Rancho Los Amigos National Rehabilitation Center

A specific assay has been developed for a blood-borne non-A, non-B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post-transfusion NANBH (PT-NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.

BACKGROUND AND PURPOSE: The limited walking ability that follows a stroke restricts the patient's independent mobility about the home and community, a significant social handicap. To improve the in-hospital prediction of functional outcome, the relationships between impairment, disability, and handicap were assessed with clinical measures in 147 stroke patients. METHODS: The patients' level of functional walking ability at home and in the community was assigned by expert clinicians to one of the six categories of a modified Hoffer Functional Ambulation scale at least 3 months after discharge. A 19-item questionnaire was further used to assess current customary mobility of the subjects. Functional muscle strength and proprioception were tested, and walking velocity was measured. RESULTS: The significant indicators of impairment, upright motor control knee flexion and extension strength, differentiated household from community ambulators. The addition of velocity improved the functional prediction. Proprioception was clinically normal in all walkers. The validity of the criteria for the six levels of walking handicap was confirmed statistically. Stepwise discriminant analysis reduced the ambulation activities on the questionnaire from 19 to 7. Redefinition of the criteria for patient classification using the coefficients and constants of the seven critical functions improved the prediction of patient walking ability to 84%. CONCLUSIONS: The results of this study offer a quantitative method of relating the social disadvantage of stroke patients to the impairment and disability sustained. The measurement of therapeutic outcome in relation to the social advantage for the patient would allow more efficient standardization of treatment and services.

Excellent models have been presented in the literature which relate membrane potential to transverse membrane current and which describe the propagation of action potentials along the axon, for both myelinated and nonmyelinated fibers. There is not, however, an adequate model for nerve excitation which allows one to compute the threshold of a nerve fiber for pulses of finite duration using electrodes that are not in direct contact with the fiber. This paper considers this problem and presents a model of the electrical properties of myelinated nerve which describes the time course of events following stimulus application up to the initiation of the action potential. The time-varying current and potential at all nodes can be computed from the model, and the strength-duration curve can be determined for arbitrary electrode geometries, although only the case of a monopolar electrode is considered in this paper. It is shown that even when the stimulus is a constant-current pulse, the membrane current at the nodes varies considerably with time. The strength-duration curve calculated from the model is consistent with previously published experimental data, and the model provides a quantitative relationship between threshold and fiber diameter which shows there is less selectivity among fibers of large diameter than those of small diameter.

Nonhuman primate and human studies have suggested that populations of neurons in the posterior parietal cortex (PPC) may represent high-level aspects of action planning that can be used to control external devices as part of a brain-machine interface. However, there is no direct neuron-recording evidence that human PPC is involved in action planning, and the suitability of these signals for neuroprosthetic control has not been tested. We recorded neural population activity with arrays of microelectrodes implanted in the PPC of a tetraplegic subject. Motor imagery could be decoded from these neural populations, including imagined goals, trajectories, and types of movement. These findings indicate that the PPC of humans represents high-level, cognitive aspects of action and that the PPC can be a rich source for cognitive control signals for neural prosthetics that assist paralyzed patients.

This laboratory experiment was undertaken to identify factors contributing to intrapeduncular screw fixation in the vertebra. Testing was performed in axial pull-out and cyclic loading modes using multiple screw designs inserted to various depths into fresh human lumbosacral vertebra. The degree of osteoporosis played a major role in pull-out strength. Larger diameter, full-threaded screws inserted deep enough to engage the anterior vertebral cortex resulted in the most secure fixation. In the sacrum, the second sacral pedicle was the weakest location of insertion. Screws aimed laterally into the ala at 45 degrees or medially into the first sacral pedicle resisted larger axial pull-out loads than those inserted straight anteriorly into the ala. Methyl methacrylate was found to restore secure fixation in previously-loosened screws and pressurization of cement doubled the pull-out force. In cyclic load tests, deeper-inserted screws were found to withstand a greater number of cycles before loosening. Measurements of pedicle outer cortical diameters were found in many specimens to be smaller than both the 4.5-mm and 6.5-mm diameter screws.

To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-alphabeta; that viral clearance follows the entry and accumulation of HCV-specific IFN-gamma-producing T cells in the liver; and that it may not require the destruction of infected cells.

Clinical and pathologic features of 23 patients with a distinctive histologic and clinical variant of hepatocellular carcinoma are summarized. The variant pattern of hepatocellular carcinoma is most common in the age group 5–35 years and occurs equally in either sex. The distinctive histologic features include 1) deeply eosinophilic neoplastic hepatocytes, many of which contain intracytoplasmic hyaline globules and distinct pale bodies and 2) fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes. The histologic and gross features of the tumor have been confused both with focal nodular hyperplasia and with hepatocellular adenoma. The average survival of 32 months and the high operability rate of 48% far exceed the survival or operability for ordinary hepatocellular carcinoma. Thus, this tumor type must be recognized and considered separately when evaluating therapeutic results in large series of patients with hepatocellular carcinoma.

