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PubMed2000

Cytokines and hemostasis.

BACKGROUND AND OBJECTIVES: Cytokines are low molecular weight polypeptides that act as pleiotropic mediators of inflammation and may contribute significantly to regulation of hemostatic balance in both physiologic and pathologic conditions. The purpose of this review is to underline the most significant progresses recently achieved in this rapidly growing area. DESIGN AND METHODS: The authors have been involved both at home and abroad in experimental and clinical research in this field for years and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles published in journals covered by the Science Citation Index and Medline. RESULTS: Tissue factor, a transmembrane glycoprotein that serves as a surface receptor for coagulation factor VIIa, plays a key role in the initiation of coagulation processes. Very little, if any, tissue factor activity is detectable in normal conditions on the cell surface of monocytes and endothelial cells. However, upon proper stimulation by a number of agents such activity may be expressed in these cells, which can then contribute significantly to clotting activation. Pro-inflammatory cytokines (IL-1, IL-6 and TNF) are effective inducers of tissue factor upregulation and may trigger endothelial cells to change their antithrombotic properties into a procoagulant, clot-promoting state. Indeed, much experimental and clinical evidence has been accumulated to suggest that cytokines play a key role in the pathophysiology of hemostatic abnormalities in different disease states. These include, inter alia, the coagulopathy observed during septicemia, the veno-occlusive disease of the liver after bone marrow transplantation, the prothrombotic state associated with atherosclerotic vessels, the occurrence of deep venous thrombosis after major abdominal surgery and the thrombotic tendency of patients with cancer. Several new antithrombotic strategies based on these new concepts have been attempted in experimental models of thrombosis and also in man. Examples of new possible antithrombotic agents are the tissue factor pathway inhibitor, Fab fragments of monoclonal antibodies directed against factor VII or factor VIIa, mutant forms of biologically inactive tissue factor and inhibition of cytokines involved in the regulation of tissue factor expression. Many of these studies have produced positive or interesting results, although more must be learned before the appropriate drug and the adequate dose are defined in the different clinical situations. CONCLUSIONS: Pro-inflammatory cytokines (IL-1, IL-6 and TNF) play a key role in tissue factor expression on monocytes and on endothelial cells and contribute significantly to regulation of hemostatic balance in physiologic and pathologic conditions. This effect is of great interest from both speculative and practical viewpoints.

Animals↗

PubMed1999

Peptide immunoreactivity in aged rat cortex and hippocampus as a function of memory and BDNF infusion.

Brain-derived neurotrophic factor (BDNF) modulates neuropeptide levels in hippocampus and cortex of young adult rats. Neuropeptide levels are altered in some age-related disorders, such as Alzheimer's and Parkinson's Disease. BDNF may be able to rectify peptide abnormalities but, because plasticity decreases with age, BDNF may not alter peptide levels as readily in aged animals. To determine if BDNF would regulate peptide levels in aged rats, young, aged memory-impaired, and unimpaired rats were infused with BDNF or vehicle into hippocampus and cortex. Cell profile counts, cell profile areas, fiber counts, and/or fiber terminal densities were measured for sections immunostained for neuropeptide Y (NPY), somatostatin (SOM), cholecystokinin-8 (CCK), and dynorphin A(1-8) (DYN). Results showed that BDNF upregulated cortical NPY-immunoreactivity (ir) and SOM-ir, upregulated hippocampal NPY-ir, and downregulated hippocampal DYN-ir in both aged and young rats. In addition, BDNF significantly and selectively normalized the areas of atrophied deep cortical CCK-ir cell profiles in aged-impaired rats. Finally, decreased CCK-ir fiber density was found in the hippocampal formation of aged memory-impaired rats.

Aging↗

PubMed1995

Operant learning (R-S) principles applied to nail-biting.

The principles of R-S learning were applied to a 32-yr.-old Caucasian woman to reduce the frequency and duration of fingernail-biting activity in a reversal-replication (ABAB) research design. The undesirable behavior, fingernail-biting which included frequency and duration, antecedents, and setting events, was recorded during a 28-day study. Self-monitoring recordings indicated that anxiety was the most prevalent antecedent. Through the use of a preliminary questionnaire and interview, increase in self-awareness was judged to be most effective in the extinction of the undesired behavior. The systematic desensitization techniques of deep muscle relaxation and Transcendental Meditation were used during the treatment phase.

