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Biomedical subjects

M Spranger

Publications and source records attributed to M Spranger.

At least 37 records · Page 2Linked to original sources
PubMed1997

Barraquer-Simons syndrome (with sensorineural deafness): a contribution to the differential diagnosis of lipodystrophy syndromes.

Among the lipodystrophies, the Barraquer-Simons syndrome is a rare condition. We describe a 27-year-old woman with progressive loss of subcutaneous fat after 15 years first affecting the face and spreading to the upper part of the body. She also suffered from deafness and had marked changes in cranial MRI. We discuss possible differential diagnosis such as the Cockayne, SHORT and Berardinelli-Seip syndrome.

Adult↗
PubMed1997

The dominant role of exogenous or endogenous interleukin-1 beta on expression and activity of inducible nitric oxide synthase in rat microvascular brain endothelial cells.

In the brain large amounts of nitric oxide are produced in response to various pathological stimuli such as infectious agents, ischemia and trauma. Although it is known that endothelial cells can express the inducible isoform of nitric oxide synthase (iNOS) upon activation, the impact of different cytokines on iNOS expression in rat microvascular endothelial cells remains unclear. We now investigated iNOS mRNA expression and enzyme activity in primary cell cultures of rat microvascular brain endothelial cells after treatment with the proinflammatory cytokines interleukin-1beta (IL-1beta), Tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) alone or in combination. Cells were characterized by immunocytochemistry staining for von-Willebrand-factor and the rat brain endothelial antigen recognized by monoclonal antibody Ox2. iNOS-enzyme activity was determined by measurement of nitrite in the supernatants of cell culture using the Griess-reaction. In addition mRNA expression was analysed by RT-PCR with iNOS and IL-1beta specific primers. All cells in the endothelial cell culture were found to express the antigenic phenotype vWF+/Ox2+/Ox43-, thus identifying the cells as rat brain endothelial cells of microvascular origin. IL-1beta was the only cytokine that as a single stimulus induced iNOS mRNA expression and iNOS-enzyme activity in these endothelial cells. All combinations of two cytokines, including that of TNF-alpha and IFN-gamma--or the triple combination led to expression of iNOS-mRNA and active protein. Cell activation by the combination of TNF-alpha + IFN-gamma led to an early expression of IL-1beta by the endothelial cells suggesting iNOS induction as a consequence of endogenous IL-1beta production under this challenge. The experiments prove that rat brain microvascular endothelial cells express iNOS and produce large amounts of NO under inflammatory conditions. Furthermore, our results indicate a decisive role of IL-1beta in iNOS expression and NO generation.

Animals↗
PubMed1997

Suppression of the oxidative burst in murine microglia by nitric oxide.

The effect of nitric oxide (NO) on the oxidative burst was analyzed in purified murine microglial cells in vitro. The generation of reactive oxygen derivatives was monitored with the use of luminol-dependent chemiluminescence. After inducing the endogenous NO production with interleukin 1beta (IL-1beta) and interferon-gamma (IFN-gamma) the superoxide anion release was significantly reduced, which was reversed by the inhibition of the NO synthase. Additionally, chemical NO-releasing compounds reduced the generation of reactive oxygen derivatives rapidly and independently of the pathway used to trigger the oxidative burst. This effect of NO was not mediated via guanylyl cyclase and cGMP, or due to the scavenging of released superoxide anions. This attenuation of superoxide anion generation by NO may limit deleterious effects of the release of reactive oxygen derivatives in tissue inflammation or injury.

Animals↗
PubMed1997

Myotonic dystrophy. The role of large triplet repeat length in the development of mental retardation.

