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Background: Proglucagon-derived peptides are potential mediators of the adaptive response of the terminal ileum to massive small bowel resection. Ileal proglucagon messenger RNA (mRNA) levels increase during ileal adaptation. The present study explored the cellular basis of this response., Methods: Sections of control ileum, ileum 4 days after resection, and pancreas were analyzed by in situ hybridization with 35S-labeled complementary RNA (cRNA) probes., Results: Both the proglucagon and the peptide YY cRNA probes hybridized to discrete cells in the ileal mucosa, the disposition of which corresponds to that reported for intestinal L cells. Four days after resection there was a marked increase in the intensity of the signal for both probes without an increase in cell number. Insulin and histone H3 probes were used as controls to confirm the specificity of the hybridization seen with the L-cell specific, proglucagon, and peptide YY probes., Conclusions: The increase in proglucagon mRNA levels after massive small bowel resection is caused by an increase in the cellular content. The parallel increase in PYY mRNA levels implies an L cell--rather than a proglucagon gene--specific response.

We examined in vitro the effect of ethanol at four concentrations (0g%, 0.1g%, 0.2g%, and 0.4g%) on contractile parameters of 40 fast extensor digitorum longus (EDL) and 40 slow soleus muscles from healthy mice at 35C. Preparations were curarized to avoid the possible effect of ethanol on the terminal axons or skeletal neuromuscular junction. Contractile parameters measured included: (1) twitch and tetanic tension; (2) rate of tension development; (3) time to peak tension and half relaxation for twitch; (4) time to first evidence of relaxation in the tetanus; and (5) maximum rate of relaxation. The three lower concentrations of ethanol had no significant effect on muscle contractility; however, the 0.4g% dose reduced EDL twitch tension by 9%. High doses of ethanol (2.5g%) reduced the tetanic tension produced by the EDL and soleus muscles 31% and 26%, respectively. Ethanol at 2.5g% also reduced the twitch tension of the EDL and soleus by 50% and 38%, respectively. The data suggested that the 0.4g% is the highest dose of ethanol that should be used to dilute drugs in a solution that will bathe directly stimulated curarized muscle without confounding effects. In addition, it is highly unlikely that a direct effect of ethanol on muscle contractility in humans is related to an impairment in driving.

The purpose of this study was to use direct in vivo contractility measurements to assess muscle function in patients with myotonic muscular dystrophy (MMD). The tetanic and twitch responses and several time parameters of muscle contraction were obtained from nine MMD subjects and nine able-bodied, age-matched controls. After a routine nerve conduction study, in vivo contractility measurements were obtained by stimulating the ulnar nerve at the wrist and recording the isometric flexor function of the intrinsic muscles at the metacarpophalangeal joint of the index finger. A series of single stimuli, paired stimuli, and fused tetanic stimulations were generated during a 20-minute experimental protocol. A stable tetanus was produced at 50Hz for 1.2 seconds. M-wave and contractile data were recorded at 1,000Hz by digitization of the analog signal and storage by the microcomputer. The MMD patients were weaker than controls (p less than .05), as shown by the 39% reduction in tetanic tension and 57% reduction in twitch tension. The MMD patients also had a significant impairment in relaxing their muscles as shown by the 1,100% increase in half-relaxation time after contraction, even though there was no evidence of repetitive firing after cessation of stimulus. These data show that MMD patients exhibit failure of sarcolemmal activation, altered excitation-contraction coupling mechanisms, and failure of the contractile machinery. The myotonia is due in part, to some defect in the contractile machinery; it is not solely due to failure of sarcolemmal activation.

This report describes and assesses a technique to indirectly stimulate and quantify the human in vivo muscle response for clinical use. A method has been developed to isolate, stimulate, and record the flexor function of the first dorsal interosseus and first volar interosseus at the metacarpophalangeal (MCP) joint by stimulation of the ulnar nerve at the wrist. A microprocessor-based data acquisition and analysis system was built to deliver the electric stimulus and convert the muscle action potential (M-wave) and force measurements into digital form for analysis. To evaluate the technique, the twitch, paired twitch, and tetanic contractions were analyzed in 81 normal subjects. The tension developed by the youngest subjects (14 to 19 years old) was significantly less than the tension developed by subjects in the three older groups (20 to 34 years, 35 to 50 years, and 50 to 65 years); the tensions in the older groups were not significantly different from each other. Only minor gender differences were noted. This indicates that it is necessary to use age-group controls when looking for evidence of a muscle contractile abnormality in patients with neuromuscular disorders. posttetanic potentiation of the twitch was observed in all healthy subjects, and there was no evidence of an age or gender influence. The posttetanic increase in twitch tension was not associated with a prolongation of the twitch contraction time.

