DNA probe analysis of diarrhoeagenic Escherichia coli: detection of EAF-positive isolates of traditional enteropathogenic E. coli serotypes among Bangladeshi paediatric diarrhoea patients.

Escherichia coli isolates from all surveillance patients less than or equal to 20 months of age seen for diarrhoea at the Dhaka Clinical Treatment Facility of the International Centre for Diarrhoeal Disease Research, Bangladesh between March 1 and August 31, 1988, were collected and hybridized with DNA probes to assess the potential importance of diarrhoeagenic E. coli among paediatric patients in Bangladesh. Of 396 patients evaluated, 18% were infected with enteropathogenic E. coli (EPEC) adherence factor (EAF)-positive E. coli, 23% were infected with enterotoxigenic E. coli (ETEC), 9% were infected with Shiga-like toxin-positive E. coli, and 13% were infected with diffuse adhesiveness-positive E. coli. None were infected with enteroinvasive E. coli. Ten percent of patients were colonized with more than one type of potential diarrhoeagenic E. coli. The majority of EAF-positive isolates were of traditional EPEC O:H serotypes. Although this was not a case-control study, the large number of EPEC and ETEC, which are recognized enteric pathogens, suggests these organisms are important causes of diarrhoeal diseases in this pediatric population.


Intracranial aneurysms in autosomal dominant polycystic kidney disease.

Intracranial aneurysms are a feature of autosomal dominant polycystic kidney disease, but their prevalence is uncertain. We studied 92 subjects with autosomal dominant polycystic kidney disease who had no symptoms or signs of any neurologic disorder. To determine the prevalence of intracranial aneurysms, we performed high-resolution computed tomography (CT) in 60 subjects, four-vessel cerebral angiography in 21, and both procedures in 11. Four of the 88 subjects in whom the radiologic studies were successfully completed had intracranial aneurysms (4 percent; 95 percent confidence interval, 0.1 to 9 percent), as compared with the prevalence of 1 percent reported for an angiographic study of the general population. Three of the four subjects had multiple aneurysms. Seven subjects for whom the results of CT studies were suspicious underwent cerebral angiography: two had aneurysms, and five had normal vascular structures that accounted for the suspicious results of tomography. Four subjects who had normal CT imaging studies also had normal angiographic examinations. Eight of the 32 subjects who underwent angiography (25 percent) had transient complications, as compared with 22 of 220 control subjects (10 percent) who did not have polycystic kidney disease (P less than 0.05). We could not identify any risk factor in these subjects that was related to the occurrence of aneurysm. Asymptomatic intracranial aneurysms appear to be more frequent in people with polycystic kidney disease than in the general population, although our 95 percent confidence interval includes the possibility of no difference. Because cerebral angiography is associated with increased morbidity in people with polycystic kidney disease, we recommend high-resolution CT as a screening test.


Does asthma or treatment with theophylline limit children's academic performance?

Asthma is a major cause of morbidity in childhood, restricting activity and causing absences from school. Theophylline, although effective in managing chronic asthma, has been reported to cause deficits in cognitive functioning and school performance. We therefore examined the effect of asthma and its treatment on academic achievement in a large, representative population of school-age children; matched sibling controls were used for comparison. We identified 255 consecutive children with asthma (mean age, 12.0 years) who had taken nationally standardized scholastic achievement tests administered routinely by the schools. One hundred one of these children had siblings without asthma with whom comparisons could be made in reading, mathematics, and a composite measure of achievement. Academic achievement among the children with asthma was similar to normative standards in Iowa and higher than national standards, as reflected in a mean composite T-score of 57.1 (expected mean [+/- SD], 50 +/- 10). For the 101 children with sibling controls, composite T-scores were 58.3 for the children with asthma and 57.5 for the siblings. Eighty-five of these 101 children with asthma were receiving daily maintenance medication for chronic asthma; 72 of these were receiving theophylline. The mean composite T-scores were 58.5 for the theophylline-treated patients and 58.4 for their siblings without asthma. None of the differences between the children with asthma and the sibling controls were statistically significant. Academic achievement among children with asthma, at least those whose status is closely monitored in a structured treatment program, generally appears to be unaffected by asthma or by its treatment with appropriate doses of theophylline.


Effect of the Gulf War on infant and child mortality in Iraq.

Increased malnutrition and morbidity among Iraqi children after the onset of the Persian Gulf war have been reported by several fact-finding missions. The magnitude of the effect of the war and the economic embargo on child mortality remains uncertain, however. We conducted a survey of 271 clusters of 25 to 30 households each, chosen as a representative sample of the Iraqi population. The households were selected and the interviews conducted by an international team of public health professionals independent of Iraqi authorities. In each household all women 15 to 49 years of age were interviewed, and the dates of birth and death of all children born on or after January 1, 1985, were recorded. The study population included 16,076 children, 768 of whom died during the period surveyed (January 1, 1985, to August 31, 1991). The age-adjusted relative mortality for the period after the war began, as compared with the period before the war, was 3.2 (95 percent confidence interval, 2.8 to 3.7). No material change in the relative risk was observed after adjustment for region of residence, maternal education, and maternal age. The increase in mortality after the onset of the war was higher among children 1 to less than 12 months old (relative risk, 4.1; 95 percent confidence interval, 3.3 to 5.2) and among those 12 to less than 60 months old (relative risk, 3.8; 95 percent confidence interval, 2.6 to 5.4) than among those less than 1 month old (relative risk, 1.8; 95 percent confidence interval, 1.4 to 2.4). The association between the war and mortality was stronger in northern Iraq (relative risk, 5.3) and southern Iraq (relative risk, 3.4) than in the central areas (relative risk, 1.9) or in Baghdad (relative risk, 1.7). These results provide strong evidence that the Gulf war and trade sanctions caused a threefold increase in mortality among Iraqi children under five years of age. We estimate that more than 46,900 children died between January and August 1991.


Evaluation of a palpable breast mass.

A palpable mass in a woman's breast represents a potentially serious lesion and requires evaluation by history taking, physical examination, and mammography. The initial objective is to distinguish simple cysts from solid lesions, which can be accomplished with needle aspiration (Fig. 2). A solid lesion requires a firm diagnosis, and this usually calls for removing the lesion for histologic examination. A positive result on cytologic examination after aspiration is sufficiently accurate to justify one-stage diagnosis and treatment, with confirmation by examination of a frozen section obtained during the procedure. A negative or suspicious finding on cytologic evaluation is inconclusive, and outpatient biopsy is indicated. Perfection in diagnosis will require the removal of every solid mass. This can be expected to result in the biopsy of many benign lesions, but removal of many of them is desirable on other grounds. Although in some instances the probability of cancer may be exceedingly small, it is never zero. If biopsy is not recommended, the probability of cancer should be estimated so that the patient can decide whether the level of risk is acceptable to her.


Mutagenic potentials of fumonisin contaminated corn following ammonia decontamination procedure.

Naturally contaminated corn implicated in an outbreak of equine leukoencephalomalacia (ELEM) in southeastern Arizona was analyzed for mutagenic potential using the Salmonella/microsome mutagenicity assay before and after treatment with the ammonia procedure. Crude acetonitrile: water (1 + 1) extracts of high-pressure/ambient temperature (HP/AT) ammonia decontaminated, HP/AT plus low pressure/high temperature (LP/HT), and non-ammoniated fumonisin contaminated corn were tested for mutagenic potentials. Relatively pure (approx. 90%) fumonisin B1 standard was also tested for comparison purposes. The results of this experiment indicate that there was no mutagenic potential for the fumonisin B1 standard at the concentrations tested (100 micrograms/plate). Also, neither the naturally-contaminated corn nor the ammonia decontaminated samples elicited a positive mutagenic response. Fumonisin B1 levels, as determined by HPLC methods, were reduced by an average of 79% via the ammonia decontamination process. It is encouraging to note that, while further work is necessary to increase the efficacy of the ammonia process to reduce fumonisin levels, the ammonia process did reduce fumonisin levels and no mutagenic potentials were apparent in the treated corn.


A review and update of animal toxicoses associated with fumonisin-contaminated feeds and production of fumonisins by Fusarium isolates.

During the 1989 corn harvest season, numerous reports of equine leukoencephalomalacia (ELEM) outbreaks and a pulmonary edema (PPE) syndrome in swine from several regions of the United States were received by the National Veterinary Services Laboratories (NVSL), Ames, Iowa. Previous and concurrent research linked Fusarium moniliforme and fumonisin-contaminated feeds to both diseases. Chemical and mycological investigations revealed fumonisin B1 (FB1) concentrations of 20 to 360 ppm in suspect swine feeds and 8 to 117 ppm in suspect equine feeds. Nonproblem feeds contained concentrations below 8 ppm. Fusarium moniliforme and Fusarium proliferatum were isolated from both problem and nonproblem equine and swine feeds. When cultured on autoclaved corn, the F. moniliforme and F. proliferatum isolated produced respective FB1 and fumonisin B2 (FB2) that range from less than 5 to more than 2450 ppm and less than 5 to more than 1000 ppm, respectively. Isolates from both problem and nonproblem feeds produces high levels (greater than 500 ppm) in culture. Reported here is a review of chemical and mycological data resulting from the study of several cases of PPE and ELEM.


Fumonisins: isolation, chemical characterization and biological effects.

The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826. Fumonisin B1 (FB1), the major fumonisin produced in culture, has been shown to be responsible for the major toxicological effects of the fungus in rats, horses and pigs. Recent investigations on the purification of compounds with chromatographic characteristics similar to FB1 have led to the identification of two new fumonisins, FB3 and FB4. Fumonisins A1 and A2, the N-acetyl derivatives of FB1 and FB2 respectively, were also purified and shown to be secondary metabolites of the fungus. Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05-0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals. In contrast, no biological activity could be detected for FA1 under identical experimental conditions. These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens.


Experimental reproduction of ELEM. A study to determine the minimum toxic dose in ponies.