The factors important in achieving good walking status in myelomeningocele include level of paraplegia, the additional anomalies of brain and kidney, the intelligence, and the home environment. In a group of fifty-six patients none of those with lesions of the thoracic level walked and all of those with lesions of the sacral level walked. In those with lesions at lumbar levels (twenty-one lower and nineteen upper) fourteen were community ambulators and five household ambulators. The other twenty-one were either wheel-chair (nineteen) or non-functional ambulators (two) and the level of paraplegia did not seem to matter nor did the extent of surgery. Some very young non-functional ambulators rose in functional level, but in most instances the trend was to deteriorate.

Prior to the recent discovery of the swine hepatitis E virus (swine HEV) in pigs from the midwestern United States, HEV was not considered endemic to this country. Since swine HEV is antigenically and genetically related to human strains of HEV, it was important to characterize this new virus further. The infectivity titer of a pool of swine HEV in pigs was determined in order to prepare a standardized reagent and to evaluate the dose response in pigs. Although the sequence of swine HEV varied extensively from those of most human strains of HEV, it was very closely related to the two strains of human HEV (US-1 and US-2) isolated in the United States. The U.S. strains which were recently recovered from two patients with clinical hepatitis E in the United States shared >/=97% amino acid identity with swine HEV in open reading frames 1 and 2. Phylogenetic analyses of different regions of the genome revealed that swine HEV and the U.S. strains grouped together and formed a distinct branch. These results suggested that swine HEV may infect humans. When we inoculated rhesus monkeys and a chimpanzee, experimental surrogates of humans, with swine HEV, the primates became infected. Furthermore, in a reciprocal experiment, specific-pathogen-free pigs were experimentally infected with the US-2 strain of human HEV that is genetically similar to swine HEV. These results provided experimental evidence for cross-species infection by the swine virus. Thus, humans appear to be at risk of infection with swine HEV or closely related viruses.

Injection of irritant fluid precisely into the facet joint causes referred pain patterns indistinguishable from the pain complaints frequently associated with the "disk syndrome." Even straight leg raising and diminished reflex signs can be obliterated by precise local anesthetic injection into the facet joint. The use of radiographically localized injection of steroids and local anesthetic into the facet joint has been presented as a diagnostic-therapeutic procedure. Clinical experience with a group of 100 consecutive patients suggests that this treatment alone can achieve long-term relief in one-fifth of the patients with lumbago and sciatica and partial relief in another one-third of these patients. This information suggests that the structures related to the facet joint can be a persistent contributor to the chronic pain complaints of individuals with low back and leg pain.

A total of 2,905 pedicle measurements were made from T1-L5. Measurements were made from spinal computerized tomography (CT) scan examinations and individual vertebral specimen roentgenograms. Parameters considered were the pedicle isthmus width in the transverse and sagittal planes, pedicle angles in the transverse and sagittal planes, and the depth to the anterior cortex in a line parallel to the midline of the vertebral body and along the pedicle axis. There was no significant difference between data obtained from CT scans and specimen roentgenograms. Pedicles were widest at L5 and narrowest at T5 in the transverse plane. The widest pedicles in the sagittal plane were seen at T11, the narrowest at T1. Due to the oval shape of the pedicle, the sagittal plane width was generally larger than the transverse plane width. The largest pedicle angle in the transverse plane was at L5. The posterolateral to anterolateral pedicle axis orientation in the transverse plane, seen at other levels throughout the thoracolumbar spine, reversed at T12. In the sagittal plane, the pedicles angled caudally at L5 and cephaladly from L3-T1. The depth to the anterior cortex was significantly longer along the pedicle axis than along a line parallel to the midline of the vertebral body at all levels with the exception of T12 and T11.

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in approximately 90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting.

Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma. Development of an effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV.

Feinleib, M. (National Heart, Lung, and Blood institute, NIH, Federal Bldg., Room 2C08, Bethesda, MD 20014), R. J. Garrison, R. Fabsitz, J. C. Christian, Z. Hrubec, N. O. Borhani, W. B. Kannel, R. Rosenman, J. T. Schwartz and J. O. Wagner. The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol 106:284–295, 1977. Coronary heart disease (CHD) risk factors were studied in 250 monozygotic (MZ) and 264 dizygotic (DZ) male veteran twin pairs, aged 42–56. All coronary heart disease risk factors studied showed significant correlations in both MZ and DZ twins. Substantial genetic variation was detected for height, blood pressure, glucose intolerance, uric acid, plasma triglyceride, and relative weight but little or no significant genetic variability in low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), total plasma cholesterol or hematocrit was demonstrable. These findings suggest that familial aggregation results from genetic influence on blood pressure, glucose intolerance, uric acid, triglyceride and, possibly, obesity, while largely shared environmental factors contribute to familial similarities in HDL, LDL, total cholesterol and hematocrit.

Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix genechip system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.

