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Acrolein inflicts axonal membrane disruption and conduction loss in isolated guinea-pig spinal cord.

We have examined the effect of acrolein, an aldehyde product of lipid peroxidation, on axons in isolated guinea-pig spinal cord white matter. We found that 200 microM acrolein, but not 50 microM, induced a time-dependent loss of compound action potential conduction. Such conduction loss was irreversible within 1 h after acrolein perfusion. Parallel anatomical assessment indicates membrane integrity breakdown based on a horseradish peroxidase-exclusion assay. This is the first report to suggest that acrolein inflicts severe axonal damage. Since axonal damage within white matter plays a key role in the pathology of traumatic spinal cord injury, we suggest that acrolein may be a critical factor in mediating secondary functional loss.

Acrolein↗

The predisposition to inspiratory upper airway collapse during partial neuromuscular blockade.

RATIONALE: Partial neuromuscular transmission failure by acetylcholine receptor blockade (neuromuscular blockade) or antibody-mediated functional loss (myasthenia gravis), even with a magnitude of muscle weakness that does not evoke respiratory symptoms, can evoke dysphagia and decreased inspiratory airflow, and increases the risk of susceptible patients to develop severe pulmonary complications. OBJECTIVES: To assess whether impaired neuromuscular transmission predisposes individuals to inspiratory upper airway collapse, we assessed supraglottic airway diameter and volume by respiratory-gated magnetic resonance imaging, upper airway dilator muscle function (genioglossus force and EMG), and changes in lung volume, respiratory timing, and peripheral muscle function before, during, and after partial neuromuscular blockade in healthy, awake volunteers. MEASUREMENTS AND MAIN RESULTS: Partial neuromuscular blockade (train-of-four [TOF] ratio: 0.5 and 0.8) was associated with the following: (1) a decrease of inspiratory retropalatal and retroglossal upper airway volume to 66 +/- 22 and 82 +/- 12% of baseline, which was significantly more intense in the retropalatal area; (2) an attenuation of the normal increase in anteroposterior upper airway diameter during forced inspiration to 74 +/- 18% of baseline; (3) a decrease in genioglossus activity during maximum voluntary tongue protrusion to 39 +/- 19% (TOF, 0.5) and 73 +/- 29% (TOF, 0.8) of baseline; and (4) no effects on upper airway size during expiration, lung volume, and respiratory timing. CONCLUSIONS: Thus, impaired neuromuscular transmission, even to a degree insufficient to evoke respiratory symptoms, markedly impairs upper airway dimensions and function. This may be explained by an impairment of the balance between upper airway dilating forces and negative intraluminal pressure generated during inspiration by respiratory "pump" muscles.

Adult↗

Rehabilitation of neurologic disability related to human immunodeficiency virus.

Acquired immunodeficiency syndrome (AIDS) is globally fatal; before death, it often causes a multitude of medical complications leading to significant physical impairment and functional loss. Specifically, the neuropathology associated with AIDS can be diverse, and it ranges from inconsequential cerebrovascular insults to rapidly progressive neuronosis. Moreover, physical impairments may present any time during the course of the disease and even before knowledge of seropositivity. We present three patients infected with human immunodeficiency virus (HIV), each with a different form of neuropathology, who were treated by rehabilitative services and who gained reasonable functional benefits within moderate time periods. The growing number of HIV-infected persons with physical debilitation mandates a rational, knowledgeable approach to rehabilitation intervention. This article highlights the importance of a thorough understanding of the neurologic complications of AIDS in setting realistic goals and in improving the quality of life for these individuals.

Acquired Immunodeficiency Syndrome↗

Long-term progression of Menière's disease.

A retrospective study of 161 patients with Menière's disease followed up for 9 years or more is presented. The development, with respect to hearing, caloric response, vertigo, and ability to work, was analyzed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time. A spontaneous relief in vertigo over the years has been noticed.

Adolescent↗

The nature and significance of nutritional adaptation.

