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Biomedical subjects

M Wehrmann

Publications and source records attributed to M Wehrmann.

At least 37 records · Page 2Linked to original sources

Intrathecal therapy of leptomeningeal CEM T-cell lymphoma in nude rats with anti-CD7 ricin toxin A chain immunotoxin.

We have established a new xenogeneic animal model of leptomeningeal metastasis (LM) by intracisternal inoculation of human CEM T-cell lymphoma into nude rats, and used it to evaluate the anti-lymphoma efficacy of an anti-CD7 ricin A chain immunotoxin (DA7). In vitro incubation with 2 microg/ml DA7 for 72 h inhibited CEM cells by 90% in a trypan blue exclusion assay. To establish its anti-lymphoma activity, one and four days after cisternal inoculation of 10(6) CEM cells, eight animals each were treated cisternally with 10 microg DA7 in 50 microl PBS or sham-treated with 50 microl PBS. Histopathologically, all eight sham-treated and five of eight DA7 treated animals showed typical features of LM with multilayers of tumor cells along the whole subarachnoid space and the ventricular walls, as well as subependymal and diffuse parenchymal tumor cell infiltration. Three DA7 treated animals were free of tumor. Two of these animals were asymptomatic long-term survivors (> 90 days). The third tumor-free animal suddenly died on day 51. Histology revealed viral myocarditis. Median symptom-free survival was 51 days (range 29-90+ days) in DA7 treated and 34 days (range 29-87 days) in sham-treated animals (p = 0.12, log-rank test). Histologically, no signs of neurotoxicity or systemic toxicity was found. However, DA7 treated animals showed a tendency to a slower weight increase on days 6-28 after tumor cell inoculation. Our results indicate that this model is useful in studying leptomeningeal seeding and intracisternal treatment of lymphoma. The demonstrated anti-tumor effect of DA7 treatment deserves further evaluation especially regarding the application of DA7 in early stages of LM from T-cell lymphoma.

Animals↗

Human glomerular structure under normal conditions and in isolated glomerular disease.

Investigation of the human glomerulus in health and disease shows that the human glomerulus comprises seven lobule-like structures with numerous anastomoses. The total length of the capillaries in a single glomerulus is 0.95 cm, making a total of 19 km for all 2-million glomeruli. The total surface area of all glomerular capillaries is 6,000 cm2. The total filtration surface area is 516.1 cm2. Severe isolated disease of the glomerulus, as seen in acute endocapillary glomerulonephritis, membranoproliferative glomerulonephritis types I and II, membranoproliferative glomerulonephritis plus chronic membranous glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis, does not lead to elevation of serum creatinine concentration, even if the filtration area is reduced to about 20% (as in diabetes) of the normal value. It is concluded that isolated glomerular disease does not lead to elevation of the serum creatinine concentration. Glomerulopathies in which there is acute or chronic elevation of the serum creatinine concentration are accompanied by acute renal failure or involvement of the renal cortical interstitium, respectively.

Acute Kidney Injury↗

Renal morphology in essential hypertension: analysis of 1177 unselected cases.

Morphological and clinical analysis of 1177 renal biopsies from nonselected patients with essential hypertension revealed compensated benign nephrosclerosis in 775 cases. Decompensated benign nephrosclerosis was found in 251 cases, and secondary malignant nephrosclerosis was found in 151 cases. This article describes the morphological and clinical features of decompensated benign nephrosclerosis, which has received little recognition until now. The morphological and clinical features of secondary malignant nephrosclerosis, which is induced by hypertension, are also considered. There is also a discussion of the differentiation of the latter from primary malignant nephrosclerosis, in which stenosis of the preglomerular vessels develops in the presence of normal blood pressure and leads secondarily to renal hypertension.

Biopsy↗

Diagnostic value of immunostaining for tryptase in patients with mastocytosis.

