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Biomedical subjects

H W Pfister

Publications and source records attributed to H W Pfister.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacologic interference with NF-kappaB activation attenuates central nervous system complications in experimental Pneumococcal meningitis.

This study assessed the effects of 2 different inhibitors of NF-kappaB activation on central nervous system complications and clinical symptoms in an advanced stage of experimental pneumococcal meningitis: the calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which interferes with IkappaB proteolysis, and BAY 11-7085, which inhibits IkappaB phosphorylation. Pneumococcal meningitis was associated with an increase in NF-kappaB activity, as determined by immunohistochemistry and Western blot analysis of rat brains 24 h after infection. Treatment with ALLN or BAY 11-7085 improved the clinical scores of infected rats, compared with those of untreated infected rats. This beneficial effect was parallelled by a significant reduction of the increase in intracranial pressure, blood-brain barrier permeability (as measured by the Evans blue-extravasation technique), cerebrospinal fluid (CSF) pleocytosis, CSF interleukin-6 levels, and impairment of cerebrovascular CO(2) reactivity and autoregulation. Thus, pharmacologic interference with NF-kappaB activation might be a possible target for adjunctive therapy in bacterial meningitis.

Animals↗
PubMed2000

Increased levels of soluble Fas receptor and Fas ligand in the cerebrospinal fluid of HIV-infected patients.

Analyses of serum samples and blood cells have revealed a dysregulation of the Fas/Fas ligand (FasL) system during HIV infection, which may be related to disease progression. As Fas and FasL have been suggested to participate in brain injury in a variety of CNS disorders, the aim of this study was to determine (1) whether soluble Fas and FasL can be detected in cerebrospinal fluid (CSF) samples from HIV-infected patients, (2) whether levels of these molecules are related to disease progression, and (3) whether levels of sFasL are related to other laboratory findings. Soluble Fas was detected in 38 of 56 (68%) and soluble Fas ligand in 17 of 56 (30%) CSF samples from HIV-infected patients. CSF levels of both molecules correlated neither with the CSF-to-serum albumin ratio nor with corresponding serum concentrations. This finding suggests that they are at least in part produced intrathecally. Levels of both CSF sFas and sFasL correlated significantly and inversely with the blood CD4+ cell counts, suggesting that the intrathecal release of both molecules is increased during progression to advanced immunodeficiency.

CD4 Lymphocyte Count↗
PubMed2000

Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9.

We recently showed that MMP-9 activity was detectable in the cerebrospinal fluid (CSF) of about half of neurologically symptomatic HIV-infected patients. Using an experimental animal model, we detected MMP-9 activity in CSF samples from rats that had been injected intracisternally with recombinant HIV-1 Nef protein, but not after injection of heat-treated Nef, gp120, gp160 or PBS. Nef also induced a breaching of the blood-brain barrier (BBB), which could be inhibited by pretreatment with the matrix metalloproteinase (MMP) inhibitor batimastat. In vitro Nef only slightly induced MMP-9 activity in freshly isolated human peripheral blood mononuclear cells and in the murine macrophage cell line RAW 264.7, but not in endothelial, neuronal or astroglial cell lines. Taken together, our findings indicate that HIV-1 Nef protein can induce BBB disruption in the rat - presumably via MMP induction.

Animals↗
PubMed2000

[Prevention of meningococcal meningitis].

In Germany, the incidence of meningococcal disease is approximately 1/100,000 and has not risen during recent years. Transmission occurs by direct contact with respiratory droplets, mostly from asymptomatic carriers and less frequently from patients with meningococal disease. The incubation period can vary from 2-10 days but usually is 3-4 days. Incidence is highest in children and decreases with age. The mortality from meningococcal disease is approximately 10%. In case meningococcal meningitis is clinically suspected antibiotic treatment (in Germany with penicillin G or a cephalosporin) should not be delayed. Patients must be isolated for at least 24 hours after the institution of antibiotic therapy. For early detection of local outbreaks, public health authorities should be quickly informed of suspected cases. Persons in close contact should be treated with antimicrobial chemoprophylaxis. In addition to rifampin, ciprofloxacin or ceftriaxone can be used for chemoprophylaxis. For control of local outbreaks of serogroup C meningococcal disease, the meningococcal vaccine can be used.

