[Therapy of patients with chronic back pain. Prescriptions--contentment--outcome]. / Therapie bei Patienten mit Rückenschmerzen. Verordnungsverhalten--subjektive Zufriedenheit--Effekte.

Chronic back pain is a frequent complaint in out-patient orthopaedic practice. National (DEGAM; German Society of General Medicine and Family Medicine) and international guidelines provide recommendations for diagnostic and therapeutic procedures. Regulation of the behaviour of treating orthopaedists in the context of the therapy is so far little known.In this survey it was investigated which treatments are prescribed, whether there is a link between regulations and stage of chronification and whether the subjective effects correspond to objective results. Questionnaires relating to patient anamnesis were sent to 235 orthopaedic practices and a second questionnaire was sent to all patients who took part in the survey 6 months later. A total of 630 data sets could be evaluated.It was shown that primarily passive therapies (physiotherapy, drug therapy, injections and tablets) are mostly prescribed (physiotherapy, medications, injections) and that more therapies are used with increasing stages of chronification. The prescribed therapy achieved a high subjective patient satisfaction but an objective success could not be recognized.

Short-term exposure to tumor necrosis factor-alpha does not affect insulin-stimulated glucose uptake in skeletal muscle.

It has been hypothesized that increased production of tumor necrosis factor-alpha (TNF-alpha) plays a role in causing the insulin resistance associated with obesity. Obesity with insulin resistance is associated with increased production of TNF-alpha by fat cells. Exposure of 3T3-L1 adipocytes to TNF-alpha for 3-4 days makes them insulin resistant. TNF-alpha has also been reported to rapidly (15-60 min) cause insulin resistance, with a decrease in insulin-stimulated tyrosine phosphorylation, in a number of cultured cell lines. Because skeletal muscle is the major tissue responsible for insulin-stimulated glucose disposal, we performed the present study to determine if acute exposure to TNF-alpha causes insulin resistance in muscle. We found that exposure of soleus muscles to 6 nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on insulin-stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1. Incubation of epitrochlearis and soleus muscles with 6 nmol/l TNF-alpha for 45 min or 4 h had no effect on insulin-stimulated 2-deoxyglucose (2-DG) uptake. Treatment of epitrochlearis muscles with 2 nmol/l TNF-alpha for 8 h also had no effect on insulin-stimulated 2-DG uptake. We conclude that in contrast to Fao hepatoma cells and 3T3-L1 fibroblasts, skeletal muscle does not become insulin resistant in response to short-term exposure to TNF-alpha.

Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle.

beta-Adrenergic stimulation has been reported to inhibit insulin-stimulated glucose transport in adipocytes. This effect has been attributed to a decrease in the intrinsic activity of the GLUT-4 isoform of the glucose transporter that is mediated by phosphorylation of GLUT-4. Early studies showed no inhibition of insulin-stimulated glucose transport by epinephrine in skeletal muscle. The purpose of this study was to determine the effect of epinephrine on GLUT-4 phosphorylation, and reevaluate the effect of beta-adrenergic stimulation on insulin-activated glucose transport, in skeletal muscle. We found that 1 microM epinephrine, which raised adenosine 3',5'-cyclic monophosphate approximately ninefold, resulted in GLUT-4 phosphorylation in rat skeletal muscle but had no inhibitory effect on insulin-stimulated 3-O-methyl-D-glucose (3-MG) transport. In contrast to 3-MG transport, the uptakes of 2-deoxyglucose and glucose were markedly inhibited by epinephrine treatment. This inhibitory effect was presumably mediated by stimulation of glycogenolysis, which resulted in an increase in glucose 6-phosphate concentration to levels known to severely inhibit hexokinase. We conclude that 1) beta-adrenergic stimulation decreases glucose uptake by raising glucose 6-phosphate concentration, thus inhibiting hexokinase, but does not inhibit insulin-stimulated glucose transport and 2) phosphorylation of GLUT-4 has no effect on glucose transport in skeletal muscle.

Effects of Ca2+ ionophore ionomycin on insulin-stimulated and basal glucose transport in muscle.