The term "mastocytosis" is used to describe a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs). Cutaneous and systemic variants exist. Systemic mastocytosis may show an indolent or malignant clinical course. In malignant mastocytosis (MM), the diagnosis often is missed because the MCs are morphologically abnormal and lack metachromatic granules or the underlying histologic picture is complex. The cytoplasmic serine protease tryptase is produced by MCs and is thought to be expressed at all stages of MC maturation. To assess the diagnostic value of tryptase staining in mastocytosis, tissue sections from 93 patients with mastocytosis, including MM (n = 37), systemic indolent mastocytosis (n = 47), urticaria pigmentosa (n = 5), MC leukemia (n = 2), and solitary skin mastocytoma (n = 2) were stained with the antitryptase antibody G3. The results were compared with those of Giemsa and chloroacetate esterase (CAE) staining. Using antitryptase antibody G3, MC infiltrates were identified in all patients examined, including those with MM (37 of 37), and virtually all the neoplastic MCs (> 95%) appeared to react with G3. In MM, significantly fewer MCs were positive in Giemsa (54.5%; p < 0.05) and CAE (78.8%; p < 0.05). Moreover, G3 produced clear diagnostic staining in all cases of MM, but the proportion of cases with clear diagnostic results (> 10% of neoplastic cells positive) was considerably lower with Giemsa (48.6%; p < 0.05) and CAE (75.7%; p < 0.05) staining. By contrast, tryptase, Giemsa, and CAE produced diagnostic staining of MCs in virtually all cases of systemic indolent mastocytosis, urticaria pigmentosa, and solitary skin mastocytoma. In systemic mastocytosis, survival was significantly reduced in cases with Giemsa-/tryptase+ or CAE-/tryptase+ tumor cells compared to those cases with Giemsa+ or CAE+ MC infiltrates (p < 0.001).

Adult↗

Does anti-atherogenic estradiol valerate treatment cause adverse effects on liver and uterus in NZW rabbits?

The rabbit has been a widely accepted animal model for atherosclerosis research since Anitschkow first used this animal in 1913 in identifying dietary-induced hypercholesterolemia as a major risk factor for atherogenesis. Experiments with cholesterol-fed rabbits have demonstrated the beneficial effects of estrogen treatment on the development of atheroma for more than 50 y. Clinical trials have found a reduction in cardiovascular events of up to 50% in postmenopausal women receiving estrogen replacement therapy. However, metabolic conditions in rabbits, as well as physiological estrogen serum levels, differ in some aspects from those in humans. In rabbits, experimentally-induced hormone levels are about 5- to 10-fold higher than those found in untreated animals. Normal physiological estrogen levels in rabbits are not cardioprotective under dietary-induced hypercholesterolemia. We investigated whether replacement induced "hyperestrogenemia" causes adverse effects on organs other than the cardiovascular system. Twenty-nine female rabbits were divided into 4 different groups, 2 without and 2 with estrogen treatment (1 mg estradiol valerate/kg body weight/w over 12 w). Organ weights, transaminases and uterine histology were examined. In rabbits treated with estrogen, we did not see relevant adverse effects on heart, kidney and liver weights, or on liver enzymes. But there was a significant increase in spleen weights, as well as notable changes in the endometrium with moderate inflammation. These findings indicate that the dosage of estrogen commonly used for atherosclerosis research does not cause serious disorders in the major organs of cholesterol-fed rabbits.

Animals↗

Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis.

Mixed acetylboswellic acids, pentacyclic triterpenes extracted from the gum resin of Boswellia serrata Roxb., significantly inhibited the ionophore-stimulated release of the leukotrienes (LT) B4 and C4 from intact human polymorphonuclear neutrophil leukocytes (PMNLs), with IC50 values of 8.48 micrograms/ml and 8.43 micrograms/ml, respectively. Purified acetyl-11-keto-beta-boswellic acid was about three times more potent as inhibitor of the formation of both LTB4 (IC50 = 2.53 micrograms/ml) and LTC4 (IC50 = 2.26 micrograms/ml) from human PMNLs in the same assay. The comparative agent MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]- 2,2-dimethylpropanoic acid, L-663,536, CAS 118, 414-82-7) was about 10 to 100-fold more active than the boswellic acids in inhibiting the formation of 5-lipoxygenase products in human PMNLs, with IC50 values of 0.0068 microgram/ml (LTB4) and 0.49 microgram/ml (LTC4). After daily intraperitoneal dosage the extract of mixed acetylboswellic acids (20 mg/kg) significantly reduced the clinical symptoms in guinea pigs with experimental autoimmune encephalomyelitis (EAE) between days 11 and 21. However, the inflammatory infiltrates in the brain and the spinal cord were not significantly less extensive in the treated animals than in the respective control group. The multiple intraperitoneal application of boswellic acids did not inhibit the ionophore-challenged ex vivo release of leukotrienes B4 and C4 from PMNLs separated from the blood of guinea pigs with EAE. The boswellic acids have thus been characterized as selective, non-redox and potent inhibitors of the biosynthesis of leukotrienes in vitro.

