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Biomedical subjects

P Burger

Publications and source records attributed to P Burger.

At least 37 records · Page 2Linked to original sources

Comparative localization of mannose-6-phosphate receptor with 2,6sialyltransferase in HepG2 cells: an analysis by confocal double immunofluorescence microscopy.

Recent advances in confocal immunofluorescent microscopy have led to significant improvements in delineating membrane-bounded organelles. In this study using HepG2 cells we focused on two functionally distinct but closely apposed organelles that have been difficult to distinguish by conventional immunofluorescent microscopy, namely the Golgi apparatus, the trans Golgi network (TGN) and late endosomes. The following markers were used: for the Golgi apparatus beta 1,4galactosyltransferase (gal-T), for the TGN, 2, 6(N)sialytransferase (sia-T) and for late endosomes/TGN, the mannose-6-phosphate/insulin growth factor II receptor (CIMPR). In addition, that part of the TGN previously shown to contain CIMPR was also identified using antibodies to the gamma-chain of the HA-1 adaptor (Klumperman et al. J. Cell Biol. 121, 997-1010 (1993)). True colocalization of intracellular antigens was ascertained by double staining of gal-T using both monoclonal and polyclonal antibodies. As previously reported, our results revealed essentially complete colocalization of gal-T and sia-T in this cell line. While the compartments containing CIMPR appeared to overlap with those containing sia-T by conventional immunofluorescence, both compartments were clearly distinct by double-label confocal microscopy. Differences between these organelles became more evident following treatment with brefeldin A. Finally, HA-1 gamma-chain was also localized to structures that were close to but clearly different from the sia-T-containing compartment. Absence of colocalization of CIMPR or HA-1 gamma-chain with sia-T indicates that these markers are enriched in distinct domains of the trans Golgi network.

Adaptor Protein Complex gamma Subunits↗

Validation of measurement of regional myocardial perfusion in humans by ultrafast x-ray computed tomography.

The objective was to validate the measurement of myocardial perfusion in humans by ultrafast computed tomography (CT), by comparing measurements with those from single photon emission computed tomography (SPECT). Measurement of myocardial perfusion with high spatial resolution (including the differentiation of subendocardial and subepicardial perfusion) may be possible by ultrafast CT in humans. Although there are encouraging data from experiments with dogs, the technique has not been validated in humans. In 11 patients, ultrafast CT measurement of regional perfusion in a single short-axis slice was compared with that obtained by SPECT, and in 14, reproducibility of ultrafast CT was evaluated. The ultrafast CT scanner was set to acquire 20 images, gated to end-diastole. The images were divided into 32 equal segments, and the time course and extent of opacification of the left ventricular cavity and myocardium were analyzed to calculate absolute perfusion. The thallium tomograms were also divided into 32 segments for comparison. The pattern of relative perfusion by segment was represented as a curve. In 18 of 22 paired scans, the mean difference of the position of the minimum and maximum points of the curves was less than 4, indicating close agreement between the two techniques. When scoring segmental perfusion as normal or abnormal, there was agreement between the methods in 129 of 176 segments ([symbol: see text] 0.41). Reproducibility (mean difference +/- 1 SD) of basal scans was 0.005 +/- 0.2 mL/min/mL, and during adenosine vasodilation was 0.05 +/- 0.32 mL/min/mL. Absolute perfusion (mean +/- 1 SD) at rest was 0.52 +/- 0.21 mL/min/mL. During adenosine infusion, perfusion increased to a mean of 0.84 +/- 0.42 mL/min/mL. Ultrafast CT and intravenous contrast can be used to assess relative myocardial perfusion in humans, at rest and during adenosine vasodilatation, although it may underestimate absolute perfusion, particularly at high flow.

Adenosine↗

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE: The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS: The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS: The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION: Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

Adolescent↗

Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors. A Pediatric Oncology Group phase II study.