Adult↗

PubMed2001

[The importance of neuronavigation in endoscopic operations in neurosurgery].

Intracranial endoscopy as minimal invasive surgery for the treatment of hydrocephalus and intracranial cysts cannot be disregarded after 10 years of clinical practicing. The advantages are low traumatization of brain tissue and good visual control of the operation field. Neuronavigation qualifies as a method of increased operation safety for lesions which are deep seated or difficult to access. A combination of both systems partially neutralizes the respective disadvantages. On the one hand, the neuronavigation ensures the endoscopic approach up to the intracranial caverns and especially supports the endoscopy in cases of bad vision or pathologic anatomy. Endoscopy, on the other hand, enables the surgeon to recognize discrepancies and mistakes of the neuronavigation due to optical control. Increased expenses and time and staff requirements are counterbalanced by the increased cumulated operation safety. An advantageous side-effect of the combination of neuronavigation and intracranial endoscopy is the high learning potential for assistants. For all these reasons the application of neuronavigation in intracranial endoscopy is considered very important and strongly recommended.

Brain↗

PubMed2000

Healing of untidy traumatic skin defect of the face by secondary intention.

BACKGROUND: Untidy facial skin defects manifest extensive soft tissue injury and contamination. Since modern surgical principles emphasize immediate wound closure, most surgeons should learn to convert an untidy wound to a tidy one and to reconstruct defects immediately if possible with the use of grafts and flaps. However, in some situations, healing by secondary intention remains advantageous. The purpose of this study is to reevaluate this traditional approach. METHODS: Twenty patients with untidy facial skin defects were treated conservatively over a 4-year period. The defects ranged from 2 x 2 cm2 to 6 x 4 cm2 in size. The depths of wounds were classified into partial-thickness in 9 patients, full-thickness in 7 patients, and deep defects in 4 patients. Each patient was instructed on wound care, which included daily cleaning with normal saline, followed by application of hydrocolloid occlusive dressing. Prophylactic antibiotics were not used. RESULTS: The mean follow-up period was 17 months. All wounds healed within 3 to 5 weeks. There was no wound infection. One patient developed a hypertrophic scar over the cheek, and received excision of the scar and resurfacing with full-thickness skin graft. Two patients had residual traumatic tattooing which was resolved by laser therapy. Two patients had hypopigmentation/hyperpigmentation problems. Most patients (18/20) were satisfied with both functional and cosmetic results. CONCLUSION: Conservative wound care with hydrocolloid occlusive dressing allows good healing by secondary intention for traumatic facial defects in selected patients.

Adolescent↗

PubMed2000

Neuropsychological functioning in a patient with essential tremor with and without bilateral VIM stimulation.

The effects of deep brain stimulation on motor functions, cognitive abilities, and mood were assessed in an 80-year-old, right-handed male with a chronic history of essential tremor. Electrodes were implanted bilaterally in the ventral intermediate nucleus of the thalamus during a single operation. Upon evaluation at 3 months postsurgery, bilateral stimulation was associated with a clinically significant reduction in tremor ratings and improvement in manual dexterity. At that time, a battery of neuropsychological measures was administered with and without bilateral stimulation. The patient demonstrated comparable performances on measures of visuospatial perception, attention, mental tracking, verbal learning, and verbal recognition memory in both the "on" and "off" conditions. Without stimulation, the patient demonstrated declines of greater than 1 SD on measures of verbal fluency and verbal recall compared to when the stimulators were active. Responses to mood rating scales also indicated greater subjective distress without stimulation. Results are discussed in the context of previous studies of the effects of thalamic stimulation on neurocognitive functioning.

Aged↗

PubMed2004

Periventricular leukomalacia following neonatal and infant cardiac surgery.

