Estimation of age from a tooth by means of racemization of an amino acid, especially aspartic acid--comparison of enamel and dentin. In a study of age estimation from teeth by means of measuring racemization of aspartic acid (Asp), a representative amino acid, the accuracy of data from enamel and dentin in the same tooth was compared. The correlation of D/L ratio of aspartic acid with actual age gave the following parameters: r = 0.928, sigma = +/- 5.2, k = 4.47 x 10(-4) yr-1 in enamel and r = 0.995, sigma = +/- 1.4, k = 5.75 x 10(-4) yr-1. The difference in ages between one estimated by the D/L ratio and the actual one was within +/- 3 years in dentin, while in enamel an error of from 2 to 11 years was observed. Reaction rate constants of the racemization in a dry postmortem state (15 degrees C) were calculated as k = 9.70 x 10(-8) yr-1 in enamel, and k = 1.33 x 10(-7) yr-1 in dentin. Compared to rates determined from teeth recently extracted from living subjects, the rate was higher in dentin than in enamel. These data reconfirmed that dentin is superior to enamel in making exact age estimations from teeth.


Sex determination in subadults using auricular surface morphology: a forensic science perspective. The determination of sex in subadult skeletons remains a problem for several areas of biological anthropology. To date, univariate and multivariate assessments of sex in the young using adult indicators have failed to produce reliable results. However, research in this area continues. In 1980, Weaver proposed a modification of adult differences in auricular surface morphology as an effective means for sex determination in subadult remains. His method was indirectly evaluated by Hunt through a comparison of the sex ratios produced by this technique and the expected 1:1 ratio. The present investigation expands upon both studies by using a sample of subadults of known sex, and by evaluating Weaver's method from two perspectives: 1) what percentage of individuals can be correctly sexed using Weaver's criteria? and 2) what is the probability that an individual case will be correctly sexed based on the presence or absence of auricular surface elevation? The first is of interest to those reconstructing population patterns, while the second is critical to the forensic investigator faced with the diagnosis of an individual case. The sample used in this study consisted of 58 ilia from subadults of known sex ranging in age from birth through 18. In each case, sufficient soft tissues were present to allow absolute sex diagnosis. Each ilium was subjected to a blind examination using Weaver's criteria for auricular surface elevation. Weaver's technique proved most effective on the males in our sample, with an overall accuracy of 85.3%; however, accuracy in sexing females was only slightly better than chance at 58.3%. Our results corresponded closely to Weaver's own values of 85.4 and 57.7% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Can we believe what we see, if we see what we believe?--expert disagreement. Forensic experts often disagree. The possible sources of such disagreements are analyzed and possible avenues of resolution indicated. The logic of interpreting scenes, and pattern injuries such as bitemarks, is explained to locate potential sources for interpretive error, and to recommend strategies to avoid compounding such errors when preparing cases. In one sense, two observers may not see the same thing, although their eyesight is normal and they are aware of the same artifact. Cases show that both practical and theoretical investigative expectations affect what count as observations. These expectations confer evidential status on the artifact. When two observers' expectations conflict, they do not see the same thing, so are not presented with the same evidence. Expectations can be either appropriate or inappropriate. These senses are clearly distinguished using illustrative cases. When inappropriate, they cause observational errors of a unique sort supplying one source for disagreement. When inferences are made from these inappropriately sanctioned observations,interpretive errors are compounded and resolutions of disagreement become difficult. These observational and inferential errors are explained, described, and illustrated with cases, along with recommendations for recognizing and avoiding them.


Creatinine analysis in single collection urine specimens. Controlled and uncontrolled fluid intake studies were conducted on series of volunteers over the 6 or 12 h of the study periods. Urine specimens were obtained from each subject randomly or at specified times relative to fluid ingestion. Creatinine analysis performed by a modification of the Abbott TDx procedure demonstrates that the values obtained from single collection specimens fall almost in the same range as the values from 24 h pooled collection specimens. The creatinine concentration can be used to indicate possible adulteration of urine specimens by dilution as a means of avoiding detection of use of drugs of abuse. Between 4 and 7 h are required for a decrease in creatinine concentration to about 100 mg/dL from an initial mean of about 170 mg/dL. A minimum of 6 h is needed for any creatinine value to fall to 50 mg/dL or less. Thus, it appears that creatinine output is sensitive to the amount of fluid ingested, but the relationship is neither linear nor immediate. The absence of a significant creatinine concentration in a specimen can be used as an indication of direct or indirect adulteration of the urine specimen by dilution or replacement with water. At NDSL-Great Lakes, a decline of the creatinine concentration to 30 mg/dL is used as a cutoff for differentiating between urine specimens that might have been tampered with to avoid detection of drug use and those specimens that are dilute for other reasons. Values at 10 mg/dL or less are suggestive of replacement by water. The information is provided to local commands for investigation prior to initiation of punitive action by the command.


Poppy seed ingestion: the Oregon perspective. Numerous articles have been published regarding the positive morphine and codeine urinalysis results from the ingestion of poppy seeds. Oregon's perspective towards ingestion of controlled substances focuses around driving under impaired conditions. To determine the influence of the residual opium on poppy seeds to impairment, seven volunteers each ingested 25 grams of poppy seeds baked into bundt cakes. Urine samples were screened by EMIT using 300 ng/ml cutoff levels. All of the urine specimens were found to be opiate positive shortly after consuming the cake; however, after administering a series of standardized drug recognition evaluation tests, no subjects were found to exhibit symptoms of opiate impairment.


Acute arsenic intoxication: forensic and toxicologic aspects (an observation). The authors report on an acute suicidal arsenic intoxication (di-arsenic-trioxide). Death can occur one week after ingestion, despite intensive care. The forensic, anatomopathological and toxicologic aspects are reported. Forty titrations are realized at the level of the biologic fluid in viscera, by absorption spectrophotometry. These data are compared with those in standing literature, especially with the rates determined in normal subjects, following simple environmental impregnation.


Distinctive blunt force injuries caused by a crescent wrench. Prompt recognition of patterned injuries by the forensic pathologist can greatly facilitate the investigation and resolution of injury and death cases. Careful observation and description of injuries may provide identification of an assault or murder weapon and contribute to the reconstruction of circumstances of injury. The two cases herein described manifest unusual and distinctive injuries resulting from multiple impacts by adjustable crescent wrenches. Detailed photographs and descriptions of these injuries are provided.


Insect larvae used to detect cocaine poisoning in a decomposed body. Insect larvae are often found on human remains long after disappearance of the usual toxicologic specimens. It is important for forensic pathologists and toxicologists to recognize the potential of this unique specimen when routine specimens are not available. Cocaine and benzoylecgonine was extracted from Calliphorid larvae found on a badly decomposed body of a man who had been missing 5 months and was also identified in the decomposing skeletal muscle. This toxicologic information combined with the autopsy findings and the circumstances of the death and disappearance was essential in the determination of cocaine poisoning as the cause of death.


A fatality due to propofol poisoning.

A fatality due to propofol poisoning. This report describes a suicide by self-administration of propofol in a 29-year-old female radiographer. This is the first published report of death by overdosage with propofol. Propofol was detected in tissues using high performance liquid chromatography. Post mortem femoral blood and liver concentrations of propofol were 0.22 mg/L and 1.4 mg/kg, respectively. The scene suggested that a dose of 400 mg was used.


Occupational exposure to cocaine involving crime lab personnel. The possibility of exposure to cocaine as a result of analyzing it or handling material contaminated by it has been a major concern of laboratory personnel. Several different work environments and simulated situations were examined to assess the likelihood of this type of exposure occurring. Urine specimens were collected and evaluated for cocaine and benzoylecgonine using the Syva ETS System (EMIT). Each specimen was analyzed for the two substances using gas chromatography/mass spectrometry (GC/MS). Urine specimens of laboratory-management personnel not working with drug samples showed no trace of cocaine or benzoylecgonine. A urinary benzoylecgonine level of 227 ng/mL was found in the specimen from one narcotics criminalist who was working on a routine case of 2 kilos of cocaine hydrochloride in the Narcotics Laboratory. A maximal urinary benzoylecgonine concentration of 1570 ng/mL was determined in the urine specimen from one narcotics criminalist who was sampling a case containing 50 kilos of cocaine hydrochloride over a period of 3 h. Decreasing the levels of airborne cocaine dust appears to minimize the amount of cocaine absorbed by the criminalists. Gloves, face masks, and goggles prove to be effective in minimizing exposure.


Impact of tropical conditions on thin layer chromatography in analytical toxicology: high temperatures and moderate humidities. The impact of high temperatures (24 to 39 degrees C) and low to moderately high humidities (20 to 70%) on the applicability of TLC systems for drug identification was studied during a 6 month climatologic cycle in Burkina Faso (West Africa). In general, the Rf values as observed on the plates were found to be substantially affected as compared with values obtained at temperate climates. Some TLC systems were more affected than others and the largest deviations of up to 30 Rf units were at low humidities. Tropical conditions also had a negative effect on the reproducibility of Rf values. However, when an Rf-correction procedure was applied, using reference mixtures of known drugs on each plate, accuracy as well as reproducibility of the resulting Rfc values were drastically improved and data thus corrected were found to be compatible with existing TLC data bases developed under moderate climatological conditions. The impact of high to extremely high humidities (70 to 100%) remains to be investigated.


