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Biomedical subjects

G Klima

Publications and source records attributed to G Klima.

At least 55 records · Page 3Linked to original sources

Regeneration of sympathetic activities in small bowel transplants.

In order to study the activity of noradrenergic nerve fibres along mesenteric arteries in small-intestinal grafts, the entire jejunoileum was transplanted heterotopically in an isogeneic rat model (group I, n = 12). To assess their influence on graft motility, 9 cm of jejunum were transplanted in an orthotopic position and three bipolar electrodes sutured to the seromuscular layer of the graft (group II, n = 10). Fasting motility was recorded up to postoperative day 42. Animals of group I were sacrificed from day 7 on at weekly intervals and mesenteries were analysed histochemically by fluorescence microscopy. After the 1st and 2nd week, grafts were found to be completely depleted of noradrenaline. At the end of the 3rd week, fluorescence became detectable along graft mesenteric arteries and showed normal intensity from the end of week 4. Migrating myoelectric complexes (MMCs) were present in all animals of group II. The variability of the MMC period (mean 12.6 min; SD 6.2 min) expressed as variation coefficient (median 36.5; 14.6-74) did not change during the observation period. From these findings it is concluded that there are no extrinsic noradrenergic activities in rat small-intestinal transplants for the first 3 postoperative weeks but they do recover there after. Their influence on graft function remains unclear: MMC periodicity, however, was no influenced.

Animals↗

[Model of electromyographic study of small intestinal transplants in the rat].

Adequate motility of a small bowel transplant is a prerequisite for its resorptive function as well as its self-purging capacity. The literature contains some reports on changes in motility following denervation or transplantation, but none on the impact of acute rejection on motility of small bowel grafts. Therefore an experimental model was established to meet the following criteria: orthotopic position of graft, adequate nutritional status even when graft is functionally impaired, chronically implantable electrodes attached to graft and corresponding segment of native bowel, isogeneic or allogeneic set-up. 10 cm of proximal jejunum were transplanted from Lewis donors to five Lewis recipients in an orthotopic position just distal of the ligament of Treitz without resection of native small bowel. Three bipolar electrodes were sutured to the graft and the same number to the subsequent recipient bowel. Serial myoelectric measurements were taken until the end of week 3. From day 5 on, migratory myoelectric complexes independent of myoelectric activities of native bowel were recorded. Pacemaker frequency of the graft was found to be the same as that of the transsected native small bowel. This early reappearance of myoelectric activities makes this model suitable for comparative studies of small bowel transplant motility and in particular its changes during rejection, since even in strongly allogeneic combinations Lewis small bowel does not show histological signs of rejection before day 6.

Animals↗

Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat.

Because hepatocyte transplantation into the spleen or the peritoneal cavity, although successful in rats, is more difficult and less successful in larger animals, the lung was chosen for its accessibility and its high oxygen content as a new site for hepatocyte implantation for treatment of acute hepatic failure. Acute hepatic failure was induced by a combination by a portocaval side-to-side shunt and an 80% liver resection, which was associated with a greater than 90% mortality. Hepatocyte transplantation was performed either by injection of 1 x 10(7) cells via the jugular vein (100% mortality) or 5-7 x 10(7) cells transcutaneously into the right lung (92% survival). After injection of the cell-free supernatant into the lung, 53.3% of the animals survived. If more than 90% of the liver was resected, none of the animals survived despite hepatocyte or supernatant injection. From these findings, it is concluded that the lung is a suitable home for hepatocytes. However, the hepatocytes survived only in cases of acute hepatic failure with some remaining vital liver parenchyma.

Acute Disease↗

Autonomic neuropathies in skin and its incidence in non-insulin-dependent diabetes mellitus.

The autonomic function of nerve fibres was investigated with the newly developed hyperthermal Laser-Doppler-Flowmetry in 45 patients suffering from Non-Insulin-Dependent Diabetes Mellitus (NIDDM). They were divided into 3 groups depending on the duration of NIDDM. Group A contained a duration of 1-3 years, group B 4-5 years and group C 5-6 years. All groups showed a dysfunction of autonomic nerve fibres: in group A there were 4 of 11 patients, in group B 2 of 13 and in group C no patients with values within the normal ranges. So autonomic neuropathies of skin seem to be one of the earliest complications in NIDDM

Adult↗

The immunoscintigraphic use of Tc-99m-labelled monoclonal anti-CEA antibodies (BW 431/26) in patients with suspected primary, recurrent and metastatic breast cancer.

