Effect of milk-borne epidermal growth factor on the hepatic microcirculation and Kupffer cell function in suckling rats

A Rehabilitation Information System was created in July 1993 in order to register war victims in need of physical rehabilitation all over Croatia. The system is currently operating and presented data covers the period from July 1991 to July 1995. Approximately 15,000 questionnaires had been completed and returned from medical institutions on in total 8589 disabled war victims in need of rehabilitation. People with severe disabilities comprised about 20% of all in need of rehabilitation. Those reported injured were 3.5 times more than those in need of physical rehabilitation. Most common types of injuries were fractures with a permanent disabling condition (3109 persons), peripheral nerve injuries (1213 persons) and amputations (956 persons). Traumatic brain injuries were registered for 594 and spinal cord injuries for 262 persons. Causes of injuries were explosive devices (such as mines, mortar shell shrapnel, etc.) in 37% of cases, bullets in 22%, accidents in 7%, other (such as fire, blast injuries, etc.) and unknown causes in 34%.     

Physiological stress and nerve growth factor treatment regulate stress-activated protein kinase activity in PC12 cells

The stress-activated protein kinases (SAPKs) are differentially activated by a variety of cellular stressors in PC12 cells. SAPK activation has been linked to the induction of apoptotic cell death upon serum withdrawal from undifferentiated cells or following nerve growth factor (NGF) withdrawal of neuronally differentiated PC12 cells. However, withdrawal of trophic support from differentiated cells led to only a very modest elevation of SAPK activity and led us to investigate the basis of the relative insensitivity of these enzymes to stressors. NGF-stimulated differentiation of the cells resulted in the elevation of basal SAPK activity to levels four- to sevenfold greater than in untreated cells, which was correlated with an approximate fivefold increase in SAPK protein levels. Paradoxically, in NGF-differentiated PC12 cells, exposure to cellular stressors provoked a proportionately smaller stimulation of SAPK activity than that observed in naive cells, despite the presence of much higher levels of SAPK protein. The insensitivity of SAPK to activation by stressors was reflective of the activity of the SAPK activator SEK, whose activation was also diminished following NGF differentiation of the cells. The data demonstrate that SAPKs are subject to complex controls through both induction of SAPK expression and the regulation mediated by upstream elements within this pathway.     

Genomic organization of the flt-1 gene encoding for vascular endothelial growth factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors

Impaction allografting with cement is the only technique currently available which reverses the diminution of bone stock that occurs in a revision hip arthroplasty, and as such, has great potential. It is particularly appropriate in the younger patient, though older patients may also benefit from the technique. Although the short term results are encouraging, there is a need for further basic science research to determine the optimal graft material and prosthesis design. Refinements in surgical instrumentation and technique will continue to improve the predictability of the clinical result and expand the indications for this important addition to the available options in revision hip arthroplasty.     

To stay fit inspite of injury

Optimal rehabilitation after injuries has become increasingly important in recent years. In our concept, not only the damaged local structure is treated but supplementary training to improve the general physical performance is recommended. This specific training includes the components of strength, endurance, coordination, flexibility and velocity. We explain in the present article the role of these rehabilitative methods and refer to their importance for the reintegration process following injuries.     

Neuropsychological aspects of the rehabilitation of patients with paralysis from a spinal injury who also have a brain injury

In order to examine the rehabilitation process of patients suffering from a severe spinal cord injury and who also have a cerebral injury, 322 patients with paralysis from a spinal injury were subjected to neuro-psychiatric and neuro-psychological examinations. On average 20.2% of these patients showed an associated cerebral lesion. The psychological results of such cerebral lesions are summarized under the concept of the co-called organic psychic syndrome (OPS). In 27.7% of these patients no organic psychic syndrome resulted, and in these patients a conventional paralysis rehabilitation could be carried out. 41.6% showed very minor to moderate injuries, with 30.7% being severely disabled from the cerebral injury. Rehabilitation for these patients was modified, using new therapeutic approaches, and also traditional therapeutic methods adapted to the abilities and needs of this patient group. In 25.5% of the patients there was no substantial improvement during the treatment period of initial rehabilitation (x = 12.5 weeks for the treatment of cerebral injury); but in 36.2% of the patients there was substantial improvement and in 38.3% full remission of organic psychic disorders occurred. Improvements in this sphere have a direct bearing on the rehabilitation capacity of this patient group.     