The distribution of ethanol in postmortem blood specimens. Ethanol was determined by gas chromatography in a variety of tissues and body fluids secured at autopsy in 61 cases. The specimens tested included right and left heart blood, femoral blood, pericardial fluid, cerebrospinal fluid, vitreous humor, urine, stomach contents, and brain. Statistical analysis of the cases revealed no significant differences among the various blood sites tested. However, the variations in blood ethanol concentrations among the various sampling sites within each case were as follows: 40 cases showed differences of less than 25%; 16 cases revealed variability between 25% and 50%, 4 cases had differences exceeding 50%. In one case, satisfactory blood analyses could not be accomplished. The larger variances occurred especially in those instances in which stomach alcohol concentration was 0.50% or greater. In one case, the variability amongst the different blood sites exceeded 400% (femoral blood--0.043%, right atrium--0.070%, root of aorta--0.156%); the brain was 0.050%, and the stomach contents was 1.2%. For all 61 cases, variances in blood alcohol content among the different sampling sites in a single cadaver ranged from 1.8 to 428%.


The effect of dentures and denture adhesives on mouth alcohol retention. A total of 24 alcohol-free, denture-wearing subjects were tested for mouth-alcohol retention times with an Intoxilyzer 5000. The subjects were given 30 mL doses of 80 proof brandy to swish in their mouths without swallowing for 2 min prior to expectorating the dose. Subjects were tested under three conditions: 1) with dentures removed, 2) with dentures held loosely in place without an adhesive, and 3) with dentures plus an adhesive. Beyond 20 min following expectoration, mouth alcohol made no significant contribution to the apparent breath alcohol concentration (BrAC), with trace (less than or equal to 0.01 g/210 L) readings found in only two of the subjects. Denture use, both with and without the concurrent use of adhesives does not significantly affect BrAC as long as a pretest alcohol deprivation period of 20 min is observed.


Time-course of sensitivity changes as attention shifts to an unpredictable location. Shifting visual attention is often described as analogous to a spotlight moving through empty space between locations. In the present experiment, a peripheral precue summoned attention to an initial location, and 200 ms later a second peripheral cue appeared beside one of two possible second locations, each 14 degrees away from the initial location. The target was twice as likely to appear at the location that had been indicated by the immediately preceding cue as at the location that had been previously cued or that would be cued. Fine-grained temporal analyses indicated that, as attention was shifted, sensitivity to information at the second location gradually increased while sensitivity at the first location simultaneously decreased. Average sensitivity over the two locations during the shift remained significantly greater than average sensitivity immediately following the initial precue. In contrast, an attentional "spotlight" moving from the first to the second location would produce a decrease in average sensitivity to its initial level while the spotlight was between locations.


Changing-loudness aftereffect following simulated movement: implications for channel hypotheses concerning sound level change and movement. Listening to a tone changing unidirectionally in sound level causes an illusion of changing loudness in a steady tone afterward. This aftereffect may indicate channels for detecting the feature of change in sound level, which would primarily concern dynamic sound localization. Three subjects, one of whom was the author, participated in this study. The author predicted that opposite adaptation of the ears (the adapting stimulus is heard to move from one ear to the other) should lead to a movement aftereffect. This was not reported by the subjects. However, the subjects did report a changing-loudness aftereffect in a monaural test stimulus, and the characteristics of the changing-loudness aftereffect (such as its magnitude) were consistent with previous data, suggesting a two-stage channel hypothesis: Output from channels for several features, including sound-level change, simultaneously stimulate movement channels.


Repression-sensitization differences in recovery from learned helplessness. The performance of repressors and sensitizers on a solvable anagram task was assessed after either a short delay (0 to 30 min) or a long delay (2 to 6 hr) following a standard learned helplessness induction. Results indicated that all subjects exposed to the learned helplessness induction exhibited performance deficits, compared with control subjects exposed to no induction. Furthermore, subjects who were tested after the short delay did not perform as well as subjects tested after a long delay. No difference in overall anagram performance was found between repressors and sensitizers. Consistent with theoretical predictions, however, the anagram performance of repressor subjects was significantly better in the long-delay than in the short-delay condition; this significant recovery effect between short- and long-delay conditions was not obtained for sensitizer subjects. Possible theoretical mechanisms for these effects and implications for future research are noted.


Can reading ability be measured with tests of memory and processing speed? The author investigated the possibility of estimating reading ability using tests of memory and processing speed that have significantly reduced reading requirements. Four hundred three air force trainees were given tests of their working memory and long-term memory processes, as well as a standardized reading test. A multiple correlation of .79 indicated that global reading ability is substantially correlated with memory processes. Additional analyses indicated that word knowledge and comprehension, the two major components of reading ability, were both explained by the same set of memory process factors, namely, long-term memory processes, semantic memory retrieval speed, and working memory capacity. These results, which are consistent with the view that memory ability underlies reading ability, support the endeavor of measuring reading ability with memory and processing speed tasks.


Quantitative information presentation and gender: an interaction effect. The authors investigated whether performance on mathematical test items would be influenced by an interaction between presentation format and gender. One hundred fourteen students in a management accounting course were randomly assigned either to a tabular format or to a graphics format. There were significant main effects for gender and presentation format; men outperformed women, and the subjects who received the tabular format outperformed the subjects who received the graphics format. A significant interaction supported the existence of a conditional relationship between performance on mathematical test items and presentation format. This relationship varied as a function of gender (symmetry permits the interchange of presentation format and gender). Simple effects for the interaction determined that the women who received the graphics presentation did not perform as well as their male counterparts, or as well as other women and men who received the tabular format. The results of this study indicate that presentation format is an important consideration in gender differences for mathematics performance.


Effects of reinforcement schedules on rats' choice behavior in extinction. The effects of reinforcement schedules on rats' choice behavior in extinction were studied. In a free-operant chamber equipped with two retractable bars, the experimental animals were trained to press the bars separately for a food reward. One bar delivered the reward on a continuous reinforcement (CRF) schedule, and the other delivered the reward on a partial reinforcement (PRF) schedule. Control animals earned the reward from both bars with the same reinforcement schedule, either a CRF or a PRF. When both bars were simultaneously available during extinction, the experimental animals responded more frequently to the CRF than to the PRF alternative, demonstrating a reversed within-subjects partial reinforcement extinction effect (PREE). A conventional between-subjects PREE was replicated in the control subjects. The results of this study were inconsistent with both Amsel's (1962, 1967) frustration hypothesis and Capaldi's (1966, 1967) sequential hypotheses.


White matter lesions in the elderly.

White matter lesions in the elderly. The advent of neuroimaging has brought medical attention to the frequency of unsuspected white matter lesions in the brains of elderly people. In 1987 Hachinski suggested the term "leuko-araiosis" to identify such white matter abnormalities detected by computed tomography and magnetic resonance imaging to emphasize that their etiology and clinical relevance require clarification. Since then, leuko-araiosis has been recognized among approximately ten percent of apparently normal, elderly people over age sixty-five. The severity and frequency of leuko-araiosis increases with advancing age, risk factors for stroke, history of strokes particularly of the lacunar type and dementia of both the vascular and Alzheimer type. Current concepts concerning the pathogenesis and neurological concomitants of leuko-araiosis are reviewed. The etiology of leuko-araiosis may be heterogeneous but is most likely ischemic in nature. However, as white matter lesions progress among the elderly they are likely to become associated with cognitive impairments and motor dyspraxias presumably resulting from cortico-subcortical disconnections, particularly involving the frontal cortex and basal ganglia and may themselves be considered a radiological "risk factor" or precursor for dementia.


Development of myelinated and unmyelinated fibers of human vagus nerve during the first year of life. As an important component of cardiorespiratory control, the vagus nerve and its maturation were evaluated in normal infants in order to provide standards of comparison with infants with dysfunctional neural control mechanisms. Myelinated and unmyelinated fibers in the cervical vagus nerve were examined in 27 term infants. Number of fibers, axon diameters, and myelin thickness were compared among four age groups. The histograms of axon size exhibited a skewed distribution that persisted during the age range examined for both myelinated and unmyelinated vagus fibers. Fiber size distributions of myelinated fibers, however, already showed an incipient multimodal distribution after 3 months. No major increase was observed in the average axon size of myelinated and unmyelinated fibers. A significant increase was observed, however, in the average content of myelin in myelinated fibers expressed as myelin thickness, number of lamellae or g ratio (internal/external diameter). These results suggest an active myelination during the first 9 months of life without a major change in the axonal characteristics of the fibers. A marginal increase in the density of myelinated fibers with age, both in terms of total number and the relation to unmyelinated fibers, suggests a slow transition from unmyelinated to myelinated fibers during the first year of life, particularly during the first 3 months. The present morphometric parameters indicate an active deposition of myelin before the maturation of cross-axonal dimensions. The distribution of g ratios also suggests that optimal conduction velocity is compromised only in a fraction of all vagal myelinated fibers.