An experiment to gain insight into the minimum toxic dose of fumonisins was conducted by feeding ponies rations with known fumonisin concentrations. Naturally contaminated corn screenings (CS) were blended with pellets, corn, and molasses to formulate individual daily diets. One group of 4 ponies was fed a ration with fumonisin B1 (FB1) varying from less than 1 ppm to 22 ppm. A second group of 5 ponies was fed a ration at varying rates containing 8 ppm FB1 for 180 days. A panel of clinical chemistry parameters was evaluated twice weekly for both groups. One pony in the first group died of equine leukoencephalomalacia (ELEM) after 225 days of which the final 55 days' diet contained 22 ppm FB1. Approximately 9 days prior to death, this animal experienced elevated liver chemistry values. All 5 ponies in the second group experienced mild, transient, clinical signs; were euthanized at 180 days; and had mild, histopathological brain lesions.


Biosynthesis of labeled fumonisins in liquid cultures of Fusarium moniliforme.

Fumonisins were readily produced in cultures of Fusarium moniliforme using a defined liquid medium. Addition of 200 mg of d3-methyl L-methionine to 100-ml cultures of F. moniliforme gave increased overall yields and high levels of deuterium (2H) incorporation into fumonisin B1. Approximately 90% of the resulting fumonisin B1 contained 6 deuterium atoms, while 9% of the product contained 3 deuterium atoms. Deuterium was shown to be incorporated exclusively in the methyl groups of the fumonisin backbone. The addition of as little as 5 mg of labeled methionine stimulated fumonisin production, but only about 5% of the fumonisin produced contained 3 deuterium atoms.


A new fumonisin from solid cultures of Fusarium moniliforme.

A new fumonisin has been isolated from Fusarium moniliforme isolate MRC826 grown on corn. It was shown by NMR and mass spectrometry to be an isomer of fumonisin B2 that has free hydroxyl groups at C-3 and C-10 instead of the normal C-3 and C-5. This new fumonisin was detected in cultures of most isolates of F. moniliforme that were examined and was usually present at concentrations similar to those of fumonisin B2. Two isolates of F. moniliforme that produce significantly higher levels of this new isomer were identified.


Taxonomy and biology of Fusarium moniliforme.

Fusarium moniliforme is one of the most prevalent fungi associated with basic human and animal dietary samples such as corn. This fungus has been suspected of being involved in human and animal diseases since its original description. Fusarium moniliforme is in the section Liseola along with F. proliferatum, F. subglutinans, and F. anthophilum. Cultural mutation often occurs when F. moniliforme is grown on a medium rich in carbohydrates. Mutants may be either the mycelial or pionnotal type and often lose virulence and the ability to produce toxins. Toxins produced by F. moniliforme are fusaric acid, fusarins, gibberellins, moniliformin, and fumonisins. The fumonisins are produced most often when F. moniliforme grows on corn. Fusarium moniliforme causes ear rot and stalk rot of corn and infection of corn kernels by this fungus is widespread. Infection of developing corn kernels may occur through the silks, through holes and fissures in the pericarp or at points where the pericarp is torn by the emerging seedling, and as a result of systemic infection of the corn plant by F. moniliforme. These models of infection as well as infestation of the kernel surface are important factors when considering the production of fumonisins in corn.


The implications of naturally occurring levels of fumonisins in corn for human and animal health.

Contamination of corn with the fungus Fusarium moniliforme and its secondary metabolites, the fumonisins, has been associated with several human and animal diseases. This paper summarizes present knowledge and presents new data on the levels of fumonisins present in foods and feeds associated with these diseases as well as in commercial corn and corn-based products. The doses of fumonisins to which humans and animals consuming these products would be exposed are compared with those doses known to produce LEM in horses and hepatocarcinogenesis in rats. It is concluded that the known naturally occurring levels of fumonisins present a potential threat to human and animal health and realistic tolerance levels need to be set.


Fumonisin B1 production and vegetative compatibility of strains from Gibberella fujikuroi mating population 'A' (Fusarium moniliforme).

We examined 25 strains of Fusarium moniliforme from eight states known to be associated with equine leukoencephalomalacia, a disease caused by the mycotoxin fumonisin B1. We determined the mating population, mating type, and vegetative compatibility group to which each of these strains belonged. All 25 strains were in the 'A' mating population; 12 were A+ and 13 were A-. Seventeen of the 25 strains were female fertile; these strains also averaged higher levels of fumonisin B1 production than did the strains that were female sterile. Nitrate non-utilizing (nit) mutants were generated in all 25 strains and each strain was assigned to a unique vegetative compatibility group based on the inability of the derived nit mutants to form a prototrophic heterokaryon with complementary nit mutants derived from any of the other strains examined. From these data, we concluded that the production of fumonisin B1 is a general characteristic of strains from the 'A' mating population of Gibberella fujikuroi associated with equine leukoencephalomalacia, since all 25 of the isolates that we examined were genetically distinct individuals.


AAL toxins, fumonisins (biology and chemistry) and host-specificity concepts.

The AAL toxins and the fumonisins (FB1 and FB2) are structurally related and produced respectively by Alternaria alternata f.sp. lycopersici and Fusarium moniliforme. AAL toxin is characterized as a host-specific toxin, toxic to tomato, whereas fumonisin B1 causes equine leukoencephalomalacia. FB1 and FB2 were biologically active in susceptible tomato tissue (Earlypak-7) and animal tissue culture (rat hepatoma H4TG and dog kidney MDCK). Conversely, AAL toxin was also active in the rat and dog tissue culture cells. Both fungi produce toxin/s in culture that causes death in rats; these toxins are other than AAL and fumonisin. The peracetylated derivatives of AAL and FB1 are biologically inactive in both the tomato bioassay and the animal tissue culture systems. Acetylation of the amine renders AAL inactive. The hydrolysis product of AAL (phentolamine) is toxic to the susceptible tomato line whereas the phentolamine of fumonisin is not. AAL and FB1 can be analyzed by Continuous Flow Fast Atom Bombardment (CFFAB) and Ionspray Mass Spectrometry (ISM), both sensitive to the picomole range. The N-acetyl of the TFA hydrolysis product of AAL and FB1 is determined by comparing the fragment ions at m/z 86 and 140 for FB1 and 72 and 126 for AAL.


In vitro toxicology of fumonisins and the mechanistic implications.

The effects of fumonisins B1(FB1), B2(FB2), and the backbone of fumonisin B1 remaining after hydrolysis of the tricarballylic groups with base (HFB1) on sphingolipid biosynthesis were studied in both primary rat hepatocytes and pig kidney epithelial cells (LLC-PK1). Fumonisins were potent inhibitors of sphingolipid biosynthesis in hepatocytes (IC50 of FB1 = 0.1 microM), but overt toxicity was not observed. In renal cells, fumonisins also inhibited sphingosine biosynthesis (IC50 for FB1 = 35 microM), and caused decreased cell proliferation as well. Higher doses (greater than or equal to 70 microM) killed renal cells after exposure for 3 days. The inhibition of de novo sphingolipid biosynthesis was specific, and appeared to be at the site of ceramide synthase, which catalyzes the formation of dihydroceramide or ceramide by the addition of the amide-linked fatty acid to sphinganine or sphingosine. These results may account for the ability of fumonisins to cause equine leucoencephalomalacia and to promote tumor formation.


Fumonisin-induced pulmonary edema and hydrothorax in swine.

Pulmonary edema and hydrothorax were observed in mature swine that died approximately 5 days after consuming corn screenings. These postmortem observations were reproduced in younger pigs that died within 1 week when fed the corn screenings under experimental conditions. Additionally, pulmonary edema and hydrothorax were induced in a pig that died after receiving 4 daily intravenous injections of fumonisin B1, a toxic metabolite produced by Fusarium moniliforme.


Subchronic toxicological investigations of Fusarium moniliforme-contaminated corn, culture material, and ammoniated culture material.

The fungus Fusarium moniliforme is ubiquitous on corn throughout the world and is a likely co-contaminant on corn infested with aflatoxin-producing Aspergillus flavus. Ammoniation has been used to detoxify aflatoxin-contaminated commodities. To determine the effect of ammoniation on the toxic potential of Fusarium moniliforme, male Sprague-Dawley rats were fed either diets containing 10% sound corn, ammoniated corn, corn culture material of hepatotoxic F. moniliforme strain MRC 826 (CM), or ammoniated CM for four weeks. They were observed for signs of toxicity and hematological, serum chemical and histopathological evaluations were made. Groups of male Balb/c mice were fed diets fortifies with 10% sound corn or CM for four weeks and evaluated by serum chemical and histopathological means to determine the suitability of mice as a model species for investigation of F. moniliforme-induced hepatotoxicity. Ammoniation was ineffective for detoxification of the CM. Hepatotoxicity and renal toxicity of CM and ammoniated CM were qualitatively similar, although renal tubular lesions appeared more advanced in rats fed ammoniated CM. Adrenal cortical cellular vacuolation was also found in CM and ammoniated CM-fed rats, while focal seminiferous tubular degeneration and aspermia were found only in the testes of ammoniated CM-fed rats. Fumonisin B1 concentrations of the CM and ammoniated CM diets averaged 99 and 75 ppm, respectively. CM containing 99 ppm fumonisin B1 also produced hepatotoxicity in mice similar to that found in CM-fed rats. Thus, mice may be useful for investigations of F. moniliforme-induced hepatotoxicity.


An interview with Daniel Carr and Ada Jacox. Interview by Carmella A. Bocchino.

When clinicians are aware of inappropriate variations in practice and have access to science-based recommendations for care, they usually change their practice styles and prescribing behavior. The first in a series of guidelines supported by the Agency for Health Care Policy and Research, "Acute Pain Management," was released in early March and recommended an aggressive, proactive, and collaborative approach to managing pain in patients recovering from surgery, medical procedures, or trauma cases. Co-chairs of the pain management panel, Drs. Daniel Carr and Ada Jacox, share their views on guideline design, the expert panel, consensus building, and their expectations for use by the clinical practice and research communities.


