Action of antibiotics on respiratory tract. IV. Tetracyclines and 4-epiderivatives.
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Five genetically confirmed spinocerebellar ataxia type 2 (SCA2) patients were admitted to our sleep laboratory for two all-night video-polysomnographies. A standard montage was used, including electroencephalography, vertical and horizontal electrooculography, electromyography of mental, submental, and tibialis anterior muscles, and respiratory monitoring. Four of five SCA2 patients had insufficient muscle atonia during rapid eye movement (REM) sleep. All patients exhibited myoclonic jerks during REM sleep, while elaborated behavior was not observed in the video. Abnormal motor control during sleep with periodic leg movements and REM sleep without atonia occurs frequently in SCA2. This finding may reflect a dysfunction of dopaminergic and/or brainstem and cerebellar outflow pathways.
Weakness and failure of voluntary activation of the quadriceps femoris muscles often occur after anterior cruciate ligament (ACL) rupture. Side-to-side strength comparisons are used as a measure of progress, and are inaccurate if the quadriceps has activation failure. Burst superimposition testing is commonly used to assess quadriceps strength and activation during a maximal volitional isometric contraction (MVIC), using the central activation ratio (CAR) calculation. A recently developed mathematical model predicts the MVIC from submaximal efforts. The purpose of this study was to compare the CAR calculation to the mathematical model. We hypothesized that the model would be a more accurate predictor of strength than the CAR calculation when voluntary activation failure is present. Data from the involved and uninvolved quadriceps muscles of 100 consecutive subjects with complete, isolated ACL rupture were retrospectively evaluated. Subjects who required multiple trials to produce an MVIC with full activation (true MVIC) were used to compare the CAR calculation, the mathematical model, and this true MVIC. Subjects unable to produce a true MVIC with multiple trials were used to compare the mathematical model to the CAR calculation. Results demonstrate that both methods reliably and accurately estimate the quadriceps weakness associated with ACL rupture. We recommend use of the CAR calculation to provide estimations of true quadriceps strength to facilitate clinical decisions about progress in rehabilitation after ACL rupture.
Experimental procedures are described that were designed to assess central motor disorders quantitatively. Initially delineated is a study of triggered ballistic movement performed in a reaction-time situation. The reciprocal triphasic EMG pattern recorded in an antagonistic muscle pair was clearly abnormal in Parkinsonian patients; increased duration, diminished synchronization of motor units, and a tendency for coactivation of agonist and antagonist muscles and for action tremor were observed. Transport time of elbow movement was prolonged, particularly in a choice reaction-time situation. Rapid, passive displacements of the forearm combined with excitability measurements of hindlimb motoneurons in monkeys revealed the existence of a transcortical loop that may contribute to increased muscle tone in Parkinsonian patients.
The specific locus of impairment in excitation-contraction coupling that is associated with skeletal muscle fatigue has not been identified. In the present study the phenomena of staircase and fatigue were studied in the rat gastrocnemius muscle in situ, and the effect of caffeine (50 mg kg-1) given prior to or during 5 minutes of stimulation was observed. A 10 Hz indirect stimulation resulted in a staircase response that proceeded for 10.4 +/- 1.6 (mean +/- SD) seconds, reaching a peak force value that was 70-75% higher than the initial contraction. After 5 minutes of stimulation and 20 minutes of rest, the staircase response was longer (17 +/- 3.1 seconds) and proceeded more slowly when the stimulation regimen was repeated. Caffeine accelerated the fatigue and reversed the effect of fatigue on the staircase response. Since caffeine enhances the release of Ca2+ from terminal cisternae, it is postulated that the accelerated fatigue in the presence of caffeine is indicative of a reduced availability of Ca2+ for release. This hypothesis would also explain the slower progression of staircase in the fatigued muscle.
The forward pulling tension exerted by individual mice was measured nearly isometrically in a simple apparatus designed to determine whole body tension (WBT). WBT determinations on control (C57Bl10/SnJ) and experimental (C57Bl10-mdx) mice indicate a muscle weakness which lasts throughout the lifespan of mdx mice. Direct muscle stimulation experiments in vivo also showed significant decreases in peak twitch and tetanic tensions in adult mdx muscle with no obvious alterations in twitch time course or in twitch: tetanus ratios. We suggest that the noninvasive WBT procedure may be used to partially assess various therapies on this murine model of Duchenne muscular dystrophy.