Increase in diameter of the axonal initial segment is an early change in amyotrophic lateral sclerosis. We measured the diameter of the most distal portion of the axonal initial segment, the neuronal size of anterior horn cells, and the length of the axon hillock plus the initial segment (AH+IS) in the lumbar spinal cord in motor neuron disease. Three patients with amyotrophic lateral sclerosis (ALS) and one with lower motor neuron disease (LMND) were compared with 11 controls. Serial plastic sections stained with toluidine blue and electron micrographs were studied. A total of 214 axons directly emanating from the somata (n = 207) and the primary dendrites (n = 7) were observed in the patients. Approximately 19% of the proximal myelinated axons (24 axons out of 155 in ALS, and 17 axons out of 59 in LMND) were swollen at the first internode, and most of the swellings extended to the middle portion of the initial segment. Electron microscopy showed that the swellings of the proximal axons (the initial segment and the first internode) directly connected with their somata consisted mainly of accumulations of 10-nm neurofilaments. The average diameter of the most distal initial segment was markedly larger in ALS (n = 155) (P less than 0.0001) and LMND (n = 59) (P less than 0.0001) than in the controls (n = 258). Moreover, the average diameter of the most distal portion of even normal-appearing initial segments of the non-swollen axons was larger in ALS (n = 131) (P less than 0.0001) than in the controls. The perikarya and axon hillocks connected with the normal-appearing and swollen proximal axons and their dendrites almost always appeared normal.(ABSTRACT TRUNCATED AT 250 WORDS)


Hereditary motor and sensory neuropathy with deafness, mental retardation and absence of large myelinated fibers. Two brothers with a presumably hereditary motor and sensory polyneuropathy (HMSN), sensory-neural hearing loss and mental retardation had clinical features and neuropathological changes in the sural nerve which may set the disorder apart from previously described types of HMSN. Consecutive sural nerve biopsies from one case showed absence of large myelinated fibers and a normal complement of small fibers. We infer from our findings that a developmental abnormality with faulty growth and subsequent axonal atrophy may be responsible.


Maximal and minimal motor nerve conduction velocities determined by a collision method: correlation with axonal conduction velocity of type-identified motor units. Maximal and minimal motor nerve conduction velocities of the medial gastrocnemius (MG) muscle nerve were measured by a new collision method in 20 rats of 8-9 weeks of age; the rate of tension increase produced by the muscle was also recorded. Single motor unit analysis in the other 20 rats obtained axonal conduction velocity and contractile properties of type-identified MG motor units. Comparison of the data from these experiments revealed that the maximal and minimal motor nerve conduction velocities obtained by this collision method were most likely to be the axonal conduction velocity of fast-twitch and slow-twitch motor units, respectively. Therefore, these motor nerve conduction velocities in man may also be used as functional parameters of human fast-twitch and slow-twitch motor units, respectively.


Inositol 1,4,5-trisphosphate metabolism in the cerebella of Lurcher mutant mice and patients with olivopontocerebellar atrophy. We have investigated inositol 1,4,5-trisphosphate (InsP3) metabolism in cerebellar membranes of normal humans and patients with dominant ataxia ('C' kindred), and also in cerebellar microsomes of Lurcher mutant mouse (a suggested model for cerebellar ataxia). Various [3H]InsP3 metabolites formed were separated by HPLC using 3 successive convex gradients of 1.7 M ammonium formate, pH 3.7. [3H]InsP3 metabolism was rapid and in 15- and 45-day-old control mice cerebella about 50% of [3H]InsP3 was metabolized within 20 s. In 15-day-old Lurcher mice the rate of [3H]InsP3 metabolism was significantly low (40% of normal). [3H]InsP3 metabolism was almost absent in 45-day-old Lurcher mice cerebellar microsomes. The decreased [3H]InsP3 metabolism was consistent with decreased recovery of the various inositol polyphosphates formed. Similarly, in cerebellar membranes of human patients with olivopontocerebellar atrophy (OPCA) a significant decrease in [3H]InsP3 metabolism was observed when compared with normal controls. These data suggest that altered phosphoinositide turnover may be associated with the onset of neuronal degeneration in human OPCA.


Dystrophin deficiency causes lethal muscle hypertrophy in cats. Two 5-month-old male Domestic Shorthair littermates showed general skeletal muscle hypertrophy, multifocal submucosal lingual calcification with lingual enlargement, and excessive salivation. Both cats had a reduced level of activity, walked with a stiff gait, and tended to "bunny hop" when they ran. These clinical features were similar to those of previously reported dystrophin-deficient cats. Using multiple dystrophin antibodies, we found that the cats described in this report also showed marked dystrophin deficiency. The histopathology was remarkable for hypertrophy and splitting of fibers, and progressive accumulation of calcium deposits within the muscle. There was little or no endomysial fibrosis at 2 years of age. The natural history of dystrophin-deficiency in cats has not been described: both previous cats had been euthanized at 2 years of age prior to experiencing any life-threatening problems. At 6 months of age, one of the new cats developed megaesophagus because of severe progressive hypertrophy of the diaphragmatic muscles. The diaphragm completely occluded the esophagus, and the cat was euthanized for humane reasons. The second cat remained in good condition until age 18 months when it developed acute renal failure attributed to severe prolonged dehydration and hyperosmolality. The cat recovered after receiving supportive treatment but was unable to maintain fluid homeostasis. The insufficient water intake was attributed to glossal hypertrophy and dysfunction. At age 2 years, the cat received regular subcutaneous injections of low-sodium fluids to maintain proper hydration. The clinical consequence of dystrophin deficiency in cats is lethal muscle hypertrophy. We have called the feline disease "hypertrophic feline muscular dystrophy" (HFMD).


Increased leakage of calcium ion from the sarcoplasmic reticulum of the mdx mouse. Using a single skinned muscle fiber, the function of the contractile system and the sarcoplasmic reticulum (SR) were analyzed in the skeletal muscle of the mdx mouse. Activation of the contractile system by calcium ion and the maximum force generation was normal. Ca2+ uptake of the SR was normal as well as regulation of the Ca-induced Ca release (CICR) by Ca2+. However, contracture by caffeine was more prominent in mdx than in control mice. Ca2+ leaked more from the SR of mdx in the presence of EGTA and ATP or its analogue. These abnormalities are probably interrelated; increased leakage of Ca2+ might cause the enhanced response to caffeine, since Ca2+ itself facilitates Ca release by caffeine. The abnormal leakage of Ca2+ might also activate the Ca pump of SR in the resting state, which consume extra ATP and disturb energy metabolism.


Delayed expression of dystrophin on regenerating muscle from two siblings with Becker muscular dystrophy. We present here a unique expression of dystrophin on biopsied muscle from 2 siblings with Becker muscular dystrophy (BMD). They had neither muscle weakness nor atrophy. Clustered dystrophin-deficient fibers were constituted to regenerating basophilic fibers (mainly type 2C fiber) based on histochemical stainings. We speculate that the developmental delay in the expression of dystrophin is a characteristic finding in regenerating fibers from asymptomatic and young BMD patients, such as the siblings in this report.


Production of soluble autocrine inhibitory factors by human glioma cell lines. Gliomas in vitro exhibit density-limited growth upon the attainment of confluency, an effect usually attributed to cell-cell contact inhibition. Since gliomas have been demonstrated to secrete an array of soluble factors which can enhance tumor growth, we undertook this study to ascertain whether production of soluble factors by the tumor may also inhibit growth in an autocrine manner, and whether production of such factors is associated with the growth phase of the glioma. We observed that cell-conditioned medium (supernatants) from non-confluent glioma cultures induced growth, while confluent culture supernatants produced pronounced growth suppression. These latter supernatants enhanced proliferation of non-transformed astrocytes. Supernatants derived from all stages of confluency produced inhibition of lymphocyte proliferation. To characterize these factors, dialyzed supernatant was tested and found to continue to produce lymphocyte suppression but no glioma growth limitation. Growth of tumors in indomethacin or in acetylsalicylic acid to abolish prostanoid synthesis abrogated the inhibitory influence on glioma growth but only partially reversed the lymphocyte suppressive capacity. These studies suggest that gliomas do produce a growth phase dependent autocrine inhibitory factor(s), and that the production of these small molecular weight factors is at least partially under control of the cyclooxygenase pathway.


Physiological and biochemical studies on the cerebellar cortex of the murine mutants "jolting" and "motor end-plate disease". The activity of cerebellar Purkinje cells in the murine mutants "jolting" and "med" has been determined using extracellular electrical recordings in vivo and in isolated cerebellar slices. Most of the cells in the mutant brains failed to generate simple spontaneous action potentials, but they responded to climbing fibre inputs by generating complex potentials. The few mutant cells that were spontaneously active exhibited much lower firing frequencies than normal cells, and interval histograms of spontaneous activity were skewed towards longer intervals. The silent cells in mutant cerebellar slices could be activated by direct intracellular stimulation, by antidromic excitation and by the application of glutamate and high [K+]0. Activity was not restored by the application of bicuculline. It seems that the failure of the cerebellar Purkinje cells to generate simple spontaneous action potentials is not due to an inherent inexcitability of the soma or to the excessive activity of GABA-ergic inputs onto the cells. It is suggested that an abnormality in the behaviour of a Ca2+ channel is the most likely origin for the deficit in these mutant mice.