OBJECTIVE: To describe mental retardation and microcephaly as initial clinical signs in myotonic dystrophy (MD) with high trinucleotide repeats. PATIENTS AND METHODS: Two patients with maternally inherited MD were examined. Southern blot analysis was performed and trinucleotide repeat expansions were related to the findings of clinical and magnetic resonance imaging investigations. RESULTS: Both patients had the large CTG trinucleotide repeat expansions often seen in congenital MD, but they lacked the typical clinical signs. Mental retardation and microcephaly were the leading features present in infancy. Muscular weakness, in contrast, developed after age 35 years. Although there was no evidence for perinatal asphyxia or sleep apnea, magnetic resonance imaging disclosed reduced brain volume and subcortical demyelination. CONCLUSIONS: Mental retardation preceding the development of muscle weakness suggests that the cerebral involvement in MD is a direct consequence of the genetic disorder and not mediated by muscle disease. Careful clinical examination of the parents for signs of MD should be considered in patients with cognitive deficits even without apparent muscular involvement.

Adult↗
PubMed1997

Stimulation of interleukin-6 secretion and gene transcription in primary astrocytes by adenosine.

During cerebral ischemia, the expression of interleukin-6 (IL-6), which has neuroprotective properties, increases. To understand the underlying mechanism, the regulation of IL-6 expression by neurotransmitters that accumulate during cerebral ischemia was investigated. Adenosine stimulated IL-6 secretion in primary astrocytes four- to 10-fold. The effect was concentration dependent, the EC50 being approximately 8 microM. Although the nonselective analogue 2-chloroadenosine (2CA) increased IL-6 secretion to a similar extent, the A1-selective agonist N6-cyclopentyladenosine or the A2a agonist CGS-21680 had only a marginal effect on IL-6 secretion. IL-6 secretion stimulated by 2CA (10 microM) was inhibited by the nonselective adenosine antagonist 8-(p-sulfophenyl)theophylline, whereas the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine or the A2a-selective antagonist 8-(3-chlorostyryl)caffeine had no effect, to a concentration of 0.1 microM. Transcription of the IL-6 gene was investigated by transfecting primary astrocytes with a reporter fusion gene containing the human IL-6 promoter (-179/+12). 2CA stimulated IL-6 gene transcription 2.5-fold. Mutations of the binding site for NF-kappaB or NF-IL6 abrogated the response to 2CA. Thus, an increase of extracellular adenosine during focal cerebral ischemia may stimulate IL-6 expression via A2b receptors. The induction of IL-6 expression appears to involve a transcriptional effect that depends on NF-kappaB and NF-IL6.

2-Chloroadenosine↗
PubMed1997

Intraventricular brain-derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats.

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls (P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/- 56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/- 19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

Animals↗
PubMed1997

Muscular involvement in the Holt-Oram syndrome.

Holt-Oram syndrome is an autosomal dominant disorder characterised by radial ray and congenital heart defects. Recently, a gene for this disorder has been identified on chromosome 12q24.1, encoding a T box transcription factor. However, the functional role of the gene product is not completely understood. We present results of neurological, radiological, and muscle magnetic resonance imaging (MRI) investigations in 13 patients from eight unrelated families. Besides heart defects, clinical signs ranged from thenar abnormalities to bilateral phocomelia. The former were present in all patients. MRI showed hypoplasia of discrete muscles which clinically showed as non-progressive weakness. The structural pattern of residual muscles was normal on MRI, which together with normal muscular power, electromyography, and muscle enzyme investigations excluded a progressive neuromuscular disorder. The number and location of hypoplastic muscles correlated with the severity of skeletal involvement. Thus, patients with hypoplasia of large and proximal muscles had phocomelia, and those with mere intrinsic hand muscle hypoplasia had only a triphalangeal thumb or no skeletal malformation. On the basis of these observations, we conclude that disturbed fetal limb muscle development is involved in the bony malformations of the upper limbs.

Adult↗
PubMed1997

Proximal and distal spinal muscular atrophy in one family: molecular genetic studies provide further evidence for the non-allelic origin of both diseases.

We present the results of clinical and molecular genetic investigations of a family in which the father suffers from distal spinal muscular atrophy and the younger son is affected by infantile autosomal recessive SMA type I. The molecular analysis of the SMN gene showed homozygous deletions of telSMN exons 7 and 8 in the son only. This was probably the result of a new mutation in the paternal haplotype, since the affected boy did not inherit one copy of the marker Ag1-CA. These results indicate that distal and proximal SMA in this family are not caused by the same gene on chromosome 5q.