To assess the response rates and toxicity of AZQ in children with recurrent brain and other malignant solid tumors, a phase II study was implemented by the Pediatric Oncology Group. Eligible patients received AZQ 18 mg/M2/week i.v. for 4 doses followed by a 2 week rest period. Each dose was given over four hours (1/3 over the initial 20 minutes). After the first year, the dosage was reduced to 13 mg/M2 due to myelotoxicity resulting in treatment delays. No objective responses were observed in 73 evaluable children with various non-central nervous system tumors. Of the 91 patients with brain tumors, there were 4 CR's and 2 PR's in patients with astrocytoma, ependymoma, glioblastoma multiforme, oligodendroglioma, brain stem glioma and intracranial yolk sac tumor (median duration, 10 months; range, 2-20+ months). Three of 4 CR's were achieved with a dosage of 18 mg/M2/week. An additional 13 children with brain tumors experienced stable or improved disease (duration, 2-36 + months; median 7.5 months). The principal toxicity was myelosuppression which was cumulative but there were also 3 allergic reactions to AZQ. We conclude that for selected brain tumors, the rates of objective response and stable disease plus the duration of responses support further assessment of AZQ in combination with other agents. Furthermore, the 18 mg/M2 dosage may provide better responses.

Adolescent↗

Effects of pancreatic acinar cell surface antibodies and complement on isolated rat acinar cells in vitro.

Surface directed pancreatic acinar cell antibodies raised by immunization of rabbits with suspensions of viable isolated rat acinar cells were utilized to study immune cytolytic processes as a model of in vitro pancreatic injury. The antibodies produced were bound to rat pancreatic acinar cell surface determinants and significantly damaged freshly separated acinar cells by immune cytolytic mechanisms. Addition of complement accelerated the cytolytic effects on the target cells in a dose-dependent manner. The decline of acinar cells was dependent only on the presence of the immune cytolytic potential and not on the number of already damaged cells. Morphologic changes in the cells induced by the agents applied were revealed by both transmission and scanning electron microscopy. The presented experimental model seems a valuable tool for further investigations at the cellular level into the contribution of primarily occurring acinar cell injury in triggering the subsequent pathophysiological mechanisms initiating autodigestion of the pancreatic gland in the pathogenesis of acute pancreatitis.

Animals↗

Prognostic criteria for experimental protocols in pediatric brainstem gliomas.

Prognostic criteria were developed to select children with high-risk brainstem gliomas for experimental treatment with hyperfractionated radiation. Patients were required to have (a) tumors confined primarily to the brainstem; (b) positive findings in two of three groups of neurologic signs (cranial nerve deficits and long-tract and cerebellar signs), and (c) symptom duration of less than 6 months. The 18-month survival of only 1 of 33 evaluable patients suggests that these criteria did in fact select tumors of poor prognosis. Such noninvasive predictors provide a valuable means of selecting for experimental treatment those children who would not be expected to benefit from standard therapies for malignant brainstem tumors. These criteria do not require routine biopsy for prognostic purposes, and avoid exposing the children to unnecessary risk.

Adolescent↗

[Planned reoperation following perforation of peptic ulcer with a simple suture. A differentiated treatment concept].

Even after perforation of chronic peptic ulcer with simple closure, patients continue to be in danger for additional complications of the ulcer ailment. Postoperative conditions of patients with perforated ulcer were analysed for a period of ten years. Classical indications for re-operation were recorded from 60 per cent. A differentiated concept for treatment of ulcer perforation is presented in this paper.

Adult↗

Oligodendroglioma. An analysis of the value of radiation therapy.

The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

Adolescent↗

[Late clinical and phlebographic findings in Paget-von Schroetter syndrome].

Of altogether 33 patients (20 males and 13 females) with clinical and phlebographically ascertained Paget-von-Schroetter syndrome the informations of the medical records from 1975 to 1985 were retrospectively analysed. From one to nine years 23 patients could clinically be followed up according to different forms of therapy and 17 of them underwent a phlebographic follow-up examination. The self-estimation of the load capacity of the diseased arm was approximately 50-100%. In 30% of the patients we observed subcutaneous dilations of the veins of the shoulder-arm region. Only in three of 17 cases an unhandicapped patency of the veins could be proved phlebographically one, three to four years after treatment. In ca. 80% of the cases the control phlebograms distinctly showed postthrombotic obstruction stenoses and changes of the wall, respectively. By the formation of a widely branched collateral circulation a compensation of the venous outflow is obtained. This functional "healing" reflects also in the good and very good results, respectively, of the clinical after-examination.

Axillary Vein↗

Magnetic resonance imaging in multiple sclerosis: decreased signal in thalamus and putamen.

High-field strength (1.5 Tesla) magnetic resonance imaging in 15 patients with multiple and extensive white-matter lesions and clinically definite multiple sclerosis delineated a previously undescribed finding of abnormally decreased signal intensity on T2-weighted images in the thalamus and putamen. The decreased signal intensity (preferential decreased T2 relaxation time) is most likely to be related to abnormally increased iron accumulation causing local magnetic field heterogeneities.

