Biomedical subjects
Publications and source records attributed to W Brenner.
We present a case of a 25 year old patient who underwent double-sided lung transplantation and suffered from recurrent pneumonia. Silent aspiration was suspected clinically. Aspiration was proved by scintigraphy enabling to discriminate between direct oro-pulmonal aspiration and aspiration after gastro-esophageal reflux.
Monoclonal antibodies (mabs) have considerable potential for specific cancer treatment. However, due to the antigen heterogeneity and especially the low uptake in solid tumors, mabs have not been used successfully in most clinical trials to date. This study investigates the effects of a mab-cobra venom factor (CVF) conjugate in vitro and in vivo in an orthotopic pancreatic cancer model using nude rats. CVF, a nontoxic glycoprotein from cobra venom, permanently activates the alternative pathway of complement. Coupled to a mab with tumor-binding properties, the complement activation can be targeted to the tumor tissue. We studied the activity of a mab CA19-9-CVF conjugate with the human pancreatic cancer cells PancTu I. PancTu I cells express the complement resistance factors CD46, CD55, and CD59, as we demonstrated by immunostaining, an observation that may explain the lack of cytotoxicity of the CA19-9-CVF conjugate. However, using ELISA, Western blot, and immunostaining, we showed that CA19-9-CVF activates the complement cascade, including the release of the anaphylatoxin C3a, a mediator of an inflammatory reaction. The in vivo studies of CA19-9-CVF-treated nude rats showed an increased tumor infiltration by natural killer cells and macrophages. The tumor uptake of 99Tc-labeled anti-carcinoembryonic antigen antibody was increased approximately 2-fold in rats pretreated with 70 micrograms of CA19-9-CVF, compared to animals that received an equimolar mixture of noncoupled mab and CVF. This study indicates the value of mab-CVF conjugates in adjuvant immunotherapy. mab-CVF conjugates might be useful in pretargeting approaches by increasing the uptake of a therapeutic mab.
Adhesion of tumor cells to endothelial cells is a crucial step in the complex sequence of metastasis. In addition to type and local density of adhesion molecules on both cell types, shear forces exerted by the blood flow have been described to be of major importance in governing cell adhesion. Most of the experiments on the molecular basis of tumor-endothelial cell adhesion have been performed as static assays which lack shear forces. We have developed an artificial venule which shares the following in vivo characteristics. A confluent layer of endothelial cells lines the luminal surface of a glass capillary of 1 mm i.d. with pores of 30 nm diameter to allow diffusion of molecules from outside the capillary. Physiological pressure of 16 mbar, flow rate of 2 cm/s, and shear forces of 2 dynes/cm2 are maintained. This device allowed us to show that under dynamic conditions adhesion of B16 mouse melanoma cells to EA.hy926 endothelial cells is mediated most likely by a lectin-like structure on B16 cells and oligosaccharide(s) on endothelial cells. In addition, endothelial activation-independent adhesion was found to be restricted to only a fraction of endothelial cells, as the number of B16 cells that adhered was independent of the number of B16 cells applied.
The aim of this study was to examine patients with long-standing Graves' ophthalmopathy using 111In-octreotide scintigraphy. Sixteen patients with inactive ophthalmopathy of up to 114 months duration and 14 normals were investigated for 48 h following an injection of 200 MBq 111In-octreotide. No significant tracer accumulation in the orbital region could be identified in any of the patients with long-standing Graves' ophthalmopathy. The orbit to brain (O/B) ratios after 24 and 48 h were 2.39 +/- 0.36 and 2.15 +/- 0.44 versus 2.17 +/- 0.33 and 2.20 +/- 0.37 for the patients and normals, respectively (N.S.). 111In-octreotide accumulation in ophthalmopathy described in the literature may thus be a passing event limited to its active stage, which is consistent with the concept of imaging a lymphocytic infiltration. In this study, the lack of accumulation of 111In-octreotide in the orbital region during the inactive stage demonstrates an absence of somatostatin receptors in orbital tissue itself. Thus, in patients with inactive Graves' ophthalmopathy, there is no basis for a diagnostic approach with somatostatin.