Adult↗
PubMed1997

Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury. Correlation with clinical course and infarct size.

BACKGROUND AND PURPOSE: Superoxide dismutase (SOD) is one of the major free radical scavenging systems that might play a role in both degenerative and acute diseases of the central nervous system. METHODS: We measured SOD activity in the serum of 41 patients with acute ischemic stroke with a chemiluminometric assay based on the generation of oxygen free radicals by xanthine and xanthine oxidase. RESULTS: SOD activity was significantly lower in patients with ischemic stroke than in age-matched control patients with nonvascular, neurological illnesses (n = 24; P < .034, Wilcoxon rank test). The activity was inversely correlated with the size of infarction on CT (P = .01, Spearman correlation) and the severity of neurological deficits (P < .001, Spearman correlation). The decreased SOD activity recovered within 5 days after stroke to values found in serum of control patients. CONCLUSIONS: Our data suggest that the SOD activity in serum is reduced in stroke patients, and replacement of antioxidative activity could be beneficial in the acute treatment of cerebral ischemia.

Acute Disease↗
PubMed1997

Plasma insulin-like growth factor I and IGF binding protein 3 levels in patients with acute cerebral ischemic injury.

BACKGROUND AND PURPOSE: The insulin-like growth factors (IGF) are synthesized in the brain and are involved in fetal brain development. An increased expression of IGF-I and IGF-II occurs in cerebral regions with neuronal damage after experimental hypoxic injury. Furthermore, the expression of mRNAs coding for IGF-I and the binding proteins IGFBP-2 and IGFBP-3 is augmented in response to unilateral ischemia in animal models. The secretory dynamics of IGF-I in human cerebral ischemia have not yet been investigated. METHODS: Plasma IGF-I and IGFBP-3 were measured sequentially in 20 patients with acute ischemic stroke (within 24 hours and 3, 5, and 10 days thereafter). For analysis the patients were assigned to three groups according to the diameter of the infarct area as measured on CT scan: small (< 1.5 cm), moderate (> or = 1.5 cm and < or = 5 cm), and large (> 5 cm). Eight age-matched patients with nonvascular, neurological illnesses served as controls. RESULTS: Plasma IGF-I and IGFBP-3 plasma concentrations after acute cerebral ischemia were strikingly lower than those in control subjects and healthy individuals reported in the literature. Plasma IGF-I levels in patients with large infarcts were significantly statistically lower than those in control subjects (P < .05), and plasma IGFBP-3 levels were significantly lower than those in control subjects on days 5 and 10. CONCLUSIONS: IGF-I and IGFBP-3 plasma levels are decreased in patients after cerebral ischemia. After acute ischemic stroke, increased demand for growth factors, altered tissue distribution, and accelerated metabolic clearance rate or central inhibition of the somatotrophic axis may contribute to these low plasma concentrations. Growth factors such as IGF-I and IGFBP-3 may play an important role in the pathophysiology of acute cerebral ischemia, and growth factors may have a considerable effect on future therapeutic regimens.

Acute Disease↗
PubMed1997

Meningeal involvement in Wegener's granulomatosis confirmed and monitored by positive circulating antineutrophil cytoplasm in cerebrospinal fluid.

MRI and CSF investigations revealed meningeal involvement in a 29-year-old patient with biopsy-confirmed Wegener's granulomatosis. The intracranial manifestation of Wegener's granulomatosis was supported by the detection of pathologic circulating antineutrophil cytoplasm (c-ANCA) in the CSF. We monitored disease activity by c-ANCA measurement in the CSF. After repeated cycles of intrathecal administration of methotrexate and corticoids, progression of meningeal infiltration stopped, and CSF c-ANCA titers became negative.

Adult↗
PubMed1997

Craniectomy: an aggressive treatment approach in severe encephalitis.