The dramatic reduction in surgical mortality following repair of congenital heart defects has been accompanied by increasing recognition of adverse neurodevelopmental sequelae in some children. Neurodevelopmental abnormalities following neonatal and infant cardiac surgery include mild cognitive impairment, expressive speech and language abnormalities, impaired attention and executive function, impaired visual and spatial motor skills, as well as learning disabilities. These defects result in a significant need for early intervention, as well as rehabilitative and special education services. Central nervous system injury following repair of congenital heart defects results from a complex interaction of patient specific and environmental factors. Recent studies suggest that cerebral white matter injury characterized by periventricular leukomalacia (PVL) is common in infants with congenital heart disease particularly following cardiac surgery. Studies at our institution show that this occurs in greater than 50% of neonates following cardiac surgery, but is rare in older infants. Prolonged exposure to cardiopulmonary bypass (with or without deep hypothermic circulatory arrest) is a risk factor for PVL, possibly secondary to the systemic inflammatory response to cardiopulmonary bypass. Hypotension and hypoxemia in the early postoperative period, especially diastolic hypotension, significantly increase the risk of PVL. Future studies are needed to determine significance of PVL as a marker for long-term developmental dysfunction.

Cardiac Surgical Procedures↗

PubMed2002

Building coalitions: lessons from the Alliance for a Healthy New England.

Official pronouncements that the U.S. economy is in recession have confirmed the bad news that health care advocates began experiencing months ago. State budgets are deep in deficit. Medicaid programs are in jeopardy. And making the case for expanded health care access now seems harder than ever. There is good news, though: in the Alliance for a Healthy New England, health advocates may have found a new funding mechanism. Built on a broad-based coalition model, the Alliance is seeking to raise tobacco taxes in all six New England states, with the revenue generated to be used for tobacco control and expanded health care access. This States of Health looks at how the diverse organizations that make up the Alliance are learning to work together--and why working together is so valuable.

Health Care Coalitions↗

PubMed2006

Does the rate of rewarming from profound hypothermic arrest influence the outcome in a swine model of lethal hemorrhage?

BACKGROUND: Rapid induction of profound hypothermic arrest (suspended animation) can provide valuable time for the repair of complex injuries and improve survival. The optimal rate for re-warming from a state of profound hypothermia is unknown. This experiment was designed to test the impact of different warming rates on outcome in a swine model of lethal hemorrhage from complex vascular injuries. METHODS: Uncontrolled lethal hemorrhage was induced in 40 swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 minutes later (simulating transport time) by laceration of the descending thoracic aorta. Through a thoracotomy approach, a catheter was placed in the aorta and hyperkalemic organ preservation solution was infused on cardiopulmonary bypass to rapidly (2 degrees C/min) induce profound (10 degrees C) hypothermia. Vascular injuries were repaired during 60 minutes of hypothermic arrest. The 4 groups (n = 10/group) included normothermic controls (NC) where core temperature was maintained between 36 to 37 degrees C, and re-warming from profound hypothermia at rates of: 0.25 degrees C/min (slow), 0.5 degrees C/min (medium), or 1 degrees C/min (fast). Hyperkalemia was reversed during the hypothermic arrest period, and blood was infused for resuscitation during re-warming. After discontinuation of cardiopulmonary bypass, the animals were recovered and monitored for 6 weeks for neurologic deficits, cognitive function (learning new skills), and organ dysfunction. Detailed examination of brains was performed at 6 weeks. RESULTS: All the normothermic animals died, whereas survival rates for slow, medium and fast re-warming from hypothermic arrest were 50, 90, and 30%, respectively (p < 0.05 slow and medium warming versus normothermic control, p < 0.05 medium versus fast re-warming). All the surviving animals were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. CONCLUSIONS: Rapid induction of hypothermic arrest maintains viability of brain during repair of lethal vascular injuries. Long-term survival is influenced by the rate of reversal of hypothermia.

Animals↗

PubMed1991

General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on central nervous and sensory systems and other functions.