Of rabbits and turtles: a time of change for unions.

Radical changes must take place if either the work place or the union is to succeed in the 21st century. Newer models of collective relationship must emerge to ensure the effectiveness and value of both union and management.


Quantifying ambulatory care activities by time and complexity.

As economic considerations increasingly drive decisions in health care, the staffing mix and nursing roles in ambulatory care are often questioned. A patient classification system that quantifies nursing activities by time and complexity can be used to assist with the difficult task of matching nursing resources with patient care needs.


The economic value of nursing.

The economic value of nursing relates to the purchaser's perspective. A three-level model of nursing services purchasers is presented. Selected economic/management concepts are examined in relation to nursing's economic value and these three purchaser perspectives.


SEPPD and HPPD: more effective control of nursing care costs.

A study of acute care hospital inpatient units demonstrates that the level of correlation between salary expenses per patient day (SEPPD) and hours per patient day (HPPD) is not strong enough to support the continued use of HPPD as the only parameter for monitoring and controlling nursing salary expenses. Findings indicate that chief nursing executives (CNEs) must consider hours and dollars, if they are to achieve effective fiscal management and appropriate influence within the organization.


Severity of illness and resource allocation in DNR patients in ICU.

This study examined the differences in severity of illness and resource allocation between patients with do-not-resuscitate (DNR) orders and non-DNR patients in intensive care units. Severely ill intensive care patients with DNR orders continued receiving aggressive medical care following cardiac or respiratory arrest. The continued use of advanced therapies for DNR patients raises important questions about the use of costly intensive care resources.


[Double orientation tuning of neurons of the primary visual cortex of the cat at various levels of alertness].

Orientation tuning (OT) of 225 visual cortex neurons was studied in immobilized cats by their responses to flashing light bars. It was found that 43% of neurons had monomodal OT and preferred the horizontal and vertical orientations, while 57% of neurons had double OT, i.e. they had main preferred orientation (PO) and additional PO (aPO). The mean angle between PO and aPO was equal to 71.4 +/- 2.4 degrees. In half of the cases the second maximum of OT was equal to the first one (mean: 0.7 +/- 0.03 from PO). Orientation characteristics of PO and aPO were practically identical. Under light and middle levels of narcosis half of the neurons with double OT became monomodal and 12% of monomodal neurons receive bimodal OT. Monomodal neurons had more often simple RF and invariance of OT to narcosis. The neurons with double OT had simple and complex RF equally often and their OT changed in narcosis. It is supposed that the neurons with double OT can be an angle and line cross detectors. Monomodal neurons may be the stable bench mark system of orientation coordinates. Interaction of these neuronal systems permits conducting an effective analysis of image features in the primary visual cortex.


[Effect of the quantal composition, membrane potential and cholinoreceptor density on the temporal flow of the end plate current in the rat under conditions of acetylcholinesterase inhibition].

The factors determining the decay of multiquantal end plate currents (EPC) were studied in the diaphragm muscle of rat by the comparison of EPC and miniature EPC (MEPC) amplitude--temporal characteristics. The decay of EPC (quantal content 25-100) was 1.2 times slower than the decay of MEPC when AChE was active. The AChE inhibition by armine or neostigmine made this difference 10-100 times higher. In most synapses the decay of multiquantal EPC can be approximated by a sum of two or three exponents. It depended on the quantal content and 3-exponential EPC could be transformed in 2-exponential and later to monoexponential ones if increasing concentration of magnesium ions. A slow component of EPCs (but not of MEPC) decay was highly sensitive to concentration of magnesium ions and had 3 times higher dependence of the membrane potential value than that one of MEPC. The irreversible blocking of receptors by alpha-bungarotoxin (alpha-BuTX) accelerated the decay of MEPC but the decay of multiquantal EPC changed in two phases: it was prolonged at the beginning of alpha-BuTX action followed by its acceleration, but never the time of the decay of EPC had achieved the apparent open time of ACh-activated ionic channels. It is suggested that during the multiquantal EPC generation not only the synchronization of opening but the kinetic of ACh-activated channels is changed, probably by blocking of this channels by high concentrations of endogenous ACh.


[Structural changes induced by diethyl ether in cultured neuroblastoma cells].

It has been found that neuroblastoma cells retract their neurites under the influence of ether in dose 1 ml in 15 ml of the cultural medium. Application of ether for two hours increases the ratio of the number of cells to the number of neurites from 9.94 +/- 2.12 in the initial state to 19.66 +/- 1.93 (P less than 0.002). An essential alteration of the cell shape and a decrease of their volume are observed as well. The reaction is typical of cells at different stages of morphological differentiation. The data obtained can be helpful for investigation of pharmacological preparations which prevent destruction of neurons under narcosis.


[Serotonin-induced changes in the responses of electrically stimulated neuronal membrane of the mollusk].

Serotonin (5-HT) added to washing solution has been studied for its effect on plastic properties of electrically excitable membranes of the parietal ganglion and identified PPa2 neurons in the isolated nerve system of snails. It is shown that neurons habituated to intracellular stimulation are able to restore action potential generation in the presence of 5-HT. Contrary, neurons possessing endogenous rhythmic activity (PPa2) generate train activity on the background of appearance of the membrane potential slow waves under the influence of 5-HT. A comparative analysis of 5-HT and chemicals with the known effect on activity of Ca and Ca-dependent K-channels (quinine, CoCl2, CdCl2) has demonstrated diversity of mechanisms underlying the 5-HT-ergic regulation of plasticity of the neuronal electrically excitable membrane. This difference stems from the processes of activation and blockade of Ca-dependent channels.


[Changes in muscle tissue in vertebrogenic myofascial syndromes].

The carrying ability of a spinal disc disturbed under axis load is found to be due to the displacement of a vertebra lying above it. The constant stretching of the extensively innervated soft tissues of the spine brings about a steady irritation process within the limits of the segmental part of the spinal cord and dysfunction of short profound muscles of the back.


[Evoked activity of spinal cord neurons in the early period after cutting the sciatic nerve].

The character of evoked activity of motoneurons, interneurons and Renshaw cells of white rats in low lumbar segments of the spinal cord was studied 5 days after cutting of sciatic nerves. A trustworthy rise of the amplitude of the excited postsynaptic potential (EPSP) of motoneurons on the side of nerve cutting was found. No reliable change of the membrane potential and threshold of the action potential emergence in these motoneurones was observed. Character of evoked activity of the Renshaw cells and interneurons did not differ essentially from the same of animals with the intact nerve. Possible mechanisms taking part in rising of the EPSP amplitude after cutting of the nerve are discussed.


[Characteristics of skin thermo-mechano-sensitive receptors in animals and man].

Changes in impulse activity of afferent fibres of the spinal dorsal roots connected with thermal receptors of cat's skin have been studied during acute experiments. Thermal sensitivity of the man skin has been studied in psychophysical experiments. Three types of reactions of fibers from heat receptors of the animal skin and two types from cold ones are obtained. All of them are mechano-sensitive reactions. They differ from each other in the depth of changes in frequency of average impulse activity, dynamic sensitivity, latent period of the reaction as well as in thresholds of thermal and mechanic sensitivity. It is supposed that there exists certain analogy between thermoreceptors of animals and men.


[Hysteretic properties of movements in the elbow joint of unanesthetized cats with various methods of activation of muscle-antagonists].

Movements of the elbow joint were studied in unanesthetized cats. These movements were evoked by microstimulation of the motor cortex or by vibration of the forepaw and then compared with reaction from direct stimulation of muscles in the anesthetized animals. Interaction of the hysteretic effects in the antagonistic muscles of the joint was studied during stimulation of two points of the motor cortex which produced opposite-directed movements. Coactivation of the antagonists was shown to increase both the joint stiffness and the uncertainty of the equilibrium value of the joint angle. The uncertainty myotatic reflexes during intracortical microstimulation were more significantly depressed in the muscle receiving more intensive activation from the given point in the motor cortex. On the contrary, myotatic reflexes during vibration were well expressed in the both antagonistic muscles. At the same time the uncertainty effects during forepaw vibration were displayed similarly as it was in the cortically evoked movements.


[Muscle stretching and unloading reflexes during cortically evoked movements in unanesthetized cats].

Extension and flexion cortically-evoked movements (CEMs) were studied in the framework of the experimental approach developed in the previous paper [5]. Movements in the elbow joint of an unanesthetized cat were evoked by intracortical microstimulation (ICMS) applied to the motor cortex, then they were tested using a torque disturbance method. Similarity of flexion and extension CEMs allowed producing their combined quantitative analysis and comparing the obtained characteristics with those defined for the movements which were evoked by direct stimulation of the biceps and triceps muscles in an anesthetized animal. Resulting stiffness and uncertainty index (UI) served as the main characteristics of the movement in the presence of torque disturbances. Depending on the relationship between the directions of the preceding movement and the initial phase of the disturbed one, CEMs were divided into two types: coinciding (1) and opposing (2) CEMs. When the preceding movement was evoked by switching on of ICMS, both types of the disturbed movements could be considered as realizations of the phasic myotatic reflexes: unloading (1) and stretch (2). Disturbed movements of type 1 were characterized by the narrow range of mean values of UI: 0.43-0.91 (1.2 Hz wave of torque disturbance) and 0.24-0.73 (3.2 Hz). Transition to type 2 enlarged sharply the spread in the means, they could be both positive and negative, variances of UI in separate realizations significantly increased as well. It is supposed that intensity of central processes controlling the disturbed movements is mainly connected with changes in their direction but not with the movement per se.


[Inhibition of neuronal responses in the cat motor cortex, associated with attainment of a conditioned reflex when waiting for a flash of light].

