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F Hefti

Publications and source records attributed to F Hefti.

267 records · Page 15Linked to original sources
PubMedDate not supplied

Intraventricular nerve growth factor administration prevents lesion-induced loss of septal cholinergic neurons in aging rats.

In young adult rats transection of the fimbria results in loss of cholinergic cell bodies in the septum and this lesion-induced loss is prevented by intraventricular administration of NGF. The present study examined whether NGF administration is equally effective in aging animals. Eighteen-month-old rats received fimbrial transections and were given intraventricular injections of NGF during four weeks. Septal cholinergic neurons were then visualized using NGF receptor immunohistochemistry, which represents a reliable marker for cholinergic neurons in the septal area. The fimbrial transections reduced the number of septal NGF receptor-positive cells to a similar extent as in young animals. NGF treatment of aging rats protected these cells as effectively as in young adult rats.

Aging↗
PubMedDate not supplied

Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases.

This review summarizes the current knowledge of characterized neurotrophic factors, including nerve growth factor (NGF) which serves as paradigmatic example when studying novel molecules. Special consideration is given to the function of neurotrophic factors in the adult and aging brain. Strategies are discussed for the eventual development of pharmacological applications of these molecules in the treatment of neurodegenerative diseases.

Aging↗
PubMedDate not supplied

Detrimental actions of neurotrophic agents.

There is little experimental evidence supporting the speculation that neurotrophic agents in general stimulate the pathological process in Alzheimer's disease. Nevertheless, possible detrimental actions of neurotrophic agents represent a concern when considering the pharmacological use of neurotrophic factors.

Alzheimer Disease↗
PubMedDate not supplied

BDNF and trkB mRNA expression in the hippocampal formation of aging rats.

Quantitative in situ hybridization and northern blot analysis techniques were used to determine the topographical distribution and levels of mRNA coding for brain-derived neurotrophic factor (BDNF) and the tyrosine receptor kinase (trkB) mRNA in the hippocampal formation of two strains of male rat during aging. Age did not change the prevalence or regional distribution patterns of BDNF or trkB mRNA in the hippocampal formation throughout the lifespan of male Sprague-Dawley rats. There also were no significant differences in the prevalence or topographical distribution patterns of trkB mRNA transcripts during aging. Northern blot analysis of hippocampal RNA from male Fischer 344 confirmed that neither BDNF mRNA nor trkB mRNA levels changed with age. These findings suggest that age-related neurodegenerative changes, including the atrophy of the cholinergic septo-hippocampal pathway, are not the result of changes in hippocampal BDNF or trkB mRNA expression. Moreover, the prevalence and distribution of synaptosomal-associated protein 25 (SNAP-25), a neuron-specific protein located in synaptic terminals and a putative marker of synaptic integrity, did not change with age. These findings indicate that altered hippocampal synaptic plasticity which occurs in the aged rat brain is not a reflection of changes in the expression of BDNF or trkB receptor mRNA.

Aging↗
PubMedDate not supplied

Chronic administration of nerve growth factor and other neurotrophic factors to the brain.

Intracerebral chronic administration of nerve growth factor (NGF) is able to counteract age-related cholinergic dysfunction. This finding suggests that intracerebral administration of neurotrophic factors may become a generally valuable approach when attempting to ameliorate age-related neuronal deficits in experimental animals and humans. This commentary briefly discusses possible strategies for the development of such "neurotrophic factor treatments."

Animals↗
PubMedDate not supplied

Localization of nerve growth factor receptors in the normal human brain and in Alzheimer's disease.

NGF receptors were visualized in human brain sections with an immunohistochemical procedure using a monoclonal antibody. This method results in the selective visualization of a population of neurons in the medial septal nucleus, the nucleus of the diagonal band of Broca, and the nucleus basalis of Meynert. Several lines of evidence indicate that this neuronal population is identical to the cholinergic neurons of the basal forebrain. NGF receptor immunohistochemistry therefore represents a sensitive and reliable procedure to selectively visualize forebrain cholinergic neurons for post-mortem analysis. NGF receptors were found to be expressed during the entire life span. However, the intracellular staining intensity was reduced in normal aging, suggesting the tentative conclusion that NGF receptor synthesis may decline in the aged brain. In Alzheimer's disease, the number of NGF receptor-positive cells was decreased. The morphological characteristics of surviving neurons were similar to immuno-positive neurons visualized in normal aged brains.

Adult↗
PubMedDate not supplied

[New treatment concept for children with thoracic insufficiency syndrome due to congenital spine deformity].