Massive small bowel resection with re-anastomosis of the residual jejunum and terminal ileum results in marked adaptive responses. Various luminal and humoral factors have been implicated in the adaptive response, which may be analogous to the changes occurring in the ileum in the postnatal growth phase. Enteroglucagon, which is synthesized in the L cells of the intestinal mucosa, is thought to be an important humoral factor in this response. In this study, the levels of glucagon gene expression in the rat ileum both after massive small bowel resection and during development are examined. Glucagon messenger RNA levels are increased threefold as part of the adaptive response; the increase is maximal at 2 days and is at least partly dependent on luminal nutrition. Levels of glucagon messenger RNA in the developing ileum increase in the postnatal period until weaning when they decrease somewhat before gradually reaching adult levels.

In vitro studies were performed on fast and slow muscles from mice to determine if secobarbital sodium (SCB) has a direct effect on muscle contractility. All preparations were curarized and stimulation was direct. After baseline studies, SCB was added to the muscle bath in 1 of 4 concentrations-10, 20, 100 and 200 microgram/ml. Tetanic tension was reduced for both muscle types at SCB concentrations greater than or equal to 20 microgram/ml, and loss was progressive with increasing dose. In contrast, twitch tension (P) was increased by SCB at the 2 higher concentrations. The increase in P was due to an increase in rate of tension development plus prolongation of the time parameter (duration) of the twitch. Fatigue was accelerated by SCB for both muscle types. The results indicate that SCB has a direct and similar effect on fast and slow skeletal muscles. The probable sites of action of the drug are the excitation contraction coupling mechanisms and the mechanisms for energy production and/or utilization.

Simultaneous study of the function of fast and slow twitch skeletal muscles in the same in vitro preparation has obvious advantages. Equipment, method and technique are described for study of the soleus (slow) and extensor digitorum longus (fast) muscles from the mouse, and the problems involved in preparing and standardizing these studies are discussed. For nearly maximum function to be obtained from both muscles, careful attention must be given to the stimulus parameters used. Three separate studies were necessary to determine the appropriate stimulus duration, frequency and rest interval between the stimulus trains. The results indicate that for study of tetanic tension and rate of tension development of these muscles from the C57 NAB strain of mice at 20C the most satisfactory stimulus parameters are : duration 2 msec, frequency 100 pulses per second and duration of the stimulus train 700 msec. Rest interval between stimulus trains was two minutes as problems developed with rest intervals less than two minutes or greater than four minutes.

The purpose of this study was to evaluate a technique for in vitro study of mouse skeletal muscle, to determine if paired stimuli would allow estimation of new time parameters of contraction. Conventional tension measurements were obtained, plus the time measurements from the paired stimulus studies. The muscles were also subjected to fatigue by repetitive tetanization. A fast muscle (extensor digitorum longus or plantaris) and a slow muscle (soleus) were studied in each preparation. Studies were conducted at physiologic (35C) and at nonphysiologic (20C) temperatures. Data obtained indicate that this isometric in vitro method allows subdivision of results into 3 categories of effect due to treatment related to the functional muscle compartments: 1) chronotropic-excitation contraction coupling mechanisms, 2) inotropic- contractile elements, and 3) metabolic (fatigue)-energy supply mechanisms. When results as 20C were compared with physiologic temperature, a negative chronotropic effect was observed for all parameters in all 3 muscles. A positive inotropic effect was observed for twitch with no change or a negative effect for all other tension parameters. The lower temperature produced slight protection from fatigue. Models were developed to demonstrate how data from isometric studies fit the original concepts developed using isotonic methods. The model and method should prove of value in detecting the acute effect of drugs or of other therapy imposed on skeletal muscles.

The effects of serotonin on the contractile properties of the soleus and extensor digitorum longus muscles in mice were studied after chronic intraperitoneal administration with and without a recovery period, and compared to contractile studies of the same muscles performed after acute administration of serotonin. A curarized in vitro preparation of both muscles was used throughout for the contractile studies. In addition, structural changes were studied in the chronic preparations. Chronic serotonin administration produced histologic changes in type 1 and 2A fibers and a reduction in twitch and tetanic tension and the rate of twitch and tetanic tension development limited to the slow (aerobic) soleus muscle. Acute in vitro administration of serotonin altered the contractile properties of both soleus and extensor digitorum longus muscles with the latter being more involved. The effects of chronic serotonin administration appear to be primarily related to ischemia while the effects of acute administration appear to be mediated by direct, nonvascular action on skeletal muscle.

