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Biomedical subjects

H Ostertag

Publications and source records attributed to H Ostertag.

At least 19 recordsLinked to original sources

Primitive neuroectodermal tumors after prophylactic central nervous system irradiation in children. Association with an activated K-ras gene.

Three patients had supratentorial malignant brain tumors 7 to 9 years after prophylactic central nervous system (CNS) treatment for acute lymphocytic leukemia or malignant T-cell lymphoma. Therapy was administered at the age of 3 to 8 years and included cranial irradiation (total dose, 1800 to 2400 cGy) and intrathecal methotrexate. The brain tumors had histologic and immunohistochemical features of primitive neuroectodermal tumors (PNET), including neuroblastic rosettes, rhythmic arrangement of tumor cells, and immunohistochemical expression of glial, and in one patient neuronal, marker proteins. Using polymerase chain reaction-mediated DNA amplification from paraffin-embedded tissues and subsequent DNA sequence analysis, an activating point mutation was detected in the K-ras protooncogene in one tumor. This mutation was a G to A transition in position 2 of codon 12, substituting aspartate (GAT) for glycine (GGT). This type of mutation has not been observed before in human brain tumors, but it is frequent in radiation-induced murine lymphomas. These observations suggest that PNET can be induced after completion of the embryonal and fetal development of the human CNS. Oncogene-activating point mutations may represent a pathogenetic mechanism involved in the genesis of radiation-induced brain tumors.

Aspartic Acid

Low incidence of bronchus-associated lymphoid tissue (BALT) in chronically inflamed human lungs.

The relevance of bronchus-associated lymphoid tissue (BALT) in man is still under discussion. Animal experiments indicate that the development of BALT is dependent on microbial stimulation. Therefore, the incidence of BALT was investigated retrospectively in specimens removed during surgical procedures on patients with chronic pulmonary inflammation. All these patients had severe chronic bronchitis and bronchiectasis, but BALT was found in only 8%. In patients with BALT and a malignant tumor, occlusion of a bronchus with poststenotic pneumonia was always present and BALT was observed exclusively in areas peripheral to the occlusion. In man other compartments of the lung must be responsible for the immune function of BALT found in animals.

Adolescent

Meningeal melanocytoma of the C8 nerve root: case report.

A case of a meningeal melanocytoma involving the C8 nerve root is presented. The clinical symptoms and the radiological investigations resembled a neurinoma of the spinal nerve root. Intraoperatively the tumor was seen to be firmly attached to the dural covering of the dorsal nerve root. By using microsurgical technique, complete removal of the tumor with preservation of the ventral nerve root was accomplished. Histological examination revealed a typical meningeal melanocytoma as described by Limas and Tio in 1972. Ten additional cases of previously reported spinal meningeal melanocytomas are reviewed. The importance of differentiating this benign lesion from meningeal malignant pigmented tumors is stressed.

Adult

Pathological fractures and lytic bone lesion of the femoral neck associated with beta 2-microglobulin amyloid deposition in long-term dialysis patients.

A correlation is demonstrated between chronic hemodialysis using cuprophane membranes (mean duration: 13 years) and pathological fractures (n = 7 in 6 patients) after lytic bone deposits of beta 2-microglobulin amyloid (n = 13 patients). The characteristic symptom complex includes painful impingement syndrome of the shoulder, carpal tunnel syndrome, painful hip and recurrent knee effusions. The first steps of the clinical diagnostic procedure are to demonstrate lytic defects in skeletal radiographs and to verify the presence of beta 2m by biopsy or puncture. Due to reduced regeneration capacity in amyloid bone lesions the resulting surgical therapy should aim at total joint replacement or augmented osteo synthesis. Definitive operative treatment should be aspired even in the absence of manifest fractures, as the natural course of the disease is characterized by progression of the bone destruction and a continuous pain syndrome.

Amyloid

PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy.