The discrepancy between serum CEA levels and CEA tissue expression in patients with breast cancer is well known. Whereas immunohistochemistry shows positive CEA expression in 70-90%, the serum CEA levels are often within the normal range. We performed immunoscintigraphy and SPECT with a Tc-99m labelled anti-CEA monoclonal antibody (MAb BW 431/26) in 46 women with suspected breast cancer or recurrence. The results of anti-CEA immunoscintigraphy, mammography, serum CEA levels and immunohistochemistry were evaluated according to the histology of the tumor. Histology verified breast cancer or recurrence (pT1 [n = 7], pT2 [n = 17], pT3 [n = 3], pT4 [n = 3]) in 30 out of 46 patients; benign breast disease such as fibrocystic disease, fibroadenoma, fatty necrosis or chronic mastitis was responsible for suspicious mammographic findings in 16 patients. Immuno-SPECT showed 25 true-positive, 5 false-negative, 11 true-negative and 5 false-positive findings (sensitivity 83%, specificity 69%). Anti-CEA immuno-SPECT of 2 patients with bone metastasis showed all lesions previously detected by bone scintigraphy to be CEA-expressing metastases. In contrast, serum CEA levels were slightly elevated in only 5 out of 30 patients with histologically verified breast cancer (sensitivity 17%). The results of immuno-histochemistry were surprising; tissue CEA expression could be demonstrated in only 5 patients with breast cancer. According to our experiences with this Tc-99m labelled anti-CEA MAb, immuno-SPECT is a suitable additional method for the diagnosis of breast cancer and especially of recurrence. Pre-operative serum CEA levels give no support for the differentiation between benign and malignant breast tumors.

Antibodies, Monoclonal↗

Histological features of acute pancreatic allograft rejection after pancreaticoduodenal transplantation in the rat.

For characterization of histopathological changes during pancreas graft rejection, pancreaticoduodenal transplants were performed in three groups: (1) Brown Norway into diabetic Lewis rats without immunosuppression, (2) Brown Norway into diabetic Lewis rats with cyclosporin A, and (3) Lewis into Lewis rats. Diffuse inflammatory infiltration of the acini by mononuclear cells indicated the onset of rejection (stage I). Shortly after acinar infiltration, damage to small and large interlobular excretion ducts occurred. This took the form of florid circumferential inflammation and vacuolar degeneration of epithelium similar to the bile duct damage seen in primary biliary cirrhosis, graft-versus-host disease, and liver allograft rejection (stage II). Thereafter, endothelialitis and destruction of islets were evident, consistent with a more advanced and irreversible stage of rejection (stage III). Acinar inflammation and moderate duct lesions were not prevented by immunosuppression but were delayed. Nonetheless, severe vascular changes and loss of islets were avoided. We conclude that duct lesions are a reliable criterion for pancreas allograft rejection. They are more sensitive than vascular changes and more specific than cellular infiltration of acinar tissue, which may also occur in infection.

Acute Disease↗

Morphology of acute rejection and corresponding cytological findings in exocrine secretion after pancreas transplantation in the rat.

Reliable and timely rejection diagnosis still represents a major problem of pancreas allotransplantation. The aim of this study was to confirm the clinical findings of exocrine function impairment and pancreatic juice cytology during rejection, to refine the latter by means of flow cytometry, and to correlate these changes with graft histology. Heterotopic pancreatic transplants were performed in a modified technique in Lewis rats rendered diabetic by means of streptozotocin from LEW donors (group I, n = 10), Brown Norway rats without immunosuppression (group II, n = 16), and from BN rats where recipients were given cyclosporine 12 mg/kg/BW (group III, n = 10). Pancreatic juice was obtained by daily aspiration from a self-made fully implantable catheter reservoir system. In group II animals acute rejection diagnosed on histomorphological grounds was clearly associated with a decrease in the amount of exocrine secretion and its enzyme content from day 8 on. In contrast to groups I and III, a significant increase in lymphocytes in the pancreatic juice up to 13.5% occurred in group II between days 5 and 7. Activated lymphocytes increased from 7% to 13%, pan-T cells from 193 to 340 events. Histology revealed three distinct phases of acute rejection--phase I: diffuse infiltration of acinar structures; phase II: destruction of interlobular ducts; phase III: vasculitis associated with islet cell damage. The anatomy of the pancreas with the slackness of its highly vascularized interstitial connective tissue facilitates early infiltration of inflammatory cells and migration of these cells into the lumen of the pancreatic duct. Thus pancreatic juice cytology together with an impaired exocrine graft function is highly indicative of acute rejection.

Amylases↗

Small bowel transplantation in the rat: impact of various immunosuppressive regimens on graft-versus-host reaction.

