[Effect of the form of pathological tortuosity of the internal carotid artery on cerebral haemodynamics].

The prevalence of pathological tortuosity of carotid arteries according to the findings of angiographic studies varies from 10% to 43%. This pathology is morphologically diversified, requiring detailed verification of its forms in order to specify the character of impaired cerebral haemodynamics in each individual case. All patients presenting with manifestations of cerebral insufficiency underwent ultrasonographic duplex scanning of the vessels of the system of the brachiocephalic arteries according to the standard methods, measuring the volumetric velocity of blood flow before and after the pathological bend, the blood-flow linear velocity gradient. Revealing haemodynamically significant alterations was followed by contrast-enhanced computed tomography with subsequent 3-D reconstruction based on which we selected an optimal projection making it possible to measure the angles of the pathological bends. The second stage of the study consisted in mathematical calculations of the haemodynamic indices (the Reinolds number allowing of determining the regimen of the blood flow along the vessels, local losses of head according to the Weisbach formula, loss of pressure for local resistance), and statistical treatment of the data (two-tailed exact Fisher's test, Statistica 6.0). The obtained findings suggest a statistically significant increase in the prevalence of ischaemic stroke in patients with the angle of the pathological bend measuring 60° and less. Patients of this group are found to have an increase in the linear velocity of blood flow exceeding 150 cm/s and the value of the gradient over 2.4, thus suggesting haemodynamic significance. An increase in the acuity of the angle of a smooth turn from 60° to 30° was accompanied by a 3-fold increase in loss of pressure on the portion of local resistance from 509 to 1,466 Pa. Thus, in the vessels with the angle of a smooth turn of 90° and more haemodynamic alterations to a large extent depend on the internal surface of the vascular wall, in the bends of the vessel with a turning angle of less than 90° they depend on the value of the angle of a smooth turn.

Oxidation of a Polymer Surface with Gas-Phase Singlet (1Dgrg) Oxygen.

Singlet molecular oxygen ((1)Delta(g)) produced by the microwave discharge of ground state oxygen in a flow system was passed over a film of cis-polybutadiene. This treatment resulted in the formation, at the surface, of hydroperoxides which were detected by internal reflection infrared spectroscopy.

Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles.

The nonsteroidal anti-inflammatory drug, flurbiprofen, a potent cyclooxygenase inhibitor, significantly decreases the resorption of alveolar bone in naturally occurring chronic destructive periodontal disease in beagles. This observation indicates that arachidonic acid metabolites are important in the alveolar bone loss of periodontitis and suggests a use for flurbiprofen in the management of bone resorption disease.

Tetracycline-regulated cardiac gene expression in vivo.

Tight regulation of foreign genes expressed in vivo would facilitate studies of many biologic processes and would be useful for gene transfer-based therapies. To test the ability of a tetracycline-regulated gene expression system to function in vivo, we directly injected chimeric tet repressor-VP16 transactivator expression plasmids and luciferase target genes into the hearts of adult rats. Cardiac luciferase activity increased over two orders of magnitude in response to small changes in input tetracycline-controlled transactivator DNA. Transactivation was repressed to background levels by subtherapeutic concentrations of tetracycline in a dose-dependent manner. Target gene expression could be rapidly and reversibly controlled by manipulating antibiotic administration. This system may be particularly useful for in vivo studies of gene function or gene therapies where the timing or extent of expression are critical variables.

Suicidal behaviors in adult psychiatric outpatients, I: Description and prevalence.