Anti-Bacterial Agents↗
PubMed2000

[Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic findings].

The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure. The clinical course, differential diagnosis, and literature are summarized briefly.

Biopsy↗
PubMed2000

Intracranial dural arteriovenous fistula with spinal medullary venous drainage.

We report on a 46-year-old patient in whom an intracranial dural arteriovenous (AV) fistula, supplied by a branch of the ascending pharyngeal artery, drained into spinal veins and produced rapidly progressive symptoms of myelopathy and brainstem dysfunction including respiratory insufficiency. Magnetic resonance imaging studies demonstrated brainstem oedema and dilated veins of the brainstem and spinal cord. Endovascular embolization of the fistula led to good neurological recovery, although the patient had been paraplegic for 24 h prior to embolization. This case demonstrates the MRI characteristics of an intracranial dural AV fistula with spinal drainage and illustrates the importance of early diagnosis and treatment. Even paraplegia may be reversible, if angiography is performed and the fistula treated before ischaemic and gliotic changes become irreversible.

Central Nervous System Vascular Malformations↗
PubMed2000

Cerebral vasculopathy and multiple infarctions in a woman with carcinomatous meningitis while on treatment with intrathecal methotrexate.

We report on a 33-year-old woman with carcinomatous meningitis due to carcinoma of the breast who developed multiple cerebral infarctions within four days after intrathecal chemotherapy with methotrexate. MR angiography revealed a narrowing of basal cerebral arteries, which is consistent with vasculopathy. The vasculopathy was probably due to carcinomatous meningitis itself, an acute toxic effect of methotrexate, or a combination of both.

Adult↗
PubMed2000

Reduction of intracranial pressure by nimodipine in experimental pneumococcal meningitis.

OBJECTIVE: In this study, we investigated the effect of the calcium channel blocker nimodipine on the pathophysiologic alterations during experimental pneumococcal meningitis in rats. DESIGN: Prospective, controlled trial. SETTING: University center, animal laboratory. SUBJECTS: A total of 37 adult male Wistar rats (290-360 g). INTERVENTIONS: Meningitis was induced by the intracisternal injection of pneumococci. Anaesthetized animals were treated with nimodipine (30 microg/kg/hr iv) either 15 mins before (pretreatment) or 5 hrs after (posttreatment) pneumococcal challenge. MEASUREMENTS AND MAIN RESULTS: Treatment with nimodipine (30 microg/kg/hr iv) significantly decreased the pneumococci-induced rise in intracranial pressure irrespective of the time of administration. Moreover, pretreament with nimodipine also significantly reduced the pneumococci-induced increase in cerebrospinal fluid white blood cell counts. To ascertain possible mechanisms of the beneficial effect, we investigated the influence of nimodipine on reactive oxygen species (ROS) and cytokine production. By using lucigenin-enhanced chemiluminescence, we found that nimodipine inhibited the pneumococci-induced production of ROS in human whole blood samples. Moreover, nimodipine significantly reduced the pneumococci-induced increase in the interleukin-6 concentrations in the cerebrospinal fluid. CONCLUSION: Our results demonstrate that nimodipine decreases the intracranial pressure during experimental pneumococcal meningitis, possibly by mechanisms including the reduction of ROS and interleukin-6 production.

Animals↗
PubMed2000

Upregulation of matrix metalloproteinase-9 in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis.