Phospholipids in X-linked adrenoleukodystrophy white matter: fatty acid abnormalities before the onset of demyelination. Changes in fatty acid composition of complex lipids were analyzed in postmortem white matter from a patient with late onset adrenoleukodystrophy (ALD). The specimen showed three regions with progressive myelin breakdown: morphologically normal white matter; areas with active demyelination and perivascular lymphocyte and macrophage infiltration; and areas with marked gliosis. In the morphologically intact region, cholesterol esters were similar in amount and fatty acid composition to those in control tissue, although marked changes were observed in the actively demyelinating area. Galactolipids in these areas were also similar to those in controls. In contrast, glycerophospholipids were increased in amount and in very long chain fatty acids (VLCFA), which are the hallmark of ALD, at the active edge of the demyelinative lesion and even in the apparently intact sample. Further fractionation of the glycerophospholipids by high performance liquid chromatography showed a significant (up to 39-fold) accumulation of hexacosanoic acid (C26:0) in phosphatidylcholine, but not in other phosphatidyl derivatives. The consistent increases in phosphatidylcholine VLCFA in all samples from the ALD brain, which are postulated to represent progressive stages in the development of the disorder, suggest that phosphatidylcholine may be involved in antigen formation and may underlie an immunological basis for the pathogenesis of ALD.


Effects of chronic catecholamine depletions on muscarinic M1-receptor and its mRNA in rat brain. In order to compare the effects of total catecholamine (CA) or noradrenaline (NA) depletions on cholinergic systems, and the mechanisms of receptor regulation in various brain regions, the regional changes in the levels of acetylcholine (ACh), M1-receptor (M1-R) binding, and M1-R messenger RNA (mRNA) were mainly examined in rats which had received either repeated reserpine treatment or a single injection of the selective noradrenergic neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP-4). The levels of dopamine (DA), its metabolites, NA, binding to both D1 and D2 sites, and the mRNA encoding the D2 receptor were also measured. Administration of reserpine (0.5 mg/kg/day, s.c.) for 2, 7 and 14 days depleted DA and NA in virtually all brain regions, while the short-term treatment increased DA metabolites in the striatum (at 2 days) and basal forebrain (at both 2 and 7 days). Administration of DSP-4 (50 mg/kg, i.p.) resulted in a specific loss of NA in the brain 10 days after the injection. These DSP-4 treated rats showed no change in the levels of ACh or M1-R except for an increase in ACh in the frontal cortex. In contrast, numerous changes in cholinergic indices were seen in the reserpine treated groups, and these changes varied from region to region of brain and with the length of drug treatment. In the striatum, ACh levels were increased in rats treated for 2 or 7 days but were normal after 14 days. M1-Rs were decreased at 14 days. These changes suggest that striatal DA, initially released by reserpine, inhibits the release of ACh from striatal cholinergic interneurons, while prolonged depletion of DA relieves this inhibition, leading to a subsequent down-regulation of M1-Rs. In the frontal cortex, ACh and M1-R levels were all decreased by reserpine treatment for 2 or 7 days, and the M1-Rs remained depressed at 14 days. In the basal forebrain, which contains the cholinergic cells that project to the cortex, DA metabolism was increased by 2 or 7 day reserpine treatment. This increased DAergic activity in the basal forebrain may facilitate cholinergic neurons, causing increased release of ACh in the frontal cortex. This, in turn, may lead to a down-regulation of the M1-Rs in that region. The levels of mRNAs encoding M1-Rs were increased in the striatum and frontal cortex by reserpine treatment, despite the decreases in the M1-Rs themselves.(ABSTRACT TRUNCATED AT 400 WORDS)


Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome. A modified maintenance of wakefulness test was performed in 58 patients with obstructive sleep apnea (OSA) syndrome before treatment and after long-term (554 +/- 28 days) home therapy with nasal continuous positive airway pressure (CPAP). Before treatment the patients had a shorter mean sleep latency than controls (16 +/- 1 vs. 27 +/- 1 min, mean +/- SEM, P less than 0.001). After treatment, the mean sleep latency increased to 20 +/- 1 min (P less than 0.002 as compared to baseline), but was still shorter than in controls (P less than 0.001). The incomplete normalization of the mean latency contrasted with the patients' claim that they no longer felt sleepy. The improvement in daytime alertness was significantly correlated with the reduction in sleep fragmentation after CPAP treatment and with the baseline mean sleep latency. These results support the hypothesis that sleep disruption related to respiratory events plays a role in the pathogenesis of daytime sleepiness.


Imipramine induced lipidosis and dexamethasone effect: morphological and biochemical study in normal and chronic GM2 gangliosidosis fibroblasts. A large heterogeneous group of lysosomotropic compounds with a common cationic amphiphilic structure induces in vitro and in vivo lysosomal lipid storage. The biochemical mechanism underlying the lipidosis is still the subject of investigation. The authors report the experimental effect of imipramine and dexamethasone on lysosomal system in cultured skin fibroblasts. Morphological and ultrastructural observations of cells treated with imipramine showed vacuoles with lipidic storage, enlarged lysosomes with electron translucent zones and normal appearance of all the other cytoplasmic organelles. The lysosomal enzyme activities were decreased on biochemical study. On the contrary, an increased enzyme activity was detected in the culture medium. Pretreatment with dexamethasone partially prevented the effect of imipramine. Our results suggest that tricyclic antidepressants may induce lysosomal lipidosis through a dysfunction in the recycling of mannose-6-phosphate receptors and in the trafficking of newly synthesized lysosomal enzymes. Moreover the data presented may provide a clue in understanding some of the side effects observed in patients chronically treated with antidepressant drugs.


Comparison of the effects of selective and nonselective muscarinic agonists on cognition and thermoregulation in primates. Peripheral toxicity may explain the disappointing therapeutic effects of nonselective muscarinic agonists in Alzheimer's disease. Partial agonists might exhibit an improved therapeutic index. We compare the central and peripheral cholinergic effects of RS86 with the M1/M3 partial agonists AF 102B and L-689,660 ((-)-3-[2-6 chloropyrazin)yl]-1-azabicyclo[2.2.2]octane) in primates. Administration of RS86 (1.5-2.25 mg/kg i.m.) or L-689,660 (0.1-0.3 mg/kg i.m.), but not AF 102B (up to 6 mg/kg i.m.), caused partial reversal of the disruptive effects of scopolamine on cognition. However, performance remained significantly poorer than in untreated control animals. Adverse effects prevented examination of higher doses. Centrally-mediated hypothermia was induced by RS86 (0.05 mg/kg p.o.) and L-689,660 (0.01 mg/kg p.o.) but only by a high dose of AF 102B (7 mg/kg p.o.). The putative therapeutic advantages of partial M1/M3 agonists over RS86 are discussed.


MRI findings of multiple sclerosis with acute transverse myelopathy. We classified clinically definite multiple sclerosis (MS) patients who underwent brain MRI with superconductive magnet into 2 subgroups: group A, consisting of 14 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 35 patients without ATM, and the same neuroradiologist, blinded to clinical profiles of the patients, investigated the MR scans. We analyzed some parameters such as distribution, size, shape and number of the lesions. Although the total number of lesions were similar in each group, and the number of small size or patchy shape solitary lesions were not different, the moderate, large, ovoid or confluent lesions were lower in number in group A, compared with group B. The degree of cerebral white matter lesions and periventricular lesions were higher in group B. Brainstem lesions were significantly less common in group A. These results show characteristic differences in MR-detected, possibly pathological, changes between these 2 groups, and support our previous report that group A may constitute a distinct subgroup in patients with MS.


Hemi-parkinsonism in multiple system atrophy: a PET and MRI study. We selected 6 patients presenting with hemi-parkinsonism from a total of 20 patients with probable multiple system atrophy (MSA) and studied their nigrostriatal lesions using magnetic resonance (MR) imaging and positron emission tomography (PET) with 18F-labeled 2-deoxy-2-fluoro-D-glucose (FDG). T2 weighted MR images demonstrated a decreased signal intensity in the putamen of all patients. This decreased signal was more intense in the nucleus contralateral to the affected body side in 5 patients. A decreased signal in the substantia nigra was found, expanding more on the contralateral side in 3 patients. T1-weighted images showed that the contralateral putamen was smaller in size than the ipsilateral. These findings indicated that the iron deposit and the neuronal cell loss in the degenerative process were more remarkable in the contralateral nuclei. FDG uptake in 5 patients had likewise declined more in the contralateral than in the ipsilateral putamen. The study shows that these patients have the nigrostriatal lesions as described in previous reports on MSA and that an asymmetric lesion relating to clinical signs is present in the nigrostriatal system. When a patient presents with hemi-parkinsonism alone, MR imaging and PET/FDG are useful for the clinical diagnosis of MSA.


Quantitative EEG mapping and PET in Alzheimer's disease. Quantitative analysis of topographical EEG was studied in comparison with measurement of regional glucose metabolism by PET in 42 patients with clinical diagnosis of probable dementia of Alzheimer type (AD) and in 15 age-matched normal controls. Measures analyzed included global and regional data from areas typically affected and not affected by AD pathology. While disturbance of metabolism followed a typical regional pattern, relative alpha, theta and delta power were more globally altered without selectivity for specific regions. Separation between AD and age matched controls by relative theta power was correct in 86% and was close to that by temporo-parietal glucose metabolism (correct classification 87%). Relative theta power as well as temporo-parietal glucose metabolism were significantly correlated (tau B = 0.54 and -0.53, respectively) to severity of AD assessed by the global deterioration scale. These results indicate that EEG measures may be used with an accuracy close to metabolic values from PET for the assessment of severity of AD.