OBJECTIVE: Because the findings of previous studies of suicidal behaviors in psychiatric outpatients may not necessarily generalize to outpatients with a wide spectrum of psychiatric diagnoses, the authors evaluated the prevalence of suicidal behaviors in a large general psychiatric outpatient clinic whose patients represented a full spectrum of psychiatric illness. METHOD: A total of 651 patients participated in the study between 1987 and 1989. These patients had sought treatment at the outpatient psychiatry department of a private nonprofit hospital. Before being interviewed for treatment, all patients were given a comprehensive self-rating survey packet that included the Harkavy Asnis Suicide Survey and the Hopkins Symptom Checklist-90. The Harkavy Asnis Suicide Survey is a self-report questionnaire that assesses demographic variables, current and past history of suicidal behaviors of the patient as well as family members and peers, and a detailed description of each previous attempt. RESULTS: Fifty-five percent of the patients had a history of suicidal ideation, and 25% reported at least one previous suicide attempt. Approximately half of the suicide attempters reported multiple attempts. The predominant methods of attempt were overdose (53%), jumping (17%), and wrist cutting (17%). Suicidal behavior was prevalent in most diagnostic groups. The rates of suicidal ideation among patients with mood disorders (major depression, dysthymia, and bipolar disorder), adjustment disorders, and alcohol/substance abuse were significantly greater than that of the patients with generalized anxiety disorder. CONCLUSIONS: The authors conclude that suicidal behavior is prevalent among patients who seek treatment in a general outpatient department.

Calorigenic response in obese and nonobese women.

The calorigenic response to a high protein test meal was studied in women with a history of childhood onset obesity. Obese and nonobese individuals were fasted overnight and basal oxygen consumptions determined the following morning. A semisynthetic 823 kcal high protein test meal was ingested within a 1-hr period followed by hourly determinations of oxygen consumption and plasma levels of insulin, free fatty acids, triglycerides, glucose, amino acids, and urea nitrogen. Amino acid levels increased faster and to a higher plateau in the nonobese group, while insulin levels increased and eventually decreased in a similar fashion in both groups. No differences in basal metabolic rate were detected. The postprandial increment in oxygen consumption was significantly less among the obese subjects. Diminished calorigenesis after each meal would result in accumulation of extra calories provided that caloric consumption is not appropriately decreased. These data suggest that a physiological aberration of energy metabolism may contribute to the development of childhood onset obesity.

Pork with a high content of polyunsaturated fatty acids lowers LDL cholesterol in women.

BACKGROUND: Animal products contribute significantly to the saturated fat and cholesterol content of the American diet. Contrary to dietary advice, consumers have not limited their consumption of animal products. Thus, an alternative approach might be to modify the fatty acid composition of animal products. OBJECTIVE: We tested the hypothesis that modified pork with a high content of polyunsaturated fatty acids (PUFAs) and a low content of saturated fatty acids (SFAs) would lower plasma LDL-cholesterol concentrations in women. DESIGN: Twenty women aged 19-24 y completed a crossover study with 2 diets. Nutritionally complete diets containing 42% of energy from fat differed only in the inclusion of either standard or modified pork. Venous blood samples were collected at weeks 0, 4, and 8. RESULTS: The diet containing modified pork significantly lowered total plasma (P < 0.0076) and LDL (P < 0.0382) cholesterol. The modified diet also resulted in an increase in the PUFA and a decrease in the SFA and monounsaturated fatty acid contents of the cholesteryl ester, free fatty acid, phospholipid, and triacylglycerol lipid classes in both plasma and erythrocytes. Plasma concentrations of glucose, insulin, triacylglycerol, and free fatty acids did not change significantly. CONCLUSIONS: Consumption of pork with a high PUFA content resulted in a decrease in the subjects' total plasma and LDL cholesterol and shifted the fatty acid composition from SFAs to PUFAs in the plasma and erythrocytes. Modification of the fatty acid composition of animal foods will be a useful approach to lowering the saturated fat consumption of Americans.

Biodistribution and dosimetry of N-isopropyl-p-[123I]iodoamphetamine in the primate.

The biodistribution of N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) in the Macaca fascicularis monkey was determined at 15 min and at 1, 4, 24, and 48 hr after intravenous injection. Brain uptake was 7.8% of the injected dose at 1 hr, with little change in concentration between 15 min and 1 hr, falling thereafter. Eye uptake reached a maximum of 0.23% of injected dose at 24 hr, with activity primarily in the pigmented layers. The human absorbed radiation dose was calculated on the basis of biodistribution data. The critical organ is the eye (0.407 rad/mCi of I-123 IMP). The eye dose increased to 1.11 rad/mCi with 4% contamination from I-124 IMP and to 0.535 rad/mCi with 0.4% contamination from I-125 IMP. The absorbed dose to the liver was 0.127 rad/mCi for pure I-123 IMP and the thyroid dose was 0.120 rad/mCi, both increasing with either I-124 or I-125 contamination. While delayed eye uptake has not yet been reported in the human, care should be exercised in limiting the amount of contaminating I-124 or I-125 to the lowest practical level.

