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Biomedical subjects

J Lichtenberg

Publications and source records attributed to J Lichtenberg.

At least 19 recordsLinked to original sources

Spontaneous fusion between cancer cells and endothelial cells.

Endothelial cells line the inside of blood and lymphatic vessels, and cancer cells must cross this barrier, first to gain access to the circulation, and, second, to exit and metastasize. How this occurs is incompletely understood. We now demonstrate that human cancer cells are able to fuse with endothelial cells to form hybrid cells displaying proteins and chromosomal markers characteristic of both parent cells. The hybrid cells are viable and capable of undergoing mitosis. Fusions between cancer cells and endothelial cells were shown to occur both in vitro, in co-cultures of human breast cancer cells and endothelial cells, and in vivo, following intravascular dissemination of human breast cancer cells in nude mice. These observations demonstrate a new type of cancer-endothelial cell interaction that may be of fundamental importance to the process of metastasis.

Animals↗

Sample preconcentration by field amplification stacking for microchip-based capillary electrophoresis.

A microchip structure for field amplification stacking (FAS) was developed, which allowed the formation of comparatively long, volumetrically defined sample plugs with a minimal electrophoretic bias. Up to 20-fold signal gains were achieved by injection and separation of 400 microm long plugs in a 7.5 cm long channel. We studied fluidic effects arising when solutions with mismatched ionic strengths are electrokinetically handled on microchips. In particular, the generation of pressure-driven Poiseuille flow effects in the capillary system due to different electroosmotic flow velocities in adjacent solution zones could clearly be observed by video imaging. The formation of a sample plug, stacking of the analyte and subsequent release into the separation column showed that careful control of electric fields in the side channels of the injection element is essential. To further improve the signal gain, a new chip layout was developed for full-column stacking with subsequent sample matrix removal by polarity switching. The design features a coupled-column structure with separate stacking and capillary electrophoresis (CE) channels, showing signal enhancements of up to 65-fold for a 69 mm long stacking channel.

Adsorption↗

Multi-layer microfluidic glass chips for microanalytical applications.

A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed. When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described.

Journal Article↗

The rat Subcutaneous Air Sac model: a quantitative assay of antiangiogenesis in induced vessels.

A new in vivo experimental model--the Subcutaneous Air Sac (SAS) model-has recently been presented to replace a previous in vivo rabbit cornea assay where neovascularisation was induced by chemical injury of the cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model, an air sac is induced by injection of air subcutaneously on the back of the animal. After 10-14 days the air sac appears as an almost transparent avascular membrane in which induction of new vessels can be studied. We present recent developments of this technique: In the SAS-tumour technique, vascular endothelial growth factor-producing tumour cells are inoculated subcutaneously directly on the membrane, and the formation of new vessels is measured 8 days later. In the SAS-pellet technique, slow-release pellets containing angiogenic factors, basic fibroblast growth factor or vascular endothelial growth factor are implanted on the subcutaneous membrane by a simple operation. The formation of new vessels is measured 10 days later. The ability of the SAS-tumour- and SAS-pellet techniques to detect an antiangiogenic effect of a systemically administered compound was investigated using the fumagillin analogue TNP-470 (o-chloroacetyl-carbamoyl)-fumagillol) as a positive control given subcutaneously for 7 and 9 days, respectively. At a dose of 10 mg TNP-470/kg/day the angiogenesis was reduced by approximately 70% in the SAS-tumour technique and by 40-60% in the SAS-pellet technique. The animals were unaffected by the SAS methodology. The SAS-tumour and SAS-pellet models are considered complementary and make use of simple and almost similar techniques which facilitate the evaluation.

Air Sacs↗

The rat subcutaneous air sac model: a new and simple method for in vivo screening of antiangiogenesis.

An experimental rat model, the Subcutaneous Air Sac (SAS) model, was developed to provide an animal model in which neo-vascularization can be easily assessed in situ and quantified using a radiolabelled plasma marker. The SAS model was designed to replace a previous model where neovascularization was induced by chemical injury of rat or rabbit cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model the air sac replaces the cornea as a transparent avascular substratum in which vascularization can be observed. The air sac is induced by injection of air subcutaneously on the back of the animal. After 8 to 10 days a sufficient air sac has been established. The animal is anaesthesized and by a minor operation the cellulose sponge is implanted upon the air sac under the skin. The vasoproliferative effect of the cellulose sponge causes formation of new vessels which are macroscopically visible 10 days after implantation. The ability of the in vivo SAS model to show an antiangiogenic effect of a systemically applied test compound was investigated using the fumagillin analogue TNP-470 (ochloro-acetylcarbamoyl)-fumagillol) as a positive control at dose levels of 0, 1, 2.5, 5 and 10 mg/kg/day given subcutaneously for 10 days. The neo-angiogenesis was scored both in situ using a subjective point system and by measuring the 125I-activity of the implant and the membrane after an intravenous injection of 125I-labelled antibodies. The neo-angiogenesis was reduced by approximately 45-50% in animals treated with 5 or 10 mg/kg/day of TNP-470 compared to animals treated with the vehicle. The animals treated with 10 mg/kg/day TNP-470 showed signs of toxicity. The SAS model is considered highly relevant for in vivo testing of potential antiangiogenic drugs on humane grounds. The high reproducibility, the low cost and the technical simplicity of the method makes it attractive.

