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Biomedical subjects

P Tanner

Publications and source records attributed to P Tanner.

At least 19 recordsLinked to original sources

O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma.

PURPOSE: Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery. METHODS: Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated. RESULTS: At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression. CONCLUSION: FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Antineoplastic Agents↗

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Craniocerebral Trauma↗

Acute radiation toxicity assessment of a 3-D conformal head and neck radiation treatment technique.

Patients undergoing radiation treatment for head and neck cancer have many critical structures within or adjacent to the treatment area. Avoiding these critical structures is more efficient and easier using 3-D conformal planning. At Sir Charles Gairdner Hospital an investigation into the acute radiation toxicity was undertaken when the head and neck treatment technique was changed from the conventional 2-D plan to the conformal 3-D plan. Although the primary target volume (PTV), fraction size and overall dose remain the same for the two techniques, differing beam configurations mean that treatment fields enter and exit through different parts of the head and neck. Ten patients were initially assessed to gain a baseline appearance of their head and neck region, and then graded weekly according to the toxicity criteria during treatment and at 4, 8 and 12 weeks after treatment. The results of the assessment indicate that there is no increase in toxicity as a result of treating using the conformal head and neck technique.

Acute Disease↗

Ciguatera fish poisoning. A southern California epidemic.

Ciguatera fish poisoning results from the bioconcentration of a variety of toxins produced by marine dinoflagellates. Signs and symptoms vary widely, but it usually presents as gastrointestinal and neurologic complaints beginning shortly after the ingestion of fish containing the toxins. Symptoms may persist for months and sometimes even years. Although cases have been reported throughout the United States, epidemics are most common along tropical and subtropical coasts and usually involve the ingestion of large carnivorous fish. We review the literature and report the first epidemic of 25 cases of ciguatera fish poisoning presenting to area hospitals in Southern California that were successfully tracked by the Department of Health Services and isolated to fish caught off the coast of Baja California, Mexico.

Adolescent↗

Cytomegalovirus gastritis with perforation and gastrocolic fistula formation.

A 76-year-old man with lymphoma involving cervical and mediastinal lymph nodes and abdomen was treated by radiotherapy and chemotherapy. He subsequently developed cytomegalovirus gastritis and gastric ulcers with a gastrocolic fistula and a jejuno-jejunal fistula, necessitating a partial gastrectomy. The pathogenesis of cytomegalovirus gastritis and its complications are discussed.

Aged↗

Endogenous interference in immunoassays in clinical chemistry. A review.

The increasing availability and use of immunoassays in clinical chemistry have revealed a number of endogenous interferences. Solid-phase sandwich immunoassays based on monoclonal antibodies are particularly sensitive to any factor able to bridge immunoglobulins together. Heterophilic immunoglobulin antibodies have been demonstrated in up to 40% of patient samples and to cause spuriously elevated results unless certain precautions are taken. Rheumatoid factors belong to the same category, but their affinity is usually too low to cause significant interference. Immunoscintigraphy generates high-titre anti-immunoglobulin responses causing serious interferences in immunoassays. Recently interfering factors of unknown nature causing nonspecific binding of enzyme-labelled antibodies have been observed. Spuriously decreased values can be caused by complement, which may interfere with antigen-binding to solid phase antibody. The aforementioned and other endogenous interferences in immunoassays are reviewed and methods for their elimination discussed.

Antibodies↗

A monoclonal antibody-based immunoradiometric assay for low molecular weight insulin-like growth factor binding protein/placental protein 12.

We describe a sensitive immunoradiometric assay for insulin-like growth factor binding protein/Placental Protein12 (IGF-BP/PP12) using monoclonal antibodies. This assay has a detection limit of 0.25 micrograms/l IGF-BP/PP12. Parallel dose response curves were obtained with purified IGF-BP/PP12, amniotic fluid, decidual cytosol extract, and serum. The assay is reproducible (intra-assay variation 4.3-8.2% and interassay variation 9.7-11.1%) and fast (less than 5 hours). A crossreactivity of less than 0.01% for all other proteins tested reflects high specificity. Using this method the mean serum IGF-BP/PP12 concentration in healthy women was 5.2 micrograms/l. During pregnancy, the mean IGF-BP/PP12 at 7-11 weeks was 43.3 micrograms/l, and at 36-40 weeks 121 micrograms/l. After early pregnancy termination the serum IGF-BP/PP12 decreased rapidly reaching a mean level of 8 micrograms/l within 4 days.

Amniotic Fluid↗

Rapid determination of C-reactive protein by enzyme immunoassay using two monoclonal antibodies.

Several monoclonal antibodies for human C-reactive protein (CRP) were characterized, and two antibodies binding to separate domains were used to construct a rapid and simple immunoenzymometric assay for CRP. The assay consists of a single 15 min immunological reaction during which CRP forms a complex with a peroxidase-labelled antibody and with another antibody attached to the test-tube wall. The immobilized complex is detected by a 3 min colour reaction using peroxidase substrate. The quantitative measuring range of the assay is 0.04-5 mg/l, and no hook occurs at five-fold higher values. The sensitivity of the method allows reliable determination of low CRP levels, eg. in paediatric samples. The values obtained with the present assay correlated well with turbidimetric results.

Adult↗

Effect of complement binding on a solid-phase immunometric TSH assay.

The binding of serum thyrotropin (TSH) to plastic beads coated with a monoclonal antibody to human TSH was inhibited unless EDTA was present during the incubation. The inhibitory factor in serum was heat labile, and its effect could be abrogated by the addition of human albumin-anti-albumin immune complexes. Subsequently it was shown that the antibody-coated beads were able to bind the first component of complement, C1q, and that this binding was inhibited by addition of albumin-anti-albumin complexes. The results show that a surface coated with a monoclonal murine antibody is able to bind complement, and that binding of complement may interfere in solid-phase immunometric assays.

