The role of teriparatide in the management of fracture non-union: A systematic review of case reports

@#Teriparatide has been known to aid in the treatment of osteoporosis but its use in the management of fracture disorders is poorly documented. This review aims to show that teriparatide administration may improve the healing process in fractures that fail to unite after sustaining trauma. A total of 22 reported cases have been identifi ed from 2009 to 2017. Teriparatide doses were given in a median duration of 5.6 months with a median time to complete union of 8.5 months. This review systematically summarizes all clinical case reports of non-union treated with teriparatide for us to gain insight into its off-label use.

Diverse migration strategy between freshwater and seawater habitats in the freshwater eel genus Anguilla.

The freshwater eels of the genus Anguilla, which are catadromous, migrate between freshwater growth habitats and offshore spawning areas. A number of recent studies, however, found examples of the temperate species Anguilla anguilla, Anguilla rostrata, Anguilla japonica, Anguilla australis and Anguilla dieffenbachii that have never migrated into fresh water, spending their entire life history in the ocean. Furthermore, those studies found an intermediate type between marine and freshwater residents, which appear to frequently move between different environments during their growth phase. The discovery of marine and brackish-water residents Anguilla spp. suggests that they do not all have to be catadromous, and it calls into question the generalized classification of diadromous fishes. There has been little available information, however, concerning migration in tropical Anguilla spp. Anguilla marmorata, shows three fluctuation patterns: (1) continuous residence in fresh water, (2) continuous residence in brackish water and (3) residence in fresh water after recruitment, while returning to brackish water. Such migratory patterns were found in other tropical species, Anguilla bicolor bicolor and Anguilla bicolor pacifica. In A. b. bicolor collected in a coastal lagoon of Indonesia, two further patterns of habitat use were found: (1) constantly living in either brackish water or sea water with no freshwater life and (2) habitat shift from fresh water to brackish water or sea water. The wide range of environmental habitat use indicates that migratory behaviour of tropical Anguilla spp. is facultative among fresh, brackish and marine waters during their growth phases after recruitment to the coastal areas. Further, the migratory behaviours of tropical Anguilla spp. appear to differ in each habitat in response to inter and intra-specific competition. The results suggest that tropical Anguilla spp. have a flexible pattern of migration, with an ability to adapt to various habitats and salinities. The ability of anguillids to reside in environments of various salinities would be a common feature between tropical and temperate species without a latitudinal cline. Thus, the migration of Anguilla spp. into fresh water is clearly not an obligatory behaviour. This evidence of geographical variability among Anguilla spp. suggests that habitat use is determined by environmental conditions in each site.

Notes on the occurrence of the tropical eel Anguilla bicolor bicolor in Peninsular Malaysia, Malaysia.

Previous studies indicated that a tropical freshwater eel Anguilla bicolor bicolor occurs in Africa, India, Sri Lanka, Bangladesh, Myanmar, Indonesia and Australia, but an intensive survey has indicated an extended distribution range for the species into Peninsular Malaysia. Thus, A. b. bicolor is a native subspecies of Malaysia.

Changes of reflex size in upper limbs using wrist splint in hemiplegic patients.

We evaluated the effect of prolonged wrist extension on H reflex in the flexor carpi radialis (FCR) muscle and tendon jerk (T) reflex in the biceps brachii (BB) muscle of 17 chronic hemiplegic patients. H reflex of the FCR and T reflex of the BB were assessed every 5 minutes within 20 minutes during prolonged wrist extension and post-20 minutes after the extension. As a result, H reflex in the FCR was reduced by passive wrist stretch in 82% of the spastic limbs. The effect was larger in the higher spastic group. In 45% of the spastic limbs, T reflex in the BB also was reduced by passive wrist stretch. The inhibitory effects had a tendency to strengthen in accordance with the grade of muscle tone. We considered from these results, prolonged wrist extension generated inhibitory projections via probably group II afferents of the FCR in the homonym and in the transjoint in spastic limbs.

Cortical neuromagnetic activity associated with cutaneomuscular reflex.