It was investigated (1) whether metalloproteinase-9 (MMP-9), MMP-3, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, the natural tissue inhibitor of MMP-9) are increased in the CSF of patients with Lyme neuroborreliosis and (2) whether macrophages can express MMP-9 when stimulated with Borrelia burgdorferi. Zymography showed MMP-9 activity in 26 of 31 (84%) CSF samples from patients with acute stage 2 Lyme neuroborreliosis, but not in 20 controls with non-inflammatory neurological disorders. Activity of MMP-2 was detected in all CSF samples in both patients with neuroborreliosis and controls, suggesting a constitutive release of MMP-2. Using enzyme linked immunosorbent assay (ELISA) MMP-3 (which can activate MMP-9) was detected in low concentrations in the CSF of 13 of 29 patients with neuroborreliosis, but not in controls. TIMP-1 was increased twofold in CSF samples from patients with neuroborreliosis in comparison with the controls. MMP-9 activity was induced in vitro in a mouse macrophage cell line (RAW 264.7) when stimulated with two different genospecies of B burgdorferi (B garinii, B afzelii ). This MMP-9 activity was reduced in a dose dependent manner when macrophages stimulated with B burgdorferi were coincubated with NF-kappaB SN50, a cell permeable peptide which inhibits the translocation of NF-kappaB into the nucleus of stimulated cells. The data show that (1) MMP-9 activity is present in the CSF of patients with neuroborreliosis, (2) macrophages stimulated with B burgdorferi are a possible source of MMP-9 increase, and (3) activation of NF-kappaB may play a part in the upregulation of MMP-9 by B burgdorferi.

Acute Disease↗
PubMed2000

Primary diffuse leptomeningeal gliomatosis: unusual MRI with non-enhancing nodular lesions on the cerebellar surface and spinal leptomeningeal enhancement.

A 28 year old man presented with a 1 month history of symptoms of intracranial hypertension. Examination showed bilateral papilloedema and meningeal signs. Magnetic resonance imaging showed nodular lesions on the cerebellar and pontine surface and thickening of the thoracic spinal leptomeninges. Throughout the course of the disease, contrast enhancement was detected in the spinal leptomeninges but not intracranially. Primary diffuse leptomeningeal gliomatosis (PDLG) was diagnosed by biopsy and later confirmed on necropsy. The present case is remarkable for the nodular superficial cerebellar lesions and the absence of intracranial contrast enhancement of the leptomeninges.

Adult↗
PubMed2000

Late onset postpartum eclampsia without pre-eclamptic prodromi: clinical and neuroradiological presentation in two patients.

In two patients eclampsia started 9 days postpartum. Headache and visual disturbances preceded seizures but none of the classic pre-eclamptic signs oedema, proteinuria, and hypertension were present until shortly before seizure onset. Brain herniation (patient 1) and status epilepticus (patient 2) necessitated neurointensive care management. Brain MRI initially showed only frontal sulcal effacement in one patient but later showed white matter hyperintensities on T2 weighted images and a previously undescribed pattern of cortical-subcortical postgadolinium enhancement on T1 weighted images in both. Neurological deficits and MRI findings were reversed with therapy in both patients. It is concluded that late postpartum eclampsia can manifest without classic prodromi and that characteristic MRI findings may lag behind clinical manifestation.

Adult↗
PubMed1999

Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis.

The CD14 antigen, an important cell surface molecule of monocytic cells, is involved in cellular activation: it binds lipopolysaccharide and other cellular lipid structures. Brain macrophages play a pivotal role during inflammatory reactions of the CNS parenchyma, ventricles and meninges. A soluble form of CD14 (sCD14) was measured in paired cerebrospinal fluid (CSF) and serum samples from 91 patients with different neurological diseases. Mean levels of circulating sCD14 in CSF in a control group of 22 patients with neurologic complaints but no neurological deficit on clinical examination were 0.19 +/- 0.06 (mean +/- SD) mg/l. The CSF/blood ratios of sCD14 was 49 +/- 16 x 10(-3), while those of albumin were 4.4 +/- 1.4 x 10(-3). These extremely high CSF/blood ratios of the sCD14 molecule compared to albumin indicate a local cerebral production. No significant changes in CSF sCD14 levels were found in patients with non-inflammatory neurological diseases (NID). In contrast, CSF sCD14 levels were markedly elevated during acute meningitis, but there was no direct correlation between sCD14 and monocyte count in the CSF. Thus, sCD14 could not originate in the CSF compartment from monocytes alone. The highest values for sCD14 were found in CSF during infections with various pathogens such as Staphylococcus aureus or Listeria monocytogenes. While sCD14 serum levels dramatically increased during acute bacterial meningitis, sCD14 ratios did not correlate with albumin ratios during the course of disease. Therefore, increased CSF sCD14 may originate from cerebral production by activated or infiltrated macrophages rather than passive diffusion from the blood, while elevated sCD14 serum levels resulted from enhanced local production. Increased CSF and serum sCD14 values were also observed in meningitis caused by viral infection. As in bacterial meningitis, sCD14 in CSF specimens did not correlate with the function of the blood/CSF barrier. Repeated lumbar punctures revealed a normalization of CSF sCD14 levels during clinical recovery. These results provide the first evidence for local production of sCD14 within the CNS. Our findings further indicate that sCD14 in CSF is a reliable marker for activation of macrophages within the CNS during inflammatory processes.