Evaluation of the prognostic value of general motor activity for rehabilitation of patients after cerebral stroke

Following cerebral stroke motor activity of the patient is dependent on the extensiveness of brain ischemia. Evaluation of this activity may be an exponent of brain ischemia extent. It can be used for the determination of predictability of patient survival and results of rehabilitation. Using Mathew and Barthel scales effectiveness of treatment and rehabilitation was evaluated four times during 12-month follow-up in patients of General Motor Activity Clinical Group II i III. The results obtained may be evidence of significant prognostic importance of evaluation of general motor activity of the organism in the initial period of treatment and rehabilitation only, i.e. within 3 months following cerebral stroke. However, it is no importance for evaluation of remote results (one year following cerebral stroke). The evaluation of general activity cannot be used to predict the dynamics of the improvement of neurological and functional status of patients undergoing rehabilitation following cerebral stroke.     

Antibody to transforming growth factor beta reduces collagen production in injured peripheral nerve

Epineurial scarring in peripheral nerve after injury inhibits normal axonal regeneration primarily due to fibroblast deposition of type I collagen. The transforming growth factor beta (TGF-beta) family is an important class of signaling molecules that has been shown to stimulate fibroblasts to produce collagen. The aim of this study was to design a prototypic therapeutic system in which the neutralization of TGF-beta in crushed rat sciatic nerve would decrease collagen formation. A total of 45 experimental Lewis rats were used. Group 1 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate buffer solution. Group 2 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate-buffered saline and goat, anti-rat, panspecific TGF-beta antibody. Group 3 control animals (five rats) underwent only exposure of sciatic nerve with injection of antibody. All animals were killed at 14 days and sciatic nerve specimens were harvested at that time. Slides of experimental tissue were processed using a 35S-labeled oligomer for procollagen alpha-1 mRNA, then dipped in photographic emulsion and examined by darkfield autoradiography. Morphometric analysis of pixel counts was then performed. A significant reduction in total pixel count per high-power field and in total number of fibroblasts per high-power field was found in crushed rat sciatic nerve treated with anti-TGF-beta antibody when compared with those treated only with phosphate-buffered saline. These findings are consistent with successful reduction in procollagen induction after a crush injury by topical administration of blocking antibody against transforming growth factor beta. The concept of growth factor blockade for therapeutic collagen reduction is attractive in the context of nerve injury, and the current article provides a model for future clinical application.     

Replantation of the hand and fingers

Using microsurgical techniques to replant an amputated hand or digit is one of the most important progress in the field of hand surgery during the last three decades. The result of a replantation depends on: the mechanism and the level of amputation, the length and the type of ischaemia of the amputated segment, the surgical techniques, the postoperative care, the rehabilitation and so on. Although the success of a replantation is first judged on the survival of the replanted segment, it nevertheless should be assessed on the function achieved. Thanks to the 30-year clinical experience, the final functional result of a replantation can now be anticipated at initial examination; thus indications can be better established by patient selection criteria. The replantation of the hand and the digits is henceforth reasonable only if there is a possibility of a useful functional result.     

The time course of nerve growth factor content in different neuropsychiatric diseases--a unifying hypothesis