Inhibition of neuronal spike reactions associated with reflex movements and induced by the light flare at different moments during the conditioned stimulation (1 s.) has been found in chronic experiments on cats. The light flare in the interval of maximum probability of the reflex realization has promoted a rise in the neuronal latency by 300-400 ms and a decrease of their duration almost twice. Other realizations of the inhibition effect were weaker.


[Effect of stimulation of the thalamic reticular nucleus on spino-bulbo-spinal reflex activity].

The effect of the thalamic reticular nucleus (RN) stimulation on the spino-bulbo-spinal reflex was studied in chloralose-anesthetized cats. RN stimulation was found to exert an inhibitory influence on this reflex. The same stimulation has also exerted an inhibitory influence on the spinal units activated during the spino-bulbo-spinal reflexes.


[Mechanoreceptor system of the respiratory center and its role in the control of respiration].

The paper is concerned with the study of localization, firing properties, methods of activation and projection into the neuronal structures of the medulla oblongata as well as the reflex action of two types of mechanoreceptors of the lungs: slow- and rapid-adapting stretch receptors. Data on the first relay neurons monosynaptically connected with slow-adapting pulmonary stretch receptor afferents are presented.


Comparison of the effects of volatile anesthetics in varying concentrations on brain energy metabolism with brain ischemia in rats.

The effects of varying concentrations and types of volatile anesthetics on neurochemical sequelae of brain ischemia were evaluated in the rat. Rats were assigned to treatment defined by a 3 x 3 design (anesthetic type and dose) with 5 rats/cell. Each group received halothane, enflurane, or isoflurane 0.5, 1.0, or 2.0 MAC (minimal alveolar concentration). This was followed by preischemic plasma glucose sampling, 5 min hypotension (30 mmHg) and 5 min decapitation cerebral ischemia. Preischemia plasma glucose increased with increasing anesthetic concentration and was highest in the isoflurane groups, varying from a low (+/- SD) of 7.19 +/- 1.79 mumol/ml in the 0.5 MAC halothane group to a high of 12.68 +/- 3.65 mumol/ml in the 2.0 MAC isoflurane group. End-ischemic brain lactate correlated with preischemic plasma glucose (r = 0.5, alpha = 0.5). We conclude that increasing concentration of volatile anesthesia with iv phenylephrine blood pressure support produces higher levels of plasma glucose and brain lactate with cerebral ischemia.


Effects of bicuculline on [3H]SR 95531 binding in discrete regions of rat brains.

Effects of bicuculline in vitro, and acute and chronic treatment of a subconvulsive dose of bicuculline on [3H]SR 95531 binding to discrete regions of rat brains were studied in Sprague-Dawley rats. Scatchard analysis of the binding isotherms exhibited two populations of binding sites for [3H]SR 95531 in frontal cortex, cerebellum, striatum and substantia nigra. The apparent KD for high-affinity sites was significantly increased in the frontal cortex and cerebellum in the presence of bicuculline (1 microM) with no change in Bmax. In contrast, the apparent affinity for low-affinity sites was not altered in the presence of bicuculline in these regions, whereas the Bmax was significantly decreased in the cerebellum. Following acute (2 mg/kg, i.p.) or chronic (2 mg/kg, i.p. for 10 days) bicuculline treatment, [3H]SR 95531 binding was also investigated in various regions of brains. The acute bicuculline treatment did not affect the [3H]SR 95531 binding in any of the regions studied. In contrast, apparent affinity for [3H]SR 95531 was significantly decreased in low-affinity sites of all regions studied in rats treated chronically with bicuculline. The Bmax values of high and low-affinity sites were significantly increased in the cerebellum with no change in the frontal cortex, striatum and substantia nigra. The present study demonstrates that chronic bicuculline treatment decreases apparent affinity of [3H]SR 95531 binding whereas the treatment increases apparent affinity of [3H]muscimol binding (1) in various brain regions. The results indicate that significant increase in Bmax of [3H]SR 95531 and [3H]muscimol binding in the cerebellum may be due to true up-regulation of GABA binding sites, involving increased de novo synthesis of receptor protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Post-ischemic regional changes in acetylcholine synthesis following transient forebrain ischemia in gerbils.

The synthesis rate of brain acetylcholine (ACh) was estimated 30 min and 5 days following transient forebrain ischemia performed by 10 min bilateral carotid occlusion in gerbils. ACh synthesis was evaluated from the conversion of radiolabeled choline (Ch) into ACh after an i.v. administration of [methyl-3H]Ch. Endogenous and labeled Ch and ACh were quantified by HPLC. The synthesis rate of Ach was significantly decreased following 30 min of recirculation. The reductions reached 55.4% in the hippocampus, 51.2% in the cerebral cortex and 44.4% in the striatum. Five days after ischemia, the values returned to normal in the cerebral cortex and in the striatum, while ACh synthesis remained selectively lowered (-30.4%, p less than 0.01) in the hippocampus. These cholinergic alterations may account for both early and delayed post-ischemic behavioral and mnesic deficits.


On the activity of gamma-aminobutyric acid and glutamate transporters in chick embryonic neurons and rat synaptosomes.

The uptake of radioactive gamma-aminobutyric acid (GABA) and D-aspartate and the effect of SKF 89976-A, a non-substrate inhibitor of the GABA transporter, on this uptake have been investigated. Neuronal cultures from eight-day-old chick embryos grown for three or six days in vitro, were used as a model. For comparison, we also used the P2-fraction from rat. Neuronal cultures grown for three and six days expressed high-affinity uptake systems for [3H]GABA and for D-[3H]aspartate with an increasing Vmax during this period. The lipophilic non-substrate GABA uptake inhibitor, SKF 89976-A, inhibited transporter mediated uptake of GABA both in cell cultures from chicken, and in P2-fractions from rat. The results also showed that SKF 89976-A was a poor inhibitor of the uptake of D-aspartate. We found no non-saturable uptake of D-aspartate.


Is there a high molecular weight glutamic acid decarboxylase?

Gel-filtration chromatography from crude extracts of mouse brain indicates the presence of a high molecular weight (HMW) (more than 750 kd) and a low molecular weight (LMW) (87.5 Kd) glutamic acid decarboxylase (GAD) when they are concentrated prior chromatography either by precipitation with salts or ethanol. Kinetically both peaks of GAD-activity exhibit an almost identical Km for L-glutamate. Only LMW-GAD appears if the concentration step is carried out by ultrafiltration or if the extract is chromatographied without the concentrating step. HMW-GAD disappears from the chromatographic profiles if ethanolic extracts of GAD are treated with Triton X-100 before the chromatographic procedure. The sodium sulfate precipitation of a previously separated LMW-GAD gives rise to the reappearance of a HMW-GAD peak. Apparently HMW-GAD does not exist as a different molecular entity; indeed it may be an artefactual aggregation of LMW-GAD.


Isolation of a tripeptide (Ala-Gly-Ser) exhibiting weak acetylthiocholine hydrolyzing activity from a high-salt soluble form of monkey diaphragm acetylcholinesterase.

A high-salt soluble form of acetylcholinesterase (AChE) was purified from monkey (Macaca radiata) whole diaphragm by a two step affinity chromatographic procedure using m-aminophenyl trimethylammonium-chloride hydrochloride-Sepharose and procainamide-Sepharose columns. The purified enzyme showed three major protein bands at 80 kDa, 78 kDa and 60 kDa on SDS-gel electrophoresis. [3H]Diisopropyl fluorophosphate ([3H]DFP) labeled enzyme also gave three radioactive peaks corresponding to these three bands. The purified enzyme pretreated with dithiothreitol and subjected to limited trypsin digestion gave a peptide fragment of molecular weight approximately 300 Da showing weak acetylthiocholine hydrolyzing activity as identified by Sephadex G-25 gel filtration. Sequence analysis showed that the active peptide fragment was a tripeptide with the sequence Ala-Gly-Ser. When the purified AChE was labeled with [3H]DFP, digested with trypsin and subjected to Sephadex G-25 chromatography, a radioactive peak that would correspond to the tripeptide fragment was seen. The kinetics, inhibition characteristics and binding characteristics to lectins of the active peptide fragment was compared with the parent enzyme. A synthetic peptide of sequence Ala-Gly-Ser was also found to exhibit acetylthiocholine hydrolyzing activity. The kinetics and inhibition characteristics of the synthetic peptide was similar to those of the peptide derived from the purified enzyme, except that the synthetic peptide was more specific towards acetylthiocholine than butyrylthiocholine. The specific activity (units/mg) of the synthetic peptide was about 29480 times less than that of the purified AChE.


Changes of phorbol ester binding sites in rat brain following intracerebroventricular administration of thyrotropin-releasing hormone (TRH): an in vitro macroautoradiographic investigation.

We examined the influence of the intracerebroventricular (icv) administration of thyrotropin-releasing hormone (TRH) on protein kinase C (PKC) activities in various rat forebrain regions in order to cast light on the mechanism of extra-pituitary non-endocrine physiological actions of TRH in the central nervous system. An in vitro macroautoradiographic method, with [3H]phorbol 12, 13-dibutyrate (PDBu) as the radioactive ligand, was used to investigate quantitative alterations of PKC activities. The optical densities for PDBu binding sites in the striatum and hippocampal formation were significantly increased after the icv administration of TRH, while those in the frontal cortex and septum were unchanged. These findings suggest that TRH may exert some of its non-endocrine functions through striatal and hippocampal neurons which used PKC in their second messenger systems.


Arginine specific endopeptidases modify the aggregation properties of a synthetic peptide derived from Alzheimer beta/A4 amyloid.