The aim of this study was to test the impact of quantitative salivary gland scintigraphy in patients with suspected Sjögren's syndrome. Thirteen patients with suspected Sjögren's syndrome were investigated. During clinical work-up, three had severe and four had mild Sjögren's syndrome, while six were normal. Quantitative salivary gland scintigraphy was performed using a standardized method. The normal data-base consisted of 172 patients without any evidence of salivary gland malfunction. Visual and quantitative comparisons of the patients' scintigrams were made. In the patients with severe Sjögren's syndrome, uptake was 0.10 +/- 0.04% and 0.09 +/- 0.03% in the parotid and submandibular glands respectively, confirming the visual diagnosis. In the patients without Sjögren's syndrome, concordance between the visual and quantitative evaluations could also be shown. In contrast, among the patients with mild Sjögren's syndrome, uptake was diminished (P < 0.05), amounting to 0.21 +/- 0.05% and 0.16 +/- 0.02% in the parotid and submandibular glands respectively, while visual analysis indicated normal parenchymatous function. In conclusion, quantitative salivary gland scintigraphy is essential for the reliable detection of parenchymatous malfunction at an early stage of Sjögren's syndrome, which may be missed by visual analysis alone.
A simple and inexpensive solution for the complete digital management of a nuclear medical institution is presented. The starting point was provided by five different gamma cameras, one of which was equipped with a PC-based ICON computer. The remaining cameras were first adapted to ICONs and subsequently integrated into a Macintosh LAN, of 15 computers, allowing the entire image acquisition, processing, interpretation, documentation and archiving to be performed on the same comfortable menu-guided surface. Complete patient management is accomplished by a specific commercially available data base to which a specially developed image and document archive was connected. The system described provides complete digital management without the conventional filing systems at the moderate price of approximately DM 11 x 10(4) plus the cost of the new camera computers.
Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.
A patient with the typical features of Dowling-Degos disease (reticulate pigmented anomaly of the flexures) is described; the clinical picture and differential diagnosis are discussed. Systemic retinoids were used for treatment, but no essential improvement could be observed.
A case of severe preeclampsia in which hemolysis and rapid platelet consumption persisted after delivery, but in which the blood urea nitrogen and serum glutamic oxaloacetic acid transaminase levels returned to normal is presented. Antiplatelet aggregating medications and exchange plasmapheresis with fresh frozen plasma were begun on the eighth postpartum day, but the hemolysis and rapid platelet consumption did not begin to improve until the 12th postpartum day. The use of plasmapheresis in highly selected cases of severe preeclampsia with hemolysis and thrombocytopenia that do not resolve after delivery is discussed.
A case of gravida presenting with upper abdominal pain, an elevated serum glutamic oxaloacetic transaminase level, and thrombocytopenia, all of which resolved promptly after delivery, and with none of the standard signs and symptoms needed for the diagnosis of preeclampsia is presented. The issues of how this case relates to preeclampsia, nomenclature, differential diagnosis, and management are discussed.
In 1975 we started a prospective study on oral methoxsalen photochemotherapy (PUVA) in cutaneous T cell lymphoma (CTCL). The first short-term follow-up of nineteen patients (1978) showed that PUVA may induce long-lasting remission in early stages, and that eventual relapses respond comparably well when PUVA is resumed. We now present the follow-up data of the original nineteen patients, covering a period of up to 7 years, and of an additional twenty-five patients who have entered the trial since April, 1977. Similar to earlier reports, all patients with eczematoid and plaque lesions (stages IA and IB) cleared. Likewise, eczematoid and plaque lesions in patients with early tumors (stage IIB) were cleared. During a mean follow-up of 44 months, 55% of stage IA patients and 39% of stage IB patients remained free of disease. In patients who experienced relapses, the mean disease-free interval was 20 months for stage IA and 17 months for stage IB. All patients with stage IIB experienced multiple relapses and only three of seven were alive after 6 years, despite additional x-ray or cytotoxic therapy. The observation in this study that five of nine stage IA patients and ten of twenty-six stage IB patients have remained in continuous remission after a single PUVA course for up to 79 months indicates that PUVA may induce long-lasting disease-free intervals if used in the early stage of disease. However, the observation period still does not prove whether permanent cure can be achieved in some cases or not.