Cortical activity related to the late component of the cutanomuscular reflex was studied by measuring somatosensory evoked magnetic fields (SEFs) during isometric contraction of the reflex-induced muscle. After electrical stimulation to the index finger with intensity of three times of the perception threshold, three peaks of the cortical activity were detected within the somato-sensory area contralaterally to the stimulation site. Three dimentional location and the amplitude of the equivalent current dipoles for each peak were compared to that of observed SEF without muscle contraction. Significantly increased third component of SEFs (the latency of about 50 ms) always preceeded ca 20 ms against the peak of the late component of the cutaneomusucular reflex observed in the first dorsal interosseous (1DI) muscle. The conduction delay from the primary somatomotor cortex to the 1DI was determined as also ca 20 ms according to the result of the transcranial magnetic stimulation. We conclude from these evidences that all or part of the ingredient of the third component of SEFs may contribute to inducement of the late excitatory component of the cutaneomuscular reflex.

Motor strategies for initiating downward-oriented movements during standing in adults.

Sitting down and squatting are routine activities in daily living that lower the body mass by flexing the trunk and legs, but they obviously require different motor strategies for each goal posture. The former action must transfer the supporting surface onto a seat, whereas the latter must maintain the center of mass within the same base of both feet. By comparing the performance of both maneuvers, the mechanisms involved in initiating the downward-oriented movements and the process of optimizing the performance during their repetitions were studied. Twelve healthy subjects were asked to perform sitting-down and squatting actions immediately when a light cue was given, but at a natural speed. Electromyograms, angular movements of the joints of the right leg, and center of pressure (COP) displacement were recorded before and during each task. The initial mechanisms to initiate the break from the upright posture and the changes of postural adjustments during repetitive movements were analyzed separately. The sitting-down movement was achieved by a stereotyped motor strategy characterized by a gastrocnemius muscle burst coupled with deactivation of the erector spinae muscle. The former produced a transient COP displacement in the forward direction, and simultaneous unlocking of the trunk prevented a fall backward. By contrast, because of the absence of any need to produce momentum in a given direction, a variety of motor strategies were available to initiate squatting. The direction of initial COP displacement to initiate squatting varied with the muscles involved in unlocking the upright posture. During repetition of sitting down, the average COP position of the initial standing posture in the preparatory period was immediately shifted forward after the second trial. Simultaneously, the erector spinae muscle was deactivated earlier in the later trials. These resulted in a decreased momentum in the backward direction while the subjects were transferring themselves onto the seat. In the squatting task, however, these changes could not be identified, except for a slight flexed position of the knee during standing in the first trial. These findings suggest that in the case of transferring the body-mass to another supporting base the central nervous system immediately adjusts the size of the initial impetus to optimize the performance.

Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis.

BACKGROUND: Human beta-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of beta-defensins in cystic fibrosis, suggesting that beta-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. METHODS: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. RESULTS: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1beta. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. CONCLUSIONS: These results indicate that beta-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.

Synaptic connections from large muscle afferents to motoneurones in human lower limbs.

OBJECTIVES: Our study was undertaken to investigate reciprocal inhibition in humans both from ankle flexors to extensors and from ankle extensors to flexors. METHODS: Changes in the firing probability of single motor units in response to electrical stimulation of muscle nerves (the peristimulus time histogram technique) were used to derive the reciprocal projections of muscle spindle Ia afferents to the motoneurones of ankle muscles. Discharges of units in ankle flexors (the tibialis anterior muscle [TA]) and extensors (soleus [SOL] and medial gastrocnemius [MG] muscles) were investigated respectively after stimulation of the posterior tibial (PTN) and common peroneal (CPN) nerves (predominantly on the deep branch). In eight normal subjects aged 24 to 40 years, one motor unit per each muscle was studied. RESULTS: CPN stimulation produced reciprocal Ia inhibition in the SOL of 5 of 7 of them and in the MG of 3 of 5, whereas PTN stimulation produced reciprocal Ia inhibition in the TA of only 2 of 6 subjects. CONCLUSIONS: These findings suggest that at low level contraction reciprocal Ia inhibition from ankle flexors to extensors may be stronger than that from ankle extensors to flexors.

A new method of superficial peroneal nerve conduction studies.