Forty-four patients with recurrent colorectal carcinoma were examined prior to a combination of conventional photon radiotherapy (40 Gy) and neutron therapy (10 Gy). Twenty-one of these underwent a PET examination after photon therapy and 12 also were studied after the end of combined therapy. CEA plasma levels were measured from blood samples taken immediately before the PET study. A significant decrease in FDG uptake despite good palliative results were observed in only 50% of the patients. This may be explained by inflammatory reactions caused by radiation injury. Inflammation and metabolically active residual tumor tissue cannot be distinguished. It is concluded that an observation interval longer than 6 mo may more effectively detect residual tumor activity. In 14 of 41 examinations, an increased FDG uptake was associated with a normal CEA value, and in only two cases were normal FDG uptake values and increased CEA levels found, suggesting that PET is more sensitive than the measurements of CEA plasma levels for tumor recurrence.

Adult

Metabolism and actions of 2-deoxy-2-fluoro-D-galactose in vivo.

The synthetic D-galactose analog 2-deoxy-2-fluoro-D-galactose (dGalF) offers unique advantages for studies of the D-galactose pathway by non-invasive techniques using 19F-NMR spectroscopy or positron emission from the 18F-labeled compound. The metabolism of 2-deoxy-2-fluoro-D-galactose was studied in rodents using the unlabeled, the 18F-labeled, and the 14C-labeled D-galactose analog. Analyses for the metabolites of 2-deoxy-2-fluoro-D-galactose were performed by HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The metabolism of 2-deoxy-2-fluoro-D-galactose was most active in the liver which took up the major part of the administered dose of the 14C-labeled D-galactose analog, but renal excretion was also pronounced. This was confirmed by in vivo scanning of the rat using the 18F-labeled sugar (1.5 microCi/g; 25 nmol/g) and examination by positron-emission tomography and gamma camera. The dose dependence of the levels of the hepatic metabolites of 2-deoxy-2-fluoro-D-galactose was investigated for doses between 25 nmol/g body mass and 1 mumols/g body mass. After 1 h, the major part of the acid-soluble uracil nucleotides consisted of UDP-2-deoxy-2-fluoro-D-hexoses when the dose was at least 0.1 mumols/g. With higher doses, 2-deoxy-2-fluoro-D-galactose 1-phosphate became the predominant initial metabolite. After a dose of 1 mumols/g 2-deoxy-2-fluoro-D-galactose 1-phosphate accumulated rapidly (5.3 +/- 0.4 mumols/g liver after 30 min) followed by the formation of UDP-2-deoxy-2-fluoro-D-galactose and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 mumols/g and 1.8 +/- 0.1 mumols/g, respectively, after 5 h). The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of 2-deoxy-2-fluoro-D-galactose at a dose of 1 mumols/g. The UTP-depleting action was minimal, however, at a dose of 25 nmols/g or less, indicating that interference in uridylate metabolism would be negligible at the doses required for positron-emission tomography of the liver using the 18F-labeled compound. At higher doses, the UTP deficiency induced by 2-deoxy-2-fluoro-D-galactose could be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose.

The metabolism of 2-deoxy-2-fluoro-D-galactose (dGalF) was studied in rodents using HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The liver took up the major part of the administered dose of the 14C-labeled D-galactose analog. This was confirmed in vivo by use of the 18F-labeled sugar (1.5 mCi/kg; 25 mumol/kg) and examination by positron emission tomography. After a dose of 1 mmol/kg, dGalF-1-phosphate accumulated rapidly (5.3 +/- 0.4 mmol/kg after 30 min), followed by formation of UDP-dGalF and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 and 1.8 +/- 0.1 mmol/kg, respectively, after 5 hr). Good quantitative agreement was obtained between the measurements by HPLC and enzymatic analyses and by 19F-NMR. The noninvasive in vivo 19F-NMR technique is particularly advantageous, since it allows the simultaneous analysis of all dGalF metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of dGalF at a dose of 1 mmol/kg. The UTP-depleting action was minimal, however, at a dose of 25 mumol/kg or less, indicating that interference in uridylate metabolism will be negligible at the doses required for positron emission tomography of the liver using the 18F-labeled compound. At higher doses the UTP deficiency induced by dGalF may be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma. At moderate doses of dGalF, 19F-NMR spectroscopy in vivo or in vitro could be used to pinpoint defects of the enzymes that cause galactosemia, i.e. of galactokinase, uridyltransferase, or 4-epimerase.

Animals

[Tumor-like bone lesions in sternocostoclavicular hyperostosis and palmoplantaris pustulosis].