There is evidence that an increase in sarcoplasmic Ca2+ stimulates glucose transport in muscle. Recent studies have provided the apparently conflicting finding that a sustained increase in cytosolic Ca2+ has little effect on basal glucose transport but inhibits insulin-stimulated transport. This study was done to try to explain this discrepancy. Continuous exposure of rat epitrochlearis and soleus muscles to the Ca2+ ionophore ionomycin (2 microM) had no effect on basal 2-deoxyglucose (2-DG) transport but blunted, by approximately 40%, stimulation of 2-DG transport by insulin. Decreasing Ca2+ in the medium to a very low level prevented this inhibition. Ionomycin induced a small increase in adenosine 3',5'-cyclic monophosphate (cAMP); however, studies with the protein kinase A (PKA) inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not mediate the inhibition of glucose transport. When muscles were allowed to recover in the absence of ionomycin for 15 min, basal 2-DG transport was significantly increased. Our results agree with previous studies showing that a sustained influx of Ca2+ into the cytoplasm can inhibit insulin-stimulated glucose transport. They further show that stimulation of glucose transport by Ca2+ is also inhibited. A recovery period that allows this inhibition to wear off unmasks the stimulation of glucose transport by an increase in sarcoplasmic Ca2+.

Kinetics of 2-deoxyglucose transport in skeletal muscle: effects of insulin and contractions.

There is some controversy regarding whether insulin or contractile activity alters the affinity of skeletal muscle glucose transporters for glucose and its analogues. The effects of insulin and contractions on the kinetics of glucose transport were therefore reexamined in isolated rat skeletal muscles. Concentration-dependent rates of 2-deoxyglucose (2-DG) transport were measured in the absence or presence of insulin (2 mU/ml) in the epitrochlearis and split soleus muscles. The apparent half-maximal saturating substrate concentration (Km) for basal 2-DG transport (approximately 12 mM) was similar for the split soleus and epitrochlearis, and the apparent Km was not changed by insulin in either muscle type. The presence of 2 mU/ml insulin increased the maximal transport velocity (Vmax) approximately fourfold in the epitrochlearis and approximately eightfold in the split soleus. In the epitrochlearis, in vitro muscle contractions also resulted in an approximately fourfold increases in Vmax with no change in apparent Km. The combined effects of insulin and contractions on Vmax were completely additive, but the apparent Km was not different from insulin alone. The apparent Km values for basal and insulin-stimulated glucose transport were further characterized in the epitrochlearis isolated from transgenic mice overexpressing the GLUT-1 isoform in the sarcolemma and their nontransgenic littermates. The apparent Km for basal 2-DG transport in the transgenic muscle (9 mM) was not significantly different from the apparent Km for insulin-stimulated transport in the control muscle (10 mM). The present study provides evidence that insulin and contractions, either alone or in combination, increase glucose transport activity in skeletal muscle by increasing Vmax, with no significant change in Km. Our results also suggest that, in intact skeletal muscle, the Km for basal glucose transport (a process mediated primarily by GLUT-1) is similar to the Km values for stimulated transport, mediated predominantly by GLUT-4.

Lithium increases susceptibility of muscle glucose transport to stimulation by various agents.

Lithium is thought to have an insulin-like effect on glucose transport and metabolism in skeletal muscle and adipocytes. However, we found that lithium had only a minimal effect on basal glucose transport activity in rat epitrochlearis muscles. Instead, lithium markedly increased the sensitivity of glucose transport to insulin, so that the increase in glucose transport activity induced by 300 pM insulin was approximately 2.5-fold greater in the presence of lithium than in its absence. Lithium also caused a modest increase in insulin responsiveness. This enhancement of the susceptibility of the glucose transport process to stimulation was not limited to insulin, because lithium induced increases in the susceptibility of glucose transport to stimulation by contractile activity, hypoxia, a phorbol ester, and phospholipase C. Lithium also blunted the activation of glycogen phosphorylase by epinephrine. These effects were not mediated by inhibition of adenylate cyclase, because neither basal- nor epinephrine-stimulated muscle cAMP concentration was affected by lithium treatment. The effects of lithium on glucose transport and metabolism in skeletal muscle are strikingly similar to the persistent effects of exercise. These results support the possibility that lithium might be useful in the treatment of insulin resistance in patients with non-insulin-dependent diabetes mellitus.

Shortening velocity and ATPase activity of rat skeletal muscle fibers: effects of endurance exercise training.