A synthetic peptide corresponding to the first 28 amino acids of the Alzheimer disease amyloid beta/A4 peptide (3.2 kDa) aggregated to a high molecular weight (15 kDa) on SDS/urea polyacrylamide gels. Proteinase K, V8 protease, trypsin, and endopeptidase Lys-C readily degraded the aggregate. By contrast, when digested by endopeptidase Arg-C, a new polypeptide aggregate of higher molecular weight (16 kDa) was observed on denaturing gels without degraded smaller products. The new aggregate was comprised of three peptides: an intact beta/A4(1-28) and partially degraded peptides beta/A4(1-5) plus beta/A4(6-28). The results were confirmed by treatment of beta/A4 with other arginine-specific proteases: the gamma subunit of nerve growth factor and clostripain. The results indicate that arginine-specific proteases, including a growth factor processing enzyme, can nick aggregated beta/A4(1-28) amyloid and alter the configuration to produce a more complex aggregated form. If similar highly specific proteolytic mechanisms occur in the Alzheimer disease brain, the processing may promote the formation of high molecular weight aggregates that contribute to the development of relatively insoluble senile plaque core protein.


Differences in the functional responses of two cell lines each expressing Pi-hydrolysis-coupled muscarinic receptors.

Fluorescent oxonol dyes were used to measure changes in the membrane potential of two different cell lines each expressing Pi-hydrolysis coupled muscarinic receptors. Both SK-N-SH human neuroblastoma cells and m1-transfected A9 L cells express muscarinic receptors which, when stimulated, elicit a large increase in intracellular calcium, and release of inositol phosphates. Despite the similarity in this second-messenger response, muscarinic stimulation resulted in a hyperpolarization in the transfected A9 L cells whereas a small depolarization was observed in the neuroblastoma cells. The carbachol-mediated hyperpolarization of the transfected A9 L cells could be mimicked by increasing intracellular calcium with the ionophore A23187, suggesting that it may be mediated by calcium-activated potassium channels. Exposure of SK-N-SH cells to A23187, on the other hand, had no effect on the membrane potential. These studies demonstrate that the activation of a second messenger system does not solely dictate the electrophysiological response of a cell, but that other factors such as the expression of ion-channels is critical in the determination of that response.


Autoradiographic study on [3H]flunitrazepam binding in rat cortex and hippocampus after chronic ethanol treatment.

Ethanol alters almost all membrane functions, but it behaves essentially like a benzodiazepine-type GABAergic agonist. The mechanism by which ethanol affects the GABA/benzodiazepine complex is not clear. We studied the possible changes in [3H]flunitrazepam binding induced by chronic ethanol treatment, using light microscopic autoradiography, to try to elucidate the controversy underlying this topic. This technique allows us to measure densities of benzodiazepine receptors in different anatomical brain areas--visual cortex and hippocampus--which seem to constitute the anatomical support for the behavioral and physiological responses affected by ethanol. Autoradiographic studies on the visual cortex and hippocampus from rats chronically treated with ethanol do not show statistically significant differences in the binding of [3H]flunitrazepam with respect to control animals. Furthermore, we did not find either rostro-caudal or medio-lateral differences in benzodiazepine receptor densities in each layer of the visual cortex.


Ganglioglioma: 13 years of experience.

A 13-year retrospective review of 17 patients with gangliogliomas treated at the University of Iowa was conducted to investigate the association between tumor location, extent of resection, pathological findings, and patient prognosis. Thirteen were in the cerebral hemispheres and 4 in the midline. The mean ages at diagnosis and symptom onset were 16 and 8.8 years, respectively. The most common presenting symptom was seizures (11 patients); focal neurological deficit was seen in 5 patients and headache in 1. Patients with hemispheric tumors had an older age at time of diagnosis and a longer duration of symptoms. Pathologically, they had more microcalcifications, lymphocytic infiltration, microcystic degeneration, and eosinophilic bodies. Cerebral hemispheric tumors were more amenable to total resection than midline neoplasms, 77% versus 25%, respectively. In the patients with hemispheric tumors, 10 patients were tumor-free after total resection. Two of the 3 patients with partial resection had stable residual tumors. The third died of tumor progression. In the 4 patients with midline neoplasms, one was tumor-free after total resection. The other 3 had subtotal resection and radiation therapy. Two died within 2 years; the third is still alive with progressive tumor. Five of 9 patients who had seizure disorders and who underwent total tumor removal were seizure-free postoperatively. The other 4 patients and the 2 with partial surgical resection continued to have seizures.


Peritumoral brain edema in meningiomas--influence of vascular supply on its development.

In a series of 35 patients with intracranial meningiomas, factors influencing the development of peritumoral brain edema (PTBE) were analyzed. We used numbers of the Edema Index as the extent of PTBE, which was obtained from the size of the meningioma and associated PTBE on a T2-weighted image of magnetic resonance imaging. We evaluated a relationship between the Edema Index and some factors that may play a role in the development of PTBE. Tumors in the frontal region and at the sphenoid ridge tended to be associated with larger PTBE than those in other locations (P less than 0.05). Histologically, meningotheliomatous and transitional meningiomas tended to be associated with larger PTBE than fibroblastic meningiomas (P less than 0.05). The meningiomas that had a vascular supply from the intrinsic cerebral arteries on angiography significantly correlated with severe PTBE compared with those supplied only from the meningeal side (P less than 0.01). We concluded that location, histology, and vascular supply from intrinsic cerebral arteries were the factors influencing PTBE. It is stressed that the vascular supply from the intrinsic cerebral arteries may have an influence on the extensive PTBE of meningioma.


Proton magnetic resonance spectroscopy of pediatric brain tumors.

1H magnetic resonance spectroscopy allows the regional quantitation of a number of metabolites from the brain in a noninvasive fashion. Spectra were obtained from 5 normal children and 25 children with brain tumors. Choline (Cho), N-acetylaspartate (NAA), creatine and phosphocreatine, and lactate were quantitated in the form of ratios. The brains of normal children showed relatively high concentrations of Cho and NAA and virtually no lactate, as has been shown in adults. Benign astrocytomas and ependymomas were characterized by an elevation of the Cho:NAA ratio and an abnormal accumulation of lactate. Intrinsic malignant tumors were remarkable for an even higher Cho:NAA ratio but had no more lactate than was found in the benign tumors. Proton magnetic resonance spectroscopy may prove useful in characterizing neoplastic tissue in conjunction with more conventional imaging modalities.


Decompression of the optic nerve sheath for vision-threatening papilledema caused by dural sinus occlusion.

Obstruction of the dural sinuses produces a clinical syndrome that resembles pseudotumor cerebri. In these patients, unremitting papilledema can cause blindness. We performed decompression of the optic nerve sheath in four patients who had occlusion of the dural sinuses. The operation achieved rapid relief of papilledema and recovery of vision. In three patients, fenestration of the nerve sheath of only one eye resulted in resolution of papilledema in both eyes. The procedure appears to relieve papilledema by filtering small quantities of cerebrospinal fluid into the orbit. It did not lower cerebrospinal fluid pressure in three patients who underwent lumbar puncture after surgery. Optic nerve sheath decompression is an effective operation for salvage of vision in patients with obstruction of the dural sinuses.


The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients.

Regional hemodynamic disturbances may complicate the treatment of certain cerebral arteriovenous malformations (AVM) and occasionally produce life-threatening situations. Acetazolamide-enhanced quantitative regional cerebral blood flow studies were performed preoperatively in 35 patients to determine if patterns of vasoreactivity could be identified that might be markers for postoperative morbidity. Ipsilateral and contralateral regions of hypoperfusion were identified on resting studies, and a steal index was calculated by dividing the regional cerebral blood flow in the steal region by the flow in a normal cerebellar region. Flow in these regions of interest was again quantitated after the administration of acetazolamide, a known cerebral vasodilator. A delta value was calculated by subtracting the resting index values from the acetazolamide indices. Abnormally enhanced vasoreactivity (vasodilation) to acetazolamide stimulation was noted in these threatened territories in AVM that had perforating vessel feeding and angiographic steal phenomena, that developed hyperemic disturbances, and that resulted in poor outcomes. These findings call into question traditional theories of AVM-related hemodynamic decompensation and suggest unique smooth muscle derangements in cerebral vasculature in some AVM patients.


Intramedullary cavernous angiomas of the spinal cord: clinical presentation, pathological features, and surgical management.

Cavernous angiomas of the spinal cord are rare lesions that can cause severe neurological symptoms. We add a series of 6 patients with intramedullary cavernous angiomas of the spinal cord to 30 patients with 31 histologically verified lesions already described in the literature. Four types of clinical presentation were seen in the 36 patients: 1) discrete episodes of neurological deterioration with varying degrees of recovery between episodes (13 patients); 2) slow progression of neurological decline (12 patients); 3) acute onset of symptoms with rapid decline (8 patients); and 4) acute onset of mild symptoms with subsequent gradual decline lasting weeks to months (3 patients). Of the 36 patients, 25 (69%) were women and 11 (31%) were men. The peak age of presentation was in the fourth decade. The thoracic spinal cord was affected in more than half the patients, with the cervical cord being the next most common location. Histological examination demonstrated the closely apposed vascular channels characteristic of cavernous angiomas. While most vascular channels were thickened and hyalinized, three angiomas had foci of small vessels resembling a capillary angioma. The available data suggest that surgical management of intramedullary angiomas should attempt complete extirpation. The lesions are often well circumscribed with a glial plane between the lesion and normal cord. However, spinal cord angiomas, unlike cranial lesions, have little room for enlargement before devastating symptoms occur. We achieved complete excision in all of our patients, who are all ambulatory and have improved symptoms. Little, if any, increase in neurological deficit was caused by myelotomy and lesion excision. These spinal lesions should be considered for surgery early, before repeated hemorrhage or enlargement can occur.


Surgical treatment of syringomyelia based on magnetic resonance imaging criteria.