Nerve growth factor (NGF) is the prototype of related neurotrophic proteins, the so-called neurotrophins. NGF is essential for proper development of sympathetic and neural crest-derived sensory neurons of the peripheral nervous system (PNS) as well as of the neurons in the cholinergic basal forebrain (CBF). In the mature peripheral and central nervous system (CNS) NGF is also biologically active; NGF facilitates neuronal plasticity and regulates synaptic transmission and connectivity. Besides this well established neurotrophic function, recent findings suggest a role of NGF in neuroimmune and stress-associated processes, which NGF imparts not only as the classical "target-derived messenger", that is retrogradely transported within NGF-sensitive neurons, but also as para- and autocrine cytokine modulating the function of non-neuronal cells. Since neurotrophins are produced in very small amounts in vivo, NGF-sensitive cells have to compete for the limited NGF even under physiological conditions, so that normally only less than 10% of NGF receptors (NGFR) are saturated with their endogenous ligand. Consequently, it is feasable that minute changes in NGF concentrations can influence neuronal function in an extensive way. Hence, one plausible pathomechanism of disease(s) may be that a deficiency in NGF leads to malfunction of NGF-sensitive neurons. The change in NGF concentrations in the course of several diseases, namely during alcoholic and diabetic neuropathy as well as in Alzheimer's disease (AD) and several lesion-models of the CBF, indicates that fluctuations of endogenous NGF concentrations in PNS and CNS follow a distinctive pattern. An initial deficit of NGF at the onset of pathological processes is typically followed by its temporary elevation, during which some neuronal deficits may be partially ameliorated. However, if the disease progresses a decrease of NGF is typically observed, which appears to be a "normalization" of formerly elevated NGF concentrations. In our hypothesis we postulate that after acute or chronic injuries NGF is up-regulated as an intrinsic attempt to regenerate NGF-sensitive neurons. After long-term exposure to noxious processes, however, this compensatory increase of NGF cannot be maintained and eventually breaks down. The extent of such a compensatory up-regulation may depend on age and condition of NGF-sensitive neurons as well as on the type of lesion (acute or chronic). Furthermore, we also postulate that an exceeding level of NGF or its chronic elevation could even be detrimental to neuronal functioning under certain conditions. Thus, endogenous NGF has the capacity to modulate and even to compensate different kinds of harmful processes and in this way it may reinstate the homeostatic equilibrium. In our view, it seems to be a more appropriate approach to regard NGF changes as independent of classical constructs of neuropsychiatric diseases. Perhaps our understanding of NGF may even model for a new approach to the aetiology of multifactorial neuropsychiatric disorders.     

Rapid suppression of free radical formation by nerve growth factor involves the mitogen-activated protein kinase pathway

Neurotrophins such as nerve growth factor (NGF) regulate neuronal survival during development and are neuroprotective in certain models of injury to both the peripheral and the central nervous system. Although many effects of neurotrophins involve long-term changes in gene expression, several recent reports have focused on rapid effects of neurotrophins that do not involve synthesis of new gene products. Because enhanced formation of reactive oxygen species (ROS) represents one consequence of many insults that produce neuronal death, we hypothesized that neurotrophins might influence neuronal function and survival through acute alterations in the production of ROS. Using an oxidation-sensitive compound, dihydrorhodamine, we measured ROS formation in a central nervous system-derived neuronal cell line (GT1-1 trk) and in superior cervical ganglion neurons, both of which express the transmembrane NGF receptor tyrosine kinase, trkA. There was enhanced production of ROS in both cell types in the absence of NGF that was rapidly inhibited by application of NGF; complete inhibition of ROS generation in GT1-1 trk cells occurred within 10 min. NGF suppression of ROS formation was prevented by PD 098059, a specific inhibitor of MEK (mitogen/extracellular receptor kinase, which phosphorylates mitogen-activated protein kinase). The observation that NGF acutely blocks ROS formation in neurons through activation of the mitogen-activated protein kinase pathway suggests a novel mechanism for rapid neurotrophin signaling, and has implications for understanding neuroprotective and other effects of neurotrophins.     

Epidemiology of motor vehicle crash-related serious eye injuries

The Eye Injury Registry of Alabama has been collecting epidemiologic, treatment, final outcome, and rehabilitation information on serious ocular trauma since 1982. By December 31, 1989, 150 motor vehicle crash-related eye injuries had been registered. This is the largest series of motor vehicle crash-related serious eye injuries reported. The mean age of those injured was 29 years; 61% were between 16 and 35 years of age, and 73% were males. Ten individuals (7%) suffered bilateral eye injuries. The retina was injured in 47% of eyes. The initial visual acuity was 19/200 or worse (legal blindness) in 47% of eyes. Of eyes with at least 3 months of follow-up, 63% had worse than 20/200 initial visual acuity and 41% remained legally blind. Twelve percent of eyes required removal. Possibly due to the large number of blunt ruptures, motor vehicle crash-related eye trauma carries a particularly unfavorable treatment prognosis. Prevention of these injuries is therefore of extraordinary importance.     

Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae

The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells.     