Air↗

Toxicity of 1,25-dihydroxyvitamin D3, tacalcitol, and calcipotriol after topical treatment in rats.

To investigate and compare the effects on calcium metabolism of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the synthetic vitamin D analogs tacalcitol and calcipotriol after topical treatment, we treated groups of rats topically once daily with three dose levels of each test compound in a vehicle of propylene glycol plus ethanol for 28 d. The urinary calcium excretion was measured after 14 d, and serum calcium and parathyroid hormone were measured at termination. The rats were autopsied, and the kidneys were examined microscopically for mineralizations. Based on the urinary calcium excretion and the serum calcium level, calcipotriol was found to be 60 times less calcemic, and tacalcitol was slightly less calcemic, than 1,25(OH)2D3 after repeated topical application to rats. Serum parathyroid hormone was suppressed to a lower degree by calcipotriol and tacalcitol than by 1,25(OH)2D3, and the incidence and severity of renal corticomedullary mineralization were higher in rats treated with 1,25(OH)2D3 and tacalcitol than with calcipotriol. We conclude that calcipotriol is much less calcemic than 1,25(OH)2D3 or tacalcitol when applied topically to rats in a vehicle that enhances penetration into the skin. We attribute the lower calcemic effect of calcipotriol to the pharmacokinetic profile of the compound, particularly its rapid metabolization into inactive compounds.

Administration, Topical↗

[Aneurysms of the left atrium and left atrial appendage].

BACKGROUND: The authors deal with the problem of rare congenital and acquired aneurysm of the left atrium and auricular appendage. The authors attempted to compare findings on operation with results of preoperative examinations and evaluate the yield of echocardiographic and angiocardiographic examinations. METHODS AND RESULTS: The authors had the opportunity to encounter this unusual finding of cardiac aneurysms in five patients operated in 1987-1990 on account of an advanced mitral defect associated in two patients with ischaemic heart disease. In all patients acquired aneurysms were involved. In two a large thrombus was found. CONCLUSIONS: In the diagnosis of aneurysms of the left atrium and auricular appendage transoesophageal echocardiography proved to be the most reliable method.

Aged↗

[Survival in patients after surgical closure of post-infarction rupture of the ventricular septum].

The authors discuss in the introduction hitherto reported data on the incidence and course of post-infarction ruptures of the interventricular septum and the results of conservative treatment. The high mortality rate after the conservative procedure led to attempts to resolve post-infarction ruptures of the interventricular septum surgically. The authors discuss in detail the indications for early and delayed operations has a decisive influence on the patients' survival. The authors had the opportunity to operate since 1978 till February 1986 five patients with post-infarction perforation of the interventricular septum. Four of the patients were women, one was a man. The mean age of the operated patients was 61 years, the oldest patient was a 75-year-old man and the youngest a 46-year-old woman. During the last check-up in 1994 it was revealed that of five operated patients three had died. One of them three years after operation and two after seven years. One female patient survives for 13 years and one for 11 years. Both are in a satisfactory conditions.

Aged↗

[Advantages of lung surgery via medial sternotomy and use of extracorporeal circulation in very advanced lung tumors].

The authors present their initial experience with surgery of pulmonary affections in 32 patients where they used medial sternotomy as the route of approach. They provide evidence of the advantages of this approach, in particular in high-risk patients, and of the favourable effect of this approach on the postoperative course. Successful radical surgery under conditions of extracorporeal circulation, although a very advanced tumour was involved where posterolateral thoracotomy was unequivocally contraindicated, indicates that there is a possibility to extend indications of surgical therapy of otherwise inoperable pulmonary tumours.

Extracorporeal Circulation↗

[A new method of retrograde hypothermic cardioplegia].

Application of the cardioplegic solution dramatically improved the results of the operations in ECC. Authors discussed the methods of application of the cardioplegic solution, mainly in the connection with its applications to the sinus coronarius. This is then discussed from another point of view of its use. In the field of the cardioplegy there is referred about new authors' method, and so on the possibility of its use, and the most propriete indications. Described method is available and its parameters, verified clinically and experimentally, are advantageous in the stated situations.

Heart Arrest, Induced↗

[Retrograde myocardial revascularization using a bypass into the cardiac vein].