67 patients, 41 with chronic plaque-psoriasis and 26 with acute eruptive or seborrhoic psoriasis, were treated in a stand-up unit equipped with UV-B fluorescent bulbs. 92 per cent of the latter group of patients showed satisfactory results (13 exposures, total UV-B dose: 464 mJ/cm2), whereas only 46 per cent of the patients with plaque psoriasis responded comparably (19 exposures, total UV-B dose: 994 mJ/cm2). A split comparison study of PUVA and UV-B on plaque-psoriasis revealed the superiority of PUVA in both initial treatment phase and duration of the remission. For certain types of psoriasis, UV-B phototherapy represents an alternative option. With regard to long-term hazards, however, as carcinogenicity in particular, UV-B has to be judged with the same scrutiny as PUVA.
Portal-systemic shunting in rats results in altered plasma concentrations of the large neutral amino acids (NAA), and increased blood-brain barrier NAA transport. Bacterial ammonia production in the bowel, especially the colon, is thought to play a major role in the etiology of portal-systemic encephalopathy (PSE). In order to isolate the role of bacteria in PSE, plasma and brain amino acids and ammonia (NH3) were studied in germ-free (GF) rats with portacaval shunts (PCS). Germ-free rats underwent end-to-side portacaval shunt or sham operation under germ-free conditions and were kept in a germ-free isolator under careful bacteriologic control. Similar operations were carried out on conventional animals. Two weeks post-operatively blood-brain transport of the neutral amino acid tryptophan was studied and the animals sacrificed. Plasma NH3 rose after PCS both in GF and in conventional rats. In germ-free and conventional rats with PCS, there was a significant elevation in plasma of the aromatic amino acids and decreased concentrations of the branched-chain amino acids. In the brain, both groups had elevated aromatic amino acids, while the branched-chain amino acids remained normal. The blood-brain transport of tryptophan was elevated in portacaval shunted rats, whether germ-free or conventional. These studies suggest the elevated plasma levels of ammonia and disturbances in plasma and brain amino acids seen after portacaval shunt are not dependent on the presence of gut bacteria.
A case report is given demonstrating changes of the intestinal tract in a patient with Morbus Cowden. The clinical picture of the disease is described including differential diagnosis. The high risk of accompanying malignant lesions and the need of early detection of the disease are pointed out.
In a quantitative study we have compared the serum levels, the time course and the photosensitizing capacity of a conventional crystalline 8-methoxypsoralen brand and an investigational liquid formula. Evidence is presented showing that the liquid preparation is superior to the crystalline form: it peaks earlier after ingestion, it produces higher and more constant degree of photosensitization, it is eliminated more rapidly from the blood, and it requires a lower UV-A dose for eliciting photosensitivity reactions aiming at a reduction of the total cumulative UV-A dose required for clearing psoriasis.
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This report deals with a female patient with multiple hamartoma syndrome (Cowden's disease) exhibiting characteristic cutaneous lesions and involvement of several inner organs.
An unusual case is presented of repeated, life-threatening self mutilation, elicited by the topical application of sodium hydroxide, which necessitated several operations, including amputation of the left lower leg. Histological examination revealed colliquation necrosis and a striking eosinophilia. The latter feature, which was not reproducible in an animal experiment, may be related to a defect of leucocyte locomotion in the present case.