BACKGROUND AND OBJECTIVE: Focal encephalitis may be associated with brain edema, which is often fatal. The control of intracranial pressure (ICP) is therefore crucial for further therapeutic strategies in space-occupying edema following encephalitis. However, aggressive treatment strategies such as hemicraniectomy have not been described in a larger series of patients. PATIENTS AND METHODS: We describe the clinical course and outcome in six patients who developed severe brain edema associated with acute encephalitis. All received maximum medical treatment for elevated ICP, but with signs of brainstem compression emerging, hemicraniectomy was performed to control ICP. RESULTS: All patients had a very severe encephalitic syndrome and were treated over the course of weeks in the neurocritical care unit (NCCU). However, all patients recovered almost completely and showed only mild or no neurologic deficit when reexamined after 4 months to 3 years. CONCLUSIONS: Hemicraniectomy should be considered in patients with severe brain edema following encephalitis as a potentially lifesaving therapeutic measure. Moreover, the initial neurologic deficit seems to have no impact on the long-term clinical outcome.

Adult↗
PubMed1997

Brain temperature monitoring and modulation in patients with severe MCA infarction.

BACKGROUND: Brain temperature has been measured only occasionally in humans. After head trauma, a temperature gradient in brain temperature compared with body temperature of up to 3 degrees C degrees higher in the brain has been reported. Elevated temperature facilitates neuronal injury after ischemia. At present, no information concerning changes in brain temperature after acute stroke is available. METHODS: In 15 patients who had suffered severe ischemic stroke in the MCA territory, intracerebral temperature was recorded with use of two different thermocouples, with intraventricular, epidural, and parenchymatous measurements. Body-core temperature (Foley catheter temperature) and jugular bulb temperature (n = 5) were recorded simultaneously. Measures for reducing brain temperature were compared. RESULTS: In all patients, brain temperature exceeded body-core temperature by at least up to 1 degrees C (range, 1.0 to 2.1 degrees C). Temperature in the ventricles exceeded epidural temperature by up to 2.0 degrees C. Brain temperature modulation was independent of single pharmacologic (paracetamol, metamizol) treatments. Only systemic cooling was effective and sustained hypothermic (33 to 34 degrees C) brain temperatures. CONCLUSION: After MCA stroke, human intracerebral temperature is higher than central body-core temperature. There is also a temperature gradient within the brain, with the ventricles warmer than the surface. Mild hypothermia in the treatment of severe cerebral ischemia with use of cooling blankets is both easy to perform and effective in the therapy of severe hemispheric infarction.

Adult↗
PubMed1997

Barbiturate coma in severe hemispheric stroke: useful or obsolete?

Barbiturates are administered in a variety of clinical conditions to control elevated intracranial pressure (ICP). However, their routine use to treat elevated ICP has been questioned because it may cause severe side effects. We therefore investigated the effect of high-dose barbiturate therapy on ICP and outcome in patients with severe brain edema after severe middle cerebral artery (MCA) or hemispheric infarction. Barbiturate coma was induced with thiopental infusion in 60 patients with critically increased ICP due to large hemispheric or MCA territory infarction, defined by CT. ICP was monitored in all patients during barbiturate therapy. Barbiturate coma was induced after a standardized treatment protocol for increased ICP after failure of osmotherapy and mild hyperventilation. During barbiturate administration, cerebral perfusion pressure (CPP) and mean arterial pressure were recorded. Clinical outcome of these patients and the individual effect on ICP were analyzed. Only five of 60 patients who were treated with barbiturate coma survived (8%). All other patients died after transtentorial herniation with subsequent brain death. Barbiturate infusion was followed by a drop in ICP in 50 patients and showed no effect on ICP values in 10 patients. CPP decreased with a mean of 9 mm Hg (range, 5 to 20 mm Hg). Although barbiturates were initially effective, only in some patients was ICP control sustained. Severe side effects of barbiturate therapy, besides arterial hypotension, were seen in 15 patients (25%). Barbiturate coma in the therapy of increased ICP after severe ischemic hemispheric stroke can lower critically elevated ICP levels. However, it seems to have no positive effect on neurologic outcome.

Adult↗
PubMed1996

'Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs.