We present two unusual cases of sternocostoclavicular hyperostosis (SCCH) in conjunction with palmoplantar pustulosis (PPP) and additional tumour like manifestations in a scapula and a femur respectively. The association of SCCH with complexes of signs and symptoms such as chronic multifocal osteomyelitis (CRMO), or other nosological entities such as seronegative spondylarthropathies, is discussed.

Adult

Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.

In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

Animals

Measured attenuation correction methods.

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68Ge/68Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible.

Humans

[Fundamentals of positron emission tomography].

Positron emission tomography is a modern radionuclide method of measuring physiological quantities or metabolic parameters in vivo. The method is based on: (1) radioactive labelling with positron emitters; (2) the coincidence technique for the measurement of the annihilation radiation following positron decay; (3) analysis of the data measured using biological models. The basic aspects and problems of the method are discussed. The main fields of future research are the synthesis of new labelled compounds and the development of mathematical models of the biological processes to be investigated.

Humans

Pathology of laser-induced experimental aneurysms.

Aneurysms were produced in the common carotid artery of 35 rats by milliwatt CO2 laser welding of an adventitia patch over a hole. The aneurysmal sac was formed by collagen; the lumen was covered by an endothelial-like lining and partially thrombosed. The pathology of these aneurysms is similar to spontaneously occurring intracranial human aneurysms. This aneurysm model has properties (reliability, spontaneous bleeding tendency, minimal vessel manipulation, and pathological features) that make it theoretically advantageous for the induction of experimental intracranial aneurysms in larger animals.

Aneurysm

Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma.

The tissue uptake of [13N]glutamate (glu) was related to that of [11C]butanol (but), a highly diffusible perfusion tracer. In 25 rats bearing Walker-256 carcinomas tumor-to-muscle glu uptake averaged 6.34 +/- 2.84 (s.d.) prior to interventions and the respective uptake of but was 6.79 +/- 3.08 (y = 0.03 + 0.94x). One hour after selective intraarterial administration of methotrexate (mtx), glu uptake fell by 47%, whereas blood flow remained within the pretreatment range (N = 9). Four hours after mtx, perfusion was reduced by approximately 40%, and 2 days later both perfusion and glu uptake reached extremely low levels. No significant difference in the effect of 10 and 50 mg/kg mtx was observed. Regional tissue mtx uptake estimations using 77Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (13N/11C-index) was 0.94 +/- 0.015 (s.e.m., N = 25) before intervention. After methotrexate (1 hr, 4 hr, and 2 days) this index was 0.58 +/- 0.06 (N = 9), and 0.85 +/- 0.04 (N = 11) and 1.03 +/- 0.05 (N = 5), respectively. These values demonstrate an early mtx-induced uncoupling of glu uptake with respect to perfusion.

Animals

[Incidence, etiology and risk of rupture of aortic aneurysm. An autopsy study].

In an unselected series of 3,375 autopsies performed during five years there were 114 cases of aortic aneurysm (3.4%). Males were affected 9.4 times as often as females. Average age at death of those with aneurysm was 72.8 years, of those with rupture 69 years. Of the aneurysms 73.8% were located in the lumbar aorta, 22.8% in the thoracic aorta and 3.5% involved the entire aorta. Saccular or fusiform aneurysms accounted for 73.4%, dissecting ones for 18.4% and pseudoaneurysms for 1.8%. Arteriosclerosis was the underlying cause of the aneurysm in 95.6% of cases; in 41.2% rupture was the direct cause of death. Aneurysms of the thoracic aorta were ruptured in 65.4%, of the lumbar aorta in 32.1%. The incidence of rupture was highest for dissecting aneurysm of the thoracic aorta and the entire aorta--75% each. Hypertension was found to be a risk factor of rupture.

Aged

[Quantification of pulmonary alveolar microlithiasis in the CT].

Pulmonary alveolar microlithiasis is a rare, familial disease with massive symmetrical intra-alveolar calcium deposition. Conventional CT findings and CT measurements with a dual energy technique were carried out in a 26-year-old patient suffering from this disease. The importance of the findings in the differential diagnosis and for estimating the progression and prognosis of the disease is discussed.

Adult