Possible adaptations to a low protein intake are: a decrease in the obligatory nitrogen loss, which would be too small to detect in short-term studies, but would be significant over a longer term; an increase in the efficiency of protein utilization, which has been demonstrated in depleted subjects; and a decrease in lean body mass, mainly at the expense of muscle. However, we do not know the extent to which this last mechanism may really be an adaptation without significant functional loss. In the case of energy there is controversy about the extent to which the gross efficiency of muscular work can be improved. One mechanism might be an alteration in the distribution of fibre types, with a shift from fast to slow fibres. A possible way of reducing the cost of both muscular work and basal metabolism would be a reduction in the mitochondrial proton leak. Both these mechanisms are at least partially under the control of the thyroid gland, which therefore may play an important role in economizing energy expenditure.

Adaptation, Physiological↗

Paired comparison of contrast sensitivity in diffractive multifocal IOLs and conventional monofocal IOLs.

Multifocal intraocular lens (IOL) optics produce a retinal image of reduced contrast, which results from splitting incoming light between multiple focal points. This study sought to determine whether the reduced-contrast image results in functional loss of contrast sensitivity. Contrast sensitivity was measured in patients in the US Food and Drug Administration (FDA) study of the 3M Diffractive IOL, using the Pelli-Robson Letter Chart. Fifty-eight of these patients, including six from our clinic, were 'best-case' patients with no pathology, and also had paired multifocal/monofocal implants. Data from these 'best-care' patients with paired eyes indicate no functional difference in contrast sensitivity. Additional data obtained on our six patients with the Regan Low Contrast Charts suggest small predictable differences may exist for some patients at very low contrast levels. Further study is needed to determine whether these differences have functional significance.

Aged↗

Improvement in upper airway function after weight loss in patients with obstructive sleep apnea.

Overweight patients with obstructive sleep apnea (OSA) are improved by weight reduction, although the underlying mechanisms are not clear. We tested the hypothesis that improvement in OSA after weight loss is associated with improvement in pharyngeal function. Consequently, we measured pharyngeal area at functional residual capacity (AFRC) and at residual volume (ARV), the percent change in pharyngeal area between FRC and RV (delta Aph%) defined as (AFRC - ARV)/AFRC x 100, and lung volume dependence of pharyngeal area (LVD) defined as the difference between AFRC and ARV normalized for the expiratory reserve volume (ERV)--in 12 overweight apneic patients before and after weight loss. We found that after a 26 +/- 18 kg weight loss, there was a significant reduction in the apnea/hypopnea index from 57 +/- 29 to 14 +/- 10 (p less than 0.0005) and increase in the lowest nocturnal oxygen saturation from 54 +/- 20% to 80 +/- 8% (p less than 0.001). This improvement was associated with a significant reduction in delta Aph% from 25 +/- 15% to 9 +/- 18% (p less than 0.05) and a significant decrease in LVD from 1.98 +/- 1.52 cm2/L to 0.16 +/- 0.88 cm2/L (p less than 0.005). There were four patients in whom baseline LVD was low and relatively unchanged after weight loss. Three of these patients exhibited paradoxical inspiratory narrowing of the glottis, which reversed after weight loss; these glottic abnormalities were not present in the rest of the patients with OSA. We conclude that improvement in obstructive sleep apnea after weight loss may be related to improvement in pharyngeal and glottic function.

Adult↗

Neural induction, neural fate stabilization, and neural stem cells.

The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural-fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

Animals↗

Bronchial reactivity to cigarette smoke in smokers: repeatability, relationship to methacholine reactivity, smoking and atopy.