BACKGROUND: Children with congenital thoracic scoliosis associated with fused ribs and unilateral unsegmented bars adjacent to convex hemivertebrae will inevitably develop thoracic insufficiency syndrome and curve progression with hemithorax compression without treatment. It is assumed that the concave side of such curves and their unilateral unsegmented bars do not grow. In the past early spinal fusion was performed with consecutive short thoracic spines and loss of lung volume. Little attention has been paid to lung function. These patients often suffered from lung failure and early death due to a small thorax. METHOD: A new surgical technique is based on an indirect deformity correction and enlargement of the thorax due to a longitudinal implant, the vertical expandable prosthetic titanium rib (VEPTR). The spine is not fused, thus promoting growth of the spine, the thorax and the lungs. Elongation of the implant is done every six months. Since 2002 this method has been performed on fifteen children in Basel as the first European center. RESULTS: Patients (mean age 6 years; 11 months to 12 years) were suffering from thoracic insufficiency syndrome due to unilateral unsegmented bars with fused ribs (n = 4), absent ribs (n = 2), bilaterally fused ribs (n = 2), hemivertebrae (n = 3) or neuromuscular scoliosis (n = 6). Doing fifteen primarily implantations and thirteen elongations there were three complications (two hook dislocations, one skin breakage). All patients improved cosmetically, functionally and radiologically which was shown on X-rays as a reduction of the Cobb angle from an average of 76 degrees (40-110 degrees ) to 55 degrees (30-67 degrees ). CONCLUSIONS: Expansion thoracoplasty and VEPTR implantation is a new treatment concept for children with thoracic insufficiency syndrome due to spinal deformities, which is based on distraction and expansion of the thorax thus allowing growth of the spine, the thorax and probably lungs. Presently it seems to be superior to any other method for the treatment of small children with progressive scoliosis and thoracic insufficiency syndrome.

Age Factors↗
PubMedDate not supplied

[Acute spinal syndromes in children and adolescents].

23 children with acute spinal syndromes are presented. The clinical signs were caused by trauma in 11 patients, by extramedullary tumors in 6, by operations (coarctation of the aorta, scoliosis) in 4 and by encephalomyelitis in 2. Motor signs (flaccid paraplegia or paraparesis, monoplegia, bilateral weakness) and changes of reflex intensities were always observed. Most children presented with disturbances of sensory functions and micturition, some exhibited ataxia. In addition to the neurological signs, plain films of the spine were of diagnostic importance after trauma, for tumors myelography and/or computerized tomography were most useful. The unfavourable prognosis of posttraumatic paraplegia may be improved by early application of corticosteroids in very high doses. The value of GM1-ganglioside is controversial. In cases of external compression by tumors a decompression of the spinal cord is urgent. "Spinal cord monitoring" can be used intraoperatively in surgery of scoliosis and coarctation of the aorta to detect neurological complications early. Differential diagnosis and therapies of encephalomyelitis and Guillain-Barré-Syndrome are discussed.

Adolescent↗
PubMedDate not supplied

[Spherical calculation of the contact surface between the acetabulum and femur head].

A template for calculating the contact area between the femoral head and the acetabulum is described. The projected image of a sphere is divided into segments of equal surface areas, each segment comprising 0.5% of the total surface area of the sphere. By adding the segments and multiplying the resulting percentage by the total surface area resulting from the radius of the sphere, any partial area of the sphere can be calculated. It is thus possible, without any special mathematical knowledge, to calculate the contact area between the femoral head and the acetabulum, as well as any partial surface area relevant to loading of the joint, on the a.p. roentgenogram. A prerequisite for this is a sufficient area of spherical femoral head in the region in question. In addition, the template can also be used to calculate the biomechanically relevant angle between the frontal plane, set through the center of the femoral head, and the anterior limit of the acetabulum, on the a.p. roentgenogram of the hip.

Acetabulum↗
PubMedDate not supplied

Pediatric hematology and oncology at the University Children's Hospital, Basel, Switzerland.

The department offers the management and research of benign and malignant pediatric hematology and oncology at a comparable European standard. It serves as a referring department for BMT, thoracic and visceral pediatric surgery, and pediatric orthopedic surgery and is equipped with all facilities of modern oncology and surgery. Psychooncology is a continuing interest at our department and may help children and their families to better understand and accept their situation and to receive the support necessary for coping with the threat of malignant diseases. Our department aims at practicing a highly sophisticated communication culture essential for a multidisciplinary approach to the child with cancer, representing a central condition for the success of the treatment of malignant diseases.

Child↗
PubMedDate not supplied

Cardiovascular effects of the new angiotensin-converting-enzyme inhibitor, cilazapril, in anesthetized and conscious dogs.

Cilazapril is a new angiotensin-converting-enzyme inhibitor. In conscious renal-hypertensive dogs, cilazapril (2 X 10 mg/kg/day p.o.) caused a long-lasting (greater than 24 h) decrease in systolic arterial blood pressure, the magnitude of which was potentiated by pretreatment with furosemide. A maximal fall in systolic blood pressure of 39 +/- 6 mm Hg (from 145 +/- 5 to 106 +/- 7 mm Hg) was recorded. The antihypertensive effect did not decline with repeated administration and was accompanied by only a slight increase in heart rate. Cilazapril also reduced systolic blood pressure in furosemide-pretreated normotensive dogs. Hemodynamic studies in anesthetized dogs revealed that cilazapril (0.03-1 mg/kg i.v.) caused a fall in mean arterial and left ventricular systolic pressures. At the highest dose of 1 mg/kg i.v., the blood-pressure-lowering effect (-27%) was due to a decrease in total peripheral resistance (-12%) and cardiac output (-16%). Intravenous administration of cilazapril to anesthetized dogs resulted in a rise in plasma renin activity and a significant fall in plasma angiotensin II levels. In conscious normotensive dogs, cilazapril (0.3-10 mg/kg p.o.) exerted diuretic and saluretic effects, which were accompanied by a significant increase in renal plasma flow (46%), but only a slight rise in the glomerular filtration rate. These results characterize cilazapril as an effective and long-lasting antihypertensive drug, with diuretic activity and, possibly, preload- as well as afterload-reducing properties.

