The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial.

Essentials Perioperative blood loss and inflammatory response can significantly affect recovery after surgery. We studied the effects of multiple-dose oral tranexamic acid on blood loss and inflammatory response. A postoperative four-dose regimen brought about maximum reduction in postoperative blood loss. A postoperative four-dose regimen reduced inflammatory response and promoted early rehabilitation. SUMMARY: Background Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined. Objectives To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response. Patients/Methods Two hundred and seventy-five patients were randomized to receive a placebo (group A), a single 2-g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications. Results Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple-dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified. Conclusion The four-dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.

Effect of skeletal muscle fibers on porcine meat quality at different stages of growth.

In this study, we examined changes in meat quality and content of muscle types during porcine growth. The influence of the longissimus dorsi muscle fiber composition on meat quality and the correlation between 2 fiber-typing methods (histochemistry and real-time quantitative polymerase chain reaction) were examined. Type IIx and type IIb fibers accounted for most of the total number of fibers; the proportion of these fibers increased during porcine growth (75.42, 80.09, and 79.88%, respectively, at 3 different stages of growth). There was a strong positive correlation between the 2 fiber-typing methods; the correlation coefficients of type I, IIa, and IIx+IIb fiber contents were 0.65, 0.88, and 0.92, respectively. The a* value of meat color was significantly lower at 98 days and negatively correlated with white fiber content (r = -0.69, P < 0.01). Water-holding capacity decreased during porcine growth. The drip loss parameter was positively correlated with type IIx+IIb fiber content (r = 0.55, P < 0.05). Decreased pH was strongly positively correlated with type IIx+IIb fiber content (r = 0.61, P < 0.01) and negatively correlated with type IIa fiber content (r = -0.44, P < 0.05). Therefore, we found that the composition of muscle fibers influenced the establishment of meat quality and its alteration during the early postmortem period.

Transcranial magnetic stimulation in ALS: utility of central motor conduction tests.

OBJECTIVE: To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS). METHODS: We prospectively studied 60 patients with ALS subtypes (sporadic ALS, familial ALS, progressive muscular atrophy, and primary lateral sclerosis) using single pulse TMS, recording from abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We evaluated three measures: 1) TMS motor response threshold to the ADM, 2) central motor conduction time (CMCT), and 3) motor evoked potential amplitude (correcting for peripheral changes). Patients were evaluated at baseline, compared with controls, and followed every 3 months for up to six visits. Changes were analyzed using generalized estimation equations to test linear trends with time. RESULTS: TMS threshold, CMCT, and TMS amplitude correlated (p < 0.05) with clinical upper motor neuron (UMN) signs at baseline and were different (p < 0.05) from normal controls in at least one response. Seventy-eight percent of patients with UMN (41/52) and 50% (4/8) of patients without clinical UMN signs had prolonged CMCT. All three measures revealed significant deterioration over time: TMS amplitude showed the greatest change, decreasing 8% per month; threshold increased 1.8% per month; and CMCT increased by 0.9% per month. CONCLUSIONS: Transcranial magnetic stimulation (TMS) findings, particularly TMS amplitude, can objectively discriminate corticospinal tract involvement in amyotrophic lateral sclerosis (ALS) from controls and assess the progression of ALS. While central motor conduction time and response threshold worsen by less than 2% per month, TMS amplitude decrease averages 8% per month, and may be a useful objective marker of disease progression.

High doses of botulinum toxin effectively treat disabling up-going toe.

Involuntary up-going toe can be a disabling consequence of dystonia or spasticity. In this study, we treated eight patients with botulinum toxin (BTx) in the extensor hallucis longus (EHL) and applied objective and subjective outcome measures to determine treatment efficacy. Using 100% higher doses than generally reported, patients noted 62+/-20% mean benefit and scores on a modified Fahn-Marsden Dystonia Scale decreased significantly by 1.8+/-0.6 (p=0.010). High doses (up to 160 BTx A units) into the EHL were safe and dosage correlated highly and significantly with treatment efficacy (rho=0.859, p=0.006).

Kinematic analysis of motor dysfunction in Niemann-Pick type C.

OBJECTIVE: To provide the first descriptive analysis of upper limb motor physiology in Niemann-Pick Type C disease (NP-C). METHODS: Fifteen patients with confirmed NP-C underwent motor physiology testing using accelerometry and surface EMG (sEMG). Tremor amplitude and frequency were quantified using accelerometry, and sEMG was examined for abnormal patterns consistent with various movement disorders. RESULTS: Forty-seven percent of patients had postural tremor in the upper limbs, generally bilateral, with frequencies ranging from 0.3 to 3 Hz, and an average amplitude of 1.20+/-0.98 mm. Eighty-seven percent of patients had bilateral action tremor with frequencies ranging from 2.0 to 3.7 Hz, and an average amplitude of 5.25+/-3.76 mm. sEMG revealed long but variable duration, variable amplitude muscle burst discharges during action in some patients, as well as short high frequency irregularly timed bursts in others. CONCLUSIONS: Accelerometric findings correlated with the clinical findings were most consistent with cerebellar outflow tremors. sEMG revealed a mix of dystonic, myoclonic and choreiform movements. SIGNIFICANCE: These quantitative methods may serve as ancillary measures of disease pathophysiology, markers of change over time, and methods to evaluate efficacy, and side effects, of new treatments as they are developed.