The treatment of syringomyelia includes many surgical options. We report a retrospective study of 65 patients with cavitary lesions of the spinal cord in whom the results of magnetic resonance imaging were used to develop specific treatment strategies. Intramedullary cavities were classified into three general types: 1) communicating syrinxes, which occurred with hydrocephalus and were anatomically continuous with the 4th ventricle (9 patients); 2) noncommunicating syrinxes, which were separated from the 4th ventricle by a syrinx-free segment of spinal cord (42 patients); and 3) atrophic syrinxes, which occurred with myelomalacia (14 patients). Noncommunicating syrinxes were further subdivided according to type: Chiari II malformations with hydrocephalus (5 patients), Chiari I malformations without hydrocephalus (11 patients), extramedullary compressive lesions (12 patients), spinal cord trauma (6 patients), intramedullary tumors and infections (6 patients), and multiple sclerosis (2 patients). Of the 65 patients, 39 underwent surgical treatment for progressive symptoms. Syrinxes occurring with hydrocephalus were treated empirically with a ventriculoperitoneal shunt. Excellent results were achieved in 7 of 7 patients with communicating syrinxes and in all 5 patients with Chiari II malformations. Two approaches were used in the treatment of syrinxes occurring with Chiari I malformations: Posterior fossa decompression improved symptoms but did not reduce syrinx size in 2 of 3 patients. In the third patient and in 3 patients who were not treated with decompression, shunting from the syrinx to the cerebellopontine angle cistern collapsed the cavity and resolved symptoms over the interval of follow-up (average follow-up, 1.5 years). Excision of extramedullary obstructions at the rostral end of noncommunicating syrinxes resulted in collapse or disappearance of the cavity in 6 of 7 patients. The remaining patient was treated effectively by a syringocisternal shunt. In all 4 patients with posttraumatic syringomyelia, good results were achieved by a spinal or syringocisternal shunt. Syrinxes associated with intramedullary masses were managed by biopsy or excision of the causal lesion and appropriate adjunctive therapy (6 patients). Patients with atrophic syrinxes were not operated upon except to relieve symptoms referrable to the causal lesion (4 patients). Recurrent syrinxes were not encountered in the 35 surviving patients over an average follow-up of 2.5 years. It is concluded that syringomyelia is a complex pathological disorder with several mechanisms of pathogenesis that requires a number of different treatment strategies.


Estimating energy expenditure in traumatic brain injury: comparison of indirect calorimetry with predictive formulas.

A high degree of variability in energy expenditure has characterized the metabolic response to traumatic brain injury. A goal of parenteral or enteral repletion in this population is the precise estimation of caloric requirement to avoid complications associated with overfeeding and underfeeding. The first aim of this study was to evaluate three predictive formulas for comparison to measured energy expenditure (MEE) derived from indirect calorimetry in patients with traumatic brain injury. A total of 385 measurements were obtained in 102 patients and were compared concurrently with these predictive formulas. The best predictive method in this phase (bivariate regression) yielded r = 0.39 and P less than 0.001 (231 repeated measures). This best prediction, when compared with MEE, however, was able to capture values within 75 to 125% of MEE in only 56% of measurements. The two remaining formulas yielded r = 0.38 (P less than 0.001) and r = 0.23 (P less than 0.001) in 386 and 267 repeated measures, respectively. The second aim of this study was to evaluate the ability of additional nutritional markers to improve predictive ability. Regression analyses were performed on nutritional markers including indices of severity of injury, concurrent drug therapy, vital signs, neurological status, gluconeogenesis, protein synthesis/excretion, and immune response. The statistical results of the analysis on these multiple nutritional markers showed only heart rate, temperature, and number of days elapsed after injury to be significant predictors of MEE by indirect calorimetry in multiple regression analyses (R = 0.32; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of survival and severity of disability after severe brain injury in children.

Seventy-five children, 16 years of age or younger, consecutively admitted to a level I trauma center over a 2-year period with severe nonpenetrating traumatic brain injuries were studied to assess factors predictive of survival and level of disability. The mortality rate was 33%; 31% had good recovery, 12% had moderate disability, 19% had severe disability, and 5% remained in a vegetative state. Factors were analyzed separately for potential effects on survival and, with fatalities excluded, for potential effects on the level of disability in survivors. Clinical status in the field and emergency room, although highly associated with survival, was less predictive of the level of disability in survivors. Glasgow Coma Scale scores 72 hours after injury, especially the motor component, were significantly better predictors of quality of survival. The severity of the brain injury and the presence and severity of extracranial injuries were strongly related both to survival and quality of survival. Chest injuries, in particular, were associated with increased mortality and morbidity, as was level of oxygenation; these factors were highly correlated. Factors most significantly predictive of survival were severity of total injuries as assessed with the Injury Severity Score and pupillary responses in the emergency room; factors most predictive of disability were Glasgow Coma Scale motor responses 72 hours after injury and level of oxygenation in the emergency room. These findings of differential predictive factors for outcomes of survival versus quality of survival have implications relevant both to clinical care and to research involving severely brain-injured children.


Penetrating injuries restricted to the cauda equina: a retrospective review.

Thirty-three patients with penetrating injuries to the cauda equina were admitted to Ben Taub General Hospital (1980-1989). Thirty received gunshot injuries, and three had stab wounds. The average age was 30 years, and 30 patients were male. All patients had been admitted within 1 hour of injury and received spine films, myelography, or computed tomography. Deficits were "complete" if total loss of function existed and were "incomplete" if any function remained below the level of injury. Improvement at the end of followup was defined as any recovery of motor strength or regaining of a unilateral sensory level. Twenty-nine (88%) patients had incomplete neurological deficits. Of these, 15 (52%) had surgery, and of this patient group, 7 (47%) improved, 7 (47%) showed no change, and 1 (6%) worsened. Fourteen (48%) patients with incomplete deficits were treated conservatively; 10 (71%) improved, and 4 (29%) had no change. Four patients (12%) had complete deficits, 3 of whom had surgery, and all improved. One patient with a complete deficit was treated conservatively and did not improve. Ten (34%) patients had bowel or bladder dysfunction, and none improved regardless of the type of treatment. Complications (cerebrospinal fluid leak, pseudomeningocele, or wound infection) occurred in 5 (28%) operative patients and 1 (7%) conservatively treated patient. Early neurosurgical intervention for penetrating injuries of the cauda equina may be beneficial but carries an increased risk of complication.


Radiobiology of radiosurgery: Part I. The normal rat brain model.

Because limited histological information is available from clinical radiosurgical experience, animal investigations are needed to answer questions regarding the biological response of both normal and pathological tissues. To determine the radiosurgical dose-response relationship of normal brain, we irradiated the right frontal lobe of 18 rats with a single 4-mm isocenter of stereotactic irradiation using the 201-source 60Co gamma unit. Maximal single-fraction doses varied from 30 to 200 Gy (2 rats per dose). All animals were observed for 90 days, killed, and histologically examined. No animal developed neurological dysfunction during that interval, regardless of dose. Animals that received 30, 40, 50, or 60 Gy had no pathological changes. In those given 70 Gy, we found occasional shrunken neurons, and at 80 Gy, rare arteriolar wall thickening. One animal that received 100 Gy had marked capillary endothelial cell degeneration and protein extravasation in the target volume, and the other had a 4-mm diameter necrotic region. Circumscribed cerebral necrosis also was identified in all 4 rats treated with either 150 or 200 Gy; astrocytosis, edema, and microhemorrhage were noted within the surrounding 1 to 2 mm of adjacent brain, and tissue outside that volume had a more normal appearance. We constructed a dose-response relationship based on the cellular, spatial, and temporal effects of focused single-fraction irradiation of the rat brain. To determine the temporal evolution of a known necrotic lesion (200 Gy), 12 other animals were killed (2 each) 1, 7, 14, 21, 30, or 60 days after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of halothane, enflurane, and isoflurane on motor evoked potentials.

The influence of the inhalational anesthetics halothane, enflurane, and isoflurane on motor evoked potentials was studied in a total of 10 rabbits. Motor evoked potentials were recorded from the extremity muscles as well as from the epidural space of the spinal cord and cauda equina in response to electrical stimulation of the motor cortex at baseline conditions and equianesthetic concentrations (0.25 to 1.5 minimal alveolar concentration). Our results show a dose-dependent suppression of the electromyographic responses, which was similar with all anesthetics. Beyond 0.5 minimal alveolar concentration of any of the agents, electromyographic responses were absent. In contrast, spinal evoked responses representing neural activity were only slightly affected by the anesthetics. We hypothesize that the descending impulse elicited by the electrical stimulation of the motor cortex is mainly inhibited at the level of the spinal interneuronal or motoneuronal systems, because 1) electromyographic responses evoked by the stimulation of the cervical and lumbar nerve roots were only minimally affected by 1.5 minimal alveolar concentration halothane; and 2) spinal evoked responses were stable several minutes after cardiac arrest, indicating a subcortical action site of the electrical impulse. In conclusion, intraoperative monitoring of descending pathways by means of motor evoked potentials during anesthesia with the inhalational agents halothane, enflurane and isoflurane is only feasible when neural activity is evaluated.


Subacute hydrocephalus after experimental subarachnoid hemorrhage: its prevention by intrathecal fibrinolysis with recombinant tissue plasminogen activator.

It is investigated whether intrathecal fibrinolysis may prevent subacute hydrocephalus after subarachnoid hemorrhage (SAH). In 19 cats, SAH was induced by the intracisternal infusion of 1 ml/kg body weight of fresh autologous blood at a rate of 0.6 ml/min. Eleven of those animals were treated by intrathecal fibrinolysis performed 24 hours after experimental SAH by intracisternal infusion of 3 mg of recombinant tissue plasminogen activator. Included were eight animals suffering from experimental SAH and four healthy animals retained for control. A computed tomographic scan performed 24 hours after the SAH displayed an acute hydrocephalus from the experimental procedure. Cerebrospinal fluid outflow resistance was 71 +/- 5.0 mm Hg/ml/min in the healthy animals, 265 +/- 19.8 mm Hg/ml/min in the nontreated animals 7 days after SAH, and 151 +/- 6.4 mm Hg/ml/min in the recombinant tissue plasminogen activator-treated animals 7 days after SAH (mean +/- standard deviation; changes significant with P less than 0.01). Postmortem planimetry of both lateral ventricles gives a mean of 3.7 +/- 2.7 mm2 in the healthy animals, 11.1 +/- 3.9 mm2 in the nontreated group after SAH (P less than 0.01), and 3.5 +/- 1.1 mm2 in the animals treated with recombinant tissue plasminogen activator. Intracranial pressure monitoring demonstrated marked intracranial pressure waves only in the nontreated animals after SAH. It is concluded that intrathecal fibrinolysis may prevent subacute hydrocephalus after experimental SAH.