Acute Disease↗
PubMed1999

HIV type 1 Nef protein is a viral factor for leukocyte recruitment into the central nervous system.

Recombinant HIV-1 Nef protein, but not Tat, gp120, and gp160, provoked leukocyte recruitment into the CNS in a rat model. The strong reduction of bioactivity by heat treatment of Nef, and the blocking effect of the mAb 2H12, which recognizes the carboxy-terminal amino acid (aa) residues 171-190 (but not of mAb 3E6, an anti-Nef Ab of the same isotype, which maps the aa sequence 168-175, as well as a mixture of mAbs to CD4) provided evidence for the specificity of the observed Nef effects. Using a modified Boyden chamber technique, Nef exhibited chemotactic activity on mononuclear cells in vitro. Coadministration of the anti-Nef mAb 2H12, as well as treatment of Nef by heat inhibited Nef-induced chemotaxis. Besides soluble Nef, chemotaxis was also induced by a Nef-expressing human astrocytoma cell line, but not by control cells. These data suggest a direct chemotactic activity of soluble Nef. The detection of elevated levels of IL-6, TNF-alpha, and IFN-gamma in rat cerebrospinal fluid 6 h after intracisternal Nef injection hint at the additional involvement of indirect mechanisms in Nef-induced leukocyte migration into rat CNS. These data propose a mechanism by which HIV-1 Nef protein may be essential for AIDS neuropathogenesis, as a mediator of the recruitment of leukocytes that may serve as vehicles of the virus and perpetrators for disease through their production of neurotoxins.

Animals↗
PubMed1999

Superoxide production by primary rat cerebral endothelial cells in response to pneumococci.

Animal studies of experimental bacterial meningitis have provided evidence for an involvement of reactive oxygen species (ROS) in the pathophysiology of this disease. Using a lucigenin-enhanced chemiluminescence (CL) method, we tested whether primary rat cerebral endothelial cells can be induced to release ROS upon stimulation with pneumococci. In addition, we determined CSF levels of two markers of lipid peroxidation in patients with bacterial meningitis, compared to patients with viral meningitis and noninflammatory neurological disorders. Malondialdehyde/4-hydroxynonenal concentrations were significantly elevated in CSF samples obtained from patients with bacterial meningitis (23.12+/-5.47 microM), as compared to both control groups (5.43+/-0.18 microM and 7.80+/-0.33 microM, respectively). Cerebromicrovascular endothelial cells, granulocytes, and the macrophage cell line RAW 264.7 (but not astrocytes and neuron-like cells) produced an increase in CL intensity after stimulation with pneumococci. The peak value produced by endothelial cells (500+/-83 cpm) was significantly lower than the maximum CL response in macrophages (1386+/-142 cpm; p<0.05). After addition of superoxide dismutase (SOD), the CL signal returned to baseline values. Equal to the CL technique, nitroblue tetrazolium (NBT) staining of RAW 264.7 showed SOD-inhibitable formazan precipitation when stimulated with pneumococci. In conclusion, this study suggests an important role of endothelial cells in the pathophysiology of bacterial meningitis-namely as a source for ROS production.