A model of the mechanics of smooth muscle reservoirs was derived from the stress-strain relation in smooth muscle strips. The model was applied to the intestinal bladder reservoir but may also be applied to natural reservoirs such as the bladder. The relation between reservoir volume and pressure was calculated at different values of smooth muscle tone and was found to accord with clinical results. The muscle tone of the bowel when measuring off the bowel to construct the reservoir was found to have a profound influence on its ultimate volume. Stiffening of a part of the reservoir wall as a result of edema or fibrosis will cause a substantial decrease in functional capacity, both directly as a result of a reduced expansion of the diseased part and indirectly by enhancing the stretching of the adjacent normal wall. The pressure rise produced by a slow peristaltic contraction was calculated to depend both upon the strength of contraction and on the degree of reservoir filling: Almost no pressure rise will occur in the near empty reservoir, while the highest pressure rise was calculated to occur at a volume of about 300 ml. If only a part of the reservoir contracts, more filling is needed before the pressure increases and the maximum pressure will be reached at a substantially higher volume. Localized contractions will stretch the resting reservoir wall and so activate stretch receptors, which may cause a desire to void, resulting in reduced functional capacity.
AIMS: Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role of urothelium and eicosanoid-release in ischemic bladder smooth muscle instability. MATERIALS AND METHODS: Male New Zealand white rabbits were divided into treated (n = 12) and age-matched control (n = 10) groups. The treated group underwent balloon endothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium was removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs). RESULTS: A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro-) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro- tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF(2-alpha) and thromboxane A(2) release from the ischemic suburothelial tissue. Ischemia increased the release of LTB(4), LTC(4), and LTE(4) from both urothelium and suburothelial tissue. CONCLUSIONS: Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder.
AIMS: The objectives of this study were (1) to identify differences between men with chronic pelvic pain syndrome (CPPS), compared with pain-free men, in surface electromyography/biofeedback (sEMG/BFB) readings of pelvic floor muscles and (2) to determine which pelvic floor muscle sEMG readings may have differential diagnostic and treatment selection value by accurately predicting group membership, CPPS versus normal. METHODS: Twenty-one men with CPPS and 21 healthy men without pelvic pain underwent a standardized sEMG examination by a licensed physical therapist. RESULTS: On group difference measures men with CPPS showed significantly greater sEMG instability in preliminary resting baseline. Three sEMG measures reliably categorized CPPS versus normals with CPPS showing greater preliminary resting baseline hypertonicity and instability with lowered voluntary endurance contraction amplitude. CONCLUSIONS: CPPS patients manifest pelvic floor muscle instability compared to normals. Prebaseline resting hypertonicity and instability along with endurance contraction weakness reliably predicts subject membership in the CPPS vs. normal group. Pelvic floor muscle sEMG may be a valuable screening tool to identify patients with CPPS who may benefit from therapies aimed at correcting pelvic floor muscle dysfunction.
Sustained steady contractural or catchlike tension (CT) occurs in the metathoracic extensor tibiae muscle of the primitive insect the weta (Orthoptera: Stenopelmatidae) during its characteristic leg-extension defense behavior or following leg-position conditioning. Similar action occurs occasionally in semi-intact preparations and is abruptly turned off by a single peripheral inhibitory impulse. These phenomena were reproduced routinely by first infusing saline containing 10(-8) M (or stronger) octopamine into the muscle for 12 min, and then stimulating the slow excitatory motor neuron SETi with a brief burst. Direct stimulation of the dorsal unpaired median neuron, innervating the extensor tibiae (DUMETi) prior to SETi stimulation, also led to CT. Both octopamine and DUMETi markedly enhanced the tension developed in response to a burst of impulses in SETi.
The patterns of myographic activity in the flexor and extensor tibiae muscles of the locust which accompany learned tibial extension were examined. Three distinct motor strategies were identified: (1) repeated flexion-extension movements, each of which resulted in a momentary excursion beyond the required, pre-set joint angle (demand angle) and in sum met the criterion for learning; (2) changes in basic muscle tonus, which resulted in maintained shifts in tibial position without discernible myographic activity; (3) tonic activity in the single slow excitatory motoneuron of the extensor tibiae ( SETi ) which produced maintained tibial extension. These strategies were selectively employed depending on the particular range of joint angle required. These strategies were compared and their effectiveness evaluated using a variety of behavioral criteria. Neuronal mechanisms which might underlie each of these strategies are discussed.
Muscle biopsies were obtained from three infants under the age of 12 mth, each of whom was diagnosed as having Pompe's disease. The biopsies revealed a severe vacuolar myopathy with accumulation of large amounts of PAS positive material within the muscle fibres, changes similar to those in adult cases of the disease. In addition large amounts of metachromatic material were found within the muscle fibres in all three cases and in two of them scattered, rather sparse perivascular lymphocytic infiltrates were seen in the interstitial tissue. Review of material previously obtained from two adult cases showed no accumulation of metachromatic material in the older case and only moderate amounts in the younger. However, dense interstitial lymphocytic infiltrates were seen in the former, some concentrated around small vessels. These observations suggest that the pathogenesis of the muscle disorder in acid maltase deficiency may not depend on abnormal glycogen storage only.