Immunoreactive parvalbumin concentrations in parahippocampal gyrus decrease in patients with Alzheimer's disease. By using a sensitive enzyme immunoassay system for rat parvalbumin, we determined parvalbumin contents in the 4 cerebrocortical regions (superior frontal gyrus of frontal lobe, parahippocampal gyrus of temporal lobe, superior parietal lobule of parietal lobe, and calcarine area of occipital lobe) of patients with Alzheimer's disease and age-matched controls. Among the 4 regions, concentrations of parvalbumin were the highest in calcarine area (68.6 +/- 6.7 ng/mg protein, rat parvalbumin equivalents, mean +/- SE) and the lowest in the parahippocampal gyrus (11.0 +/- 1.7 ng/mg protein) in the controls. A similar regional difference of the concentration was observed also in the patients with Alzheimer's disease. When compared with the controls, however, concentrations of parvalbumin in parahippocampal gyrus of patients with Alzheimer's disease (4.0 +/- 0.9 ng/mg protein) were significantly low (P less than 0.01), showing less than a half of the control values. In contrast, the concentrations in the 3 other regions showed little difference between Alzheimer's disease and the controls.


Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction. In order to support the concept that a lesion of the thalamus is sufficient to cause a Korsakoff syndrome, we are presenting 5 patients, all of whom developed the syndrome after sustaining a left (dominant) thalamic infarction. Two patients had pure thalamic strokes followed by a permanent Korsakoff syndrome. One of these patients was studied with neuropsychometric testing, as well as with a modern MRI scan. In 2 other patients, clinical and imaging data indicate that infarction was not limited to the thalamus. Another patient had bilateral thalamic infarcts but only a temporary Korsakoff syndrome. Neuropathological data are needed to elucidate the exact anatomical substrate of dominant thalamic Korsakoff syndrome.


Surface electromyographic study of idiopathic cranial dystonia focused on the orbicularis oculi muscles. We studied 115 Japanese patients with idiopathic cranial dystonia (Meige disease), using surface electromyography (EMG) focused on the orbicularis oculi muscles to classify the findings of the abnormal involuntary movements of this disease and to evaluate the pathophysiology of blepharospasm (BS). Surface EMGs at rest and at voluntary eyelid opening after eyelid closing were investigated. We found 62 (53.9%) patients exhibiting the overblinking type, 37 (32.2%) the tonic BS type, and 16 (13.9%) the normal type of behavior, considering the frequency of spontaneous blinking and presence of spasms. The present results suggest that BS is not a summation of blinking but a spatial and temporal extension of the orbicularis oculi muscle activity engaging in blinking, and the classification of the present study can support the investigation of the temporal characteristics of patients with this disease.


Pathological changes in skeletal muscle in HTLV-I-associated myelopathy. The main lesion site of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the pyramidal tract. In some HAM patients, clinical symptoms and findings indicate neuromuscular involvement, such as muscular atrophy, fasciculation, elevated serum creatine kinase (CK) or significant electrophysiological data. Cases of HAM/TSP complicated with polymyositis or motor neuron disease have been reported. But no investigation has been directed to muscular pathology in many patients of HAM/TSP. We conducted muscle biopsies on 13 HAM patients. Four patients showed neurogenic changes. Six patients showed histological findings indicative of inflammatory myopathy. We investigated surface marker of invading cells in these 6 patients. In all patients, T lymphocytes were more predominant than B lymphocytes and in three of them T helper/inducer cells were more predominant than T suppressor cells. In 2 patients, only slight myopathic change could be seen, such as variation in fiber diameter and increase in the number of internal nuclei. In 1 patient, type 2 fiber atrophy was seen, and was possibly the result of disuse. Disturbance of secondary motor neurons or inflammatory myopathy is thus shown to be possibly associated with HAM/TSP.


Modification of cervical dystonia by selective sensory stimulation. Cervical dystonia is often refractory to all forms of therapy. Many patients, however, are able to transiently abolish their spasms following a specific gesture that presumably enhances sensory input. Such observations prompted us to develop a protocol to determine if various forms of sensory stimulation could modify the motor control patterns in cervical dystonia. Surface EMG recordings of multiple neck and trunk muscles were obtained in 11 consecutive cervical dystonia patients. Baseline patterns of voluntary and involuntary muscle activation were established during a series of motor and non-motor tasks. The tasks were repeated during the application of vibratory or electrical stimulation to select muscle groups or to cutaneous and mixed nerves. Analysis of the results was made on the basis of paper and computer recordings of the data. Sensory stimulation decreased involuntary muscle activity and reduced spasms in 5 subjects. However, objective or subjective improvement usually occurred only after specific stimuli were applied to specific anatomical sites. In these cases, the protocol identified the site at which a specific sensory stimulus could be applied to control the dystonia. We conclude that selective sensory stimulation can beneficially modify cervical dystonia in some patients. Such findings warrant further investigation of the use of sensory stimulation for control of cervical dystonia.


Protein energy malnutrition and the nervous system. Protein-energy malnutrition (PEM), a natural ramification of poverty, continues to be a perennial source of concern to a large segment of the world population. The developing nervous system of a child is specially vulnerable to deprivations in nurture. Peripheral nerve and muscle derangements are clinically evident by weakness, hypotonia and hyporeflexia in accordance with severity and duration of PEM. Motor and sensory nerve conduction studies exhibit significant abnormalities and often furnish useful and ominous correlation with grades of PEM. The human sural nerve histology in cases of severe PEM is characterized by persistence of small myelinated fibres, striking failure of internodal elongation and significant segmental demyelination. Young rhesus monkeys are ideal experimental PEM models and they show myopathic EMG changes amenable to rehabilitation. Muscle pathology comprises obliteration of cross-striations, streaming of Z bands, increased interfibrillary spaces, mitochondriomegaly and small-for-age fibres. Radioisotope assays reveal anomalous incorporation into various nerve and muscle constituents. Central nervous system, specially the neuropsychological functions are affected in a lasting manner. Learning deficits, behavioural problems and manual indexterity are most obtrusive features.


Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI. Previous studies of the neurocontrol of movement in spinal cord injury (SCI) subjects revealed that even those without volitional movement may retain some degree of preservation of distal brain influence. We previously defined a discomplete lesion as one which is clinically complete but which is accompanied by neurophysiological evidence of residual brain influence on spinal cord function below the lesion. In order to document the nature and extent of such neurocontrol, we recorded surface EMGs from multiple muscle groups to study patterns of motor unit activity in response to tendon vibration, activation of muscles below the lesion by reinforcement maneuvers above the lesion and by voluntary suppression of plantar withdrawal reflexes. We analyzed data from this brain motor control assessment (BMCA) procedure in order to describe the frequency of occurrence and characteristics of residual control in discomplete SCI subjects, comparing with findings in (clinically and neurophysiologically) complete and in (clinically and neurophysiologically) incomplete SCI subjects. From a group of 139 SCI subjects seen for management of spasticity, 88 had clinically complete lesions. Of these, 74 (84%) were discomplete as defined by responses to the above maneuvers. The selection of management and intervention strategies, whether physiological, pharmacological, behavioral or surgical, should give consideration to the high likelihood that clinically complete subjects may be neurophysiologically incomplete.


Hypoxic neuropathy versus diabetic neuropathy. An electrophysiological study in rats. In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypoxic conditions (10% O2) for a 10-week period. Two factors are held responsible for the development of diabetic polyneuropathy: metabolic deterioration and hypoxia. However, until now the relative roles of metabolic deterioration and hypoxia in the development of polyneuropathy have not been settled. To test both explanations further with more sophisticated electrophysiological techniques, the H-reflex (motor and sensory NVC) and the stimulated SF-EMG (measures terminal nerve branch and neuromuscular transmission) were measured in 3 groups of 10 rats, a healthy control group, a diabetic group, and a hypoxic group, every 5 weeks, for 6 months. In the control rats an age-related increase in motor and sensory conduction velocity was found, whereas in the diabetic rats as well as in the hypoxic rats a marked decrease in sensory and a slight decrease in motor nerve conduction velocity was observed. The jitter measured in the stimulated SF-EMG was significantly increased in both the diabetic and the hypoxic group. The results of the present study support the possible role of hypoxia, in addition to metabolic factors, in the development of experimental diabetic neuropathy.


The relationship of nerve to myoblasts and newly-formed secondary myotubes in the fourth lumbrical muscle of the rat foetus. The formation of normal numbers of skeletal muscle fibres depends on functional innervation of the muscle before and during the period of secondary myotube formation, but little has been known about the physical relationship between nerve terminals and the myoblasts and secondary myotubes over the critical period. This paper reports the results of a serial-section electron microscopic study of the IVth lumbrical muscle of the rat hindlimb, studied on embryonic day 20 (E20), a time when all secondary myotubes are less than 24 h old, and new ones are rapidly forming. Most myoblasts lying within the endplate region of the muscle received some direct neural contact; in almost all cases, the contact originated from an extension of a differentiated nerve terminal present at the endplate of an adjacent primary myotube. At six of 15 neural contact sites on myoblasts, primitive synaptic specialization was present. The newly-formed secondary myotubes were also directly, although sparsely, innervated in nine of ten instances. One secondary myotube was never seen to be innervated, despite extensive serial tracing. Nerve terminals passing to secondary myotubes were also principally derived from the innervation zone of the earlier-formed primary myotubes. Primary myotubes were profusely innervated by multiple axons. The results suggest that most nerve terminals are initially accommodated on the primary generation of myotubes, but progressively transfer to pre-fusion myoblasts or to secondary myotubes as these appear. In general, very young secondary myotubes are innervated by only a single axon, rather than being polyneuronally innervated. The existence of some secondary myotubes which lack any direct innervation suggests that intimate nerve contact may not be obligatory for formation of new secondary myotubes.


