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Biomedical subjects

M Huber

Publications and source records attributed to M Huber.

At least 199 records · Page 11Linked to original sources

Early diagnosis and successful treatment of acute cytomegalovirus encephalitis in a renal transplant recipient.

We report the case of a 40-year-old male HIV-negative renal transplant patient with allograft rejection and immunosuppressive therapy who presented with acute cytomegalovirus (CMV) encephalitis. CT and MRI of the brain were normal but EEG showed diffuse slowing and dysrhythmia. In cerebrospinal fluid (CSF) initially 81 cells/microliters were found and immunocytochemistry showed a decreased CD4/CD8 ratio and increased values of activated lymphocytes, natural killer cells and immunoglobulin-containing cells. CMV-specific IgM antibodies in CSF and serum, immunostaining of CMV antigen in CSF cells and virus culture from CSF and urine were negative. During the first 3 weeks of illness no intrathecal production of immunoglobulins could be detected. Early diagnosis of CMV encephalitis was made by in situ hybridization (ISH) on CSF cell preparations and the polymerase chain reaction (PCR) which was positive in CSF and blood. On day 26 diagnosis was confirmed by detection of CMV-specific intrathecal IgG production. The patient was treated with ganciclovir, anti-CMV immunoglobulins and intrathecal beta interferon. He recovered completely after 2 months. Our data demonstrate the usefulness of ISH and PCR in the early diagnosis of CMV encephalitis and perhaps may encourage the use of intrathecal beta interferon in other patients with this disease.

Acute Disease↗

Subcortical damage and cortical dysfunction in progressive supranuclear palsy demonstrated by positron emission tomography.

Regional cerebral glucose metabolism was studied in nine patients with progressive supranuclear palsy (PSP). (18F)-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) revealed general cerebral hypometabolism in all PSP patients in comparison with an age-matched reference group. When comparing the degree of regional metabolic deterioration, a consistent pattern of the most affected brain regions became obvious: the strongest significant alteration of cerebral glucose metabolism was observed in subcortical regions, e.g. in caudate nucleus, lentiform nucleus and upper mid-brain, which showed nerve cell loss in previous pathological studies. Less severe, but still significant hypometabolism was observed in frontal cortex. This pattern of hypometabolism was distinctly different from that typically seen in dementias of Alzheimer's type. The present data show that PET findings agree with histopathological studies: PSP is a primarily subcortical disease with secondary inactivation of cortical, especially of frontal brain regions.

Aged↗

Positron emission tomography in degenerative disorders of the dopaminergic system.

21 patients who had Parkinson's disease (PD), PD plus dementia of Alzheimer type (PDAT) or progressive supranuclear palsy (PSP), were studied with positron emission tomography (PET) using (18F)-2-fluoro-2-deoxy-D-glucose (FDG). In one patient with strictly unilateral PD side differences in striatal dopa uptake were studied with 6-(18F)fluoro-L-dopa (F-dopa). In patients with PD PET with FDG did not show any significant change in regional cerebral metabolic rates for glucose (rCMR(Glu)). In PDAT glucose metabolism was generally reduced, the most severe decrease was found in parietal cortex. The metabolic pattern was similar to that typically found in patients with Alzheimer's disease (AD). In the patient with strictly unilateral PD rCMR(Glu) was normal, F-dopa PET, however, revealed a distinct reduction of dopa uptake in the contralateral putamen. In PSP glucose metabolism was significantly decreased in subcortical regions (caudatum, putamen and brainstem) and in frontal cortex. Thus PET demonstrated a clear difference of metabolic pattern between PDAT and PSP.

Adult↗

Progressive derangement of periinfarct viable tissue in ischemic stroke.

Sixteen patients were studied by multitracer positron emission tomography (PET) within 6-48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13-25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 +/- 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 +/- 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke.

Adolescent↗

Functional and morphological imaging of small striato-capsular infarction by CT, MRI and multitracer PET.

Regional cerebral blood flow, oxygen consumption, blood volume and glucose metabolism were studied by positron emission tomography (PET) in 16 patients with striato-capsular infarction during the acute phase. Visual evaluation of tomograms and quantitative analysis of PET data detected in all patients severe flow disturbances and metabolic derangement within the territory of the penetrating branches of the middle cerebral artery. Additionally remote effects were observed. The correspondence of early PET changes with the diagnosis of striato-capsular infarction was verified later on by computerized three-dimensional alignment of PET scans and MRI. These results demonstrate that PET allows localization of small striato-capsular infarction with high accuracy in the acute phase by demonstrating both severe local flow disturbances and metabolic derangement, as well as remote effects.

