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Biomedical subjects

P Freitag

Publications and source records attributed to P Freitag.

At least 37 records · Page 2Linked to original sources
PubMed2001

Successful diffusible brachytherapy (dBT) of a progressive low-grade astrocytoma using the locally injected peptidic vector and somatostatin analogue [90Y]-DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC).

We present the therapeutic effect of diffusible brachytherapy (dBT), an innovative approach for the management of symptomatic low grade gliomas [1]. This protocol uses a radiolabelled small diffusible peptidic vector which is a somatostatin analogue to target somatostatin type 2 (sst-2) receptors. The stable radioconjugate [90Y]-DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) is repeatedly injected via catheters placed into the resection cavity or into tumour nodules. We report on the four year follow-up after initiation of dBT to treat progressive disease in a patient with a complex eleven year history of fibrillary low-grade astrocytoma. The radiopharmakon was not only locally injected into the resection cavity following debulking surgery, but also administered by slow infusion technique to target recurrent and infiltrative tumour zones in the subventricular region around the inferior and posterior horns. In conclusion, peptidic vector based dBT was found to be safe, of mild and transitory toxicity, and effective in long-term tumour control.

Adult↗
PubMed2001

Improved interobserver agreement for visual detection of active T2 lesions on serial MR scans in multiple sclerosis using image registration.

The aim of this study was to analyse the effect of image registration on interobserver agreement in the visual detection of active multiple sclerosis (MS) lesions from serial magnetic resonance (MR) scans. T2W spin-echo MR scans (3-mm slices) of 16 MS patients participating in a treatment trial were selected. For each patient, two pairs of scans were used: an original (i. e., non-registered) and a registered pair. For the original pair, baseline and month 6 were used, and for the registered pair month 3 and 9. For registration an automatic matching algorithm based on Mutual Information was used. Six observers identified active lesions on both original and registered scans. Kappa values were calculated to assess interobserver agreement. Reslicing caused a slight blurring of the images, but near perfect registration. The kappa value of 0.35 +/- 0.07 for new lesions on original images improved to 0.62 (+/- 0.06) by registration (p = 0.004). For enlarging lesions on original images it was extremely poor (kappa 0.11 +/- 0.05), and did not benefit much by registration (kappa 0.20 +/- 0.11). Thus, image registration improved interobserver agreement for visual detection of new lesions. For enlarging lesions, registration improved agreement but still not to a satisfactory level.

Adult↗
PubMed2001

The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis.

In multiple sclerosis, matrix metalloproteinases (MMPs) are effectors of crucial pathogenetic steps, such as blood-brain barrier breakdown, invasion of brain parenchyma by immune cells and demyelination. However, only limited data are available on the types of MMPs induced in the course of multiple sclerosis, and on the role of their endogenous antagonists, the tissue inhibitors of metalloproteinases (TIMPs). We quantified the transcriptional expression of six MMPs and the four TIMPs in lesions and in normal appearing white matter (NAWM) from post-mortem multiple sclerosis brain tissue by real-time polymerase chain reaction, and compared levels with those in brain tissue from six control patients without neurological disease. The mRNA expression of MMP-7 and -9, but not of other metalloproteinases [MMP-2 and -3, and tumour necrosis factor (TNF)-alpha-converting-enzyme] was equally upregulated throughout all stages of lesion formation with active inflammation, and in most of matched NAWM tissue. The transcription of cytokines TNF-alpha/beta and IL (interleukin)-2, known modulators of MMPs, was upregulated only in distinct stages of lesion formation, while their receptors were not induced at all, which suggests that additional signalling molecules participate in the sustained upregulation of MMP-7 and -9 in multiple sclerosis. None of the TIMPs showed a significant induction over baseline expression of controls. We hypothesize that an imbalance between MMP and TIMP expression may cause a persistent proteolytic overactivity in multiple sclerosis, that may be a factor for continuous tissue destruction, and hence for secondary disease progression.

ADAM Proteins↗
PubMed2001

fMRI response during visual motion stimulation in patients with late whiplash syndrome.

After whiplash trauma, up to one fourth of patients develop chronic symptoms including head and neck pain and cognitive disturbances. Resting perfusion single-photon-emission computed tomography (SPECT) found decreased temporoparietooccipital tracer uptake among these long-term symptomatic patients with late whiplash syndrome. As MT/MST (V5/V5a) are located in that area, this study addressed the question whether these patients show impairments in visual motion perception. We examined five symptomatic patients with late whiplash syndrome, five asymptomatic patients after whiplash trauma, and a control group of seven volunteers without the history of trauma. Tests for visual motion perception and functional magnetic resonance imaging (fMRI) measurements during visual motion stimulation were performed. Symptomatic patients showed a significant reduction in their ability to perceive coherent visual motion compared with controls, whereas the asymptomatic patients did not show this effect. fMRI activation was similar during random dot motion in all three groups, but was significantly decreased during coherent dot motion in the symptomatic patients compared with the other two groups. Reduced psychophysical motion performance and reduced fMRI responses in symptomatic patients with late whiplash syndrome both point to a functional impairment in cortical areas sensitive to coherent motion. Larger studies are needed to confirm these clinical and functional imaging results to provide a possible additional diagnostic criterion for the evaluation of patients with late whiplash syndrome.