The authors submit a review of the surgical treatment of ischaemic heart disease, and based on data from the literature and their own experience, they evaluate the asset of so-called indirect revascularization operations under conditions when an aortocoronary bypass is impossible or has only a short-term effect due to the diffuse sclerotic affection of the coronary circulation. Special attention is paid to attempts of retrograde revascularization of the heart muscle by bypasses into the coronary veins. Because at present the possibility of indirect revascularization of the myocardium by a retrograde approach via the cardiac veins still remains a by far not yet resolved problem, the authors recommend for situations where the aortocoronary bypass is out of question a procedure making use of the advantages of a direct aortocoronary bypass and Vineberg's operation performed so as to relieve the blood flow through the sclerotic coronary artery beneath the anastomosis. In special situations also a sequential bypass could be considered with a side-to-side anastomosis into the artery and end-to-side into the appropriate vein.

Coronary Artery Disease↗

[One-stage surgery in concomitant heart and lung disease].

The authors evaluate the advantages and disadvantages of one-stage operations in concomitant cardiac and pulmonary diseases and define the optimal indications for this procedure. The justification of one-stage operations in selected patients is confirmed by the authors' own experience assembled in two patients. One suffered from lung cancer and ischaemic heart disease and the other one from a tuberculoma and ischaemic heart disease. The one-stage operation in both patients was without complications.

Coronary Artery Bypass↗

[An unusual finding of annular sclerosis of the mitral valve during heart surgery].

The authors present an uncommon finding of annular sclerosis of the mitral valve in four patients. On operation in three instances severe and in one instance a mild degree of annular sclerosis of the mitral valve was revealed. Two men were 55 and 67 years old and two women were 40 and 67 years old. In two instances the operation was indicated by a myxoma in the left atrium and in two instances by advanced insufficiency of the mitral valve.

Adult↗

Model scenes: implications for psychoanalytic treatment.

Model scenes are constructed by analyst and patient to organize puzzling information, integrate previous understanding, and initiate further exploration of experience. They are derived from a variety of sources: literature (oedipal myth); transference; ordinary or traumatic childhood events that occupy a pivotal position. Model scenes may conceptualize experiences of any age and motivational system, and are contrasted with screen memories and "telescoping" of events. Two clinical examples are used to illustrate the relation between the model scene and the transference. Model scenes provide a valuable clinical tool for moving from general to specific experience. They afford empathic entry into the transference experience and the opportunity through which the experience of motivations representative of past and present can be conceptualized and integrated into a cohesive self organization.

Adult↗

[A mobile thrombus simulating a myxoma of the right atrium].

Two-dimensional echocardiography is due to the detailed visualization of the right atrium and adjacent structures an indispensible non-invasive method for the detection pathological masses. In the differential diagnosis of these masses most frequently a mobile thrombus and myxoma are involved. The authors are presenting the case-history of a 71-year-old female patient where during hospitalization on account of a suspect non-Q-wave myocardial infarction in an anteroseptal position echocardiography revealed a pathological mass in the right atrium. From the case-history and results of examinations it was not possible to evaluate unequivocally the nature of the revealed mass. In view of the considerable risk of embolization into the pulmonary artery and coinciding ischaemic heart disease the patient was indicated for surgery and a mobile thrombus was removed. The described case draws attention to the differential diagnosis of right atrial masses and the optimal therapeutic approach.

Aged↗

Uncommon findings on surgery of benign heart tumours.

The authors describe four cases of uncommon surgical findings in patients with the diagnosis of cardiac myxoma. In the first patient an encapsulated tumourous growth in the left atrium was present which was in the mural annulus of the mitral valve and in the adjacent parts of the atrial and ventricular wall and was evaluated from the histological aspect as annular sclerosis. In the second patient a tumour-like thrombus was detected in the right atrium which had the shape of a basket handle and was attached by two stalks to the atrial septum. The third patient had a myxoma of the left atrium covering a concurrent defect of the interatrial septum and the fourth patient had a large myxoma in the left atrium with three calcified small tumours in the area of the mural annulus of the mitral valve.

Adult↗

[Coronary arteritis and its clinical significance].

The authors submit a report on a 47-year-old man with the syndrome of angina pectoris and history of myocardial infarction who died after a revascularization operation of the heart from left ventricular insufficiency. On necropsy extensive arteritis of the coronary vessels with aortitis was revealed and with arteritis of the small intramyocardial and lienal arteries and arteries in the renal pelvis. They describe in detail the histological finding on the blood vessels, and consistent with some data in the literature, they assume that this disease forms a separate unit. It must be considered in particular in middle-aged men who have signs of coronary ischaemia and risk factors suggesting atherosclerosis, not occur in the case-history.

Angina Pectoris↗