Acridines↗
PubMed1999

Bacterial meningitis in adults: demonstration of inner ear involvement using high-resolution MRI.

OBJECTIVE: To visualize the sites involved in audiovestibular dysfunction during bacterial meningitis in adults and to relate these findings to the extent of hearing impairment and vestibular dysfunction. BACKGROUND: Hearing impairment is among the most frequent complications of bacterial meningitis. METHODS: High-resolution MRI (HR-MRI) of the inner ear was performed in seven adult patients with hearing loss as a complication of bacterial meningitis. RESULTS: Five patients had unilateral (n = 1) or bilateral (n = 4) contrast enhancement of vestibulocochlear structures. The structures most frequently involved were the cochlear nerve (n = 9), the first cochlear turn (n = 9), the vestibulum (n = 9), and the semicircular canals (n = 7). There was a significant correlation between clinical and MRI findings: all nine ears with cochlear enhancement were deaf (hearing loss >90 dB), whereas none of the five ears with normal MRI findings had hearing losses of more than 90 dB (range, 30 to 70 dB; p = 0.0005). Vestibular dysfunction as revealed clinically and by quantitative vestibular function testing was found in six of seven patients (11 of 14 ears). Five of these patients (nine ears) also demonstrated enhancement of the vestibular organ on high-resolution MRI of the inner ear. CONCLUSIONS: High-resolution MRI can visualize the involvement of vestibulocochlear structures in bacterial meningitis in both cooperative and consciously impaired patients. These findings suggest a correlation between abnormalities on MRI and the extent of cochlear dysfunction.

Adolescent↗
PubMed1999

Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-gamma inducible protein 10.

Central nervous system (CNS) involvement is a prominent feature of human immunodeficiency virus (HIV-1) infection. Monocytes and CD4+ T cells traverse the blood brain barrier (BBB), and serve as vehicles for the virus and perpetrators for brain pathology by their production of neurotoxins. In the present study cerebrospinal fluid (CSF) samples from HIV-1-infected patients were analyzed for the presence of chemotactic factors. All 36 CSF samples from the patients were positive for the CXC chemokine interferon-gamma inducible protein (IP-10), which was not detected in CSF samples of 14 controls. The IP-10 concentrations were higher in HIV-1-infected patients with HIV-1 associated neurologic disorders than in those without neurological deficits. In contrast to IP-10, other chemotactic factors including the CC chemokines MCP-1, MIP-1alpha, MIP-1beta and RANTES and the cytokines IL-15 and IL-16 were either not detected or increased in only less than 30% of the patients. Unlike the CSF samples of controls, all CSF samples from HIV-1-infected patients induced chemotaxis of T cells activated with IL-2. The significance of IP-10 as a T cell chemotactic cytokine in HIV-1-infected CSF is shown by (1) the correlation of the IP-10 levels with the extent of T cell chemotaxis, (2) the neutralization of T cell chemotaxis by anti-IP-10 antibodies and (3) the correlation of the chemotactic response of CSF samples on activated T cells and the CSF white cell count in the patients. Our data provide evidence that IP-10 contributes to the accumulation of activated T cells in the CSF compartment in HIV-1-infected individuals.

AIDS Dementia Complex↗
PubMed1999

[Cerebral ischemia as initial manifestation of neoplastic low-malignancy changes. 2 case reports and review of the literatures].

Thrombembolic events as paraneoplastic complications in malignant disease account for severe morbidity and mortality in these patients. In some cases disturbance in hemostasis is the first manifestation of a neoplastic process. We report the cases of two patients with cerebral and extracerebral vessel occlusions, in whom epithelial tumors of low malignant potential (borderline-tumors) of ovary and peritoneum were diagnosed later on. In one case the removal of the tumor stopped the coagulation problems. The second patient died a few days after the first symptoms with devastating multiple vessel occlusion. In stroke of unknown aetiology a paraneoplastic process should be kept in mind. The diagnosis is more probable with recurrent thrombembolism in different body regions and when warfarin therapy was ineffective. Thoughtful coagulation studies and a tumor search program is recommended in these cases.

Adult↗