Adult↗
PubMed2001

Adenosarcoma of the uterine body in a 19-year-old woman--three year survival: case report.

BACKGROUND: Uterine adenosarcoma is a rarely by occurring tumor. It is composed of a benign adenoid structure and a sarcomatous stromal component. The average age of patients with a diagnosis of uterine adenosarcoma is about 70 years. CASE: We present a case of a 19-year-old woman with a rarely occurring uterine adenosarcoma manifesting itself by irregular bleeding and producing fragile polypous matter which was spreading into the vagina. The final diagnosis was made only by repeated biopsies. Abdominal hysterectomy with bilateral salpingo-oophorectomy, appendectomy and revision of iliac lymph nodes were performed. Teleradiotherapy was applied from 4 fields in 25 fractions to a total exposure of 50 Gy. It was followed by six cycles of chemotherapy containing 50 mg/m2 doxorubicin and 5 g/m2 ifosfamid administered in 21-day dose intervals. CONCLUSION: This case should demonstrate the difficulty of making the right diagnosis. Since the end of therapy the patient has been regularly seen in our onco-gynecologic department. Now, 40 months after the end of chemotherapy and 46 months after making the diagnosis, there are no signs of relapse.

Adenosarcoma↗
PubMed2000

Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis.

Free radicals including peroxynitrite are induced in Multiple Sclerosis (MS). Antioxidant and peroxynitrite inhibitor uric acid (UA), suppresses the MS animal model experimental autoimmune encephalomyelitis (EAE). MS patients have lower average serum UA than controls. An inverse relationship exists between MS and gout Glatiramer acetate (GA) suppresses EAE and is beneficial in relapsing MS. We investigated serum UA changes during open-label treatment of relapsing MS with GAA. Ten patients (six females, four males, aged 19 to 39 years, mean age 32 years) completed 6 months of GAA (Copaxone 20 mg s.c daily). Of these, nine completed 12 months. After 6 months on GAA, serum UA (normal, 173359 micromol/ml for women, 258-491 micromol/ml for men) increased in nine and marginally decreased (302 to 300 micromol/ml) in a single patient. Mean UA significantly increased from 240 to 303 micromol/ml (P=0.0014). At 12 months, UA remained significantly higher than at start (P=0.006) decreasing in only one patient. In contrast, we found no significant UA changes after 6 and 12 months of treatment in 21 MS patients treated with interferon beta1-a (Avonex), or in 11 treated with interferon beta1-a (Rebif), or in five placebo-treated controls. Increasing UA, a natural inhibitor of free radicals, may represent a mechanism of action of glatiramer acetate in MS.

Adjuvants, Immunologic↗
PubMed2000

[Granulosa cell tumor--clinical group and literature review].

OBJECTIVE: To present a review of literature and to analyse a clinical retrospective series of patients with granulosa cell tumor. DESIGN: Retrospective study and review. SETTING: Department of Obstetrics and Gynaecology, First Faculty of Medicine, Prague, Czech Republic. METHODS: Retrospective analysis of age, stage, surgery, radiotherapy and chemotherapy, survival curve, number of recurrences and time to recurrence. Literature and information database (Medline 1997-1999) review. RESULTS: In a group of 43 patients the median of age was 53.5 years. 83.7% of cases were in a stage I. There were two duplicate tumors in a series. Conservative surgery was performed in 9/43 cases, 5 of them were reoperated on. The most frequent chemotherapy regimens were platinum-cyclophoshamide and BEP (bleomycin, etoposide, platinum). The 5-year overall survival was 86% and specific survival 90.7%. There were 3/43 recurrences, median time to recurrence was 22 months. CONCLUSION: A good prognosis of a patient with granulosa cell tumor requires a precise histopathologic examination, an adequate surgery and a comprehensive clinical analysis of a case to evaluate an indication of adjuvant therapy. Concentration of patients in oncogynaecological centres is advisable. A careful follow-up because of a risk of late recurrences is necessary.

Female↗
PubMed2000

[Gynecologic operations in patients after kidney and liver transplantation--case report].