Brain↗

Metabolic derangement in viable periinfarct tissue in the course of acute ischaemic infarction: a multitracer positron emission tomography (PET) study.

We used a multitracer positron emission tomography (PET) approach to assess metabolic changes in infarcted and periinfarct tissue in acute ischaemic stroke. 16 patients were studied within 6-48 hours (mean, 23 h) after onset of symptoms from a first hemispheric stroke and again 13-25 days later (mean, 15.6 days). Regional cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRGlc), blood flow (CBF) and blood volume (CBV) were measured and oxygen extraction (OEF) as well as glucose extraction (GEF) and microvascular transit time were calculated. PET images were three-dimensionally aligned using serial CT or MRI scans. Regions of interest on the side of the infarction were individually compared to contralateral mirror regions. In the infarction core CBF, CMRO2 and CMRGlc were significantly lower than on the contralateral side and did not change during time. In the periinfarct regions there was a decreased CMRO2 with progressive deterioration over time while CBF slightly increased. Only in a few ischaemic regions with initially increased OEF oxygen metabolism was preserved during the course of time.

Blood Volume↗

Long-term care personnel assess their attitudes and knowledge of the older adult.

The purpose of this study was to compare long-term care employees' attitude and knowledge about myths of ageing and normal age changes, before and after exposure to formal educational sessions. The researchers investigated if there was a difference in knowledge level and change in attitudes of long-term care employees after educational sessions. The subjects for this study were defined as persons who had any contact with the residents at St Charles Care Center. The final data set used in the analysis contained 84 observations. Each participant attended three 1-hour classes which consisted of simulation of handicaps, normal age-related changes, and myths and realities of ageing. Overall, there was a significant increase in knowledge from the pre-test to the post-test. The study also tested for a negative (anti-aged) bias attitude and a positive (falsely pro-aged) bias attitude among the individuals. At the end of the study there was still a slight negative biased attitude towards ageing. The data suggest that continuing education is an effective means of influencing the knowledge and attitudes of personnel in long-term care facilities. Recommendation for future research should be that this study be replicated in another long-term care facility with the addition of a job satisfaction tool.

Aged↗

Comparison of MRI, CT and angiography in cerebral arteriovenous malformations.

Computed tomography (CT), magnetic resonance imaging (MRI) and cerebral angiography were performed in 30 patients with cerebral arteriovenous malformations (AVMs). Clinical data and radiographic findings are presented. The diagnostic values of CT and MRI are compared. 25 of 30 AVMs were seen on CT-scans, 27 on MR-images, 26 by angiography. Typical CT-findings were irregularly hyperdense areas with spotlike contrast enhancement. 4 out of 5 AVMs not depicted by CT were diagnosed for tumor, in one case the malformation was hidden by a hematoma. MRI mostly showed the AVM as round or oval lesions with spongelike structure of low signal intensity in T1-weighted sequences or as single enlarged vessels. The 26 AVM revealed by angiography presented typically enlarged vessels; in 2 cases angiography was without any pathological findings, 2 cases showed signs of a space occupying lesion. The results confirm that MRI is superior to CT in detecting and recognizing AVM. Its strength lies in the possibility to detect abnormal vessels even in presence of fresh or older hematoma, and in the precise information on size and location of the AVM. In our series, MRI and CT-scans together showed 28 of 30 AVMs, the remaining 2 cases were not seen with angiography either but only proven histologically. Although today MR-angiography is able to provide three dimensional images of blood vessels, it cannot yet replace angiography in the exact study of the vessels which is required for surgical planning.

Adolescent↗

[Cerebrospinal fluid cytology in meningeal invasion of leukemia and malignant lymphoma. Reliable diagnosis by immunocytochemistry].

Cerebrospinal fluid cytology was performed in 64 patients who were suspected of having a meningeal infiltration of malignant lymphoma or leukemia. Conventional staining with May Grünwald Giemsa revealed a positive result in 51 cases, and a negative result in one case. In 4 cases diagnosis was hampered by blood contamination or a lack of CSF cells. In the remaining 8 cases with doubtful cytologic specimens, additional immunocytochemic staining allowed definite diagnosis. In 5 of these cases malignancy was confirmed, while in the remaining 3 an inflammatory cell pattern was found and later confirmed by follow-up. In summary, immunocytochemistry was essential for definite diagnosis in 12% of CSF cell specimens suspected of leukemia or malignant lymphoma. It may be concluded that immunocytochemistry in CSF cytology is a valuable tool for enhancement of diagnostic reliability.