The relationship of the eye uptake of N-isopropyl-p-[123I]iodoamphetamine to melanin production.

Eye uptake has been a potential concern with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) because it has been observed in certain animal species. We have investigated the cause of the eye uptake and its relationship to melanin synthesis. In a 1-yr-old cynomolgus monkey, high concentration of the tracer was seen in the eyes regardless of the type of anesthesia (pentobarbital or ketamine) or the oral administration of Lugol's solution. The eye uptake at 24 hr after injection of I-123 IMP was equally high in an 8-yr-old rhesus monkey. The ratio of radioactivity in the eye of black compared with white albino mice was 10:1 at 30 min, 18:1 at 2 hr and 36:1 at 24 hr after injection of I- 123 IMP. No eye uptake above soft-tissue background was seen in five patients at 2, 24, and 48 hr after injection. I-123 IMP is avidly incorporated into melanocytes actively producing melanin, but substantially less in melanocytes where production of melanin has ceased as in the human eye.

Chemical and in vivo studies of the anion oxo[N,N'-ethylenebis(2-mercaptoacetimido)]Technetate(V).

Studies of the anionic coordination complex 99Tc-oxo[N,N'-ethylene-bis(2-mercaptoacetimido)]technetate(V) ([TcO(ema)]-) are described. Syntheses performed both at carrier levels (10(-5)M) and with no carrier added (less than 10(-8)M) indicate that the complex is formed virtually quantitatively from pertechnetate ion over this range. Tissue distributions in normal rats are similar at both concentrations up to one hour after administration. It has been shown--using a combination of high-pressure liquid chromatography and field-desorption mass spectrometry--that the anion is excreted unchanged into both urine and bile. The effectiveness of this N2S2 donor set in sequestering Tc-99m, and the in vivo stability of the resulting complex, suggest that modified chelates of this structural class could provide a series of useful diagnostic agents.

Consumption of O2 and early detection of fa/fa genotype in rats.

Oxygen consumption was determined in 10--12-wk-old fa/fa and non-fa/fa rats at ambient temperatures of 10 degrees--40 degrees C. The fa/fa rats exhibited a lower oxygen consumption than non-fa/fa rats from 10 degrees--30 degrees C, but not at 35 degrees C and 40 degrees C. A lower oxygen consumption was also observed among fa/fa rats as early as 18 days of age, prior to the phenotypic expression of apparent obesity. Fourteen hundred microliter O2 consumed/hr/g body weight at STP was used as a value, below which future obese rats could be identified among 18-day-old pups from fa/+ X fa/+ crosses. Only a 10% error was found in the use of this value for the early identification of the fa/fa genotype.

Adipocyte size distribution in fa/fa rats during development.

Epididymal fat pad adipocyte frequency distributions of obese (fa/fa) and nonobese (non-fa/fa) Zucker rats were determined from 2 to 20 wk of age. The fa/fa rats consistently displayed a higher proportion of larger adipocytes than the non-fa/fa rats of all ages studied. Increased adipocyte size preceded an increase in the number of adipocytes during the early phases of obese development. Among the fa/fa rats, the frequency of small cells continued to increase, which resulted in a bimodal distribution by 20 wk of age. Discriminant analysis suggests that the differences in adipocyte size frequency distributions at 2 wk of age may be another useful means to identify fa/fa and non-fa/fa pups prior to expression of overt obesity. Increased fat storage may reflect the lower energy expended by the very young fa/fa rats.

Semiconductor probe measurements in beagle dogs with periodontal disease.

A miniaturized semiconductor probe was used to measure alveolar bone uptake of a bone-seeking radiopharmaceutical in dogs with destructive periodontal disease. Radiopharmaceutical uptake in localized, advanced disease was greater than in incipient disease and was generalized, with increased uptake occurring in radiographically normal areas and in areas with bone loss.