Acetylation↗

[In vitro study of morphology of the bladder wall using MR tomography at 1.0 Tesla: correlation with histology].

PURPOSE: Evaluation of the potential of various MR techniques to differentiate bladder wall layers verified by histological findings. MATERIAL AND METHOD: 6 bladder specimens of pigs were examined in vitro using T1-weighted spin-echo-sequences, T2-weighted Turbo-SE, fat suppressed T2-weighted SE, and inversion recovery sequences. The MR images were obtained before and after fixating the specimens in formalin. Measurements of the thickness of bladder wall layers were performed on both sets of MR images as well as on histological sections, RESULTS: T2-weighted SE images showed three layers of different signal intensities: one innermost band of very high signal, one inner band of low and one outer band of intermediate signal corresponding histologically tunica propria and two different muscle layers. Inversion recovery technique provided similar findings but were able to avoid chemical-shift artifacts. After 24 hours in formalin, the signal intensity relation of the two muscle layers was inverted. The thickness of total bladder wall was not reduced significantly. Concerning the thickness of urinary bladder wall, histological measurements and evaluation of MR images correlated well. CONCLUSION: MR imaging enables the differentiation of three bladder wall layers. Inversion recovery technique achieved the best image quality by avoiding chemical shift artifact.

Animals↗

Occurrence and magnitude of pressure waves during Er:YAG laser ablation of atherosclerotic tissue: comparison to XeCl excimer laser ablation.

BACKGROUND AND OBJECTIVE: Since excimer laser ablation has not shown advantages in comparison to conventional balloon angioplasty, the search for other laser light sources came up with the Er:YAG laser, operating at a wavelength of 2.94 microns. STUDY DESIGN/MATERIALS AND METHODS: Normal and atherosclerotic human vessel segments were irradiated in vitro, using pulsed Er:YAG laser systems. The laser beam was either focused onto the tissue in air or delivered via a fibre system onto the tissue being immersed in saline. Needle-type hydrophones were used for pressure pulse detection. RESULTS: Er:YAG laser irradiation results in effective tissue ablation of normal and calcified atherosclerotic vessel segments. In comparison to excimer lasers, ablation rates can be increased by a factor of 5 to 10 at least. Er:YAG laser ablation is also associated with a generation of pressure waves. On calcified plaque, the acoustic signals differ significantly from those on normal tissue. Histological tissue analysis reveals small zones of discoloration and tissue fissures that are found 100-200 microns lateral to the crater edge, depending on the energy density used. CONCLUSION: Er:YAG lasers generate pressure waves that are comparable to excimer laser ablation. Er:YAG lasers, however, show a markedly improved ablation efficiency, which may favour these systems as effectively cutting, less traumatic tools for removal of atherosclerotic plaque.

Aortic Diseases↗

Multifocal extra-abdominal desmoid tumor--diagnostic and therapeutic problems.

The case of an 18-year-old girl is described who 1 year after surgical stabilisation of a spine injury developed a multifocal desmoid tumor in the scar region and another at a distance away from the scar in the area of the left scapula. After nononcological resection of both tumors subsequent diagnosis with magnetic resonance imagins (MRI) showed a questionable recurrence only in the scar; positron emission tomography failed to elucidate the local situation. Because a radical re-resection would mean mutilation, and local radiation may damage the spinal cord, a 'wait-and-see' strategy was chosen for further follow-up.

Adolescent↗

Significance of postglomerular capillaries in the pathogenesis of chronic renal failure.