Adult↗

Peroxisomal degradation of leukotrienes by beta-oxidation from the omega-end.

Chain shortening via beta-oxidation from the omega-end has been recognized as the major pathway for the degradation of cysteinyl leukotrienes as well as leukotriene B4 (LTB4). The metabolic compartmentation of this pathway was studied using peroxisomes purified from normal and clofibrate-treated rat liver. beta-Oxidation products of omega-carboxy-LTB4, including omega-carboxy-dinor-LTB4 identified by gas chromatography-mass spectrometry, were formed by the isolated peroxisomes. The reaction was dependent on CoA, ATP, and NAD and was stimulated by FAD. NADPH was necessary for the further metabolism of omega-carboxy-dinor-LTB4. Together with microsomes a degradation of omega-carboxy-LTB4 also proceeded in isolated mitochondria in the presence of CoA, ATP, and carnitine. beta-Oxidation of the cysteinyl leukotriene omega-carboxy-N-acetyl-leukotriene E4 was observed only with isolated peroxisomes in combination with lipid-depleted microsomes. Direct photoaffinity labeling using omega-carboxy-[3H] LTB4 and omega-carboxy-N-[3H]acetyl-LTE4 served to identify peroxisomal leukotriene-binding proteins. The bifunctional protein (EC 4.2.1.17 and 1.1.1.35) and 3-ketoacyl-CoA thiolase (EC 2.3.1.16) of the peroxisomal beta-oxidation system were the predominantly labeled polypeptides as revealed by precipitation with monospecific antibodies. In vivo studies with N-acetyl-[3H2]LTE4, N-acetyl-[3H8]LTE4, and N-[14C]acetyl-LTE4 after treatment with the peroxisome proliferator clofibrate indicated formation and biliary excretion of large amounts of metabolites more polar than omega-carboxy-tetranor-N-acetyl-LTE3 including omega-carboxy-tetranor-delta 13-N-acetyl-LTE4 and omega-carboxy-hexanor-N-acetyl-LTE3. Increased formation of beta-oxidized catabolites of N-acetyl-LTE4 and LTB4 was also observed in hepatocytes isolated after clofibrate treatment. Our results indicate that peroxisomes play a major role in the beta-oxidation of leukotrienes from the omega-end. Whereas omega-carboxy-LTB4 was beta-oxidized both in isolated peroxisomes and mitochondria, the cysteinyl leukotriene omega-carboxy-N-acetyl-LTE4 was exclusively degraded in peroxisomes.

Affinity Labels↗

Malaria parasite chitinase and penetration of the mosquito peritrophic membrane.

Malaria parasites (ookinetes) appear to digest the peritrophic membrane in the mosquito midgut during penetration. Previous studies demonstrated that lectins specific for N-acetylglucosamine bind to the peritrophic membrane and proposed that the membrane contains chitin [Rudin, W. & Hecker, H. (1989) Parasitol. Res. 75, 268-279]. In the present study, we show that the peritrophic membrane is digested by Serratia marcescens chitinase (EC 3.2.1.14), leading to the release of N-acetylglucosamine and fragmentation of the membrane. We also report the presence of a malaria parasite chitinase that digests 4-methylumbelliferyl chitotriose. The enzyme is not detectable until 15 hr after zygote formation, the time required for maturation of the parasite from a zygote to an ookinete, the invasive form of the parasite. At 20 hr, the enzyme begins to appear in the culture supernatant. The chitinase extracted from the parasite and found in the culture supernatant consists of a major band and two minor bands of activity on native polyacrylamide gel electrophoresis. The presence of chitin in the peritrophic membrane, the disruption of the peritrophic membrane during invasion, and the presence of chitinase in ookinetes suggest that the chitinase in ookinetes is used in the penetration of the peritrophic membrane.

Aedes↗

Cerebellar haemorrhage: management and prognosis.

Of 26 patients with CT confirmed intracerebellar haematoma, 17 had ventricular drainage performed and 7 patients had the haematoma evacuated. Eleven patients died. Mortality was clearly related to state of consciousness. Seven out of 8 non-comatose patients survived but 10 out of 18 comatose patients died. As there was no incidence of deterioration immediately following placement of a ventricular drainage, the actual risk of upward transtentorial herniation seemed low. Absence of evoked potentials in 6 patients accurately predicted a fatal outcome but normal SEP and BAEP were of lesser value for predicting survival.

Aged↗