The clinical courses of heterotopic ossification (HO) as a consequence of trauma and central nervous system insults have many similarities as well as dissimilarities. Detection is commonly noted at two months. The incidence of clinically significant HO is 10%-20%. Approximately 10% of the HO is massive and causes severe restriction in joint motion or ankylosis. The most common sign and symptom are decreased range of motion and pain. The locations are the proximal limbs and joints. Sites of HO about a joint may vary according to the etiology of the HO. Roentgenographic evolution of HO occurs during a six-month period in the majority of patients. Treatment modalities include diphosphonates, indomethacin, radiation, range of motion exercises, and surgical excision. Surgical timing differs according to etiology: traumatic HO may be resected at six months; spinal cord injury HO is excised at one year; and traumatic brain injury HO is removed at 1.5 years. A small number of patients have progression of HO with medicinal treatment and recurrence after resection. The patients seem recalcitrant to present treatment methods regardless of the HO etiology.

Dual-photon absorptiometry characterized bone loss in males aged less than 40 years after complete traumatic paraplegic and quadriplegic spinal cord injury. Total bone mass of various regions and bone mineral density (BMD) of the knee were measured in 55 subjects. Three different populations were partitioned into four groups: 10 controls (healthy, age matched); 25 acutely injured (114 days after injury), with 12 reexamined 16 months after injury; and 20 chronic (greater than 5 years after injury). Significant differences (p less than 0.0001) in bone mass mineral between groups at the arms, pelvis, legs, distal femur, and proximal tibia were found, with no differences for the head or trunk. Post hoc analyses indicated no differences between the acutely injured at 16 months and the chronically injured. Paraplegic and quadriplegic subjects were significantly different only at the arms and trunk, but were highly similar at the pelvis and below. In the acutely injured, a slight but statistically insignificant rebound was noted above the pelvis. Regression techniques demonstrated early, rapid, linear (p less than 0.0001) decline of bone below the pelvis. Bone mineral loss occurs throughout the entire skeleton, except the skull. Most bone loss occurs rapidly and below the pelvis. Homeostasis is reached by 16 months at two thirds of original bone mass, near fracture threshold.

The purpose of this study was to determine the prevalence of upper extremity (UE) pain in outpatients with chronic spinal cord injury (SCI). A total of 239 SCI outpatients (136 with quadriplegia and 103 with paraplegia) were interviewed for the presence of UE pain at the shoulder, elbow, wrist, and hand. The average age of the subjects at the time of interview was 37.4 years, and the average time since onset was 12.1 years. Subjects who reported pain were referred to SCI clinics to determine the etiology. Fifty-five percent of the patients with quadriplegia reported UE pain, most commonly at the shoulder. Prevalence of reported pain was highest for subjects in the first five years postinjury. Sixty-four percent of patients with paraplegia reported UE pain. Complaints related to carpal tunnel syndrome were the most common, followed by those related to shoulder pain. This study documents the prevalence and nature of UE pain in chronic SCI patients and emphasizes the need for further research to develop strategies for prevention and treatment of pain syndromes.

BACKGROUND AND PURPOSE: Stroke recently declined from the third to the fourth leading cause of death in the United States, its first rank transition among sources of American mortality in nearly 75 years. METHODS: This is a narrative review supplemented by new analyses of Centers for Disease Control and Prevention National Vital Statistics Reports from 1931 to 2008. RESULTS: Historically, stroke transitioned from the second to the third leading cause of death in the United States in 1937, but stroke death rates were essentially stable from 1930 to 1960. Then a long, great decline began, moderate in the 1960s, precipitous in the 1970s and 1980s, and moderate again in the 1990s and 2000s. By 2008, age-adjusted annual death rates from stroke were three fourths less than the historic 1931 to 1960 norm (40.6 versus 175.0 per 100,000). Total actual stroke deaths in the United States declined from a high of 214,000 in 1973 to 134,000 in 2008. Improved stroke prevention, through control of hypertension, hyperlipidemia, and tobacco, contributed most greatly to the mortality decline with a lesser but still substantial contribution of improved acute stroke care. Persisting challenges include race-ethnicity, sex, and geographic disparities in stroke mortality; the burden of stroke disability; the expanding obesity epidemic and aging of the US population; and the epidemic of cerebrovascular disease in low- and middle-income countries worldwide. CONCLUSIONS: The recent rank decline of stroke among leading causes of American death is testament to a half century of societal progress in cerebrovascular disease prevention and acute care. Renewed commitments are needed to preserve and broaden this historic achievement.

The energy expenditure of level walking was measured in 260 normal male and female subjects walking around a 60.5m-circular outdoor track. Subjects were divided into four age groups (children, 6-12 years; teens; young adults, 20-59 years; and senior adults, 60-80 years). Oxygen consumption was measured with a modified Douglas Bag technique during the fourth and fifth minutes of each trial. Standard tables according to age and sex were derived for the average energy expenditure (rate of oxygen uptake, energy cost per meter, and heart rate) and for the gait characteristics (speed, cadence, stride length) at the subjects' customary slow, normal, and fast walking speeds. Statistical analysis was performed to determine the energy-speed relationship for the different age groups to derive normative tables for the rate of oxygen uptake throughout the range of customary walking velocities.