Herein, we report a new method for obtaining sensory nerve conduction velocities (SCVs) in the distal segment of the superficial peroneal nerve (SPN). Twenty lower extremities from 10 normal subjects (mean age: 33.4 years) were evaluated. The recording electrodes were placed on the dorsal surfaces of the ankle and foot. We stimulated the SPNs on the anterior edge of subjects' fibulas, and evoked sensory nerve action potentials (SNAPs) antidromically. SCVs were calculated based upon the distances and the latencies. The mean SCV was 41.3 +/- 4.3 m/s in the distal segment, which was slower than in the proximal segment (51.7 +/- 3.9 m/s). We were able to stimulate only the SPN with certainty. In conclusion, the described technique should be of clinical value in diagnosing peripheral neuropathy.

The effect of transcranial magnetic stimulation on reciprocal inhibition in the human leg.

The effect of magnetic stimulation on reciprocal Ia inhibition of the human leg was investigated. Stimulation of the common peroneal nerve at the fibula head at the threshold of the alpha motoneuron axons resulted in inhibition of the soleus (SOL) H reflex at a conditioning-test interval of 2 ms. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the SOL H reflex, including a short latency facilitation followed by inhibition. This inhibition may have been conveyed by Ia inhibitory interneurons projecting to SOL motoneurons. To test for convergence, whether or not the magnetic stimulation was capable of facilitating disynaptic reciprocal Ia inhibition of the SOL H reflex induced by stimulation of the peroneal nerve, the two stimuli were given together or separately. We observed the inhibition significantly increased when the two stimuli were given together than separately. These results suggest that the Ia inhibitory interneurons projecting to SOL motoneurons in humans might receive convergent input from the motor area of the brain and from Ia afferents of the tibialis anterior (TA) muscle in humans as well as in other animals.

Synchronization of single motor units during voluntary contractions in the upper and lower extremities.

OBJECTIVE: To investigate motor unit synchronization in the time and frequency domains and compare the amount and nature of this synchronization between upper and lower extremity muscles in human subjects. METHODS: A total of 120 motor unit pairs from biceps brachii (BB), first dorsal interosseous (1DI), vastus medialis (VM), and tibialis anterior (TA) on the dominant side were analyzed and compared. Pairs of motor unit spike trains were recorded from two concentric needle electrodes inserted within these muscles in healthy volunteers. Subjects were instructed to maintain a weak isometric contraction of these muscles so that an individual motor unit recorded from each concentric needle discharged at a steady rate of approximately 10 impulses/s. Pairs of motor unit spike trains were cross-correlated in the time domain, and coherence analysis in the frequency domain was performed on the same spike train data. RESULTS: Synchronization was seen in all the muscles studied. Strength of motor unit synchronization, expressed as synchronization index (SI), was greater in 1DI muscles compared to other muscles (P<0.01). Coherence analysis revealed significant association between motor unit firings in the 1--5 and 25--30 Hz frequency ranges in all the muscles studied. The incidence of 25--30 Hz coherence peaks were found to be greater for 1DI muscles compared to other muscles. CONCLUSION: The above results suggest a possible role for corticospinal projections in producing pre-synaptic inputs responsible for synchronization of motor unit firings and 25--30 Hz coherence peaks.

Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish.

Islet-2 is a LIM/homeodomain-type transcription factor of the Islet-1 family expressed in embryonic zebrafish. Two Islet-2 molecules bind to the LIM domain binding protein (Ldb) dimers. Overexpression of the LIM domains of Islet-2 or the LIM-interacting domain of Ldb proteins prevented binding of Islet-2 to Ldb proteins in vitro and caused similar in vivo defects in positioning, peripheral axonal outgrowth, and neurotransmitter expression by the Islet-2-positive primary sensory and motor neurons as the defects induced by injection of Islet-2-specific antisense morpholino oligonucleotide. These and other experiments, i.e., mosaic analysis, coexpression of full-length Islet-2, and overexpression of the chimeric LIM domains derived from two different Islet-1 family members, demonstrated that Islet-2 regulates neuronal differentiation by forming a complex with Ldb dimers and possibly with some other Islet-2-specific cofactors.

The relationships between trunk function and the findings of transcranial magnetic stimulation among patients with stroke.