Predicting alveolar bone loss in beagles using bone-seeking radiopharmaceutical uptake.

Measurements of bone-seeking radiopharmaceutical uptake obtained at the beginning of this two-year study of beagles with periodontal disease were correlated with the amount of bone loss which occurred during the study. Uptake correlated with bone loss (r = 85), which suggests that uptake may be an indicator of future bone loss.

Semiconductor probe measurements in beagle pups during deciduous tooth development.

Bone-seeking radiopharmaceuticals were used together with clinical and radiographic procedures to study tooth development in dogs. Similarities in the pattern and time course of radiopharmaceutical uptake in jaw areas studied suggest that changes in alveolar bone metabolism are not closely related to eruption times of individual teeth.

Violence and homicidal behaviors in psychiatric disorders.

Our review evaluating the relationship between violent/homicidal behaviors and mental illness/psychiatric disorders used many different data including that assessing the prevalence of violent/homicidal behaviors in former psychiatric inpatients (just before hospitalization, during hospitalization, and after discharge) as outpatients and in community samples as well as evaluating the prevalence rate of psychiatric disorders in people who actually engaged in violent/homicidal disorders (jail detainees, prison inmates, and community samples). Irrespective of which line of investigation, there was convincing evidence that violent/ homicidal behavior was associated significantly with mental illness. Although earlier investigations failed to control for important variables, such as age and sociodemographics, most studies reviewed in this article did control for these items, further underlining the association of violence and mental illness. The question of whether specific psychiatric diagnostic categories are associated with violent/homicidal behavior is less definite across the various studies reviewed. The presence of substance abuse and dependence and alcohol abuse and dependence as well as antisocial personality disorder are particularly associated with an increased risk of violent/homicidal behaviors. The risk for these latter behaviors in schizophrenia, mood disorders, and anxiety disorders may appear somewhat greater than that for a general population but are not of the same magnitude of that for substance abuse or antisocial personality disorder. Interestingly, our outpatient study found that homicidal behaviors were not associated with any specific psychiatric diagnosis. Although understanding whether specific psychiatric diagnostic categories are more prone to violent behaviors may be of importance, most studies have been shortsighted regarding this evaluation. All the studies presented in this article except the ECA project, presented diagnostic data where either the presence of one psychiatric disorder did not preclude the diagnosis of another or assigned subjects/patients into the severest disorder of a predetermined hierarchy of diagnoses or only selected their principal/primary diagnosis. Thus, the effect of having a solitary psychiatric disorder (only one disorder present) as well as the effect of comorbidity per se on the relationship of psychiatric disorders and violent/homicidal behaviors were unexplored. Only the ECA study by Swanson and colleagues reported on the effect of comorbidity. As reviewed earlier in the article, Swanson et al found that comorbidity of psychiatric diagnostic categories further increased the risk of violent/ homicidal behaviors. In most cases, it was many more times than simply adding the rates of either diagnosis alone. Because more than 54% of respondents of the National Comorbidity Survey study who had one DSM-III-R diagnosis also had at least a second Axis I diagnosis, the association of violent/homicidal behaviors to mental illness may even be stronger than originally believed. Within the relationship of violent/homicidal behaviors and mental illness, this article suggests a number of particular risk factors. As just reviewed, substance/alcohol abuse and antisocial personality disorder as well as the presence of comorbid psychiatric disorders are significant risk factors. Which particular comorbid illness increases the risk still needs further elaboration. Studies must continue to try to define and understand the relationship of violent/homicidal behaviors in mental illness. Although mental disorders per se are significantly associated with violent/homicidal behaviors, it is reasonable to believe that targeting certain subgroups of patients should be helpful. Probably the presence of psychotic symptoms is a significant risk factor in violent/ homicidal behaviors in the mentally ill. Only one of the studies reviewed in this article evaluated this issue. (ABSTRACT TRUNCATED)

Energy-conserving impact algorithm for the heel-strike phase of gait.