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotension I converting enzyme inhibitor, on the central nervous systems, were studied in experimental animals. Benazepril hydrochloride (3 or 10 mg/kg/d, p.o. for 14 days) dose-dependently inhibited the increase in the blood pressure caused by continuous norepinephrine (NE) infusion in spontaneously hypertensive rats (SHR) and suppressed in seizures induced by a monoamine oxidase inhibitor, tranylcypromine in NE infused SHR. Benazepril hydrochloride transiently increased spontaneous motor activity in mice, tended to inhibit acetic acid-induced writhing in mice and decreased fast wave sleep and slow wave deep sleep on EEG in cats at a high dose of 100 mg/kg p.o. However, benazepril hydrochloride at the same dose showed no effect on other central nervous and sensory systems in experimental animals.

Acetates↗

PubMed2000

Connections of a motor cortical region in zebra finches: relation to pathways for vocal learning.

The lateral magnocellular nucleus of the anterior neostriatum (lMAN) is necessary for both initial learning of vocal patterns in developing zebra finches, as well as for modification of adult song under some circumstances. Lateral MAN is composed of two subregions: a core of magnocellular neurons and a surrounding shell composed primarily of parvocellular neurons. Neurons in lMAN(core) project to a region of motor cortex known as robust nucleus of the archistriatum (RA), whereas neurons in lMAN(shell) project to a region adjacent to RA known as dorsal archistriatum (Ad). We studied the axonal connections of Ad in adult male zebra finches. In contrast to RA, Ad neurons make a large number of efferent projections, which do not include direct inputs to vocal or respiratory motor neurons. The major efferent projections of Ad are to: (1) the striatum of avian basal ganglia; (2) a dorsal thalamic zone (including the song-control nuclei dorsomedial nucleus of the posterior thalamus [DMP] and dorsolateral nucleus of the medial thalamus [DLM]); (3) restricted regions within the lateral hypothalamus (stratum cellulare externum [SCE]), which may also relay information to the same dorsal thalamic zone; (4) a nucleus in the caudal thalamus (medial spiriform nucleus [SpM]); (5) deep layers of the tectum, which project to the thalamic song-control nucleus Uva; (6) broad regions of pontine and midbrain reticular formation; and (7) areas within the ventral tegmental area and substantia nigra (ventral tegmental area [AVT], substantia nigra [SN]), which overlap with regions that project to Area X, a song-control nucleus of avian striatum. Inputs to Ad derive not only from lMAN(shell), but also from a large area of dorsolateral caudal neostriatum (dNCL), which also receives input from lMAN(shell). That is, lMAN(shell) neurons project directly to Ad, and also multisynaptically to Ad via dNCL. Double-labeling studies show that lMAN(shell) contains two different populations of projection neurons: one that projects to Ad and another to dNCL. These results are exciting for two main reasons. The first is that some of these projections represent potential closed-loop circuits that could relay information back to song-control nuclei of the telencephalon, possibly allowing diverse types of song-related information to be both integrated between loops and compared during the period of auditory-motor integration. Because both auditory experience with an adult (tutor) song pattern and auditory feedback are essential to vocal learning, closed-loop pathways could serve as comparator circuits in which efferent commands, auditory feedback, and the memory of the tutor song are compared in an iterative fashion to achieve a gradual refinement of vocal production until it matches the tutor song. In addition, these circuits seem to have a strong integrative and limbic flavor. That is, the axonal connections of Ad neurons clearly include regions that receive inputs not only from somatosensory, visual, and auditory areas of cortex, but also from limbic regions, suggesting that they may be involved in higher order sensory processing, arousal, and motivation.

Animals↗

PubMed2005

A phylogeny of bacterial RNA nucleotidyltransferases: Bacillus halodurans contains two tRNA nucleotidyltransferases.

We have analyzed the distribution of RNA nucleotidyltransferases from the family that includes poly(A) polymerases (PAP) and tRNA nucleotidyltransferases (TNT) in 43 bacterial species. Genes of several bacterial species encode only one member of the nucleotidyltransferase superfamily (NTSF), and if that protein functions as a TNT, those organisms may not contain a poly(A) polymerase I like that of Escherichia coli. The genomes of several of the species examined encode more than one member of the nucleotidyltransferase superfamily. The function of some of those proteins is known, but in most cases no biochemical activity has been assigned to the NTSF. The NTSF protein sequences were used to construct an unrooted phylogenetic tree. To learn more about the function of the NTSFs in species whose genomes encode more than one, we have examined Bacillus halodurans. We have demonstrated that B. halodurans adds poly(A) tails to the 3' ends of RNAs in vivo. We have shown that the genes for both of the NTSFs encoded by the B. halodurans genome are transcribed in vivo. We have cloned, overexpressed, and purified the two NTSFs and have shown that neither functions as poly(A) polymerase in vitro. Rather, the two proteins function as tRNA nucleotidyltransferases, and our data suggest that, like some of the deep branching bacterial species previously studied by others, B. halodurans possesses separate CC- and A-adding tRNA nucleotidyltransferases. These observations raise the interesting question of the identity of the enzyme responsible for RNA polyadenylation in Bacillus.