Respiration and medullary blood flow during sinusoidal hypoxia in the peripherally chemodenervated cat.

The hypothesis that hypoxic respiratory depression is mediated by changes in medullary blood flow (MBF) was assessed in 18 anesthetized, paralyzed, vagotomized, peripherally chemodenervated, ventilated cats exposed to sinusoidal hypoxic hypoxia. In nine cats, the dynamic response of the central respiratory controller to hypoxia was studied by varying the cycle time of sinusoidal hypoxia (cycle time = 2.5, 4, 6, 10, and 15 min). Peak phrenic neurogram amplitude (PNA) followed sinusoidal oscillations in the hypoxic input [arterial O2 saturation (SaO2)] at all cycle times. The relationship between PNA and SaO2 was expressed as the transfer function of the system and was approximated as a first-order differential equation with a time constant of 78 +/- 1 s, a value consistent with a previous measurement of the time constant of the change in respiration following a change in brain blood flow. In a separate study, MBF was continuously measured during sinusoidal hypoxia (cycle time = 6 min; n = 9) with a laser-Doppler flow probe to directly assess the role of MBF in production of hypoxic respiratory depression. PNA and MBF followed SaO2 oscillations during sinusoidal hypoxia. Infusion of sodium nitroprusside (20 micrograms.kg-1.min-1 iv) increased MBF by 30-40% and abolished MBF oscillations during subsequent sinusoidal hypoxia but had no effect on PNA oscillations. We conclude that the increase in brain blood flow seen during sinusoidal hypoxia is not the primary cause of the accompanying central hypoxic respiratory depression.

Respiratory and sympathetic activity during recovery from hypoxic depression and gasping in cats.

In peripherally chemodenervated, vagotomized, chloralose-anesthetized cats, hypoxia can produce central cardiorespiratory depression or excitation depending on severity. We monitored phrenic and cervical sympathetic neurograms during either hypoxic depression or gasping and 30 min of subsequent isocapnic reoxygenation to determine whether the response of these outputs during hypoxia predicts their activity during recovery. Three levels of hypoxic response were produced in cats: 1) reduction of phrenic neurogram amplitude (PNA) by 30% [fractional inspired O2 (FIO2) = 14-18%)]; 2) production of phrenic apnea (FIO2 = 9-10%); and 3) hypoxic gasping (FIO2 = 6-8%). Recovery from the milder levels of hypoxia was characterized by transient (< 10 min) depression of PNA and inspiratory synchronous sympathetic activity. Respiratory frequency was unaffected or only transiently depressed. Tonic sympathetic activity was unaffected. During reoxygenation after gasping, both PNA and inspiratory synchronous sympathetic activity were initially increased by 80% over control levels and respiratory frequency was depressed. Tonic sympathetic activity increased during hypoxia but returned to control levels after a brief undershoot on reoxygenation. All variables returned to control levels within 15 min. Measurement of medullary extracellular K+ concentration ([K+]e) in a separate group of cats indicated that a significant increase in this variable was associated with hypoxic gasping but was not correlated with PNA augmentation during reoxygenation. We hypothesize that increased [K+]e coincident with gasping may trigger a postanoxic potentiation of respiratory premotor neurons similar to that described in hippocampus.

Modulation of respiratory responses to carotid sinus nerve stimulation by brain hypoxia.

This study examines the effect of progressive isocapnic CO hypoxemia on respiratory afterdischarge and the phrenic neurogram response to supramaximal carotid sinus nerve (CSN) stimulation. Twelve anesthetized, vagotomized, peripherally chemodenervated, ventilated cats with blood pressure controlled were studied. During isocapnic hypoxemia, the amplitude of the phrenic neurogram was progressively depressed. In contrast, the increase in peak phrenic amplitude produced by CSN stimulation was unchanged, suggesting that the central respiratory response to CSN stimulation is unaffected by progressive hypoxemia. The time constant of respiratory afterdischarge (tau) was calculated from best-fit plots of phrenic amplitude vs. time after cessation of CSN stimulation. Under control conditions the value of tau was 57.7 +/- 3 (SE) s (n = 12). During progressive isocapnic hypoxemia, tau decreased as a linear function of arterial O2 content (CaO2) such that a 40% reduction of CaO2 resulted in a 48% reduction in tau. This reduction of respiratory afterdischarge may contribute to the genesis of periodic breathing during hypoxia.