Bronchial reactivity to cigarette smoke (CBR) in a cross-section of 98 smokers has been investigated. All participants were subjects to skin-prick tests to common allergens, lung function measurements and bronchial challenges with methacholine and cigarette smoke. In 38 participants a rechallenge with cigarettes was performed 1 h after the first cigarette challenge. Lung function indices analysed were: forced expiratory volume in one second (FEV1); maximal expiratory flow at 75% of the forced vital capacity (MEF75%); and forced mid-expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75%)). All participants were tested for asthma and allergy, and were required to provide information regarding respiratory symptoms, first degree relatives with asthma and allergy and smoking habits. A substantial decrease was seen in all lung function indices after 12 cigarette-smoke inhalations, but only FEV1 was related to other variables. The maximal mean percentage fall in FEV1 was 10%, which was directly related to the number of inhalations (p<0.05). In multiple regression analyses the percentage fall in FEV1 was directly related to: FEV1/vital capacity (VC) (p<0.01); to the asthmatic/bronchitic status (p<0.05); and to the accumulated and standardized cigarette consumption (p<0.05). The percentage fall in FEV1 bore no relationship to methacholine bronchial reactivity, sex or age and had a continuous distribution. The repeat challenge showed a smaller fall in FEV1 compared to the first challenge after 12 cigarette smoke inhalations (p<0.05). The percentage fall in FEV1 correlated after the first and the repeat challenge (p<0.05). Repeatability of the challenge could not be determined in this study because of tachyphylaxis. Bronchial reactivity to cigarette smoke is a tobacco smoke-specific bronchial response. All participants responded and the response showed a continuous distribution. Bronchial reactivity to cigarette smoke may be of importance for symptoms and prognosis in chronic bronchitis and chronic obstructive pulmonary disease and should be studied in relation to the degree of accelerated lung function loss in smokers and other cigarette induced lung abnormalities.

Asthma↗

[Reversible hyperuricemia in case of ureteral colics (author's transl)].

On about one fourth of the patients ureteral colics caused by oxalate and phosphate calculi lead to a reversible hyperuricemia. This result seems to be important, because we might wrongly diagnose a uric acid calculus. The reason for hyperuricemia is a temporary diuretic disturbance of the uric acid. It cannot be explained by the functional loss of the obstructed kidney, because a nephrectomy does not change the uric acid level. As a possible reason we suppose a ketose by food deficiency and vomiting caused by renal colic.

Blood Urea Nitrogen↗

Management and rehabilitation of ligamentous injuries to the ankle.

The management of ligamentous injuries to the ankle is controversial. Neither the methods for classification and diagnosis, or the procedures for treatment are clear cut. Ankle sprains are a common occurrence, with the majority involving the lateral ligament complex. Within this complex, the anterior talofibular ligament is injured most frequently, usually while the foot is in the plantar flexed position. Ankle injuries can be diagnosed through physical exam, including the anterior drawer test and/or a stress exam, or through roentgenographic evaluation. The purpose of the stress roentgenogram is to measure the degree of talar tilt. However, it does not always yield consistent, reliable results. This inconsistency has led to the use of arthrography. There is debate over its use as well, however, Ankle sprains can be classified into three groups, according to functional loss. Treatment for first and second degree sprains is usually non-operative. The best approach to Grade III sprains is debatable. The issues in the treatment of Grade III sprains are first, whether treatment should be operative or non-operative, and second, whether non-operative treatment should emphasise immobilisation or mobilisation. Brostrom's work is cited as noteworthy. He recommended adhesive strapping followed by mobilisation as the treatment of choice, and reserves surgery for cases of chronic instability. Results demonstrated that strapping yielded shorter disability periods, while surgery produced less instability. The prevention of functional instability is a major concern in the treatment of ankle injuries. There is no consensus for treating a lateral ligament rupture. The authors suggest immobilisation followed by a rehabilitative programme. Three methods of immobilisation are plaster casting, adhesive strapping, and the air-stirrup. The physiological mechanism of cryotherapy and thermotherapy are discussed briefly and recommendations for their use are provided. Aspiration is also discussed. Loss of motion is designated as a primary cause of chronic pain and reinjury, and exercises intended to restore range of motion are provided. Exercises aimed at restoring strength and proprioception are also presented. This allows for return to activity and serves to prevent reinjury.

Ankle Injuries↗

Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD.

OBJECTIVE: To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. METHODS: Seven patients with FTD and seven patients with AD were studied (Clinical Dementia Rating: four patients with FTD 0.5, three patients with FTD 1, all patients with AD 1; mean Mini-Mental State Examination score: FTD 28.0 +/- 2.1, AD 23.1 +/- 2.7). Cerebral atrophy on MRI was mild, with no differences between FTD and AD. A parametric working memory task was applied to assess frontal activation as a function of working memory load. RESULTS: The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. CONCLUSIONS: These data on regional functional loss in the frontal cortex in early FTD suggest that fMRI can identify FTD when results on structural MRI are normal.