Amino Acid Sequence↗

PubMed1979

The drama of the gifted child and the psycho-analyst's narcissistic disturbance.

In order to develop a true self, the child needs, in the first weeks and months of his life, his mother's appropriate emotional response, mirroring and respect. These narcissistic aspects have to be distinguished from the drive wishes. Only the mother's appropriate responses make it possible for the child to experience his feelings as belonging to his own self. If the child does not get the right narcissistic response, he will continue to search for narcissistic supplies for the rest of his life. The most suitable objects for this will be his own children initially, who are completely at his disposal. Specially gifted children who are sensitive, alert and have many 'antennae', will quickly learn to adapt to the narcissistic needs of their parents. Their behaviour will then give the mother all the mirroring, consideration and admiration which she had missed as a child herself. The result will be that, in spite of excellent performance, the child's own true self cannot develop. All this leads to narcissistic vulnerability and to new attempts in the adult to find at last an available 'mother' in his own child, partner, or, if he has become a psycho-analyst, in his patient. In the transference this type of analysand first experiences narcissistic rage before deep mourning is possible. This process of mourning enables him finally to accept his own deprivation as a child, to give up the unconscious idealizations and with them the hope of finding such a 'mother'. This leads regularly to the liberation of the life forces and allows creativity to develop. Only after this has been achieved is the analysis of drive conflicts possible and becomes emotionally effective.

Child Development↗

PubMed1995

[Complete deficiency of adhalin (50 kDa DAG) in skeletal muscle of malignant limb-girdle muscular dystrophy].

Malignant limb-girdle muscular dystrophy was first described by Miyoshi and co-workers in 1966, and has clinical features similar to Duchenne muscular dystrophy but is inherited through an autosomal recessive trait. This paper describes a patient with malignant limb-girdle muscular dystrophy with complete deficiency of adhalin (50 kDa dystrophin-associated glycoprotein (DAG)) in skeletal muscle. The patient was an 11-year-old Japanese girl whose parents were cousin. She learned to walk at one year and 3 months of age. Her gait became unsteady at 3 years of age, and motor dysfunction in the lower extremities progressed thereafter. At 8 years of age, she had difficulty in standing up from a sitting position, but could walk without assistance. At 11 years, she could walk with support, but could not stand up without assistance. Her intelligence was normal. Muscle atrophy was not apparent due to obesity, but her calves appeared hypertrophic. She had generalized muscle weakness, predominantly in the pelvic girdle muscle. Muscle tone was slightly hypotonic, and deep tendon reflexes of the legs were absent or hypoactive. Her sensory system appeared normal. Serum creatine kinase level was elevated to 30 times above the upper limit of the normal range in the patient and normal in her parents. EMG showed a mild myopathic pattern. CT scan of muscle revealed marked low density in the upper legs and mild in the lower legs. Muscle histology showed muscle fiber necrosis with a small number of regenerating fibers. Opaque fibers were occasionally observed, but not as many as in Duchenne type. Fiber splitting was seen frequently.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

PubMed1998

Animal models for the study of lower extremity chronic venous disease: lessons learned and future needs.