Fifty human muscle biopsies were examined for histochemical localization of acetylcholinesterase (AChE) activity. Six normal muscle samples had AChE at the myoneural junctions and around the periphery of many fibers. The AChE within the sarcoplasm itself was found in only a few atrophied fibers. However, 21 of 44 biopsies of abnormal muscles had sarcoplasmic AChE in more than 10% of their fibers. Such cases included Duchenne, limb-girdle and facio-scapulo-humeral dystrophy, neurogenic and spinal muscle atrophy, spinal cord injury, peripheral nerve injury, Schwartz-Jampel syndrome and myasthenic syndrome. Sarcoplasmic AChE is found in embryo muscle and usually declines after birth. It appears after denervation in the chicken but not the rat and remains in muscles of chickens with an inherited muscular dystrophy. The results of the human muscle study support the idea that in the human, as in the chicken, interruption of a neurally-mediated regulation of AChE results in the reappearance of high AChE activity in the sarcoplasm of the muscle fibers.

Serial phrenic nerve conduction studies in 3 patients with high cervical cord injuries have demonstrated a pattern of function that changes with time. Nerves may be responsive initially and may then become unresponsive only to have responses reappear at a later date. Before a final decision is made about phrenic nerve viability prior to diaphragm pacing, serial studies should be carried out for at least 6 weeks postinjury on initially responsive nerves, and for at least 2 years postinjury on nonresponsive nerves or those with a changing functional pattern.

The purpose of this study was to determine the effect of a high repetitive exercise program, treadmill running, on the tetanic tension and rate of tension development of the slow twitch soleus muscle of normal plus dystrophic mice and their littermates. The exercise program used would be considered to be of mild intensity since it failed to produce any detectable histochemical or biochemical changes. In the noninvolved normal and littermate mice, there was no difference in maximum tetanic tension between the exercised and nonexercised control groups. In the normal mice (eight weeks of age), there was a significant decrease in rate of tension development for those exercised for five weeks compared to nonexercised controls. In littermate mice (seven weeks old) exercised for a four-week period, there was also a significantly lower rate of tension development compared to their nonexercised controls. In dystrophic mice (seven weeks old) exercised for only one to two weeks, there was significantly lower tension as well as rate of tension developed for the exercised mice when compared to nonexercised dystrophic mice. In dystrophic mice (six weeks old) exercised for one to two weeks, there was no difference in tension or rate of tension development when compared to nonexercised controls. In both six and seven-week-old littermate mice, also exercised for one to two weeks, this reduction in tension and rate of tension development did not occur. The average life span for the dystrophic mice used in this study is about 30 weeks. Of the nine exercised dystrophic mice scheduled for study at eight weeks, only one survived, suggesting that even the mild exercise used might have shortened their life expectancy.

A syndrome of severe upper extremity pain, swelling and weakness following intraarterial injection of illicit secobarbital was evaluated in 4 patients. Although the involved muscle mass was small, serum muscle enzymes were markedly elevated. Electromyography (emg) revealed fibrillation and positive sharp wave potentials at 7 days. Motor unit action potentials were of low amplitude and of brief duration but markedly reduced in numbers, a mixture of myopathic and neuropathic changes. Motor nerve conduction velocities and latencies were normal, but M-wave amplitudes were small. Serial studies in 1 patient revealed persistent fibrillation and positive sharp waves in all involved muscles with absent voluntary contraction in the ulnar muscles and no response to stimulation of the ulnar nerve at 60 days postinjection. The emg and conduction studies for the median nerve distribution were normal except for the abnormal rest activity. A muscle biopsy (on day 66) in this patient revealed findings compatible with neuropathy, myopathy and vasculitis. The results indicate that electrodiagnostic studies may be of value for prognosis in these cases by evaluating the extent of neuromyopathic involvement.

Three cases of lower extremity reflex sympathetic dystrophy (RSD) responded dramatically to a daily low dose ultrasound (0.5 watts/cm2 X 5 minutes) therapy to the tarsal tunnel and plantar nerve distribution, and the use of a shoe insert. Two of the three cases had been refractory to more standard therapy for RSD, including pharmacologic agents. All three patients preferred a conservative approach to surgical sympathectomy. No complications were observed, and all three cases are now symptom free. Daily ultrasound treatments are time-consuming and costly but are safe and may be useful for patients who refuse surgical sympathectomy. We hypothesize that ultrasound may have affected peripheral sympathetic nerve fibers. However, more indirect effects of ultrasound, such as increased blood flow to the limb, may be part of the action mechanism as well.