Aged↗

Quantitative morphological analysis of age-related changes in flight muscle of Musca domestica L.

Electron micrographs of dorsal indirect flight muscle of 37 (adult) and 68 (old) day old female houseflies were analyzed by morphometric techniques. In the muscle of the old female housefly there is no significant atrophy and the fine structure is well preserved. There is a small loss in both the myofibril and mitochondrial volumes, an increase in average myofibril size, and a 28% decrease in myofibril number. The thin/thick filament ratio and sarcomere structure are not altered. There is little decrease of particulate glycogen. The fractional volume occupied by SR at the dyads is increased. The most marked change is in the density of mitochondrial cristae which declines by 55% in old muscle and could account for the functional loss. Cristal anomalies and SR changes indicate that the membranes may be the specific target of deleterious aging effects.

Aging↗

Implication of altered pulmonary function in pneumonectomy for tuberculous destroyed lung.

Twelve patients undergoing pneumonectomy for tuberculous destroyed lung were studied to determine the value of preoperative spirometry in the assessment of their pulmonary reserve, and prediction of their postoperative morbidity. Preoperatively, the mean functional losses (as percentage of predicted values) were 44.5% of FVC, 54% of FEV, and 44% of PFR. No significant alteration occurred in FVC, FEV1 or PFR post-pneumonectomy. All patients were in Class 1 (NYHA) pre- and postoperatively. It is concluded that operability in these patients cannot be based on broncho-spirometry. The assessment of preoperative clinical (symptomatic) stage and the cardiovascular status appears to be the major determinants of pulmonary functional results.

Adolescent↗

Tissue pressure threshold for peripheral nerve viability.

To investigate the pressure threshold for peripheral nerve dysfunction in compression syndromes (carpal tunnel and compartment syndromes), carpal canal pressure was elevated to 40, 50, 60, and 70 mm Hg in normal volunteers. Motor and sensory latencies and amplitudes of the median nerve were evaluated before compression, after 30-240 minutes of compression, and during the postcompression recovery phase. Although some functional loss occurred at 40 mm Hg, motor and sensory responses were completely blocked at a threshold tissue fluid pressure of 50 mm Hg, measured by the wick catheter. In one subject in whom diastolic blood pressure was significantly higher than in other subjects, the threshold pressure was raised slightly. The Semmes-Weinstein monofilament test and the 256-cycle vibratory test were more sensitive than two-point discrimination tests for evaluating peripheral nerve function in this compression model. These results indicate that between 40 mm Hg and 50 mm Hg there exists a critical pressure threshold at which peripheral nerve is acutely jeopardized. Compartment decompression may not be indicated when interstitial pressures are below this level.

Action Potentials↗

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Aging↗

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like PET scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Aging↗

Surgical management of complex irreparable rotator cuff deficiency.

The authors surgically treated 23 shoulders in 23 patients with disabling pain associated with irreparable tears of the musculotendinous cuff. In a total of 12 shoulders with preserved passive motion, normal deltoid function, loss of glenohumeral joint surfaces, and sculpturing of the coracoacromial arch, a standard or oversized Neer II humeral prosthesis without glenoid replacement was selected. A total of 11 shoulders that failed to meet these prerequisites or demanded heavy use after operation underwent arthrodesis. Twenty-two patients (12 from the hemiarthroplasty group and 10 from the arthrodesis group) were available for evaluation at an average follow-up period of 37.5 months. Comfort level and overall function were improved in both groups. Active forward elevation improved an average of 44 degrees in the hemiarthroplasty group and an average of 15 degrees in the arthrodesis group. The success of hemiarthroplasty and the problems of glenoid loosening in the presence of cuff deficiency with upward head displacement have led to the conclusion that humeral hemiarthroplasty is the preferred method for managing complex irreparable tears of the rotator cuff in which the articular surface is destroyed, yet the deltoid muscle is functional. Shoulder arthrodesis is reserved for those patients who have both irreparable tears of the rotator cuff and irreparable deficiencies of the deltoid muscle, or the younger patient with demands for substantial strength at low angles of flexion.

Aged↗