Overview of spasticity management in multiple sclerosis. Evidence-based management strategies for spasticity treatment in multiple sclerosis.
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Algorithms↗
Biomedical subjects
J W Little
Publications and source records attributed to J W Little.
Spinal shock revisited: a four-phase model.
Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel four-phase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.
Animals↗
Crystal structure of LexA: a conformational switch for regulation of self-cleavage.
LexA repressor undergoes a self-cleavage reaction. In vivo, this reaction requires an activated form of RecA, but it occurs spontaneously in vitro at high pH. Accordingly, LexA must both allow self-cleavage and yet prevent this reaction in the absence of a stimulus. We have solved the crystal structures of several mutant forms of LexA. Strikingly, two distinct conformations are observed, one compatible with cleavage, and the other in which the cleavage site is approximately 20 A from the catalytic center. Our analysis provides insight into the structural and energetic features that modulate the interconversion between these two forms and hence the rate of the self-cleavage reaction. We suggest RecA activates the self-cleavage of LexA and related proteins through selective stabilization of the cleavable conformation.
Amino Acid Sequence↗
Refractory heterotopic ossification with complications.
BACKGROUND: Heterotopic ossification (HO) following spinal cord injury can lead to various complications, including venous thrombosis, autonomic dysreflexia, and pressure ulcers. We report refractory, complicated HO in a 19-year-old man with C8 incomplete tetraplegia. He first presented at 9 weeks postinjury with fever and swelling of his right leg. Ultrasound indicated a deep venous thrombosis (DVT). Persistent symptoms prompted triple-phase bone scan and magnetic resonance imaging (MRI), which revealed HO compressing the right external iliac vein and no evidence of DVT. The HO was complicated by hypercoagulability. CLINICAL COURSE: The HO was refractory to oral indomethacin and etidronate; therefore, intravenous etidronate was instituted, resulting in only a transient decrease in alkaline phosphatase. Local irradiation of the right hip did not decrease the activity of HO. The patient was discharged on oral etidronate, indomethacin, and warfarin. This complicated case raises issues regarding early diagnosis and aggressive treatment of HO, as well as treatment of associated hypercoagulability.
Constriction, Pathologic↗
Supplemental corticosteroids for dental patients with adrenal insufficiency: reconsideration of the problem.
BACKGROUND: Dental patients with primary or secondary adrenal insufficiency, or AI, may be at risk of experiencing adrenal crisis during or after invasive procedures. Since the mid-1950s, supplemental steroids in rather large doses have been recommended for patients with AI to prevent adrenal crisis. METHODS: To evaluate the need for supplemental steroids in these patients, the authors searched the literature from 1966 to 2000 using MEDLINE and textbooks for information that addressed AI and adrenal crisis in dentistry. Reference lists of relevant publications and review articles also were examined for information about the topic. RESULTS: The review identified only four reports of purported adrenal crisis in dentistry. Factors associated with the risk of adrenal crisis included the magnitude of surgery, the use of general anesthetics, the health status and stability of the patient, and the degree of pain control. CONCLUSIONS: The limited number of reported cases strongly suggests that adrenal crisis is a rare event in dentistry, especially for patients with secondary AI, and most routine dental procedures can be performed without glucocorticoid supplementation. CLINICAL IMPLICATIONS: The authors identify risk conditions for adrenal crisis and suggest new guidelines to prevent this problem in dental patients with AI.
Acute Disease↗
Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment.
OBJECTIVE: To determine the prevalence of sleep apnea in a sample of persons with chronic spinal cord injury (SCI) of varying injury levels and degrees of impairment. DESIGN: Cross-sectional study. SETTING: Inpatient SCI rehabilitation unit. PARTICIPANTS: Twenty men with SCI (motor complete and incomplete; American Spinal Injury Association classes A-D) of at least 1 year's duration, randomly selected from patients with SCI undergoing elective hospitalization. MAIN OUTCOME MEASURES: Apnea index, determined by sleep study (including chest wall movement, airflow, oxygen saturation), and daytime sleepiness, determined by Epworth sleepiness score. RESULTS: Eight subjects (40%) had sleep apnea, manifested by elevated apnea index (mean +/- SD, 17.1 +/- 6.9) and excessive daytime sleepiness. Sleep apnea was commonly diagnosed in motor-incomplete injuries. A trend (p = .07) existed toward a greater prevalence of sleep apnea with tetraplegia. Age and body mass index were not associated with sleep apnea. CONCLUSION: The prevalence of sleep apnea in men with chronic SCI admitted for nonrespiratory elective hospitalization is high relative to the general population.