Anesthesia↗
PubMedDate not supplied

Cilazapril prevents hypertension in spontaneously hypertensive rats.

Chronic daily administration of cilazapril (1 X 10 mg/kg/day p.o., from age 4 to 14 weeks) to young spontaneously hypertensive rats (SHR) prevented the development of hypertension. The antihypertensive effect of a single dose of cilazapril persisted greater than 24 h. Discontinuation of long-term treatment resulted in an increase of systolic arterial blood pressure (SAP) to control hypertensive levels within 4 days. Following 10 weeks of drug administration, comparative hemodynamic studies were carried out on age-matched (14 weeks) control SHR and cilazapril-treated SHR. Cilazapril-treated SHR had a significantly lower mean arterial blood pressure (MAP) and total peripheral vascular resistance than did control SHR. The antihypertensive effect of cilazapril was not associated with changes in heart rate (HR). The myocardial performance parameters, cardiac output, and stroke volume, were similar in treated and control SHR, suggesting that the antihypertensive effect of cilazapril following chronic administration to SHR is mainly due to a reduction in peripheral vascular resistance. Vasopressor responses to angiotensin I were significantly lower in cilazapril-treated SHR than in control SHR. By contrast, pressor responses to angiotensin II and a high dose of norepinephrine (1.0 microgram/kg i.v.) were significantly enhanced. Isoproterenol elicited a fall in blood pressure in both groups, the extent of which was dependent upon the magnitude of basal blood pressure levels. Chronic cilazapril treatment resulted in a reduction of heart weight, suggesting that the drug may prevent development of cardiac hypertrophy in SHR. Kidney and adrenal weights were unaffected by the chronic treatment. Specific renin activities (SRA) in tissues of SHR were increased by factors of 20 (plasma) or 2 (kidney and adrenal) following cilazapril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Spherical assessment of the hip on standard AP radiographs: a simple method for the measurement of the contact area between acetabulum and femoral head and of acetabular orientation.

A template that allows a simple three-dimensional assessment of the hip joint is presented. The total surface of a sphere is subdivided into spherical quadrangles and triangles that cover areas of exactly identical size. On the template, these quadrangles and triangles are projected onto a plane. Each segment represents 0.5% of the total surface of the sphere. Calculation of any surface area is achieved by adding the number of segments involved of a template of appropriate radius. In addition, various angles can be measured. The template is drawn in various sizes on transparent foil. The template of the appropriate size is laid on the anteroposterior radiograph of the hip joint. It allows measurement of the contact area between the acetabulum and the femoral head and also acetabular orientation. A cadaver study showed good reliability of the measurements.

Acetabulum↗
PubMedDate not supplied

Chronic administration of tiapamil prevents hemodynamic alterations accompanying development of high blood pressure in hypertensive rats.

Daily oral administration of tiapamil (2 X 50-2 X 150 mg/kg, for 13 weeks) to spontaneously hypertensive rats (SHR) resulted in a dose-dependent inhibition of hypertension development, with complete prevention occurring at the highest dose. Tiapamil (2 X 100 mg/kg/day, p.o.) also prevented development of high blood pressure in deoxycorticosterone acetate-NaCl hypertensive rats (DOCA). A comparative hemodynamic analysis was carried out on age-matched (17-week-old) control SHR, tiapamil-treated (2 X 150 mg/kg/day, p.o.) SHR, and normotensive Wistar-Kyoto rats (WKY). Tiapamil-treated SHR and WKY had a significantly lower mean arterial pressure and total peripheral resistance as well as a higher cardiac output than untreated SHR. Vasoconstrictor responses to norepinephrine as well as to angiotensin I and II were significantly lower in tiapamil-treated than in untreated SHR. By contrast, isoproterenol elicited a fall in blood pressure in all three groups, the extent of which correlated directly with the magnitude of basal blood pressure levels. Tiapamil also caused a concentration-dependent depression of depolarization-induced vasoconstrictor responses in isolated mesenteric and renal arteries from SHR. The results of this study indicate that chronic administration of tiapamil will prevent the development of hypertension in SHR and DOCA rats as well as protect against accompanying hemodynamic alterations. This inhibitory effect on blood vessels that maintain peripheral resistance at elevated levels is a consequence of the vascular-selective calcium entry blocking properties of tiapamil.

Aging↗