Archaeological origins of cranial surgery: trephination in Mexico.

Archaeological excavations in Mexico and South America have provided evidence that trephination of the skull was performed by the pre-Hispanic Mexican and Incan cultures. Because those who performed such operations on the skull, presumably for ritual, prophylactic, or therapeutic reasons, can be considered predecessors of modern intracranial surgeons, their techniques and results are a subject of considerable current interest. This article, adapted from a lecture presented to the 1986 Congress of Neurological Surgeons, summarizes published descriptions of 34 trephined South and Central American and Mexican skull specimens, 16 of which were unearthed in Mexico and are currently available for review in anthropological museums in Mexico. Examples of several surgical techniques used on these skulls are presented. Although some trephinations were performed by these early cranial surgeons for apparently therapeutic reasons on skulls with obvious evidence of traumatic fractures, the interpretation of the medical, psychiatric, cultural, or religious significance of such procedures remains largely speculative.


Hair and neurosurgery.

The value of removing hair in preparation for neurosurgery is addressed in detail. One neurosurgeon's series, accrued over 40 consecutive months, of 638 prospectively examined, consecutive cases is the basis of this report. The overall surgical wound infection rate was 1.1%. The infection rate for the 313 cranial cases was 0.3% and 2.8% for the 218 procedures involving cerebrospinal fluid diversion (shunts). These data are discussed in the context of extensive nonneurosurgical and microbiological literature. It is concluded that the removal of hair by shaving does not lower the risk of surgical wound infection and may increase the risk. A technique for preparing skin and hair for neurosurgery and for the management of hair during neurosurgical procedures is discussed.


A technique for stereotactic aspiration of deep intracerebral hematomas under computed tomographic control using a new device.

A new device, modified from the Nucleotome (Surgical Dynamics, Alameda, CA), was used for stereotactic aspiration of deep brain hematomas. Real-time monitoring by computed tomography allows a very safe procedure, and the risk of aspirating the surrounding brain is avoided. The technique was applied in 13 cases of deep brain hematomas. The intraoperative computed tomographic scan demonstrated that the mass effect was always immediately improved. Aspiration was stopped when the midline shift disappeared or was dramatically reduced. For most of the cases, a total aspiration of the hematoma was not needed (mean value of the aspiration rate of 71, 5%). No rebleeding and no complication related to the technique was observed. This technique was easily performed in emergency conditions.


Radionecrosis secondary to interstitial brachytherapy: correlation of magnetic resonance imaging and histopathology.

Radiation-induced tissue damage in the central nervous system is a well-known complication of interstitial brachytherapy for brain tumors, yet imaging correlates have historically been based upon computed tomographic scans. We now present magnetic resonance imaging (MRI) to correlate radiation changes after interstitial brachytherapy with the histopathology. The central nervous system of a 38-year-old man with a left frontal cerebral glioma diagnosed by stereotactic biopsy was treated with interstitial brachytherapy (iridium-192, 47 Gy), followed by limited-field irradiation (45 Gy). With progressive deterioration, a second biopsy demonstrated radiation changes. Despite aggressive medical management, the patient died 9 months after completion of radiation therapy. Postmortem evaluation compared MRI scans of the intact, fixed brain with the histopathology. Axial sections (10 mm) obtained by MRI scan and autopsy brain slices were cut in the identical plane. Neuroimaging and histopathological findings of the lesion correlated within 2 to 3 mm resolution. In the peripheral white matter, MRI scan did not indicate the extent of radiation effect histologically. We suggest that MRI has limited utility in assessing the extent of impact of radiation on surrounding brain.


Extraskeletal myxoid chondrosarcoma of the falx.

Intracranial cartilaginous tumors are unusual lesions, of which myxoid chondrosarcoma is the rarest. We describe this tumor arising from the falx in a 28-year-old woman treated at recurrence with a second operation and a radiation implant. The behavior of classic chondrosarcoma and mesenchymal chondrosarcoma is also reviewed.


Surgical reversal of a subacute complete unilateral visual loss from an ovarian metastasis to the pituitary gland.

A 56-year-old woman with ovarian papillary cystadenocarcinoma that metastasized to the pituitary gland sought treatment with a 7-day history of total loss of vision in one eye. Ten days after transsphenoidal tumor resection, the patient's vision suddenly returned to baseline. This unusual case indicates that surgical decompression of the optic nerve and chiasm can completely salvage vision, even after prolonged total visual loss.


Pleomorphic xanthoastrocytoma as a component of a cerebellar ganglioglioma: case report.

A 27-year old male patient underwent surgery for a cerebellar ganglioglioma in which a pleomorphic xanthoastrocytoma constituted the gliomatous element. Neither radiation nor chemotherapy was administered. The patient was well for 12 years and then he suffered a recurrence and underwent a gross total resection. Histological examination revealed a ganglioglioma with thrombosed blood vessels, areas of tumor necrosis, and scattered mitoses. These anaplastic changes, which were restricted to the glial component of the tumor, may herald a more aggressive clinical course. However, 11 months after the second operation, there have been no signs of tumor recurrence.


"Subclinoid" carotid aneurysm with erosion of the anterior clinoid process and fatal intraoperative rupture.

We present the case of a patient with an aneurysm of the right internal carotid artery with subarachnoid hemorrhage. The aneurysm had resulted in erosion of the anterior clinoid process, but this was not recognized preoperatively. Intraoperative rupture during drilling of the clinoid necessitated vigorous packing that led to unintended carotid occlusion with subsequent fatal cerebral infarction. Preoperative recognition of the clinoid erosion may have prevented this catastrophe. To call attention to the potential for intraoperative rupture during exposure, we suggest the term subclinoid aneurysm to refer to aneurysms of the internal carotid artery that grow superolaterally and remain confined under the anterior clinoid process.


Thrombosis of a giant aneurysm after extracranial-intracranial bypass.

A patient presenting with a giant, fusiform middle cerebral artery aneurysm underwent extracranial to intracranial bypass grafting before permanent occlusion of the aneurysm. The patient was to return 4 months later for endovascular treatment. Arteriography obtained before obliteration revealed complete aneurysmal thrombosis. No further treatment was deemed necessary. Factors predisposing to thrombosis are discussed.


Pediatric brain stem infarction caused by a basilar and vertebral artery occlusion: case report.

Basilar and right vertebral artery occlusion, which caused a brain stem infarction, occurred in an 11-year-old boy. There have been nine previous cases of basilar artery occlusion with steno-occlusive lesion in the vertebral artery. It is suspected that dissection of the vertebral artery at the atlantoaxial level and a gradual progression of arterial dissection to the basilar artery were the major causes of this infarction.


Language localization with activation positron emission tomography scanning.

We report the first instance of the use of 3-dimensional magnetic resonance imaging anatomically correlated to positron emission tomography (PET) scanning to identify language areas in a patient with an arteriovenous malformation (AVM) in the posterior speech region. The patient was a 24-year-old right-handed woman with an angiographically proven AVM (3-4 cm) in the left mid-posterior second temporal convolution in whom a left intracarotid injection of sodium Amytal produced significant language disruption. A baseline PET cerebral blood flow study identified the AVM, and an activation PET scan performed during the reading and speaking of simple words showed increased activity in the left parastriate cortex (the second visual area), in the left posterior third frontal convolution (Broca's area), and in the left inferior and midtemporal gyri (Wernicke's area). Increased activity was also noted in the right and left transverse temporal (Heschl's) gyri, in the left precentral gyrus, in the left medial superior frontal gyrus (the supplementary motor area), and in the right cerebellum. We conclude that activation PET scanning is useful in the preoperative assessment of patients who harbor cerebral AVMs in classically described speech regions.


Carotid endarterectomy complicated by vein patch rupture.

Saphenous vein patch angioplasty has been used to improve the results of carotid endarterectomy by decreasing the incidence of postoperative occlusion and recurrent stenosis. A rare but potentially lethal complication of this technique is aseptic necrosis and rupture of the vein patch during the postoperative period. We report three cases of this phenomenon and review an additional 13 cases from the literature. This event generally occurs without warning 2 to 7 days postoperatively and may result in death or stroke. At reoperation, the central portion of the vein patch is necrotic, without evidence of infection. Technical considerations in the harvesting and preparation of these grafts are reviewed, as are the physical parameters predisposing certain vein patches to rupture. Saphenous vein harvested from the ankle has been linked to every reported case. Small diameter veins in particular appear to carry a higher risk of rupture.


Central nervous system disease in patients with systemic lupus erythematosus.

Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups.


Incidence of migraine headache: a population-based study in Olmsted County, Minnesota.

To determine the incidence of clinically detected migraine headache in the defined population of Olmsted County, MN, 1979-1981, we screened over 6,400 patient records from several diagnostic rubrics using the unique resources of the Rochester Epidemiology Project for population-based studies. We identified 629 Olmsted County residents who fulfilled the International Headache Society's 1988 criteria for newly diagnosed migraine headache between 1979 and 1981. The overall age-adjusted incidence was 137 per 100,000 person-years for males and 294 per 100,000 person-years for females. The highest incidence in females was among those aged 20 to 24 years (689 per 100,000 person-years), and in males, the highest incidence was among those aged 10 to 14 years (246 per 100,000 person-years). From 1979 to 1981, there was a striking increase in the age-adjusted incidence in those under 45 years of age: the incidence increased 34% in women and 100% for men. This is the first population-based study of migraine incidence across all ages.


