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Biomedical subjects

R Rüegg

Publications and source records attributed to R Rüegg.

At least 19 recordsLinked to original sources

Bone marrow involvement in Whipple's disease: rarely reported, but really rare?

Infection with Tropheryma whippelii, the causative agent of Whipple's disease, involves nearly every organ. Involvement of bone marrow may be an overlooked area of Whipple's disease. We report a case of lymphoma-like Whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. Despite minimal documentation, bone marrow may be commonly involved in Whipple's disease and, although not specific, diastase-resistant periodic acid-Schiff (PAS)-positive macrophages in bone marrow may offer an important clue to diagnosis using PAS histology of upper endoscopic biopsies, polymerase chain reaction or electron microscopy.

Adult↗

Familial persistent polyclonal B-cell lymphocytosis.

We report the occurrence of the syndrome of persistent polyclonal B-cell lymphocytosis in a brother and a sister. Both showed the morphological and immunophenotypic features of this rare disorder. In addition both had mild splenomegaly, increase of serum IgM and serological evidence of previous EBV infection. Of interest, two additional brothers had no evidence of PPBL but were indistinguishable in terms of HLA haplotype (HLA-DR7), smoking habits or evidence of EBV infection. These observations provide additional support for a genetic basis of the syndrome but suggest that pathogenic factors other than those known so far may be required for its full expression.

Antigens, Viral↗

The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease.

The use of neutrophil left-shift parameters in the diagnosis of inflammatory and infective disease (ID) was evaluated. The level of C-reactive protein (CRP), currently the best quantitative parameter of inflammation, was used as the gold standard. Of 292 patients, 230 (79%) had a level of CRP of 1.0 mg/dL or greater and were classified as having inflammation, whereas 62 (21%) had normal levels. The neutrophil band count in each patient was determined by microscopic examination of 200 WBCs. The diagnostic value of the band count as an indicator for ID was evaluated in comparison to the WBC count, the neutrophil count, and the left-shift indicators of two automated hematologic analyzers, H*1 Technicon (Bayer Technicon Instruments, Tarrytown, NY) and Coulter MAX M (Coulter Electronics, Hialeah, Fla). When receiver operating characteristics were used, the band count was superior to the immature to total neutrophil count (I/T) ratio, the total WBC count, and the neutrophil count. The sensitivity and specificity in identifying ID at designated cutoff points were as follows: band count of 20% or greater of total WBC count (53% and 79%, respectively), I/T ratio of 0.25 or greater (59% and 63%), total WBC count of 9.6 x 10(6)/mL or greater (68% and 56%), and neutrophil count of 8.0 x 10(6)/mL or greater (60% and 58%). The performance of the H*1 Technicon left-shift flag was similar but slightly inferior to the band count (sensitivity, 44%; specificity, 79%), whereas the Coulter MAX M flags had a clearly higher sensitivity (79%) and lower specificity (53%). In addition, microscopic evaluation to determine the presence of reactive morphologic changes in neutrophils, such as toxic granules, Döhle bodies, and cytoplasmic vacuoles, had a high sensitivity (80%) but a low specificity (58%) in predicting ID. The diagnostic value of both microscopic and automated neutrophil left-shift parameters as indicators for ID is limited. Morphologic changes in neutrophils, however, either have a high specificity (band count) or a high sensitivity (toxic signs) in predicting ID and therefore may be a clinically useful tool.

Adolescent↗

Early diagnosis of low grade malignant lymphoma and chronic lymphocytic leukaemia. Verification of morphologically suspected malignancy in blood lymphocytes by flow cytometry.

According to international recommendations, the diagnosis of chronic lymphocytic leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or lymphocytic infiltration of the bone marrow. The appearance of morphologically atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily overlooked, and is generally not regarded as a diagnostic criterion. We report 12 cases of CLL/NHL who were detected only by morphological screening of routine peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not suggested by the patients' history, physical or other laboratory findings, and had not been contemplated by the physician in charge. Monoclonality of peripheral lymphocytes was confirmed by immunophenotyping and Southern blotting. The lymphoma was classified histologically according to the International Working Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found by immunophenotyping in the blood of 11 patients whose lymphocytes were morphologically classified as activated-abnormal. However, 3 patients suspected to have NHL/CLL on morphological screening of blood smears had to be classified as benign after immunophenotyping. We conclude that morphological screening of routine blood smears is an inexpensive and easy additional screening method for CLL and low grade malignant NHL.

Aged↗

High grade malignant lymphoma with clinical characteristics and immunophenotype of natural killer cells.

The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3-, CD16+, CD56(+), CD57-). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor beta-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells.