OBJECTIVE: To give an overview of the complications associated with the post-transplantation period which thus presents an increased risk for subsequent gynecological surgery and also for the postoperative period. To determine the criteria and conditions under which these operations may be performed with relative safety. TYPE OF STUDY: Case report. SUBJECT OF STUDY: Described surgical treatment of gynecological diseases in three patients after liver and kidney transplantation. CONCLUSION: A summary of the principles/basics of patient care after surgery for gynecological indications with a prior organ transplant in ther patient's history. These patients should undergo surgery in hospitals with a high quality of professional care as well as high quality equipment and cooperation among the specialists from the various medical fields involved.

Adult↗
PubMed1999

[Radiation-induced submandibular extra-osseous osteogenic sarcoma].

Extraskeletal osteogenic sarcoma of the head and neck are extremely rare. This case report describes a 55-year-old patient who has suffered from four squamous cell carcinomas (SCC) of the mouth since 1985. Thirteen years after successful radical resection of the SCC of the planum buccale left and radiotherapy, the patient developed a radiation-induced extraskeletal submandibular sarcoma on the left [7, 8, 9, 12]. The primary sarcoma developed in the planum buccale, the area which had been repeatedly exposed to radiotherapy, and spread into the soft tissue. The difficulties of the clinical diagnosis, the morphology of the tumor and therapeutic procedure are described. This case demonstrates the problems of radiotherapy in SCC.

Carcinoma, Squamous Cell↗
PubMed1999

Type I osteogenesis imperfecta: diagnostic difficulties.

A 65-year-old woman presented with vertebral fractures of the lumbar spine and a history of pathological fractures following minor trauma, which had occurred before the onset of menopause. Her past medical history was significant for intermittent low back pain since childhood, which was attributed to thoracolumbar scoliosis. A diagnosis of unclassifiable osteoporosis was made until invasive diagnostic procedures suggested a mild form of type I osteogenesis imperfecta (OI). In unclear or atypical perimenopausal osteoporosis and diagnosis of OI should be considered.

Absorptiometry, Photon↗
PubMed1999

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

Adult↗
PubMed1999

[Comprehensive treatment of ileofemoral thrombosis at the end of pregnancy with cesarean section in combination with thrombectomy].

Acute deep ileofemoral thrombosis was treated at the end of pregnancy in four pregnant women. A multidisciplinary approach was selected. During a single anaesthesia the team of obstetricians and neonatologists made a Caesarean section followed by thrombectomy with a Fogarty catheter. This operation was performed by a team of specialists in cardiovascular surgery. Two women developed rethrombosis: one woman on the following day, the second one two weeks after surgery. In both instances repeated thrombectomy was performed. In one woman the cause of ileofemoral thrombosis was malignant disease of the uterine cervix II and this woman is, after oncological treatment, in a serious condition due to the basis disease. The remaining three women were repeatedly subjected to phlebographic examinations and complete patency of the deep vascular system was found. These women are free from subjective and objective complaints and can look after their children. Pregnant women where a serious ileofemoral thrombosis was diagnosed had high fibrinogen and thrombocyte levels. In two women an AT III deficiency was found. There was also a high cholesterol level and positive antiphospholipid antibodies. Thrombectomy has according to the authors' experience very good results when the operation is implemented within 72 hours after initial symptoms. This procedure reduces the risk of chronic venous insufficiency.

Adult↗
PubMed1998

Erythropoietin mRNA expression in human fetal and neonatal tissue.

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch.

Bone Marrow↗
PubMed1998

Motor, somatosensory and auditory cortex localization by fMRI and MEG.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

Adult↗
PubMed1998

Effect of eye movements on the magnitude of functional magnetic resonance imaging responses in extrastriate cortex during visual motion perception.

We have studied the effects of pursuit eye movements on the functional magnetic resonance imaging (fMRI) responses in extrastriate visual areas during visual motion perception. Echoplanar imaging of 10-12 image planes through visual cortex was acquired in nine subjects while they viewed sequences of random-dot motion. Images obtained during stimulation periods were compared with baseline images, where subjects viewed a blank field. In a subsidiary experiment, responses to moving dots, viewed under conditions of fixation or pursuit, were compared with those evoked by static dots. Eye movements were recorded with MR-compatible electro-oculographic (EOG) electrodes. Our findings show an enhanced level of activation (as indexed by blood-oxygen level-dependent contrast) during pursuit compared with fixation in two extrastriate areas. The results support earlier findings on a motion-specific area in lateral occipitotemporal cortex (human V5). They also point to a further site of activation in a region approximately 12 mm dorsal of V5. The fMRI response in V5 during pursuit is significantly enhanced. This increased response may represent additional processing demands required for the control of eye movements.

Adult↗