The proliferative effect of vascular endothelial growth factor requires protein kinase C-alpha and protein kinase C-zeta

The heparin-binding protein vascular endothelial growth factor (VEGF) is a highly specific growth factor for endothelial cells. VEGF binds to specific tyrosine kinase receptors, which mediate intracellular signaling. We investigated 2 hypotheses: (1) VEGF affects intracellular calcium [Ca2+]i regulation and [Ca2+]i-dependent messenger systems; and (2) these mechanisms are important for VEGF's proliferative effects. [Ca2+]i was measured in human umbilical vein endothelial cells using fura-2 and fluo-3. Protein kinase C (PKC) activity was measured by histone-like pseudosubstrate phosphorylation. PKC isoform distribution was observed with confocal microscopy and Western blot. Inhibition of PKC isoforms was assessed by specific antisense oligonucleotides (ODN) for the PKC isoforms. VEGF (10 ng/mL) induced a transient increase in [Ca2+]i followed by a sustained elevation. The sustained [Ca2+]i plateau was abolished by EGTA. Pertussis toxin also abolished the plateau phase, whereas the initial peak was not affected. The PKC isoforms alpha, delta, epsilon, and zeta were identified in endothelial cells. VEGF induced a translocation of PKC-alpha and PKC-zeta toward the nucleus and the perinuclear area, whereas cellular distribution of PKC-delta and PKC-epsilon was not influenced. Cell exposure to TPA led to a down-regulation of PKC-alpha and reduced the proliferative effect of VEGF. VEGF-induced endothelial cell proliferation also was reduced by the PKC inhibitors staurosporine and calphostin C. Specific down-regulation of PKC-alpha and PKC-zeta with antisense ODN reduced the proliferative effect of VEGF significantly. Our data show that VEGF induces initial and sustained Ca2+ influx. VEGF leads to the translocation of the [Ca2+]i-sensitive PKC isoform alpha and the atypical PKC isoform zeta. Antisense ODN for these PKC isoforms block VEGF-induced proliferation. These findings suggest that PKC isoforms alpha and zeta are important for VEGF's angiogenic effects.     

Rap1 mediates sustained MAP kinase activation induced by nerve growth factor

Activation of mitogen-activated protein (MAP) kinase (also known as extracellular-signal-regulated kinase, or ERK) by growth factors can trigger either cell growth or differentiation. The intracellular signals that couple growth factors to MAP kinase may determine the different effects of growth factors: for example, transient activation of MAP kinase by epidermal growth factor stimulates proliferation of PC12 cells, whereas they differentiate in response to nerve growth factor, which acts partly by inducing a sustained activation of MAP kinase. Here we show that activation of MAP kinase by nerve growth factor involves two distinct pathways: the initial activation of MAP kinase requires the small G protein Ras, but its activation is sustained by the small G protein Rap1. Rap1 is activated by CRK adaptor proteins and the guanine-nucleotide-exchange factor C3G, and forms a stable complex with B-Raf, an activator of MAP kinase. Rap1 is required for at least two indices of neuronal differentiation by nerve growth factor: electrical excitability and the induction of neuron-specific genes. We propose that the activation of Rap1 by C3G represents a common mechanism to induce sustained activation of the MAP kinase cascade in cells that express B-Raf.     

Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9

This paper provides an overview of thermal injury resulting in death or hospitalization in New Zealand adults, defined as age 15 years and over. For the 10-year period 1978-1987, there were 493 adult thermal injury deaths resulting in an overall rate of 2.1 per 100000 person-years (95%CI: 1.9-2.3). For the year 1988, there were 644 hospitalizations resulting in a rate of 25.1 per 100000 (95%CI: 23.2-27.1). The highest rates of death and hospitalization were observed in the elderly (65 years of age and over). Young males (15-29 years) also had a very high rate of hospitalization. Residential fire was the most common type of burn event resulting in death (44%), and smoking materials were the most common source of ignition in fatal residential fires (37%). Hot liquids were the most common source of thermal energy for the hospitalized injuries (34%). Typical scenarios involved burns from hot water expelled from automobile radiators, from hot water use in the workplace, from hot beverages, and from household hot tap-water. The epidemiology of the adult thermal injuries in New Zealand is similar to that reported in other developed countries. Opportunities and strategies for the prevention of these injuries are discussed.     