We obtained maximal partial expiratory flow-volume (PEFV) curves using the rapid compression technique in three infants with intrathoracic tracheomalacia. Maximum flows were quantitated at functional residual capacity (VmaxFRC). Studies were performed at baseline, after inhalation of methacholine (MCh) and after inhalation of albuterol. At baseline, all three patients had significantly lower than normal VmaxFRC values, and two patients displayed expiratory flow limitation during tidal breathing. VmaxFRC improved significantly after MCh administration, but fell back toward or below baseline after albuterol. Additionally, the ratio of forced to tidal flows at mid-tidal volume (Vmid(forced/tidal), a reflection of expiratory flow reserve, increased after MCh administration and decreased after albuterol. Two patients also received oral bethanechol: 2.9 mg/M2, q 8 hr for 10 days, after which PEFV curves were repeated. Both Vmax FRC and Vmid(forced/tidal) were increased over baseline after bethanechol administration, but decreased after albuterol. These results suggest that in patients with abnormally collapsible tracheae, stimulation of tracheal smooth muscle can improve airway stability, thereby increasing forced expiratory flows. Additionally, relaxation of airway smooth muscle by bronchodilators can have the opposite effect and exacerbate obstruction.
BACKGROUND: Nitric oxide (NO) plays the key role in the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation of prostate. We tried to determine whether nitrinergic innervation of the prostate is reduced with aging, and whether a reduction of this innervation alters the relaxant properties of prostatic tissue. METHODS: The prostate isolated from young rabbits at the age of 3 months and aged rabbits at the age of 24 months was used. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of prostate. Nitrinergic nerves were identified histochemically by the presence of NADPH diaphorase reactivity. RESULTS: The prostate weighed 0.34 +/- 0.06 g in the young and 0.78 +/- 0.13 g in the aged (P < 0.01). Electrical stimulation caused frequency-dependent relaxation that was inhibited by N-nitro-L-arginine and increased by L-arginine. Maximum relaxant rates of noradrenaline-induced tone were 41.3 +/- 1.8% and 22.7 +/- 0.6% in the young and the aged (P < 0.01), respectively. Exogenous NO caused concentration-dependent relaxation of the prostate. Both relaxation induced by electrical stimulation and exogenous NO were inhibited by LY83583 (a guanylate cyclase inhibitor). In all specimens, NADPH diaphorase activity was observed in the smooth muscle layer of the prostatic stroma and capsule. However, NADPH diaphorase positive nerves were significantly less in the aged than in the young (P < 0.01). CONCLUSIONS: As a result of these findings, it is suggested that both NO-mediated relaxation and nitrinergic innervation are reduced with aging in this animal model.
We tested the hypothesis that adrenomedullin (ADM), a recently isolated hypotensive peptide, is an autocrine transmitter in renal arterial smooth muscle cells (RASMCs). Fura-2 fluorometry revealed that ADM decreases both the cytosolic Ca2+ concentration ([Ca2+]i) and tension induced by 0.3 microM phenylephrine (PE) in porcine RASMCs. The expression of ADM mRNA in RASMCs was assessed by the reverse transcription polymerase chain reaction (RT-PCR), using the total RNA from the RASMCs and the specific primers for the porcine ADM mRNA. A band with an expected size could be detected only when the reverse transcriptase was added, thus indicating that the porcine RASMCs express ADM mRNA. These results therefore suggested that ADM plays an important role in the regulation of the renal vascular tone, not only as a circulating hormone, but also as an autocrine transmitter.
Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10 microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P < 0.001). At these concentrations, PD98059 also significantly reduced the vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These results demonstrate that pressure-induced myogenic tone is inhibited by PD98059 at the concentrations that have been reported to be selective for inhibition of MEK and the MAP kinase cascade. However, our results also demonstrate that PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular smooth muscle.
Although the brain enables us to perceive the external world and our body, it remains unknown whether brain processes themselves can be perceived. Brain tissue does not have receptors for its own activity. However, the ability of humans to acquire self-control of brain processes indicates that the perception of these processes may also be achieved by learning. In this study patients learned to control low-frequency components of their EEG: the so-called slow cortical potentials (SCPs). In particular "probe" sessions, the patients estimated the quality of the SCP shift they had produced in the preceding trial. The correspondence between the recorded SCP amplitudes and the subjective estimates increased with training. The ability to perceive the SCPs was related to the ability to control them; this perception was not mediated by peripheral variables such as changes in muscle tonus and cannot be reduced to simple vigilance monitoring. These data provide evidence that humans can learn to perceive the neural activity of their brain. Alternative interpretations are discussed.