Correlations between the relative volume of the intertubular capillaries in the renal cortex and the serum creatinine concentration in primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides are reported. In the mesangioproliferative glomerulonephritides, there are significant negative correlations between the number and area of the intertubular capillaries in the cortex and the serum creatinine concentration. In diabetic glomerulosclerosis, renal glomerular amyloidosis, decompensated benign nephrosclerosis, secondary malignant nephrosclerosis, and chronic interstitial nephritis, there is a significant negative correlation between the relative area of the intertubular capillaries and the serum creatinine concentration. Thus, in these diseases, there is progressive narrowing/ obliteration of the postglomerular capillaries which leads to a progressive decrease in glomerular filtration rate and thus to a rise in serum creatinine concentration.

Capillaries↗

Ablation characteristics of arterial vessel walls irradiated with the pulsed dye laser--an analysis of variance.

BACKGROUND AND OBJECTIVE: Since most clinical laser angioplasties require the use of over-the-wire delivery systems, we studied the effects of pulsed dye laser energy (504 nm, 1.4 microseconds on arterial vessel walls in combination with a multifiber catheter system. MATERIAL AND METHODS: Postmortem arterial segments (n = 368) were exposed under blood or saline. Laser pulses (n = 100-800) were transmitted via 9F-multifiber-catheters, at energy densities of 3-16 J/cm2. Ablation characteristics revealed by histologic examination and morphometry were analyzed by multiple analysis of variance. RESULTS: Ablation occurred more frequently in saline compared to blood. Below an energy density of 10 J/cm2 ablation occurred in saline only. Specimens irradiated under blood showed only thermal changes at 10 J/cm2. In saline, 92% of normal, 88% of fibro-fatty and 60% of calcified tissue showed ablation at 13 J/cm2. The average ablation threshold in saline was about 3-4 J/cm2 per pulse for normal tissue, 5 J/cm2 for fatty plaques, and 8-9 J/cm2 for calcified plaques. In blood, the average ablation thresholds did not differ significantly between the different stages of arteriosclerosis (12 J/cm2 for normal tissue, 11 J/cm2 for fatty plaque, and 10 J/cm2 for calcified tissue). Carbonization and vacuolization were seen regularly at energy levels > or = 13.4 J/cm2. CONCLUSIONS: Selective ablation of arteriosclerotic tissue with the pulsed dye laser could not be found. Further investigation is needed before an effective ablation of arteriosclerotic arterial tissue can be expected.

Arteries↗

[Preoperative angiographic marking of angiodysplasia of the small intestine with platinum coils].

In patients with occult lower gastrointestinal bleeding, locating of the source of hemorrhage can be quite difficult. While multiple diagnostic tests, like arteriography, enteroclysis, nuclear scans, may confirm a small bowel source of bleeding, precise localization allowing a directed, conservative surgical resection may be problematic. We describe a patient presenting with hemorrhage from an angiodysplasia in the small intestine. The preoperative use of highly selective angiographically placed platinum coils into the feeding artery allowed us to precisely locate the angiodysplasia radiographically during operation and to resect a conservative length of small intestine. We believe that preoperative bleeding site localization with platinum coils is a simple, effective tool to aid surgical resection of small bowel angiodysplastic lesions.

Aged↗

Intracoronary ultrasound following excimer-laser angioplasty. An in-vitro study in human coronary arteries.

UNLABELLED: To study the ablation effects induced by excimer laser coronary angioplasty (ELCA), we examined 41 segments of nine isolated coronary arteries. An electronic intracoronary ultrasound device (ICUS: 20 MHz, 3.5F, Endosonics) was positioned coaxially within the vessel. Angioplasty was performed using a 1.7 mm ELCA catheter (Spectranetics) which was placed in the lumen and directed vertically onto the intimal surface of the vessel (fluence: 10-50 mJ.mm-2). The laser catheter was removed after each lasing cycle to allow the stepwise evaluation of the morphological effects of ELCA and to avoid reaching the adventitia. Ultrasound images were compared with the corresponding histological specimens. In all cases, the ablation site could be correctly identified by ICUS. No penetration of the adventitia was seen at histology. Ablation depth was 0.31 +/- 0.18 mm as determined by histology and 0.34 +/- 0.18 mm as determined by ultrasound; the diameter of the crater was 0.63 +/- 0.21 mm, and 0.75 +/- 0.16 mm, respectively, and wall thickness was 0.68 +/- 0.18 mm, and 0.83 +/- 0.20 mm, respectively. A statistical relationship between ultrasonic and histology measurements was only found, however, for assessment of wall thickness (r = 0.71). CONCLUSIONS: The identification of small ablation effects by ICUS was possible with great accuracy and ELCA could be performed without penetration of the adventitial layers. However, exact quantification of the crater dimensions was not possible due to limitations of the axial and lateral resolution. Thus, for the guidance of ELCA by ICUS a further improvement in the resolution capabilities of ICUS devices is mandatory.