Adult↗
The impact on dentistry of recent advances in the management of hypertension.
Dentistry has played an important role in the detection of patients with hypertension. Patients found to have high blood pressure at or beyond defined levels should be referred for a medical diagnosis and indicated treatment. Once the hypertensive condition is under control, oral and dental evaluation and treatment can be initiated. Beginning in 1976, the percentage of the general population in the United States with undetected hypertension declined steadily. However, this decline reversed, beginning in 1994. In addition, fewer than 50% of the patients who are aware of their hypertension have it medically under control. Thus, a significant number of patients with undetected high blood pressure or uncontrolled hypertension today are seeking dental treatment. These patients are at high risk for significant complications such as stroke, heart disease, kidney disease, and retinal disease. Those with very high blood pressure are at great risk for acute medical problems when receiving dental treatment. For those reasons, dentistry must continue to place an emphasis on the detection and referral of patients with high blood pressure. In addition, increased numbers of medically compromised patients are seeking dental treatment who should have their blood pressure monitored during the more stressful dental procedures, such as oral surgery, periodontal surgery, and placement of dental implants. This article reviews the recent advances in the dental and medical management of hypertension. It is important for dentists to be aware of hypertension in relation to the practice of dentistry.
Antihypertensive Agents↗
Five-year history of the Northeastern Society of Plastic Surgeons.
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History, 20th Century↗
Volumetric perceptions in midfacial aging with altered priorities for rejuvenation.
The history of facial rejuvenation surgery has largely involved the manipulation of facial soft tissues under tension within the two-dimensional confinements of a facial plane. However, the youthful human face is not planar; it presents as a complex geometric solid with a curvilinear profile on the oblique view that forms an architectural ogee. Restoration of this shape by sculptural manipulation of the facial soft tissues is deemed the highest priority in midfacial rejuvenation, whereas improvement of the periorbital and perioral environments is deemed second. Effacement of the nasolabial fold is relegated to a third level of importance in this philosophy of altered priorities for midfacial rejuvenation. The importance of early patient photographs is stressed in operative planning to direct facial changes toward a past intrinsic facial personality. Postoperative results are presented of patients who have undergone facial rejuvenation by a new midfacial technique that targets these reordered goals. Comparisons with photographs taken earlier in life and traditional preoperative photographs can then be made.
Adult↗
Three-dimensional rejuvenation of the midface: volumetric resculpture by malar imbrication.
The rejuvenation technique of malar imbrication, which avoids dissection in the plane of the seventh cranial nerve, is presented to address the author's altered priorities in midfacial rejuvenation. These priorities target volumetric over tension-based goals in a manner that is simpler, safer, and more sculpturally effective than existing techniques. Volumetric manipulations in the subperiosteal and subcutaneous planes also bring substantial rejuvenation to the periorbital and perioral regions, without lip or lower lid incisions. Fourteen of the 172 patients (8 percent) who underwent consecutive procedures for primary facial rejuvenation suffered temporary upper lip paresis. Other complications were infrequent and limited. One patient underwent reoperation for asymmetry. Increased postoperative swelling and recovery are a necessary consequence of the subperiosteal component, just as increased operative time attends the wide undermining of the subcutaneous component. Despite these liabilities, the author recommends adding volumetric resculpture to the existing conventional tools of soft-tissue displacement under tension and topical resurfacing in pursuit of safer, more effective, and more natural rejuvenation of the aging face.
Adult↗
Analysis of Escherichia coli RecA interactions with LexA, lambda CI, and UmuD by site-directed mutagenesis of recA.
An early event in the induction of the SOS system of Escherichia coli is RecA-mediated cleavage of the LexA repressor. RecA acts indirectly as a coprotease to stimulate repressor self-cleavage, presumably by forming a complex with LexA. How complex formation leads to cleavage is not known. As an approach to this question, it would be desirable to identify the protein-protein interaction sites on each protein. It was previously proposed that LexA and other cleavable substrates, such as phage lambda CI repressor and E. coli UmuD, bind to a cleft located between two RecA monomers in the crystal structure. To test this model, and to map the interface between RecA and its substrates, we carried out alanine-scanning mutagenesis of RecA. Twenty double mutations were made, and cells carrying them were characterized for RecA-dependent repair functions and for coprotease activity towards LexA, lambda CI, and UmuD. One mutation in the cleft region had partial defects in cleavage of CI and (as expected from previous data) of UmuD. Two mutations in the cleft region conferred constitutive cleavage towards CI but not towards LexA or UmuD. By contrast, no mutations in the cleft region or elsewhere in RecA were found to specifically impair the cleavage of LexA. Our data are consistent with binding of CI and UmuD to the cleft between two RecA monomers but do not provide support for the model in which LexA binds in this cleft.