Adult↗

Epinephrine test and plasma elastase as diagnostic tools in a patient with CD3+ large granular lymphocyte proliferation.

Large granular lymphocytes (LGL) proliferation is characterized by expansion of cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL-proliferation the epinephrine stimulation test (EST) induced a striking elevation of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l and might be an additional diagnostic tool in patients with normal or low absolute numbers of circulating LGL. After treatment with steroids, plasma elastase--a marker of neutrophil destruction--decreased from 162 to 40 micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to neutrophil destruction, possibly mediated by LGL.

Aged↗

Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation.

Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."

Adolescent↗

[Clinical significance of antimitochondrial antibodies].

Clinical, histological and serological data of 72 patients with antimitochondrial antibodies (AMA) were analyzed. 56 (78%) of the patients exhibited chronic cholestatic hepatopathy; in 30 of these primary biliary cirrhosis (PBC) was diagnosed and in 26 "possible PBC". The remaining 16 patients were subsumed in an "other illness' group. A collagen or autoimmune disease was found in 8 patients of the chronic cholestatic hepatopathy group and in 3 of the "other illness" group. Histological findings were diagnostic for PBC or cirrhotic liver in 90% of the patients with clinical signs, while 64% of the symptomfree patients had unspecific histological liver alterations. In general, increasing serum IgM, alkaline phosphatase, gamma-GT and symptoms paralleled increasing AMA titers, although asymptomatic patients with high AMA titers were also seen. The prevalence of hepatopathies rose with increasing AMA titers, but otherwise no association of AMA titers and diagnosis was observed. Therefore, a positive AMA test bears out suspicion of hepatopathy, but cannot be regarded as specific for PBC when other liver signs are absent.

Autoantibodies↗

Exchange between intravascularly and extravascularly injected radioiodinated fibrinogen and its in vivo derivatives.

To test the hypothesis that circulating FDP may stem from extravascular proteinolysis of fibrin (fibrinogen), eight patients with a pleural or peritoneal effusion had an intravenous injection of 125I-fibrinogen and a simultaneous intracavitary injection of 131I-fibrinogen. Two days after injection a mean of 12% of intravascularly injected radioactivity was found in the extravascular cavity, whereas 4.8% of the extravascularly administered radioactivity could be recovered in the circulation. Of the activity exchanged in both directions, more than half was protein-bound, and more than a quarter was clottable. The results demonstrate not only a rapid and considerable extravasation but also a definite back-flow of both clottable and unclottable fibrin (fibrinogen) derivatives from the extravascular space into the circulation. Thus, in the presence of pleural or peritoneal effusion, a shortened fibrinogen t1/2 as well as raised levels of FDP should be interpreted with caution. They may be due, at least to some extent, to an exchange between intravascular and extravascular spaces rather than to intravascular coagulation or fibrinolysis, respectively. The demonstration of fibrinogen proteolysis in effusions further emphasizes that conventional compartmental analysis of plasma and urine radioactivity after intravenous radiofibrinogen injection is highly questionable in pathological conditions.

Animals↗

Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology.

A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.

Animals↗

Dihydroretinoic acids and their derivatives. Synthesis and biological activity.

The syntheses of the ring and four side-chain dihydroretinoic acids and/or their esters, 3-7, are described. The syntheses of several other retinoids containing a substituted aromatic ring are also included. The biological activity of the compounds was evaluated in vivo in a chemically induced mouse skin papilloma test and in vitro in two vitamin A deficient assays. The activity observed for 1a, 1c, and 2a in the former test was partially retained in the dihydro derivatives 4b, 4c, and 6b. Similar results were found in the in vitro assays.

Animals↗

[Hematological studies on changes caused by warming of the blood with microwaves].

Our examinations have shown, that through warming of blood with the micro-wave device "Haemotherm" there were no serious haematological alterations to be proved. The "Haemotherm" device can therefore be recommended as a useful and riskless equipment for warming blood in the usually used plastic covers during massive transfusions.

Blood Coagulation↗

[Lienal and intravascular corpuscular hemolysis in erythropoietic protoporphyria].

A report is presented on two brothers with erythropoietic protoporphyria (EPP) with massively and moderately elevated RBC-protoporphyrin content respectively. Both exhibited splenic and one also intravascular hemolysis. The mechanism of hemolysis was investigated on the basis of filterability, plasma trapping and osmotic resistance of in vivo RBCs and of incubated, UV-light exposed RBCs. Photodynamic damage to EPP-RBC, leading to increased RBC rigidity, increased splenic trapping and intravascular hemolysis, appears to play a crucial role in the causation of hemolysis in vivo as well as in vitro.

Adolescent↗