Sensory and motor components of the restless legs syndrome.

The restless legs syndrome (RLS) is characterized by two major manifestations: dysesthesias in the legs and irresistible leg movements. We developed a procedure to quantify these manifestations, and we studied their temporal interrelationships. We found that many dysesthesias may either closely precede or follow occurrences of EMG-defined leg activity, or both manifestations may occur independently. These results suggest that the sensory and motor components of RLS may represent two distinct manifestations of a common basic neurologic defect.


Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis.

We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm). Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients' RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms. The patients' memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes.


The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.


Predictors of cognitive and functional progression in patients with probable Alzheimer's disease.

We followed 65 patients with probable Alzheimer's disease, who were initially mildly to moderately impaired, with semiannual assessments of cognitive and functional performance for up to 4 years. Scores on the Mini Mental State Examination and a combination of instrumental and self-maintenance scale of activities of daily living were regressed on time of examination (measured in 6-month increments) to estimate cognitive and functional progression rates in individual patients. Lower scores on the verbal neuropsychological tests at the time of study entry, more aggressive behavior, and sleep disturbance during the first year of observation predicted faster cognitive progression. Faster functional progression was predicted by paranoid behavior, hallucinations and activity disturbances during the first year and the presence of extrapyramidal signs and lower scores on nonverbal neuropsychological tests at the time of entry into the study. Hallucinations occurred independently of cognitive severity and may identify a distinct subgroup of patients with rapid functional progression. Because of the greater significance of functional progression for caregivers' ability to manage patients, the presence of specific behavior problems early in the disease course may help to identify individuals who will experience greater functional decline and be at risk for earlier institutionalization.


Occupation during life and memory performance in nondemented French elderly community residents.

Using data obtained during the baseline screening of the PAQUID cohort, an epidemiologic study on brain aging conducted in the Bordeaux area of France, we studied the relationship between lifetime occupation and memory performance in visual recognition (Benton Visual Retention Test; BVRT) and verbal induced recall (Wechsler Paired Associates Test; WPAT) in 2,720 elderly community residents. Occupational category was strongly correlated with poor memory performance for both the BVRT and the WPAT. Independent of the educational level, the risk of having poor memory performance was two to three times greater for farmers, domestic service employees, and blue-collar workers than for professionals/managerials. Occupational category should be taken into account in future cross-national studies on brain aging.


Kynurenine pathway abnormalities in Parkinson's disease.

We measured metabolites of tyrosine and tryptophan (TRP) in the frontal cortex, putamen (PT), and pars compacta of the substantia nigra (SN) of control and Parkinson's disease (PD) brain tissues. Dopamine concentrations were significantly decreased in the PT and SN of PD tissue, regardless of L-dopa therapy. However, 3-O-methyldopa (3OMD) concentration showed a significant increase in each region of the PD group treated with L-dopa (PD[+]) as compared with both the control group and the PD group without L-dopa therapy (PD[-]). Therefore, 3OMD concentration appears to be a reliable marker of L-dopa therapy. Serotonin concentration was lower in each region of the PD groups than in the control group. Although the magnitude of decrease was greater in the PD(+) group, there was no statistical significance between the two PD groups. The same patterns of decrease were present in kynurenine (KYN) and kynurenic acid (KYA) concentrations, but the molar ratios of TRP to KYN and KYN to KYA were unchanged among three groups. In contrast, 3-hydroxykynurenine (3OHKY) concentration was increased in the PT PD(-) group and in three regions of the PD(+) group. Since the KYN pathway leads to formation of nicotinamide-adenine dinucleotide (NADH), the present results may be a further indication of a defect in NADH:ubiquinone oxidoreductase (complex I) in mitochondria in PD.


Neurologic improvement in pure motor hemiparesis: implications for clinical trials.

Knowledge of the natural history of certain stroke subtypes is essential for the proper analysis and interpretation of clinical trials of stroke therapy. We evaluated the degree of weakness on admission and again 7 to 10 days later in 62 patients with pure motor hemiparesis (PMH) and 280 patients with motor deficits from other stroke syndromes (OSS). During the 7-to-10-day study interval, we found that the OSS group worsened slightly in motor function, whereas the PMH group improved (p = 0.01). Among those who improved in both groups, those in the PMH group improved to a greater extent than did those in the OSS group (p = 0.02). This occurred despite a greater frequency of worsening during the first 12 hours after stroke onset in the PMH group. By the fourth day following PMH onset, a majority of patients had improved, and this improvement was sustained until day 10. The two groups did not differ significantly in age, race, sex, history of cardiac disease, hematocrit, anticoagulation treatment, blood glucose, or medical complications in hospital. Lacunar infarcts occurred in 84% of PMH and 23% of OSS. Patients with PMH show significant spontaneous improvement in weakness within 7 to 10 days of admission, compared with patients with OSS. Stratification by admission stroke syndrome in clinical trials may be necessary before judging the efficacy, or lack thereof, of a therapeutic agent.


Fast magnetic resonance diffusion-weighted imaging of acute human stroke.

Rapid MRI of the molecular diffusion of water demonstrated cerebral infarcts in 32 patients. We studied these patients at various times following the onset of ischemic symptoms and found that diffusion-weighted imaging revealed the infarcts sooner than conventional T2-weighted spin-echo imaging did; four hyperacute infarcts were shown only by diffusion-weighted imaging. Acute infarcts had lower apparent diffusion coefficients (ADCs) than noninfarcted regions did. This relative difference in ADC reached a nadir in the first 24 hours and rose progressively thereafter. Chronic infarcts showed a relative increase in diffusion and were readily distinguishable from acute infarcts. The technique takes less than 2 minutes to apply using a standard 1.5-tesla scanner in the clinical setting. Diffusion-weighted imaging has the potential to play a role in improving the early anatomic diagnosis of stroke and therefore in the development and implementation of early stroke interventions.


Androgen receptor abnormality in X-linked spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA) is usually associated with feminization and hypogonadism. We were unable to find androgen receptor (AR) in the scrotal skin of three patients with SBMA, and propose that AR abnormality is the cause of the disease.


Cardiovascular effects of human insular cortex stimulation.

Recent investigations indicate a site of cardiac representation within the left insular cortex of the rat. Moreover, the results of lesion studies suggest left-sided insular dominance for sympathetic cardiovascular effects. It is unclear whether similar representation exists within the human insular cortex. Five epileptic patients underwent intraoperative insular stimulation prior to temporal lobectomy for seizure control. On stimulation of the left insular cortex, bradycardia and depressor responses were more frequently produced than tachycardia and pressor effects (p less than 0.005). The converse applied for the right insular cortex. We believe this to be the first demonstration of cardiovascular changes elicitable during insular stimulation in humans, and of lateralization of such responses for a cortical site. In humans, unlike the rat, there appears to be right-sided dominance for sympathetic effects. These findings may be of relevance in predicting the autonomic effects of stroke in humans and in the explanation of sudden unexpected epileptic death.


Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.


Periodic alternating gaze deviation in infancy.

Periodic alternating gaze is a rarely reported phenomenon. We have observed two cases that are unique in their early onset at birth and infancy. Multiple congenital defects of the posterior cranial fossa were present on MRI in both cases. A prominent abnormality shared by both was absence of normal structures in the region of the inferior cerebellar vermis. Periodic alternating gaze appears to be associated with pathologic changes in the hindbrain in these and other reported cases.


Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging.

Both the amygdala and the hippocampus are involved in the pathogenesis of a number of neurologic conditions, including temporal lobe epilepsy, postanoxic amnesia, and Alzheimer's disease. To enhance the investigation and management of patients with these disorders, we developed a protocol to measure the volumes of the amygdala and as much of the hippocampus as possible (approximately 90 to 95%) using high-resolution MRI. We present the anatomic basis of these two protocols and our results in normal control subjects. These volumetric studies of the amygdala may clarify the role of this structure in the pathogenesis of temporal lobe epilepsy.


Immunologic study of vinculin in Duchenne muscular dystrophy.

Using immunologic techniques, we studied vinculin, a cytoskeletal protein associated with the membrane-skeleton of the muscle fiber. We examined muscle biopsies from five patients with Duchenne muscular dystrophy (DMD), two with Becker's muscular dystrophy (BMD), three normal human muscle samples, and four biopsies from disease control patients. All DMD patients showed patchy and low-intensity immunostain at the sarcolemma of most fibers and, by immunoblot analysis, the content of vinculin was 42 to 61% of control values. There was no significant vinculin deficiency in samples from patients with BMD and other disease controls. The data suggest that vinculin content is reduced only in muscle where dystrophin is absent or sparse.


Autosomal recessive form of hereditary motor and sensory neuropathy type I.

We studied pathologic changes in sural nerve biopsies from four patients with probable autosomal recessive (AR) hereditary motor and sensory neuropathy (HMSN) type I with a median motor nerve conduction velocity greater than 10 m/sec, comparing them with the pathologic features in autosomal dominant (AD) HMSN type I. The four recessive and two sporadic cases showed segmental demyelination. However, the classic onion bulbs of concentric Schwann cell processes, which occur in AD type I, were rare; many axons, also of a smaller size, were surrounded by onion bulbs of basal laminae. Schwann cells of the myelinated and unmyelinated types were involved in these onion bulb formations. Patients with HMSN type I who have many basal lamina onion bulbs should be considered as having AR inheritance.


P3 recordings in patients with bilateral temporal lobe lesions.

We recorded event-related potentials to an acoustic "oddball" paradigm from 19 scalp derivations in five patients (three women and two men; age range, 44 to 56) who had global amnesia following encephalitis. CT and MRI showed severe bilateral lesions of anterior and midtemporal lobes. A P3 component, with a peak latency within the normal limits for age-matched controls, was recorded to "target" stimuli in four patients from all leads except Fp1, Fp2, F7, F8, T3, and T4. In the fifth patient, the P3 peak was delayed.