In this study, we investigated the relationship between the motor evoked potentials obtained from trunk muscles and the clinical function of trunk muscle. Twenty patients with unilateral hemispheric stroke and 11 healthy adults were examined. The responses of the bilateral external oblique muscles and the erector spinae muscles to the magnetic stimulation of multiple sites over both cortical hemispheres were recorded. Trunk muscle performance was assessed using the Trunk Control Test and Stroke Impairment Assessment Set. In the stroke group, stimulation of the affected hemisphere resulted in a motor evoked potential in only one patient, while the other 19 stroke patients produced no response to stimulation of the affected hemisphere. Stimulation of the unaffected hemisphere evoked bilateral responses in 19 patients. Further, stimulation of the unaffected hemisphere in the stroke group produced larger motor evoked potentials in the ipsilateral muscles than the motor evoked potentials recorded in the ipsilateral muscles of the control group. The clinical assessment scores of trunk function (i.e. Trunk Control Test and trunk items of Stroke Impairment Assessment Set) were correlated with the amplitudes of the motor evoked potentials of the ipsilateral external oblique muscle that were evoked by stimulation of the unaffected hemisphere. Our results suggest that the recovery of trunk function after stroke is associated with an increase in ipsilateral motor evoked potentials in the external oblique muscle upon stimulation of the unaffected hemisphere, suggesting a role for compensatory activation of uncrossed pathways in recovery of trunk function.

[Characteristics of hemiplegic outpatients with stroke who try to remove their clothes unnecessarily].

We have observed that patients who suffer from hemiplegia after a cerebral stroke, tend to remove their clothes although it is not necessary to change them while they are in hospital. Not only does this activity make it difficult to manage the ward and carry out rehabilitation, but it also often becomes problematic for home care once the patient has been discharged from hospital. However, there have been no previous reports on this activity. In this study, we examined the characteristics pertaining to clothes removal in hemiplegic patients under home care. The subjects were chronic-stage, cerebral stroke hemiplegic patients hospitalized in the rehabilitation ward of this hospital since the first initial seizure. Once it was established that environmental factors, such as room temperature, were not the primary reason for the patients to try to remove their clothes, the patients were closely monitored and the circumstances under which they tried to remove their clothes (location, time and type of clothes removed) were recorded to examine the relationship among age, sex, side affected by paralysis, higher cortical function, motor paralysis and ADL. Thirty-five percent of the patients, mostly women, usually tried to remove their clothes and the tendency was for them to incompletely remove their tops without reason while they were confined to bed or sitting on the bed. This activity was also prevalent among patients with accompanying diminished intellectual function, left hemiplegia, and left unilateral spatial agnosia. The acquired level of ADL by FIM in the group in which this activity was observed was low, except regarding meals. Thus, it was inferred that in stroke hemiplegic patients being taken care of at home the removal of clothes was related to a diminished intellectual function or ADL, which suggested the importance of family guidance based on observations of the patient's behavior in the ward. Targeting a greater number of subjects, we would like to conduct further studies on home-care measures to deal with this activity.

Tonic and kinetic motor units revisited: does motor unit firing behavior differentiate motor units?

OBJECTIVE: We tried to differentiate motor unit into two distinct populations, tonic and kinetic, on the basis of the relationship between the mean inter-spike interval and its variability. METHODS: During voluntary isometric contraction myoelectric activity was recorded with a special quadrifilar electrode from first dorsal interosseous, biceps brachii, soleus, and tibialis anterior muscle. Motor unit action potentials (MUAP) were decomposed into individual MUAP trains, by electromyography (EMG) signal decomposition. The variability in the instantaneous firing rate was assessed at two or more levels of contraction in each muscle. RESULTS: We found each muscle tested had a homogeneous population. There were no tonic and kinetic motor units. But there were differences in the variability in the instantaneous firing rate in the 4 muscles tested. CONCLUSION: Motor unit firing behavior in a muscle may be fitted for its function.

Rise time or rise rate: which should be a criterion for analysing motor unit action potentials?

We measured the rise time (RT) and rise rate (RR) of motor unit action potentials (MUAPs) when sharp sounds are heard in concentric EMG in the first dorsal interosseus muscle (FDI) and biceps brachii muscle (BIC) of normal subjects. MUAPs from FDI muscle with an RT of less than 500 microseconds were 85%, and those of more than 500 microseconds were 15%. In contrast, MUAPs from BIC muscle with an RT of less than 500 microseconds were 65%, and those of more than 500 microseconds were 35%. Distributions of the RR for FDI and BIC were also determined. MUAPs from FDI muscle with an RR more than 0.3 mV/ms were 98.3%, and those of less than 0.3 mV/ms were 1.7%. In contrast, MUAPs from BIC muscle with an RR of more than 0.3 mV/ms were 93%, and those of less than 0.3 mV/ms were 7%. We conclude it is better to use RR than RT when accepting MUAPs in clinical EMG, because even when sharp sounds are heard, MUAPs do not always have an RT of less than 500 microseconds. The use of RT and the sharpness of MUAPS therefore need to be reconsidered, or RR should be used in clinical EMG by automatic program.