Bacterial Proteins↗
Neurologic recovery and neurologic decline after spinal cord injury.
Physicians caring for patients with spinal cord injury facilitate neurologic recovery by optimizing nutrition and general health, by coordinating active exercise and functional training to enhance the underlying synapse growth, reversal of muscle atrophy, and motor learning, and by controlling interfering spasticity. SCI physicians also must monitor for neurologic decline during initial rehabilitation and later in life, diagnose promptly and accurately such decline, and orchestrate the appropriate intervention.
Humans↗
Robustness of a gene regulatory circuit.
Complex interacting systems exhibit system behavior that is often not predictable from the properties of the component parts. We have tested a particular system property, that of robustness. The behavior of a system is termed robust if that behavior is qualitatively normal in the face of substantial changes to the system components. Here we test whether the behavior of the phage lambda gene regulatory circuitry is robust. This circuitry can exist in two alternative patterns of gene expression, and can switch from one regulatory state to the other. These states are stabilized by the action at the O(R) region of two regulatory proteins, CI and Cro, which bind with differential affinities to the O(R)1 and O(R)3 sites, such that each represses the synthesis of the other one. In this work, this pattern of binding was altered by making three mutant phages in which O(R)1 and O(R)3 were identical. These variants had the same qualitative in vivo patterns of gene expression as wild type. We conclude that the behavior of the lambda circuitry is highly robust. Based on these and other results, we propose a two-step pathway, in which robustness plays a key role, for evolution of complex regulatory circuitry.
Bacteriophage lambda↗
Electrodiagnosis in spinal cord injured persons with new weakness or sensory loss: central and peripheral etiologies.
OBJECTIVE: To assess the prevalence and causes of late neurologic decline of persons with spinal cord injury (SCI). DESIGN: Retrospective review of persons with SCI over a 9-year period. Those with complaints of new weakness or sensory loss were grouped into three categories based on clinical examination, electrodiagnosis, and imaging: (1) central pathology (ie, brain, spinal cord, or nerve root); (2) peripheral pathology (plexus or peripheral nerve); or (3) no identifiable etiology. The specific diagnoses of late neurologic decline were identified. SETTING: Regional Veterans Affairs Spinal Cord Injury Service. PATIENTS: Five hundred two inpatient and outpatient adults with SCI. RESULTS: Nineteen percent of the study population complained of new weakness and/or sensory loss. Neurologic abnormalities were noted in 13.5%, 7.2% with central and 6.4% with peripheral causes. The most common pathologies were posttraumatic syringomyelia (2.4%) and cervical (1.6%) and lumbosacral (1.2%) myelopathy/radiculopathy. A specific etiology was not determined in 6 cases (1.6%). Peripheral involvement was mostly from ulnar nerve entrapment (3.4%) and carpal tunnel syndrome (3.0%). CONCLUSIONS: Late-onset neurologic decline is common after SCI and can result from central or peripheral pathology. Regular neurologic monitoring of SCI patients is recommended, since many with neurologic decline respond favorably if diagnosed and treated early.
Adult↗
Incomplete spinal cord injury: neuronal mechanisms of motor recovery and hyperreflexia.