Mechanical properties were measured in single skinned fibers from rat hindlimb muscle to test the hypothesis that the fast type IIb fiber exhibits a higher maximal shortening velocity (Vo) than the fast type IIa fiber and that the difference is directly attributable to a higher myofibrillar adenosinetriphosphatase (ATPase) activity in the type IIb fiber. Additional measurements were made to test the hypotheses that regular endurance exercise increases and decreases the Vo of the type I and IIa fiber, respectively, and that the altered Vo is associated with a corresponding change in the fiber ATPase activity. Rats were exercised by 8-12 wk of treadmill running for 2 h/day, 5 day/wk, up a 15% grade at a speed of 27 m/min. Fiber Vo was determined by the slack test, and the ATPase was measured fluorometrically in the same fiber. The myosin isozyme profile of each fiber was subsequently determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mean +/- SE Vo (7.9 +/- 0.22 fiber lengths/s) of the type IIb fiber was significantly greater than the type IIa fiber (4.4 +/- 0.21 fiber lengths/s), and the higher Vo was associated with a higher ATPase activity (927 +/- 70 vs. 760 +/- 60 microM.min-1.mm-3). The exercise program induced cardiac hypertrophy and an approximately twofold increase in the mitochondrial marker enzyme citrate synthase. Exercise had no effect on fiber diameter or peak tension per cross-sectional area in any fiber type, but, importantly, it significantly increased (23%) both the Vo and the ATPase activity of the slow type I fiber of the soleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Uvulopalatopharyngoplasty for obstructive sleep apnea: a community's experience.

Uvulopalatopharyngoplasty (UPPP) has become an accepted method for treating obstructive sleep apnea (OSA), with a reported success rate as high as 77%, depending upon inclusionary and outcome criteria. The authors reviewed the records of 90 patients with moderately severe OSA (apnea plus hypopnea index [AHI] greater than 20) who underwent UPPP at either a private community or an academic hospital. Forty percent of patients experienced more than a 50% reduction in their AHI with UPPP. Only 22 (24%) of the patients had a postoperative AHI less than 50% of the preoperative AHI and less than 20, i.e., met the authors' criteria for surgical success. The success rate for community otolaryngologists was no different than that achieved in the academic institution. When data from previously published reports were analyzed using these criteria for success, similar results were observed. This study suggests that the effectiveness of UPPP performed by the general otolaryngologic community is equivalent to that reported in the literature. However, more rigorous criteria must be applied to UPPP when evaluating its results and in counseling potential candidates for this procedure.

Single night studies in obstructive sleep apnea.

The role of single night studies and the determinants of effective nasal continuous positive airway (CPAP) pressures were determined in 412 consecutive patients between 1984 and 1989. Patients chosen for analysis had an apnea index (AI) of greater than or equal to 20 hr-1 prior to CPAP. The AI was 67 +/- 30 hr-1, the body mass index (BMI) was 36 +/- 9 kg/m2, the age was 51 +/- 13 yr and the lowest oxygen saturation was 72 +/- 14%. Effective CPAP (9 +/- 3 cm H2O) was documented in 320 patients on single night studies and resulted in a 99% reduction in the frequency of obstructive events and improvement in the lowest O2 saturation to 94 +/- 5%. Only 18% of the variability in effective CPAP could be explained by AI and BMI. Single night studies are sufficient to establish effective CPAP in 78% of patients and offer considerable conservation of resources compared to routine multiple night studies. Effective CPAP pressures are variable and must be determined by incremental CPAP trials.

A retrospective outcome study and review of hypnosis as treatment of adults with sleepwalking and sleep terror.

Hypnosis has been described anecdotally to be effective in the treatment of sleepwalking and sleep terror, potentially dangerous parasomnias. The authors report the use of hypnosis in the treatment of 27 adult patients with these disorders. A total of 74% of these individuals reported much or very much improvement when followed over substantial periods after instruction in self-hypnotic exercises that were practiced in the home. Hypnosis, often preferred over pharmacotherapy by patients, required one to six office visits (mean = 1.6). This represents a very cost-effective and noninvasive means of treatment, especially when constrasted with lengthy psychotherapy and pharmacotherapy.

The determinants of skeletal muscle force and power: their adaptability with changes in activity pattern.