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.

Animals↗

[Kinetic effects of 6% hydroxyethyl starch 200.000/0.6-0.66 in hypervolemic hemodilution].

An open study was carried out in order to examine therapeutic effectivity of repeated administration of 6% hydroxyethyl starch 200.000/0.60-0.66 (HES). 10 patients aged 63 to 77 years with peripheral arterial occlusive disease Stage II b were given 500 ml Elohaest as a hypervolemic hemodilution for 12 days. Fasting levels of hydroxyethyl starch (HES) in serum, hematocrit, and serum-alpha-amylase were measured. During the first 4 treatment days, HES levels and serum-alpha-amylase increased in a significant manner; then it fluctuated towards a plateau without significant differences. The hematocrit decreased significantly from the beginning to the end of therapy. So it was possible to show, that during repeated application with the chosen dosage of 6% HAES 200.000/0.6-0.66 there is no dangerous cumulation of HAES.

Aged↗

[Hypervolemic hemodilution with medium molecular-weight hydroxyethyl starch: effect of duration of administration on viscoelasticity of blood in IIa and IIb peripheral arterial occlusive disease].

45 consecutive patients suffering from peripheral arterial occlusive disease (PAOD) stage IIa and b were integrated in a study about the effect of hemorheological parameters due to different application times. The patients were divided into 3 subgroups with different application times: group A received the infusion during 2, group B during 4, and group C during 6 hours. The used substance was 500 ml 6% HES 200,000/0.6-0.66. Except elasticity of group A all hemorheological parameters from group A to group C show a decrease after 6 hours, the trend to the same phenomenon could be observed after 24 hours in group B and C, while group A except plasma viscosity showed even a trend to increasing values compared to onset. As a conclusion of these results, long-time application should be preferred.

Adult↗

A study of lectin bindings to the fetal membranes.

Human tissues contain carbohydrates for a main component, functioning as a source and reservoir of energy, connective and supporting element, recognition site and related tasks. Our main interest is to reveal the synthesis and distribution of carbohydrate elements in human fetal membranes. The aim of our work was to clarify, which kinds of elements containing carbohydrates, existed in the fetal membranes. Therefore we applied a lectin-binding study using the following FITC labelled lectins: ConA, WGA, PNA, LCA, RCA. This lead to the result, that ConA, LCA, WGA and RCA produced a positive reaction in the amnion epithelium, which was negative when using PNA. The basement membrane I showed an intense fluorescence when we used ConA, LCA and WGA, using RCA it was weaker and using PNA fluorescence was nearly missing. The examination of the amniotic fibroblast and intercellular substance showed a positive reaction with all lectins, but the intercellular substance lead to weaker fluorescence. The chorionic fibroblasts, intercellular substance and basement membrane II produced fluorescence using ConA, LCA, WGA and PNA, but no reaction could be examined, when using RCA. The trophoblastic cells did not react with LCA and RCA. The intercellular substance reacted positively with all lectins.

Amnion↗

[Evaluating thyroid gland function in patients with protein anomalies].

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.

Blood Protein Disorders↗

[Effect of metoprolol on microcirculation and blood viscoelasticity].

In 40 patients microcirculation of skin as well as viscoelasticity of blood and plasma were investigated. 20 of them suffered from essential hypertension (group A) and were treated with metoprolol with a dosage of 50 to 200 mg per day. The rest of 20 subjects were controls (group B). In the group treated with metoprolol the values for blood viscosity were decreased in a significant manner, while skin microcirculation, blood elasticity and plasma viscosity did not show a significant difference. The results demonstrate that metoprolol is not only possible as medication in ischemic disease, but this substance can have a benefit in this indication because of its hemorheological effect.

Blood Flow Velocity↗

Hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat.

The lung was investigated as a matrix for transplanted hepatocytes in the rat model. Surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in 86% of the animals. No animal, however, survived injection of hepatocytes into the jugular vein. It was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes. After regeneration of the native liver, the majority of hepatocytes are cleared away within 6 months.

Acute Disease↗

[Modifications in erythrocyte elongation in blood samples of test subjects following gallopamil administration].

In 12 blood samples of healthy non-smokers younger than 40 years the erythrocytes-elongation was studied after Gallopamil-incubation, to obtain data for a possible rheological effect of this substance. For incubation dosages of 20, 50 and 100 micrograms/ml were used. After incubation with 50 and 100 micrograms/ml the elongation index of red blood cells increased in a significant manner. The results show, that Gallopamil does not only have a effect for vasodilatation but also for hemorheological parameters.

Adult↗