Angioplasty, Laser↗

QBEND10 for the diagnosis of myelodysplastic syndromes in routinely processed bone marrow biopsy specimens.

AIM: The assessment of the value of the antibody QBEND10, which is directed against the haemopoietic stem cell related antigen CD34, in the immunohistochemical diagnosis of myelodysplastic syndrome in routinely processed bone marrow biopsy specimens. METHODS: 581 formalin fixed, paraffin embedded trephine biopsy specimens of the iliac crest were immunostained with QBEND10 (avidin-biotin complex/ABC method). The number of CD34+ haemopoietic stem cells/blast cells (referred to hereafter as CD34+ cells) was determined in each case. The Wilcoxon test was used for statistical analysis. RESULTS: The following diagnostic categories were defined: (1) normal or reactive bone marrow (n = 356), (2) lymphoproliferative disorders, usually non-Hodgkin's lymphoma of low grade malignancy or multiple myeloma (n = 118), (3) myelodysplastic syndrome (n = 22), (4) acute leukaemia (n = 44), and (5) myeloproliferative diseases (n = 41). The average number of CD34+ cells was very low (0.2/HPF) in normal and reactive bone marrow, in lymphoproliferative disorders and in the myelodysplastic syndrome subtypes RA and RARS. Myeloproliferative diseases showed an average of three CD34+ cells/HPF. However, the average number of CD34+ cells was significantly higher (p < 0.05) in the myelodysplastic syndrome subtypes RAEB and RAEB-T (8.7/HPF) and in acute leukaemia (including both myeloid and lymphoblastic leukaemia; 111.7/HPF). CONCLUSIONS: QBEND10 is of value for the identification of RAEB and RAEB-T in routinely processed bone marrow biopsy specimens because it enables the detection of even small increases in the number of CD34+ cells.

Acute Disease↗

Nonspecific immunostaining of blast cells of acute leukemia by antibodies against nonhemopoietic antigens.

It is well known that some of the widely used antibodies directed against hemopoietic antigens exhibit cross-reactivity with normal and neoplastic nonhemopoietic cells. By contrast, relatively little is known about the immunoreactivity of hemopoietic cells with antibodies that detect nonhemopoietic antigens. In this study 43 routinely processed bone marrow biopsy specimens containing infiltrates of acute leukemia of different subtypes were stained with a panel of 20 antibodies that detect nonhemopoietic antigens in formalin-fixed and paraffin-embedded tissue. Thirteen of the antibodies applied (KL1; BMA 120; and antibodies against epithelial membrane antigen, alpha-fetoprotein, prostate-specific acid phosphatase, prostate-specific epithelial antigen, placental alkaline phosphatase, alpha-amylase, serotonin, bombesin, beta-human chorionic gonadotrophin, desmin, and S-100 protein) did not stain blast cells in any of the cases. However, anti-vimentin, HMB45, and anti-myoglobin stained blast cells in the majority of the cases; the antibodies against thyroglobulin, actin, and carcinoembryonic antigen stained blast cells in 10% to 25% of the cases; and anti-neuron-specific enolase stained blast cells in less than 10% of the cases. No correlation was found between the leukemia subtype and the pattern of immunoreactivity. The staining specificity, (i.e., the specificity of binding of the primary antibody--immunologic vs. nonimmunologic binding), was tested by increasing the dilution of the primary antibody and comparing the staining intensity in the bone marrow specimens and control tissue. Staining specificity was confirmed only for staining with the antibodies against neuron-specific enolase and vimentin. The findings show that immunoreactivity of tumor cells in bone marrow biopsy specimens for nonhemopoietic antigens does not exclude a diagnosis of acute leukemia.

Acute Disease↗