoan parasites such as Toxoplasma gondii, Trypanosoma brucei brucei, or Plasmodium berghei were even capable of reproducing inside the gut of the leech. In the case of Plasmodium parasites, this proceeded at low (3 degrees C) and high (22 degrees C) temperatures until all erythrocytes were used up. These parasites survived as long as the erythrocytes and lymphocytes were of good shape, i.e., around 5-6 weeks p.i. Single stages survived longer, especially at low temperatures. However, electron microscopy studies gave no hint of penetration of such pathogens into the unicellular salivary glands, which would initiate a direct transmission. Such transmission, however, is possible--many fish leeches directly transmit several blood parasites--when the leeches are squeezed during skin attachment or when they are manipulated by dropping salt solution on their backs while they are sucking. Consequently, the leech is a potential vector of many pathogens, especially in regions with an endemic spread of human and/or animal pathogens.

Antibody mapping of functional domains in vinculin.

We have analyzed the functional domain structure of vinculin, a protein involved in linking microfilaments to the cytoplasmic face of cell membranes in animal cells. For this purpose, we used several monoclonal antibodies raised against chicken gizzard vinculin whose epitopes could be assigned to discrete regions in the vinculin sequence by immunoblotting of proteolytic fragments combined with N-terminal amino acid sequencing. Two of these antibodies induced the disruption of stress fibers and changed the number of morphology of focal contacts after microinjection in chicken embryo fibroblasts. Based on the location of its epitope in comparison with vinculin domains previously identified by other groups, we propose that one of these antibodies (15B7) interferes with the binding of vinculin to talin, the most peripheral of the microfilament proteins. The second antibody (14C10) binds within a region comprising three internal repeats and might therefore distort the inner architecture of vinculin. A third antibody (As3) inhibited the binding of F-actin to vinculin in an in vitro assay but had no effect on the microfilament system in cells. These data emphasize the role of vinculin as a key protein in microfilament-membrane linkage and support previous work on a direct interaction between vinculin and actin.

[Internal medicine--status and perspectives]. / Die Innere Medizin--Stand und Perspektiven.

Catalysed by the scientific progress in medicine an increasing specialisation in internal medicine developed with the danger of a disunion of the specialty. Nowadays, the internal medicine is tripartite with the basis internal specialists and the subspecialist as the two poles of the care of patients in the field of internal medicine. The description of the status quo in internal medicine shows reserves in training and education of the students as well as of the physicians during the period of specialisation which must be closed. It is essential for a qualification of the physician's work that basis internal specialists and proper specialists unite in the sense of a partnership and formulate professional and health-political aims for internal medicine.

Kinetic evidence for insertion of actin monomers between the barbed ends of actin filaments and barbed end-bound insertin, a protein purified from smooth muscle.

An actin polymerization-retarding protein was isolated from chicken gizzard smooth muscle. This protein copurified with vinculin on DEAE-cellulose and gel filtration columns. The polymerization-retarding protein could be separated from vinculin by hydroxylapatite chromatography. The isolated polymerization-retarding protein lost its activity within a few days, but was stable for weeks when it was not separated from vinculin. We termed the polymerization-retarding protein "insertin". Because of the instability of the isolated insertin, we investigated the effect of insertin-vinculin on actin polymerization. Insertin-vinculin retarded nucleated actin polymerization maximally fivefold. Polymerization at the pointed ends of gelsolin-capped actin filaments was not affected by insertin-vinculin, suggesting that insertin-vinculin binds to the barbed ends, but not to the pointed ends, of actin filaments. Retarded polymerization was observed even if the actin monomer concentration was between the critical concentrations of the ends of treadmilling actin filaments. As at this low monomer concentration the pointed ends depolymerize, monomers appeared to be inserted at the barbed ends between the terminal subunit and barbed end-bound insertin molecules. Insertin-vinculin was found not to increase the actin monomer concentration to the value of the pointed ends. These observations support the conclusion that insertin is not a barbed end-capping protein but an actin monomer-inserting protein. According to a quantitative analysis of the kinetic data, all observations could be explained by a model in which two insertin molecules were assumed to bind co-operatively to the barbed ends of actin filaments. Actin monomers were found to be inserted between the barbed ends and barbed end-bound insertin molecules at a rate of about 1 x 10(6) M-1 s-1. Insertin may be an essential part of the machinery of molecules that permit treadmilling of actin filaments in living cells by insertion of actin molecules between membranes and actin filaments.

Rate of binding of tropomyosin to actin filaments.

The decrease of the rate of actin polymerization by tropomyosin molecules which bind near the ends of actin filaments was analyzed in terms of the rate of binding of tropomyosin to actin filaments. Monomeric actin was polymerized onto actin filaments in the presence of various concentrations of tropomyosin. At high concentrations of monomeric actin (c1) and low tropomyosin concentrations (ct) (c1/ct greater than 10), actin polymerization was not retarded by tropomyosin because actin polymerization was faster than binding of tropomyosin to actin filaments. At low actin concentrations and high tropomyosin concentrations (c1/ct less than 5), the rate of elongation of actin filaments was decreased because actin polymerization was slower than binding of tropomyosin at the ends of actin filaments. The results were quantitatively analyzed by a model in which it was assumed that actin-bound tropomyosin molecules which extend beyond the ends of actin filaments retard association of actin monomers with filament ends. Under the experimental conditions (100 mM KCl, 1 mM MgCl2, pH 7.5, 25 degrees C), the rate constant for binding of tropomyosin to actin filaments turned out to be about 2.5 X 10(6) to 4 X 10(6) M-1 S-1.