OBJECTIVE: To understand neuronal mechanisms of motor recovery and hyperreflexia after incomplete spinal cord injury (SCI), and their role in rehabilitation. DESIGN: Reviewed and compared clinical, neurophysiologic, and neuropathologic data from human SCI patients with behavioral, neurophysiologic, and neuroanatomic data from animals to postulate underlying neuronal mechanisms. OUTCOME: A postulation that two neuronal mechanisms-receptor up-regulation and synapse growth-act sequentially, to explain the gradual appearance of motor recovery after incomplete SCI. These same mechanisms may also act in spinal reflex pathways to mediate hyperreflexia caudal to SCI. RESULTS: After incomplete SCI, walking ability and hyperreflexia often develop. Initially, cord neurons are hyperpolarized and less excitable because of loss of normal descending facilitation; this is spinal shock. Then, gradually, voluntary movement recovers and hyperreflexia develops. Early (hours to days), these changes develop simultaneously, suggesting a common postsynaptic mechanism-likely, an increase in postsynaptic receptor excitability, possibly receptor up-regulation. Late (weeks to months), recovery and reflex changes occur at a slow rate, are no longer simultaneous, and are long-lasting, which suggests a presynaptic mechanism, such as local synapse growth in spared descending pathways and in reflex pathways. This presumed synapse growth is seemingly enhanced by active use of the growing pathway. Also, developing hyperreflexia appears to limit motor recovery. CONCLUSIONS: These observations suggest that rehabilitation for incomplete SCI should (1) increase activity in spared descending motor pathways, (2) initially use reflex facilitation or central nervous system stimulants to assist spared descending inputs in depolarizing cord neurons, and (3) later minimize reflex input, when spared descending inputs can depolarize cord neurons without reflex facilitation. Better understanding of neuronal mechanisms that underlie motor recovery after incomplete SCI promises better outcomes from rehabilitation.
Animals↗
The pattern of reflex recovery during spinal shock.
STUDY DESIGN: A prospective descriptive study of the course of recovery of reflexes following acute spinal cord injury (SCI). OBJECTIVES: The purpose of the study was to observe the pattern of reflex recovery following acute SCI in order to determine the prognostic significance of reflexes for ambulation and their relationship to spinal shock. SETTING: A regional spinal cord injury center in Philadelphia, Pennsylvania, USA. METHODS: Fifty subjects admitted consecutively over a 9 month period and on the day of injury were observed for the following reflexes; bulbo-cavernosis (BC), delayed plantar response (DPR), cremasteric (CRM), ankle jerk (AJ), knee jerk (KJ), and normal plantar response for 5 7 days a week and 6-8 weeks duration. The 50 subjects were assessed for ambulation of 200 feet at time of discharge. MRI studies were reviewed on 13/28 complete (ASIA A) injuries. RESULTS: Thirty-five subjects (28 ASIA A, 4 ASIA B, 3 ASIA C) had a DPR of 2 days or longer duration and these subjects were not ambulatory. The fourteen subjects (12 ASIA D and 2 ASIA C), who were ambulatory, either had no DPR (11/14) or had a DPR of only 1 days duration (3/14). One subject (ASIA B) was not ambulatory and had a DRP of 1 days duration. The DPR was the first reflex to recover most often, followed by the BC, CRM in the first few days and later followed by the deep tendon reflexes (AJ & KJ) by 1-2 weeks respectively. Less than 8% of subjects had no reflexes on the day of injury and the reflexes did not follow a caudal-rostral pattern of recovery. CONCLUSIONS: Prognosis for ambulation based on reflexes early after SCI should not be linked to current descriptions of spinal shock. In fact, the view of spinal shock, based on the absence of reflexes and the recovery of reflexes in a caudal to rostral sequence, is of limited clinical utility and should be discarded. The evolution of reflexes over several days following injury may be more relevant to prognosis than the use of the term spinal shock and the presence or absence of reflexes on the day of injury.
Adult↗
Family values in the age of genomics: comparative analyses of temperate bacteriophage HK022.
HK022 is a temperate coliphage related to phage lambda. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles lambda and other members of the lambda family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription. The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chain-mail armour. Its integrase and repressor proteins are similar to those of lambda, but the differences provide insights into the evolution of biological specificity and the elements needed for construction of a stable genetic switch.
Bacteriophage lambda↗
Hiding the posterior scar in rhytidectomy: the omega incision.
A periauricular pattern of incision is presented for rhytidectomy that resembles an inverted omega. Although the anterior component remains similar to existing recommended patterns, the posterior component allows confinement of the scar to the postauricular sulcus and superior scalp. Although hidden, the scar placement permits full correction of redundant neck skin. The technique entails significant posterior dissection of the scalp, adding operative time and costs, along with increased potential for hematoma and sensory alteration of the scalp. On the other hand, the pattern of scar appears to reduce significantly the incidence of scar hypertrophy, whereas it conceals the scar from view, allowing an unrestricted range of postoperative hair styles.
Cicatrix↗