Significant ground reaction forces exceeding body weight occur during the heel-strike phase of gait. The standard methods of analytical dynamics used to solve the impact problem do not accommodate well the heel-strike collision due to the persistent contact at the front foot and presence of contact at the back foot. These methods can cause a non-physical energy gain on the order of the total kinetic energy of the system at impact. Additionally, these standard techniques do not quantify the contact force, but the impulse over the impact. We present an energy-conserving impact algorithm based on the penalty method to solve for the ground reaction forces during gait. The rigid body assumptions are relaxed and the bodies are allowed to penetrate one another to a small degree. Associated with the deformation is a potential, from which the contact forces are derived. The empirical coefficient-of-restitution used in the standard approaches is replaced by two parameters to characterize the stiffness and the damping of the materials. We solve two simple heel-strike models to illustrate the shortcomings of a standard approach and the suitability of the proposed method for use with gait.

Predictive algorithms for neuromuscular control of human locomotion.

The problem of quantifying muscular activity of the human body can be formulated as an optimal control problem. The current methods used with large-scale biomechanical systems are non-derivative techniques. These methods are costly, as they require numerous integrations of the equations of motion. Additionally, the convergence is slow, making them impractical for use with large systems. We apply an efficient numerical algorithm to the biomechanical optimal control problem. Using direct collocation with a trapezoidal discretization, the equations of motion are converted into a set of algebraic constraint equations. An augmented Lagrangian formulation is used for the optimization problem to handle both equality and inequality constraints. The resulting min-max problem is solved with a generalized Newton method. In contrast to the prevalent optimal control implementations, we calculate analytical first- and second-derivative information and obtain local quadratic convergence. To demonstrate the efficacy of the method, we solve a steady-state pedaling problem with 7 segments and 18 independent muscle groups. The computed muscle activations compare well with experimental EMG data. The computational effort is significantly reduced and solution times are a fraction of those of the non-derivative techniques.

Nuclear medicine. An indicator of "active" alveolar bone loss in beagle dogs treated with nonsteroidal anti-inflammatory drug.

Nuclear medicine was used to assess the activity of alveolar bone loss in beagle dogs treated with the nonsteroidal anti-inflammatory drug flurbiprofen. Radiographic measurements of the rate of bone loss were taken during a 6-month "pretreatment" period and a 9-month treatment period. During the treatment period six dogs received a placebo, and six dogs received orally 0.02 mg/kg flurbiprofen daily for 9 months. In addition, each dog received periodontal surgery in one half of the mouth at the end of the pretreatment period. The rate of alveolar bone loss was significantly decreased in the treatment period in the flurbiprofen-treated dogs (P less than 0.001). Measurements of bone-seeking radiopharmaceutical uptake were taken 3 months after the initiation of therapy. The single measurement of uptake was compared to the rate of bone loss determined from repeated radiographs taken during the 9-month treatment period. Bone-seeking radiopharmaceutical uptake was an accurate indicator of "active" bone loss in 83.5% of the teeth studied.

Hepatic microsomal and peroxisomal docosahexaenoate biosynthesis during piglet development.

The roles of peroxisomes and microsomes on the biosynthetic pathway for docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA) were investigated. Microsomes and peroxisomes were prepared from livers of fetal and neonatal piglets by a combination of differential and gradient layer centrifugation. Microsomes, peroxisomes, and combined cell fractions were incubated with [13C-U]18:3n-3. The [M] and [M + 18] isotopomers of the fatty acids in the long-chain polyunsaturated fatty acid (LCPUFA) n-3 pathway were detected by gas chromatography-mass spectrometry. The quantity of each fatty acid was determined by gas chromatography, and synthesis of each fatty acid was calculated for a 30-min period. Synthesis of DHA was not detected in combined fetal liver fractions. The data suggest that DHA in the fetus is probably supplied from maternal sources through the placenta. In either singly incubated microsomal or peroxisomal preparations from neonatal livers, no DHA synthesis was detected. After combination of the microsomal and peroxisomal fractions, DHA synthesis was evident and increased rapidly between birth and 2 wk of age. This is the first demonstration of the entire biosynthetic LCPUFA n-3 pathway in subcellular organelles starting from isotopically labeled ALA to the final product, DHA, with all the intermediates present and isotopically labeled. The primary importance of the data is that it unequivocally demonstrates that peroxisomes are required for biosynthesis of DHA from ALA.