A kinetic model of the cross-bridge cycle in skeletal muscle is presented with special reference to the rate limiting steps regulating the peak rate of force development (dP/dt), peak force (P0), and the maximal shortening speed (Vmax). Force production in skeletal muscle is dependent on the number of cross-bridges in the strongly bound, high-force state (AM'-ADP), and during a peak isometric contraction this state is the dominant cross-bridge form. The peak force and power output of a muscle depends upon numerous factors to include: (1) muscle and fiber size and length; (2) architecture, such as the angle and physical properties of the fiber-tendon attachment, and the fiber to muscle length ratio; (3) fiber type; (4) number of cross-bridges in parallel; (5) force per cross-bridge; (6) peak dP/dt; (7) force-velocity relationship; (8) fiber Vmax; (9) force-pCa2+ relationship: and (10) the force-frequency (action potential Hz) relationship. In this paper, we discuss these determinants of force and power output, and consider how they adapt to both muscle unloading (induced by hindlimb suspension) and programs of regular endurance exercise. Slow- and fast-twitch fibers have similar capacities to generate specific tension (kg cm-2). However, fast fibers show a considerably higher peak dP/dt, Vmax, and power output. The high Vmax of the fast-twitch fiber is likely due to the high myofibrillar ATPase activity of the fast myosin isozyme. Both hindlimb suspension and regular endurance exercise have been shown to induce fiber type specific changes in single fiber function. For example, fiber size and the peak tetanic tension of the slow oxidative (SO), fast oxidative glycolytic (FOG), and fast glycolytic (FG) fiber types were generally unaltered by endurance exercise-training. In contrast, hindlimb suspension produced cell atrophy in all fiber types and a reduced specific tension in the SO but not the FOG or FG fiber types. Both exercise-training and HS shifted the force-pCa curve to the right, and increased the Vmax of the SO fiber type. From the standpoint of work capacity or the ability to move a load, the important functional property is power output. Peak power is obtained at loads considerably below 50% of PO, and it is correlated with the percentage of fast-twitch fibers. Peak power can be increased by both dynamic and isometric programs of exercise-training.(ABSTRACT TRUNCATED AT 400 WORDS)

Oxidation of tris to one-carbon compounds in a radical-producing model system, in microsomes, in hepatocytes and in rats.

The buffer substance tris(hydroxymethyl)aminomethane (Tris) is converted to formaldehyde in an hydroxyl radical producing model system and in rat liver microsomes, and to CO2 in rat hepatocytes and in the intact rat. In microsomes, formaldehyde formation from Tris is inhibited by catalase, by the antioxidant propylgallate and by the iron chelator deferoxamine, formaldehyde formation is stimulated by the addition of Fe (II) EDTA. In hepatocytes, the formation of [14C] CO2 from [14C] Tris is inhibited by propylgallate and by the iron chelator o-phenanthroline and is stimulated by the presence of a xanthine oxidase system plus Fe (II) EDTA in the medium. In the intact rat, the administration of [14C] Tris results in the exhalation of [14C] CO2. The results indicate that an oxidant formed via a Fenton-type reaction, possibly the hydroxyl radical, may be involved in the formation of one-carbon compounds from Tris.

Contractile function of single muscle fibers after hindlimb suspension.

The purpose of this investigation was to determine how muscle atrophy produced by the hindlimb suspension (HS) model alters the contractile function of slow- and fast-twitch single muscle fibers. After 2 wk of HS, small bundles of fibers were isolated from the soleus and the deep and superficial regions of the lateral and medial heads of the gastrocnemius, respectively. The bundles were placed in skinning solution and stored at -20 degrees C until studied. Single fibers were isolated and suspended between a motor arm and force transducer, the functional properties were studied, and subsequently the fiber type was established by myosin heavy chain (MHC) analysis on 1-D sodium dodecyl sulfate polyacrylamide gel electrophoresis. After HS, slow-twitch fibers of the soleus showed a significant reduction in fiber diameter (68 +/- 2 vs. 41 +/- 1 micron) and peak tension (1.37 +/- 0.01 vs. 0.99 +/- 0.06 kg/cm2), whereas the maximal shortening speed (Vmax) increased [1.49 +/- 0.11 vs. 1.92 +/- 0.14 fiber lengths (FL)/s]. A histogram showed two populations of fibers: one with Vmax values identical to control slow-twitch fibers and a second with significantly elevated Vmax values. This latter group frequently contained both slow and fast MHC protein isoforms. The pCa-force relation of the soleus slow-twitch fibers was shifted to the right; consequently, the free Ca2+ required for the onset of tension and for 50% of peak tension was significantly higher after HS. Slow-twitch fibers isolated from the gastrocnemius after HS showed a significant reduction in diameter (67 +/- 4 vs. 44 +/- 3 microns) and peak tension (1.2 +/- 0.06 vs. 0.96 +/- 0.07 kg/cm2), but Vmax was unaltered (1.70 +/- 0.13 vs. 1.65 +/- 0.18 FL/s). Fast-twitch fibers from the red gastrocnemius showed a significant reduction in diameter (59 +/- 2 vs. 49 +/- 3 microns) but no change in peak tension or Vmax. Fast-twitch fibers from the white superficial region of the medial head of the gastrocnemius were unaffected by HS. Collectively, these data suggest that the effects of HS on fiber function depend on the fiber type and location. Both slow-twitch type I and fast-twitch type IIa fibers atrophied; however, only slow-twitch fibers showed a decline in peak tension, and the increase in Vmax was restricted to a subpopulation of slow-twitch soleus fibers.