The astrocyte--extracellular matrix complex in CNS myelinated tracts: a comparative study on the distribution of hyaluronate in rat, goldfish and lamprey. The localization of hyaluronate was studied in the CNS of rat, goldfish and lamprey. Cryostat sections were incubated with glial hyaluronate-binding protein of human origin and stained by indirect immunofluorescence with glial hyaluronate binding protein antibodies not reaching with rat and fish. As previously reported for glial hyaluronate-binding protein and glial fibrillary acidic protein, hyaluronate and glial fibrillary acidic protein had a similar distribution in rat spinal cord and optic nerve, both substances forming ring-like structures around individual myelinated axons. A similar periaxonal distribution was observed in goldfish spinal cord and medulla, except that the rings were much wider, to accommodate the large goldfish axons. The glial fibrillary acidic protein-positive neuroglial tissue forming distinctive structures in goldfish vagal lobes also stained for hyaluronate. In both rat and goldfish spinal cord, motoneurons were surrounded by a hyaluronate coat. Goldfish optic nerve and lamprey spinal cord were hyaluronate-negative and, as previously reported, they stained for keratin but not for glial fibrillary acidic protein. The findings suggest that hyaluronate in CNS fibre tracts in a product of glial fibrillary acidic protein-positive neuroglia. They also suggest that the appearance of glial fibrillary acidic protein-positive neuroglia and the formation of a hyaluronate-bound extracellular matrix are related phenomena in phylogeny.


Beta-like ganglion cells in the South American opossum retina: a Golgi study. Using the Golgi technique we investigated the morphology of the ganglion cells of the South American opossum retina. We focused our attention on a type of ganglion cell which has a relatively small dendritic field diameter and a medium-sized soma, making it a morphological equivalent of beta ganglion cells of cat retina. Both radial sections of the retina, where the stratification level of ganglion cells dendrites can be observed in the inner plexiform layer (IPL), and flat preparations of the retina, where the whole dendritic field of the ganglion cells can be examined and quantified, have been studied. Usually these cells have one to three primary dendrites, giving rise to short spiny branches. The dendrites of these cells are segregated in two groups, one with dendritic trees arborizing in the inner two thirds and another group arborizing in the outer third of the IPL. The two groups of beta-like cells probably represent the physiological ON- and OFF-center types of ganglion cell as found in cat retina. The mean cell body and dendritic field diameters of 47 cells were 18.5 +/- 1.6 microns, (size range 16-21 microns) and 91.5 +/- 16 microns (range 54-133 microns), respectively. Cell body and dendritic fields sizes were homogeneous across the retina of the opossum. In the opossum the relatively large dendritic fields of the beta-like ganglion cells in the area centralis are consistent with the poor visual acuity of this species.


Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues can be salvaged only by recirculation, and any brain damage incurred is delayed, suggesting that the calcium transient gives rise to sustained changes in membrane function and metabolism. If the ischemia is less dense, as in the penumbral zone of a focal ischemic lesion, pump failure may be moderate and the leak may be only slightly or intermittently enhanced. These differences in the pump/leak relationship for calcium explain why calcium and glutamate antagonists may lack effect on the cardiac arrest type of ischemia, while decreasing infarct size in focal ischemia. The adverse effects of acidosis may be exerted by several mechanisms. When the ischemia is sustained, acidosis may promote edema formation by inducing Na+ and Cl- accumulation via coupled Na+/H+ and Cl-/HCO3- exchange; however, it may also prevent recovery of mitochondrial metabolism and resumption of H+ extrusion. If the ischemia is transient, pronounced intraischemic acidosis triggers delayed damage characterized by gross edema and seizures. Possibly, this is a result of free-radical formation. If the ischemia is moderate, as in the penumbral zone of a focal ischemic lesion, the effect of acidosis is controversial. In fact, enhanced glucolysis may then be beneficial. Although free radicals have long been assumed to be mediators of ischemic cell death, it is only recently that more substantial evidence of their participation has been produced. It now seems likely that one major target of free radicals is the microvasculature, and that free radicals and other mediators of inflammatory reactions (such as platelet-activating factor) aggravate the ischemic lesion by causing microvascular dysfunction and blood-brain barrier disruption.(ABSTRACT TRUNCATED AT 400 WORDS)


Adult intramedullary astrocytomas of the spinal cord. In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs.


Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear. Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury. But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia. Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 3.1 +/- 2.1 hours after injury). Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gm.min-1) was present. Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow. Overall, global or regional ischemia was found in 11 patients (31.4%). There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2. Ischemia was significantly associated with early mortality (p less than 0.02), whereas normal or high CBF values were not predictive of favorable short-term outcome. These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke.


Spinal arachnoid cysts in the pediatric age group: an association with neural tube defects. Between 1979 and 1991, spinal arachnoid cysts were found in 11 patients aged 19 months to 18 years (mean age 5 1/2 years). Of the 11 patients, six had a myelomeningocele and one diastematomyelia. The presenting symptoms included radicular pain (one patient), progressive weakness (three), increasing scoliosis (one), worsening spasticity (three), and recurrent urinary tract infections and progressive constipation (one). Two patients showed no symptoms from the spinal arachnoid cyst. The distribution of lesions was as follows: cervicomedullary (one patient), cervical (one), cervicothoracic (two), thoracic (four), lumbar (two), and sacral (one). Four of the 11 arachnoid cysts (all intradural) were located anterior to the spinal cord, three of which were in children with a myelomeningocele. Only two of the cysts were extradural; both were found in the lumbosacral region, and one was associated with diastematomyelia. Eight patients were treated with fenestration and/or resection of the cyst wall. Three patients with anterior cysts were treated with shunts, a cyst-to-pleural space shunt in two and a cyst-to-subarachnoid space shunt in one. All of the patients either improved or exhibited an arrest in the progression of their symptoms. Spinal arachnoid cysts are a treatable cause of progressive neurological deficits and, in this series, were frequently found in patients with neural tube defects.


Intractable pain of spinal cord origin: clinical features and implications for surgery. The clinical features and types of pain affecting 127 patients with central pain caused by lesions in the spinal cord were studied and correlated with the results of surgical procedures performed on 103 of them. The surgical procedures consisted of percutaneous cordotomy in 39 cases, cordectomy in 12, dorsal root entry zone (DREZ) surgery in four, dorsal cord stimulation in 35, and brain stimulation in 13. The three most common types of pain in the 127 patients were characterized as: steady in 95% of cases, intermittent (usually shooting) in 31%, and evoked (allodynia, hyperpathia, or hyperesthesia) in 45%. Steady pain was usually causalgic (74.8%) or dysesthetic (27.6%). The only obvious clinical correlation with pain type was the association of intermittent pain with lesions at the T10-L2 vertebral level. Destructive surgery (cordotomy, DREZ surgery, or cordectomy) affected the three chief types of pain differently from treatment with cord or brain stimulation. Destructive surgery resulted in reduction of steady pain in 26% of affected cases, of intermittent pain in 89%, and of evoked pain in 84%, while stimulation resulted in pain reductions in 36%, 0%, and 16% of cases, respectively. The differential effect of destructive surgery on steady and intermittent pain is consistent with published experience. These observations suggest differing mechanisms for the three types of pain.


Oblique sagittal magnetic resonance imaging visualizing vascular compression of the trigeminal or facial nerve. An oblique sagittal magnetic resonance (MR) imaging method was developed to provide better visualization of vascular compression of nerves. The MR images of 12 patients with trigeminal neuralgia and 24 with hemifacial spasm were analyzed. The oblique sagittal views were obtained along the nerve identified by the axial view at an angle of 105 degrees between the line along the dorsal brain stem and the line along the margin of the pontomedullary junction (in patients with hemifacial spasm) or by the midsagittal view through the midpons (in patients with trigeminal neuralgia). The T1- and T2-weighted, proton-density, and/or gradient-echo MR images were evaluated to optimize imaging conditions. The oblique sagittal gradient-echo MR image most clearly visualized vascular compression of the nerves as high-intensity lines in six patients with trigeminal neuralgia, which was confirmed intraoperatively in four. Fifteen (75%) of 20 oblique sagittal gradient-echo MR images demonstrated vascular compression of the facial nerves in patients with hemifacial spasm; 12 of these were confirmed intraoperatively. The control study used 15 oblique sagittal gradient-echo MR images of nonaffected contralateral and normal sites. Four false-positive findings were found. Oblique sagittal gradient-echo MR images are a useful planning aid, allowing differential diagnosis prior to microvascular decompression in trigeminal neuralgia and hemifacial spasm.