BACKGROUND: Although the clinical features of space-occupying ischemic stroke are well known, there are limited prospective data on the clinical course of complete middle cerebral artery territory infarction and on the predisposing factors leading to subsequent herniation and brain death. METHODS: The clinical course of patients with complete middle cerebral artery territory infarction, defined by computed tomography and vascular imaging, was evaluated. Initial clinical presentation was assessed by the Scandinavian Stroke Scale and the Glasgow Coma Scale. Serial computed tomography with measurement of midline and septum pellucidum shift and data on the presence and location of vascular occlusion by angiography or Doppler ultrasound were obtained directly after admission. Time course and outcome were analyzed with regard to the clinical findings on admission and at follow-up. The functional status of surviving patients was assessed using the Barthel Index. RESULTS: Fifty-five patients with complete middle cerebral artery territory infarction caused by occlusion of either the distal intracranial carotid artery or the proximal middle cerebral artery trunk were studied. In all patients, embolic infarction was presumed. The mean Scandinavian Stroke Scale score on admission was 20, and the time course of deterioration varied between 2 and 5 days. Forty-nine patients required ventilator assistance during the acute stage of disease. Only 12 patients (22%) survived the infarct. The cause of death was transtentorial herniation with subsequent brain death in 43 patients. Survivors had a mean Barthel Index score of 60 (range, 45 to 70). CONCLUSIONS: The prognosis of complete middle cerebral artery territory stroke is very poor and can be estimated by early clinical and neuroradiological data within the first few hours after the onset of symptoms. A space-occupying mass effect develops rapidly and predictably over the initial 5 days after presentation. Herniation occurred as an end point in 43 (78%) of these patients.

Adult↗
PubMed1996

Excess glutamate levels in the cerebrospinal fluid predict clinical outcome of bacterial meningitis.

BACKGROUND: The clinical course of bacterial meningitis still is characterized by a high mortality and frequent neurological deficits in survivors. In addition to other potentially neurotoxic mediators of inflammation, the excitatory amino acid glutamate, which has been implicated in neuronal death in a variety of other neurological diseases, may also be involved in the pathological process of bacterial meningitis. OBJECTIVES: To investigate the prognostic value of the glutamate concentration in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. PATIENTS AND METHODS: Thirty consecutive patients with bacterial meningitis were included in a prospective study. The clinical severity of the disease was assessed on admission and 14 days after the beginning of antibiotic treatment by means of the Glasgow Coma Scale. Studies of CSF were performed on admission and after 3 to 6 days. In addition to standard CSF investigations, including cell count, cytologic findings, protein analysis, glucose and lactate levels, and microbiological tests, the concentration of glutamate in the CSF was measured by an enzymatic assay. RESULTS: At admission, both CSF cell count and concentration of glutamate correlated well with the severity of the disease. After treatment, glutamate concentrations decreased significantly to normal or only slightly elevated levels in 23 patients. However, in 7 patients glutamate levels remained markedly increased. In this group, clinical outcome was significantly worse than in the group of patients with low glutamate levels in the second CSF analysis. CONCLUSIONS: A prolonged increase of glutamate levels in the CSF may predict poor clinical outcome in patients with bacterial meningitis, possibly because of the sustained neurotoxic effects of this excitatory neurotransmitter.

Adolescent↗
PubMed1996

Köbberling-Dunnigan syndrome: a rare cause of generalized muscular hypertrophy.

A 36-year-old woman presented with muscle hypertrophy (particularly of the calves) since puberty, occasional muscle cramps, a musculine habitus, and a loss of subcutaneous fat on limbs and trunk sparing her face, neck, and vulva. Multiple lipomas were found on her trunk, and acanthosis nigricans on her neck. Laboratory testing revealed hyperlipidemia and pathological glucose tolerance with hyperinsulinemia. Physical and laboratory findings are consistent with Köbberling-Dunnigan syndrome, a rare inherited form of lipoatrophy. The patient's mother had the same body habitus and insulin-dependent diabetes mellitus. These cases suggest that partial lipodystrophy also affects muscle and is a cause of genuine muscular hypertrophy.

Adult↗