Motor unit sound in needle electromyography: assessing normal and neuropathic units.

Motor unit action potentials (MUPs) recorded by a monopolar needle electrode in normal and neuropathic muscles were computer-simulated. Five experienced electromyographers acted as examiners and assessed the firing sounds of these MUPs without seeing them on a display monitor. They judged whether the sounds were crisp or close enough to accept for the evaluation of MUP parameters and whether, when judged acceptable, they were neuropathic-polyphasic. The examiners recognized motor unit (MU) sound as crisp or polyphasic when the MUP obtained was 0.15-0.2 mm from the edge of the MU territory. When the intensity of the sound decreased, they were unable to perceive it as crisp. When the intensity exceeded the saturation level of loudspeaker output, the sound was perceived as polyphasic, but the wave form of the MUP was not. When the frequency of the neuropathic MUP was lowered, the examiners were unable to determine whether the MUP was polyphasic. MUPs recognized as acceptable for evaluation can be distinguished by listening to MU sounds. The audio amplifier gain must be appropriately adjusted for each MUP amplitude in order to assess whether an individual MU sound is crisp or polyphasic before MUP parameters are measured on a display monitor.

The stroke impairment assessment set: its internal consistency and predictive validity.

OBJECTIVE: To study the scale quality and predictive validity of the Stroke Impairment Assessment Set (SIAS) developed for stroke outcome research. DESIGN: Rasch analysis of the SIAS; stepwise multiple regression analysis to predict discharge functional independence measure (FIM) raw scores from demographic data, the SIAS scores, and the admission FIM scores; cross-validation of the prediction rule. SETTING: Tertiary rehabilitation center in Japan. PATIENTS: One hundred ninety stroke inpatients for the study of the scale quality and the predictive validity; a second sample of 116 stroke inpatients for the cross-validation study. MAIN OUTCOME MEASURES: Mean square fit statistics to study the degree of fit to the unidimensional model; logits to express item difficulties; discharge FIM scores for the study of predictive validity. RESULTS: The degree of misfit was acceptable except for the shoulder range of motion (ROM), pain, visuospatial function, and speech items; and the SIAS items could be arranged on a common unidimensional scale. The difficulty patterns were identical at admission and at discharge except for the deep tendon reflexes, ROM, and pain items. They were also similar for the right- and left-sided brain lesion groups except for the speech and visuospatial items. For the prediction of the discharge FIM scores, the independent variables selected were age, the SIAS total scores, and the admission FIM scores; and the adjusted R2 was .64 (p < .0001). Stability of the predictive equation was confirmed in the cross-validation sample (R2 = .68, p < .001). CONCLUSIONS: The unidimensionality of the SIAS was confirmed, and the SIAS total scores proved useful for stroke outcome prediction.

Clinical application of the modified medially-mounted motor-driven hip gear joint for paraplegics.

PURPOSE: This paper describes a motor-driven orthosis for paraplegics which has been developed. This orthosis is composed of a medially-mounted motor-driven hip joint and bilateral knee-ankle-foot orthosis. With the gear mechanism, the virtual axis of the hip joint of this orthosis is almost as high as the anatomical hip joint. METHOD: A paraplegic patient with an injury level of T10/11 walked using bilateral lofstrand crutches and this new orthosis with or without the motor system. The motor is initiated by pushing a button attached at the edge of the grab of the crutches. RESULT: Faster cadence and speed and smaller rotation angle of the trunk was obtained in motor walking compared with non-motor walking. The patient did not feel fearful of falling. CONCLUSION: The benefit of motor orthosis is that it can be used even in patients with lower motor lesions and that it provides stable regulation of hip flexion movement in spastic patients. In conclusion, this motor orthosis will enhance paraplegic walking.