An artificial blood vessel with an endothelial-cell monolayer. An artificial blood vessel with an endothelial-cell monolayer was used as an arterial substitute in rats. Endothelial cells were isolated from the aorta of a Wistar rat by the digestion method. The cell identification was established by the cobblestone appearance of a confluent cell monolayer, by an expression of factor VIII-related antigen, and by the presence of Weibel-Palade bodies. The luminal surface of the thin-walled polytetrafluoroethylene (PTFE) graft (4 mm in diameter and 10 mm in length) was coated with an endothelial-cell monolayer for 7 days in vitro. An interpositional graft was placed using the endothelial cell-coated PTFE prosthesis on the right common carotid artery in seven rats. A total of 10 rats received an interpositional graft with the noncoated PTFE prosthesis as a control. The patency rate at 1 month after implantation was significantly higher in the coated group than in the control group. The vascular prosthesis with an endothelial-cell monolayer is a promising technique to inhibit the development of thrombosis.


Selective blood-tumor barrier disruption by leukotrienes. The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).


Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells. Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells.


Neuropeptide Y in the primate model of subarachnoid hemorrhage. The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.


Effects of vasopressin and oxytocin on canine cerebral circulation in vivo. In vivo experiments on the vasoactive effects of vasopressin and oxytocin on cerebral circulation were carried out in anesthetized dogs, using an electromagnetic flowmeter to measure vertebral blood flow and angiography to measure the internal diameter of the basilar artery. Direct bolus infusion of 1 pmol to 1 nmol of vasopressin or 10 pmol to 10 nmol of oxytocin into a femoral-vertebral artery shunt produced a dose-dependent decrease in vertebral artery blood flow without significantly affecting mean arterial blood pressure. Vasopressin was more potent than endothelin and neuropeptide Y, which have also been demonstrated to induce long-lasting decreases in vertebral artery blood flow. However, direct bolus infusion of vasopressin (100 pmol and 1 nmol) or oxytocin (1 nmol and 10 nmol) into the vertebral artery dilated major vessels including the vertebral, anterior spinal, and basilar arteries, as well as the circle of Willis and its main branches, while endothelin (1 nmol) and neuropeptide Y (5 nmol) caused no change in the diameters of major cerebral arteries. The V1 antagonist d(CH2)5tyrosine(methyl) arginine vasopressin suppressed the effects of both vasopressin and oxytocin. Vasopressin was over 10 times as potent as oxytocin in both assays. The vasodilatory effect of vasopressin, which may be mediated by an endothelium-dependent mechanism, was functionally damaged in dogs after experimental subarachnoid hemorrhage. These data suggest regional differences in the sensitivity and responsiveness of vasculature to vasopressin and oxytocin, and specifically that both peptides act through V1 receptors to decrease the resistance of large vessels and increase the resistance of small vessels.


Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study. The effect of hypothermia on neuronal injury following permanent middle cerebral artery (MCA) occlusion in the rat was examined. Moderate hypothermia (body temperature 24 degrees C) was induced before MCA occlusion (0-minute delay group) in six rats, at 30 minutes in eight rats, and at 1 (seven rats), 2 (seven rats), and 3 (nine rats) hours after occlusion. The rats were kept at a 24 degrees C body temperature for 1 hour, then allowed to rewarm over 90 minutes. The animals were sacrificed 24 hours after MCA occlusion, and infarction was visualized by staining of coronal sections with 2,3,5-triphenyltetrazolium chloride. Infarct volumes were compared to matched normothermic control rats (body temperature 36 degrees C). Additional groups of 0-minute delay hypothermic (10 rats) and control animals (nine rats) were sacrificed 72 hours after MCA occlusion to examine the effects of prolonged survival. A significant reduction in the percentage of infarcted right hemisphere was seen in the animals sacrificed after 24 hours with 0-minute, 30-minute, and 1-hour delays in inducing hypothermia (mean +/- standard error of the mean: 2.2% +/- 0.7%, 4.4% +/- 0.9%, and 3.6% +/- 1.1%, respectively) as compared to normothermic control rats (10.8% +/- 1.5%, p less than 0.01 by Student's t-test). In the 2- and 3-hour delay groups, the percentage of infarcted right hemisphere was 17.1% +/- 2.4% and 12.0% +/- 2.7%, respectively, and no decrease in infarct volume was observed. The 0-minute delay hypothermia group sacrificed after 72 hours also displayed a significant reduction in right hemisphere infarct compared to their respective controls (4.8% vs. 11.7%, p less than 0.05). These findings indicate that, in the setting of permanent MCA occlusion, hypothermia markedly decreases brain injury even when its induction is delayed for up to 1 hour after the onset of ischemia. Ischemic damage does not appear to be merely retarded but permanently averted.


Insulin and insulin-like growth factors in central nervous system tumors. Part V: Production of insulin-like growth factors I and II in vitro. The authors have previously reported the presence of insulin-like growth factor (IGF) receptors in central nervous system (CNS) tumors and the production of IGF's and their binding proteins by CNS tumors in situ. This study was designed to investigate whether CNS tumor cells are capable of autocrine secretion of IGF-I and IGF-II in vitro. Production of IGF's was studied by specific radioimmunoassay of tumor-cell-conditioned serum-free media from 34 CNS tumors: 12 gliomas, 12 meningiomas, and 10 miscellaneous tumors. Normal human serum and cerebrospinal fluid served as controls. Insulin-like growth factor I was detected in five of 12 meningiomas but in none of the gliomas studied. In contrast, IGF-II was detected in four of 12 gliomas and in six of 11 meningiomas studied. Four miscellaneous tumors produced IGF-I and/or IGF-II. These results suggest that CNS tumors differentially produce IGF-I and IGF-II in vitro. Preferential production of IGF's may be an important marker of the tumor-cell differentiation or malignancy and may be useful as a clinical diagnostic tool. These results add further support to the concept that IGF's may play a role in the regulation of the behavior of CNS tumors.


Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo. Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.


Effects of different methods of peripheral nerve repair on the number and distribution of muscle afferent neurons in rat dorsal root ganglion. The effects of three methods of peripheral nerve repair and normal controls were compared with respect to the number and distribution of muscle afferent nerve cell bodies from the extensor digitorum longus muscle in the dorsal root ganglia of the rat. Nerves were repaired using one of three methods: 1) direct epineurial suture; 2) a three-strand cable graft; or 3) a coaxially aligned freeze-thawed autologous skeletal muscle graft. In all cases the number and distribution of muscle afferent nerve cells were estimated 300 days after nerve repair. Retrograde transport of horseradish peroxidase, injected into the extensor digitorum longus muscle, was used to identify muscle afferent nerve cell bodies in dorsal root ganglia exposed at laminectomy after fixation. It was found that all methods of nerve repair were associated with a change in both the number and distribution of labeled muscle afferent cell bodies. The number of labeled muscle afferent cells was significantly different from normal controls in all methods of repair, but was not significantly different among the three methods compared. On the other hand, cell size and cell distribution departed significantly more from normal after either of the grafting procedures than after direct repair. There was no significant difference between the two grafting techniques. These results are discussed with respect to their mechanistic and clinical interpretation.


Direct embolectomy of the basilar artery bifurcation. Case report. The case is presented of a 27-year-old man who developed a basilar artery bifurcation embolus encompassing Hilal microcoil as a complication following therapeutic embolization. An immediate direct surgical approach to the basilar artery bifurcation enabled the microcoil and associated thrombus to be removed and flow to be restored in the basilar artery and its distal branches. Postoperatively, the patient made a good recovery and on discharge was neurologically normal with the exception of a right third nerve palsy. This case suggests that in selected patients a direct surgical approach to the top of the basilar artery may be possible for treatment of emboli.


Rebleeding from vertebral artery dissection after proximal clipping. Case report. The authors present the case of a patient with vertebral artery dissection that rebled after being treated by proximal clipping. This is the second report of such a case. The results indicated that proximal clipping is not free from the risk of rebleeding, and a better alternative surgical technique should always be sought when treating vertebral artery dissections.


Sinus pericranii: radiological and etiopathological considerations. Case report. Sinus pericranii is a rare vascular anomaly involving an abnormal communication between the extracranial and intracranial circulations. A case of frontal sinus pericranii is presented which appeared to be a posttraumatic sinus because it developed 2 years after a cranial injury. However, the presence of vascular endothelium in the pathological examination and its association with a vascular anomaly (persistent trigeminal artery) suggested a congenital origin. The lesion, pericranial blood sinuses, and bone were totally removed. The computerized tomography, angiography, and magnetic resonance imaging findings are presented. The literature is reviewed and the pathogenesis of sinus pericranii is discussed.


Facial pain due to vascular lesions of the brain stem relieved by dorsal root entry zone lesions in the nucleus caudalis. Report of two cases. One patient with a pontine infarct due to a fusiform basilar artery aneurysm and one with an arteriovenous malformation within the tectum of the mesencephalon developed intractable facial pain. This pain was relieved in both patients by radiofrequency lesions in the dorsal root entry zone of the trigeminal nucleus caudalis.


Retromastoid cisternal Ommaya reservoir for intrathecal therapy of coccidioidomycosis meningitis. Technical note. A method is described that simplifies placement of an Ommaya reservoir for chronic access to the basilar cisterns. This technique is useful in treating coccidioidomycosis and other fungal meningitides.


Treatment of fusiform intracranial aneurysms by circumferential wrapping with clip reinforcement. Technical note. The authors describe a new technique for treating unclippable aneurysms. The method involves a modification of the traditional wrapping technique, including a clip-reinforced cotton sling. The results of this method in four patients are presented.