Humans↗

The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours.

The monoclonal antibody Ki-67 has been tested as a marker of proliferating cells in 52 stereotactic brain tumour biopsies. The antibody reacts with a nuclear protein expressed in G1,S, G2n and M-phases of the cell cycle. Using the immunoperoxidase technique on squash preparations the percentage of Ki-67 positive cells was determined as a fraction of the total number of tumour cells present. This Ki-67 index was in close correlation with the histological grade. Highest values were found in a pineal germinoma (46.3%) and in 3 primary cerebral non-Hodgkin lymphomas (mean 39.5%). Among the gliomas, the highest fraction of proliferating cells was seen in 2 anaplastic paediatric brain stem gliomas (mean 17.4%) and in an anaplastic ependymoma (12.5%). Anaplastic astrocytomas and glioblastomas varied considerably with mean values of 9.5% and 8%, respectively. To some extent this variability may reflect tumour heterogeneity which is more likely to manifest in small stereotactic samples than in large tissue specimens obtained during open surgery. Pilocytic astrocytomas, mixed gliomas and fibrillary astrocytomas had moderate to low percentages. Ki-67 staining of squash preparations can easily be performed on a routine basis and is, in our experience, superior to frozen sections. This method allows the determination of the growth fraction of an individual tumour and could become an important additional criterion for the decision among alternative and potentially harmful therapeutic regimens.

Antibodies, Monoclonal↗

Comparison of two fluorosis indices in the primary dentition of Tswana children.

Fluorosis of the primary dentition was determined in 146 children living in a hot, dry African village with a fluoride concentration in the drinking water of 0.98-2.7 ppm. The prevalence of fluorosis was compared using DEAN's (8) and THYLSTRUP & FEJERSKOV's (14) indices. The prevalence varied according to tooth type, being highest in maxillary second molars (25%) and lowest in mandibular central incisors (4.6%). The two scoring systems produced almost identical prevalences of fluorosis but the severity scores varied. Generally THYLSTRUP & FEJERSKOV's index scores were one score higher than DEAN's. The THYLSTRUP & FEJERSKOV index is recommended for future studies.

Botswana↗

Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: increased iron content?

High-field-strength (1.5-T) MR imaging was used to evaluate 47 patients with definite multiple sclerosis and 42 neurologically normal control patients. Abnormal, multiple foci of increased signal intensity on T2-weighted images, most prominent in the periventricular white matter, were apparent in 43 of 47 MS patients and in two of 42 control patients. A previously undescribed finding of relatively decreased signal intensity most evident in the putamen and thalamus on T2-weighted images was seen in 25 of 42 MS patients and correlated with the degree of white-matter abnormality. In the normal control patients a prominently decreased signal intensity was noted in the globus pallidus, as compared with the putamen or thalamus, correlating closely with the distribution of ferric iron as determined in normal Perls'-stained autopsy brains. The decreased signal intensity (decreased T2) is due to ferritin, which causes local magnetic field inhomogeneities and is proportional to the square of the field strength. The decreased T2 in the thalamus and striatum in MS may be related to abnormally increased iron accumulation in these locales with the underlying mechanism remaining speculative.

Adult↗

Influence of antisera to pancreatic acinar cells on rat pancreas in situ.

For investigations of cell injury during pathogenesis of acute pancreatitis antisera to pancreatic acinar cells were used as experimental tool. Within one hour after intraductal injection of antiserum a strong pancreatic edema was developed. Within 24 h this edema receded to a large extent but at this time there were inflammatory cells scattered in the intra- and periductal region. As a sequel of application of antiserum pancreatic enzymes were released. At 24 h after this application serum activities of alpha-amylase and lipase were significantly increased in comparison to the control and reached that level which was found in a model of acute pancreatitis provoked by pancreatic edema plus short-term ischemia.

Acute Disease↗

[Paget-von Schroetter syndrome. Therapeutic possibilities, early and late results].

33 patients were treated for Paget-von Schroetter syndrome at the Surgical Department of the Medical Academy of Magdeburg, between 1975 and 1985. The therapeutic concepts were based on streptokinase, thrombectomy, heparin treatment or combinations of these. Phlebography and clinical follow-up checks were used to compare early results with late results (between one and nine years from therapy). The functional results were generally good, but they did not correlate in all cases with findings of patency of the lower veins in the upper extremity. Streptokinase, as compared to thrombosis of the lower extremity, should be therapeutically used with some caution.

Adult↗