Evidence for direct binding of vinculin to actin filaments.

The interaction of vinculin with actin filaments was investigated by methods which exclude interference by contaminating proteins which may occur in vinculin preparations. Vinculin which was blotted from SDS-polyacrylamide gels onto nitrocellulose, was stained specifically by fluorescently labeled polymeric actin (100 mM KCl, 2 mM MgCl2). Vinculin which was purified from alpha-actinin and an actin polymerization-inhibiting protein (HA1), was found to be cosedimented with polymeric actin. Maximally one vinculin molecule was cosedimented per one hundred actin filament subunits. Half maximal binding of vinculin was observed at about 0.25 microM free vinculin. Vinculin could be replaced from actin by the addition of tropomyosin.

Characterization of the actin polymerization-inhibiting protein from chicken gizzard smooth muscle.

An actin polymerization-inhibiting protein, occurring in crude preparations of vinculin from chicken gizzard, has been found to be heterogeneous. The molecular masses of the polymerization-inhibiting peptides have been reported to range from 20 kDa to 80 kDa [Schröer, E. & Wegner, A (1985) Eur. J. Biochem. 153, 515-520]. In this paper, a 21-kDa peptide was isolated from the bulk of the other peptides by gel chromatography. The 21-kDa peptide was identified as a polymerization-inhibiting peptide by its ability to retard nucleated actin polymerization and to bind polymeric actin when it was blotted onto nitrocellulose. Antiserum raised to the 21-kDa peptide was found to react with almost all peptides of the blotted heterogeneous polymerization-inhibiting protein. The same peptides which reacted with antiserum cosedimented with polymeric actin. The major peptides of the blotted polymerization-inhibiting protein bound polymeric actin. The largest peptide which reacted with antiserum and cosedimented with polymeric actin had a molecular mass of 85 kDa. The results suggest that the preparation of polymerization-inhibiting protein contains mainly polymerization-inhibiting peptides and only some contaminants, and that all the polymerization-inhibiting peptides are proteolytic fragments stemming from a common precursor.

[Management of elderly citizens dependent on outside help from the clinical viewpoint]. / Die Betreuung auf fremde Hilfe angewiesener älterer Bürger aus klinischer Sicht.

The increase of life expectancy has led to a higher percentage of the oldest and requiring help people. The present paper described the possibilities and situation of care for this part of the population on the basis of an analysis of a district of Berlin. It must be stated that the cooperation between social organizations and ambulatory institutions and hospitals can be improved. The hospitalisation of older people requiring help should be an exception and is ethically legitimated only then, when it is performed with the intention of the patient. The willingness for care on the side of the members of the patients' families is analysed and discussed in the sense of improvement.

[What attitude to dying do we have today?]. / Welche Haltung zum Sterben haben wir heute?

Deficient care and unfounded loneliness increasingly form the fate of dying patients. A change under the aspects of socialist norms is the task of the whole society.

[Helping to die--helping to live in the boundary between life and death]. / Sterbehilfe--Lebenshilfe im Grenzbereich zwischen Leben und Tod.

Help for the dying patient is a matter of the physician's duty in the sense of the help for life in a border-line situation of human life. Even if the activity of the physician is no more determined by the thought of the preservation of life, the aims in the care for dying patients are on principle to be compared with those in the care for other patients and contain essential principles of the activity of the physician: somatic area (treatment and care) psycho-social area (aid, care and communication). While the hospital in the somatic field has prerequisites for a careful treatment and care, the domestic milieu has advantages in the psycho-social area. It is recommended a flexible and individually adapted performance of the care of dying patients in the hospital and the domestic milieu.

[Diskography--myelography]. / Diskographie--Myelographie.

One hundred patients were submitted to a prospective, comparative study of metrizamide myelography and discography. In the 32 patients with cervical myelopathy discography yielded no additional information and was thus abandoned. The 68 patients with radiculopathy disease the following results were obtained: In view of the agreement between clinical and myelographic monosegmental findings, discography was considered unnecessary. However, in seven cases with negative myelograms it was possible to show a disc prolapse by discography. When the myelogram was pathological over several segments discography furnished additional information for the differential diagnosis between osteochondrotic or discogenic space-occupying lesions.

Cervical disk syndromes: value of metrizamide myelography and diskography.

This paper reports on the respective diagnostic values of myelography with water-soluble contrast media and diskography in a study of 100 patients examined between 1979 and 1981 and operated on because of cervical disk disease. The results of the study led to a change of the diagnostic procedures formerly applied in radicular syndromes (i.e., diskography, and then perhaps myelography) and in cervical myelopathy (myelography, rarely followed by diskography). Now cervical metrizamide myelography is always performed first. Diskography is only indicated in radicular syndromes to determine the segment causing clinical symptoms when there is a polysegmental space-occupying lesion on the myelogram in combination with a mono- or oligoradicular neurologic symptomatology; or in the case of a normal myelogram with complaints resistant to conservative treatment.