The purpose of this review is to define animal models of chronic venous disease and to demonstrate how animal studies can impact our understanding and treatment of this disorder. To this end an extensive literature search was conducted highlighting potential animal models of chronic lower extremity venous disease. Scientific investigations using animals to study particular aspects of this disease are also reviewed. This review was conducted by members of the Committee on Research of the American Venous Forum to help provide direction for future venous research endeavors. Useful models of chronic venous occlusive disease involve controlled ligation of a major lower limb vein and multiple tributaries. Such a model can provide sustained venous hypertension and studies using this model have confirmed that an isodiametric graft can provide early hemodynamic relief. Models of primary, postphlebitic, and isolated chronic deep venous insufficiency are available for study. Valve repair or transplantation can positively impact the insufficiency observed in these models. Investigations into valve substitutes have generally been disappointing or are undergoing early evaluation. In conclusion, animal models for the study of some aspects of chronic venous disease do exist and have already affected our clinical approach to patients. The scientific study of basic pathophysiology, diagnostics, end-organ response, and long-term surgical treatments of this disorder in well-controlled animal experiments have not been conducted.

Animals↗

PubMed1983

Developmental deep dyslexia?

A detailed analysis was made of the errors of a developmental dyslexic who is now 18 years of age. It was found that her error pattern was very similar to that observed in a particular form of acquired dyslexia, i.e. deep dyslexia. She made semantic, visual, derivational and function word substitution errors, and was almost completely unable to read non-words. Although the possibility of brain damage cannot be completely ruled out, her case remains an unusual one as her reading disorder is a certain extent developmental in nature in that she has never achieved fluent reading.

Adolescent↗

PubMed2002

Somatosensory cortical neuronal population activity across states of anaesthesia.

Experiments were carried out to learn about changes in sensory cortical processing associated with different levels of anaesthesia. Traditionally this question has been addressed by studying single neurons. Because state changes are likely to influence the relationships between neurons, the present experiments were undertaken to investigate the spatial and temporal firing patterns distributed across cortex. Using 5 x 5 or 10 x 10 microelectrode arrays, spontaneous and stimulus-evoked activity of multineuron clusters was recorded from rat somatosensory 'barrel' cortex (the whisker representation) during a light surgical stage of urethane anaesthesia, and after two supplemental doses of urethane which led to intermediate and deep levels of anaesthesia. At all depths of anaesthesia, spontaneously occurring action potentials at a single electrode tended to be clustered into 'bursts.' With increasing anaesthetic depth, bursts became more prominent and rhythmic, and increasingly synchronized between cortical barrel-columns. Burst frequency decreased and fewer spikes occurred outside bursts, leading to a decrease in the overall spontaneous firing rate. The cortical territory engaged by individual whiskers contracted with increasing depth of anaesthesia, leading to the spatial segregation of whisker representations. At all stages of anaesthesia, whisker stimulation produced the maximal cortical response when delivered close to burst onset. These observations show that ongoing spontaneous activity modulates sensory response properties and makes peripheral tactile information accessible to a cortical territory whose size is determined by the phase of burst cycle. The possible significance of the cyclic cortical responsiveness encountered during urethane anaesthesia to cortical processing in awake rats is considered.

Action Potentials↗

PubMed1993

[The education of neurologists for the XXI century].

The training of neurologists for the practice in the coming years requires deep changes in the system of medical education. It is critical for the medical student and the resident the acquisition of a broad knowledge of scientific information. But physicians must also know how to use knowledge they have accumulated from a variety of sources. They express their knowledge through abilities in the wards or in ambulatory settings in order to get an accurate diagnosis and the proper management of a particular condition. In addition to that they are expected to develop ethical attitudes toward their patients, peers and the greater society. They must be committed to work, to independent learning and to rationality. To accomplish its scholarly goals medical education has to emphasize the development of adequate personal attributes, skills and habits of mind rather than the transmission of factual information. With today's technology all the scientific information necessary for the practice of medicine is at the fingertips through computers. Memorization is therefore an absolute nonsense in teaching. A better education involves reducing the working load and the number of lecture hours providing students and residents with sufficient unscheduled time to seek out information independently and to assess their own learning. Problem-solving methods of teaching providing the formulation of multiple concurrent hypotheses, the critical analysis and evaluation of data and the application of new acquired knowledge as well as previously learned concepts to the solution of problems should be widely employed. Faculty members are guides who assist students and residents to develop analytical and critical skills.(ABSTRACT TRUNCATED AT 250 WORDS)

Education, Medical↗