Glial fibrillar acidic protein in peripheral nerve tumors in rats

Cancer education merits a coordinated, vertical curriculum and an integrated planning strategy. It has become clear that it is as important to teach the techniques of supportive care in oncology as it is to teach the concepts of cancer biology, pathology, epidemiology, prevention, detection and aggressive treatments. Our aim is to determine whether the medical school and nursing school curricula give the students an introduction to the concepts of supportive care of the cancer patient. The spectrum of such supportive care encompasses a wide range of issues working towards a common goal of providing overall comfort with an emphasis on quality of life, and runs parallel with specific therapeutic strategies and associated problems. Do the graduate medical student and nursing student understand that cancer management is multidisciplinary and team-based? That the approach to pain management not only includes the administration of pain medications, but should also evaluate pain assessment and anesthetic, neurosurgical and behavioral approaches? That nausea and vomiting associated with chemotherapy can be ameliorated to a certain extent? That infections are common but algorithms exist for prevention and therapy? That certain metabolic complications are unique to cancer patients? That transfusions are vital procedures in patients with neoplasms undergoing aggressive treatments but are associated with certain risks and complications? That there are serious psychosocial, ethical and legal needs to be considered? To address these issues, the American Cancer Society Professors of Clinical Oncology, the American Cancer Society Professors of Oncology Nursing and the United States Cancer Center Directors were surveyed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature

Every activity of a medical practitioner may be subjected to court control. This creates not only uncertainty gut also anger amongst most physicians. However, it is clear that no court judgement against a physician will be made without the competent support of independent medical experts. On the basis of the relevant legal literature and judgments, the present article is an attempt to consider medical errors in the administration of contrast media, to describe the required medical informed consent before such measures, and to discuss the ever increasing importance of adequate documentation in the light of malpractice proceedings. importance of adequate documentation in the light of malpractice proceedings. This is followed by a discussion of the very important medical necessity to inform the patient about recommended behaviour after injections of such contrast media, the responsibility question in both civil and criminal terms in case of an incident, and various tips for steps to be taken in the case of a liability action.     

Humanistic psychology and rehabilitation programs in mental hospitals

A humanistic growth-oriented theory, specifically Maslow's need-satisfaction theory, was used as a basis for examining the contributions work and employment make toward rehabilitation of the state mental hospital patient. Research literature reviewed indicated that if the rehabilitation program is to be viable and optimally effective, satisfying the belongingness and esteem needs of the patient is important. Research that stresses the therapeutic benefit of work, as well as research that raises the issue of workshops inhibiting independence and fostering dependence are presented. Modifications of rehabilitation programs that resulted in reports of increased program effectiveness are discussed. Fundamental features of these alternative or ancillary programs were: 1. a definite structure that allows various levels of advancement; 2. group participation; 3. patient initiative; 4. an orientation that reflects the competitive nature of employment; and 5. early community involvement. The importance of evaluating each client's needs and planning for growth before his/her job placement is considered vital to the program and to the individual.     

Quality assurance in inpatient psychosomatic treatment and rehabilitation

In addition to the requirements of quality management imposed by legislative and in consideration of research projects on the evaluation of psychotherapy the German pension funds introduced a systematic program for quality control in 1994. By the end of this year all the German rehabilitation centers will regularly have to provide information concerning the structure and concepts of the hospital and details of the rehabilitation programs. All therapeutic interventions are listed for every patient. In a subsample of patients detailed information regarding diagnosis and outcome (goal attainment) is required in addition to the final report. A subsample of the final reports is peer-reviewed. Patient's satisfaction and estimation of outcome variables are regularly assessed 3 months after discharge. Within and between institutions quality circles meet regularly. Advantages and limits of these programs are discussed and additional approaches towards total quality management in Bad Kreuznach are described.     

Optic nerve decompression in fibrous dysplasia: indications, efficacy, and safety

Optic nerve decompression is controversial in posttraumatic visual loss and as a prophylactic therapy in fibrous dysplasia involving the optic canal. It is less controversial for the treatment of optic nerve compression in fibrous dysplasia. Thirteen patients with craniomaxillofacial fibrous dysplasia who underwent 16 optic nerve decompressions at the Chang Gung Craniofacial Centre for both therapeutic (10) and prophylactic (6) indications are reported. One patient sustained a clinically useful improvement in vision in response to two therapeutic decompressions, and another demonstrated marked improvement after therapeutic decompression, with visual acuity improving from 0.4 to 1.0 in the affected eye. No patient underwent a permanent deterioration of vision as a result of either therapeutic or prophylactic decompression. One patient suffered extraocular muscle dysfunction that was corrected with strabismus surgery. A review of the literature clarifies the controversies and allows establishment of indications for optic nerve decompression.