Antibodies, Monoclonal↗

Immunocatalytic assay of pancreatic alpha-amylase in serum and urine with a specific monoclonal antibody.

In this immunocatalytic assay for alpha-amylase (EC 3.2.1.1) of pancreatic origin, a highly specific monoclonal antibody coupled to plastic beads is used to extract pancreatic amylase from samples, leaving salivary amylase in solution. The catalytic activity of the bound pancreatic amylase is then determined with blocked p-nitrophenyl maltoheptaoside as substrate. The method shows no cross-reactivity with salivary amylase, analytical recovery is 89-109% for pancreatic amylase, and interassay imprecision is 7.1-7.7%. We used the method to determine pancreatic amylase in serum and urine from healthy controls and different patient groups. The reference intervals for 34 supposedly healthy controls were: serum, 10-48 U/L (mean 27 U/L); urine, less than 20-435 U/L (mean 104 U/L). Results by the present assay correlated well with a salivary amylase inhibition assay (Boehringer Mannheim). We conclude that the described immunocatalytic assay is clinically useful for detecting increased activities of pancreatic amylase in serum and urine.

Acute Disease↗

Monoclonal antibodies to the 27-34K insulin-like growth factor binding protein.

Monoclonal antibodies were prepared against the 27-34K insulin-like growth factor (IGF)-binding protein purified from human placenta/decidua and designated placental protein 12 (PP12). Four different antibodies were characterized. Each recognized the major band at 32K on immunoblots of the purified PP12 preparation and amniotic fluid. In liquid phase RIA, IGF-I did not affect the binding of [125I] PP12 to one antibody (Mab 6303), it slightly increased the binding to two antibodies (Mab 6301 and 6304), and it slightly decreased the binding to one antibody (Mab 6302). All antibodies immunoprecipitated the cross-linked PP12-[125I] IGF-I complex, but Mab 6302 considerably less effectively than the others. Preincubation of PP12 with Mab 6302 completely inhibited the binding of [125I] IGF-I to PP12, whereas preincubation with Mab 6303 had no effect, and Mab 6301 as well as Mab 6304 increased it. These results suggest that Mab 6302 binds to an epitope at or near to the IGF-binding site, whereas the other antibodies react at other sites of the PP12 molecule. Conformational changes in PP12 probably account for the IGF-I-induced increase in the binding of Mabs 6301 and 6304 to [125I] PP12, and vice versa, for Mabs 6301- and 6304-induced increase in the binding of [125I] IGF-I to PP12.

Antibodies, Monoclonal↗

Pleural fluid ferritin concentrations in human disease.

The concentration of ferritin was measured in the pleural fluid of 108 patients with pleural effusions. In all groups of patients the ferritin concentration was higher in pleural fluid than in serum. The greatest differences, with up to 100 times more ferritin in the pleural fluid, were found for patients with rheumatoid pleurisy, malignant effusions, and empyema. In patients with non-malignant inflammatory pleural effusions the concentration of ferritin in pleural fluid correlated significantly with other pleural fluid indices of inflammation: there was a positive correlation with lactate dehydrogenase activity and a negative correlation with concentrations of glucose and complement components C3 and C4. Ferritin was detected immunocytochemically only in the macrophages found among the pleural fluid cells. Our study shows that large amounts of ferritin accumulate locally in the pleural cavity in certain types of pleural inflammation. The accumulation is probably partly the result of increased local reticuloendothelial system activity. Determination of the concentration of ferritin in pleural fluid may provide corroborative information for differential diagnosis and may further our understanding of the pathogenetic events that lead to the perpetuation of inflammatory activity in pleural effusions.

Adolescent↗

Toxicological assessment of lidocaine in the pregnant rat.

Teratogenic and toxicological effects of lidocaine administered during pregnancy were evaluated in the Sprague Dawley rat. High doses of lidocaine administered during specific periods of gestation were shown to produce no apparent adverse toxicological or teratogenic effects. Histological, enzymological, and physical features of the fetuses, utilizing conventional toxicological parameters, were all found to be normal following maternal administration of lidocaine. Analysis of these data suggests that the administration of lidocaine during pregnancy had no detectable adverse effects on the fetus.

Animals↗

Time-resolved fluoroimmunoassay of human choriogonadotropin.

We describe time-resolved fluoroimmunoassay for human choriogonadotropin involving monoclonal antibodies directed against the beta- and alpha-subunits. The latter antibody was labeled with europium, which was measured by counting for 1 s after the immunoreaction was completed. In the solid-phase sandwich assay, both a one-step and two-step procedure were used; the respective measuring ranges were 0.7-135 and 0.7-350 int. units/L, the latter covering a 500-fold dynamic range. The CV within the assay range was between 4 and 8%, depending on the dose. Cross reactivity with lutropin in the one- and two-step procedures was 1.6% and 1.0%, respectively.

Antibodies, Monoclonal↗

The use of monoclonal antibodies against human chorionic gonadotropin for immunoperoxidase staining of normal placenta, pituitary gland, and pituitary adenomas.

A monoclonal mouse antibody to human chorionic gonadotropin (hCG) was used in a modified unlabeled antibody enzyme-bridge staining method to demonstrate the localization of hCG in normal human placenta, pituitary gland, and six pituitary chromophobe adenomas. Mouse ascitic fluid containing monoclonal antibody could be diluted up to 1:500,000 for detection of hCG in the syncytiotrophoblast, whereas no staining was observed in the pituitary or adenomas even with high antibody concentrations (dilutions from 1:500 upward). Nonspecific background staining was negligible. These results demonstrate that monoclonal antibodies are suitable for immunohistochemical localization of antigens in tissues.

Adenoma↗