Interhemispheric approach with callosal resection for distal anterior cerebral artery aneurysms. Technical note. Distal anterior cerebral artery aneurysms are commonly found near the genu of the corpus callosum. While these aneurysms may be surgically obliterated through a variety of approaches, exposure via the interhemispheric fissure is used by many surgeons. Early identification of the afferent artery may be difficult with this approach, however, particularly if the aneurysm lies just beneath the genu of the corpus callosum. The authors have modified the interhemispheric approach to distal anterior cerebral artery aneurysms by electively exposing the feeding artery through a small anterior callosotomy. While this maneuver is not necessary for all distal anterior cerebral artery aneurysms, it can greatly enhance exposure in the region just below the genu of the corpus callosum. Experience with this technique in five patients is reported. In all cases, the limited anterior callosotomy enhanced surgical exposure. No morbidity could be attributed to the callosotomy in any patient. It is concluded that, when the interhemispheric approach is used, anterior callosotomy improves exposure of the region just below the genu of the corpus callosum and may be a useful maneuver when treating distal anterior cerebral artery aneurysms.


The role of the Medicare fiscal intermediary and the regional home health intermediary, Part 2. The Medicare fiscal intermediaries (FIs) are private insurance companies that serve as the federal government's agents in the administration of the Medicare program, including the payment of claims. There are two primary functions of the FI--reimbursement review and medical coverage review. Hospital-based home health agencies relate to the hospital's FI for reimbursement purposes. All home health agencies are assigned to a special FI, the Regional Home Health Intermediary (RHHI), for medical review issues. This may be the same FI or a different one than that audits the hospital's cost report. Freestanding home health agencies deal with separate reimbursement and medical review divisions within a single RHHI's office. The author reviews the role of the Medicare FI and the RHHI and their relationship to home health agencies. Part 1 was featured in the June issue.


Redesigning roles for patient-centered care. The hospitality representative. Nurses cannot always meet patients' expectations for nonclinical care. The authors describe the operational redesign of several hotel-related functions to enhance the provision of nonclinical care. This system enhances care delivery to better balance patients' perceptions of the clinical with the non-clinical components of care.


Optical resolution of (+/-)-all-trans-3-hydroxyretinal by use of high-performance liquid chromatography. Racemic all-trans-3-hydroxyretinal (3-OH-RAL) (1) was converted by a reaction with (-)-camphanic acid chloride (CpCl) into a diastereomixture of camphanates (2a) and (2b) which was separated by preparative high-performance liquid chromatography (HPLC) to give two esters (2a) and (2b) in pure state, respectively. Saponification of (2a) and (2b) independently afforded optically active (3S)- and (3R)-3-OH-RALs (3a) and (3b), respectively, whose absolute structures were determined by circular dichroism (CD) spectra. Racemic 3-OH-RAL was separated to two peaks by HPLC using chiral column (ChiraSpher, Merck). Cochromatography with authentic specimens (3a) and (3b) showed that the peak with a short retention time corresponded to (3R)-isomer and the other to (3S).


The process of VNA affiliation with a major teaching hospital. Affiliation among agencies with differing staff, resources, organizational structure, policies, and programs is never easy. The author discusses major components of an affiliation between a visiting nurse association and its former competitor--a major teaching hospital.


The effects of implementing a professional practice model. Professional practice is a reasonable and viable alternative to the traditional nursing practice models used in many hospitals. The authors describe the implementation of a professional practice model and its effects on cost per patient day, sick time, turnover rates, and job satisfaction indicators.


Effects of cyclic and continuous total enteral nutrition on 24-h rhythms of body temperature and urinary excretions. To clarify the relationship between the pattern of diet intake and circadian rhythm in man, we measured body temperature and urinary excretions at 4-h intervals over a 24-h period in 18 patients who were in vegetative states and had been receiving total enteral nutrition (TEN) for at least 4 weeks. One group of patients was given a liquid diet intraduodenally and continuously throughout a day (continuous TEN), whereas the two other groups received their daily enteral feeding during a restricted time of day, either in the daytime from 0800 h to 2000 h (diurnal TEN) or in the nighttime from 2000 h to 0800 h (nocturnal TEN). In the diurnal TEN group, there was a clear body temperature rhythm with a peak at 2000 h, whose pattern was similar to the well-established body temperature rhythm in normal subjects. The nocturnal TEN group also showed a temperature rhythm, but the peak appeared at 0400 h. The continuous TEN group did not show any consistent body temperature rhythms. These effects of the schedule of TEN were quite similar to those on the circadian cortisol rhythm reported previously (J. Nutr. Sci. Vitaminol., 35, 639-647, 1989). In contrast to the body temperature rhythm, the rhythm of urinary excretions of water, sodium and potassium was little influenced by the schedule of TEN, showing a normal pattern with more excretions during the daytime in every group. Essentially the same effects were confirmed in a patient who received the three schedules of TEN in rotation for 5 weeks of each schedule.(ABSTRACT TRUNCATED AT 250 WORDS)


Venture actualization in nursing. An analysis of innovation. From innovations shared by nurse executives and nurse intrapreneurs in acute care hospitals, The Venture Actualization in Nursing Model emerged. Derived from a nursing perspective, this model captures the steps of the nurse innovation process, linking the nurse executive and nurse intrapreneur role components to the process that leads to venture success.


A nursing management minimum data set. Significance and development. Building on Werley's nursing minimum data set, the authors identified a nursing management minimum data set (NMMDS). This collection of core data elements is needed by nurse administrators to make management decisions and compare effectiveness across institutions.


The influence of dietary medium and long chain triglycerides on growth performances and fat deposition in growing rats. The present study was undertaken to investigate the effects of dietary medium and long chain triglycerides (MCT and LCT) on fat deposition and fatty acid composition of adipose tissues of rats. Twenty-seven Wistar strain male rats were divided into three groups and fed semisynthetic experimental diets: Basal (AIN 76), MCT (basal+C8:0 10%), LCT (basal+corn oil 10%). Feed intake was measured every day and body weight was measured once a week. At the beginning, 4th and 8th week of experimental feeding, 3, 12, 12 rats were slaughtered, respectively. Liver, perirenal and epididymal adipose tissue pads were weighted and their fatty acid composition was determined. Chemical composition of wholebody carcass was measured. Body weight gain was greater in rats fed the LCT diet than in rats fed the basal and MCT diets. Feed intakes were decreased in rats fed the MCT and LCT diets compared to that of the basal group. Subsequently, when compared to the basal group rats, feed efficiencies in rats fed the MCT and LCT diets were improved at the level of 6 and 14% for 4 weeks, and then 17 and 24% for 8 weeks, respectively. The weight of perirenal and epididymal adipose tissue pads tended to be larger in rats fed the MCT and LCT diets than in the basal group, although not significant. There were not significant differences in wholebody composition among the three groups. But it appeared that in rats fed the MCT diet, moisture content tended to be decreased and crude protein content increased compared to the LCT group rats. Fatty acid composition of the rats fed the LCT diet showed a good reflection of dietary fatty acid composition. Unlike LCT, little of medium chain fatty acid (MCFA) itself were incorporated into liver or adipose tissues. However, it seems that fat deposition of the MCT group was accomplished not by incorporation of dietary fatty acids but by de novo fatty acids synthesis.


Protein and energy metabolism in patients with progressive muscular dystrophy. Studies were made on whether body weight loss in patients with muscular dystrophy is due to reduced intake and/or abnormal expenditure of energy. For this, food intakes and various physiological variables were surveyed in totals of 310 patients with Duchenne muscular dystrophy (DMD) of 11 to 29 years old and 28 patients with limb-girdle muscular dystrophy (LGMD) of 30 to 47 years old. Energy and protein intakes, expressed on a unit body weight basis, in DMD patients were comparable to, or higher than the allowances for age-matched healthy controls, whereas those in LGMD patients were 92 and 94% respectively of these allowances. The basal metabolic rate (BMR), expressed as kcal/kg/day, of DMD patients of all ages was higher than that of controls, the difference increasing with age, and being about 20 to 30% higher than that of controls in older patients with DMD. The BMR of LGMD patients was nearly normal. The maintenance requirements of conventional dietary protein in DMD and LGMD patients were 1.26 and 0.84 g/kg/day, respectively. These values were about 68 and 12% higher than the normal adult value (0.75 g/kg/day), indicating decreased protein utilization and increased protein catabolism. Daily excretion of urinary 3-methylhistidine (3MH) per unit muscle mass (micrograms/mg creatinine) by MD patients was significantly higher than that by controls, indicating increased degradation of muscle protein. The BMR, maintenance protein requirement and 3MH excretion of DMD patients suggest that DMD is a hypercatabolic disease. Comparison of the energy and protein intakes with the allowances estimated in consideration of increased requirements showed deficiencies of energy and protein in DMD patients. Thus, we conclude that the underweight of the DMD patients resulted from nutrient deficiencies due to hypercatabolism, despite their considerably high intakes of energy and protein, expressed as per kg body weight. These deficiencies were confirmed by demonstrating decreased concentrations of free essential amino acids, particularly branched chain amino acids, in their serum. The values of variables of LGMD patients were intermediate between those of DMD patients and control subjects.