[Differential malignant lymphoproliferative syndrome (LPS) diagnosis with flow cytometry: a study of 100 patients]. / Differentialdiagnose maligner lymphoproliferativer Syndrome (LPS) mittels Flowzytometrie: eine Studie von 100 Patienten.

The clinical utility of flow cytometry in diagnosis of chronic lymphoproliferative disorders (LPD) is well established. Accurate diagnosis of related but still distinct entities is relevant to therapeutic decisions. We report on the immunophenotypic findings of 100 patients with a new diagnosis of LPD established by two-color flow cytometry. A panel of > 15 monoclonal antibodies was regularly applied. The characteristic immunophenotype of B-cell chronic lymphocytic leukemia (CD5+, CD23+, FMC7-) was found in 74 patients including one with Richter's transformation. Hairy cell leukemia (CD5-, CD11c+, CD103+) was diagnosed in 6, and B-cell Non-Hodgkin lymphoma (B-NHL) in 13 patients, respectively. 6 of the B-NHLs belonged to the entity of splenic lymphoma with villous lymphocytes (CD5-, CD23-, FMC7+) and 6 were identified as mantle cell lymphomas (CD5+, CD23-, FMC7+). One B-NHL was typed as follicular center cell lymphoma (CD5-, CD10+, FMC7+). Three B-cell LPDs without a characteristic marker profile were histologically further classifiable. With a total of 4 patients T-cell LPDs were much less frequent. Sézary syndrome (CD4+, CD8-, CD56-) and T gamma lymphoproliferation (CD4-, CD8+, CD16-, CD56-, CD57+) were diagnosed twice. In 17 patients with a characteristic marker profile (1 Richter's transformation, 5 hairy cell leukemias, 3 splenic lymphomas with villous lymphocytes, 4 mantle cell lymphomas, 4 T-cell proliferations) a further histological or molecular investigation confirmed the immunophenotypic diagnosis in all cases. Clinical presentation with lymphadenopathies and B-symptoms was mainly associated with the diagnosis of mantle cell lymphoma, whereas splenomegaly and infection were suggestive of hairy cell leukemia. 94% of the B-CLL patients were diagnosed at an early clinical stage with still conserved hematopoiesis, 32% of the LPDs were diagnosed following a routine hematogramm.

[Diagnosis of thalassemias and hemoglobinopathies by HPLC (high performance liquid chromatography): study of 627 patients]. / Diagnose der Thalassämien und Hämoglobinopathien mittels HPLC (high performance liquid chromatography): eine Studie von 627 Patienten.

Red cell haemolysates of 627 patients with mainly microcytic anaemia were subjected to HPLC for diagnosis of thalassaemia (thal) or haemoglobinopathy during 1998. Thalassaemia was diagnosed in 16.3% (95 beta-thal minor, 1 beta-thal major, 2 delta beta-thal heterozygote, 4 alpha-thal1), haemoglobinopathies in 3.5% (10 Hb S including 3 Hb S-alpha-thal, 1 homozygote, 1 Hb SC and 1 Hb SE; 6 Hb E including 3 homozygotes; 3 Hb Lepore heterozygotes; 1 Hb K; 1 Hb O-Arab*; 1 Hb K-Ibadan* [* = confirmed by DNA sequencing]). In 10.7% of patients severe iron-deficiency (ferritin < 7 micrograms/l) was the cause of microcytosis (MCV 72.1 +/- 2.6 fl) and anaemia (Hb 97.2 +/- 9.8 g/l). The beta-thal minor group showed prominent microcytosis (MCV 66.9 +/- 2.6 fl) but only mild anaemia (Hb 114.1 +/- 12.9 g/l). Variant Hb K-Ibadan und Hb O-Arab were found during quantification of HbA1c. Patients with beta-thal minor or severe iron-deficiency anaemia were identified with equal frequency in adult females, children and adolescents of both sexes; however, in adult males beta-thal minor was the most frequent aetiology (> 90%) of microcytic anaemia. Our results demonstrate the diagnostic value of red cell lysate HPLC and ferritin determination when evaluating unclear microcytic anaemia. This approach, together with die HbA1c-quantification by HPLC, will render possible detailed diagnosis of thalassaemia and haemoglobinopathies.

[Hairy cell leukemia: diagnosis using monoclonal antibodies in flow cytometry]. / Haarzell-Leukämie: Diagnostik mittels monoklonaler Antikörper im Durchflusszytometer.

A prospective study was performed on peripheral EDTA blood samples mailed for screening purposes to a hematology laboratory. Twenty-one samples which were suspicious for hairy cell leukemia (H 6000, Technicon Co. or STKS, Coulter Co.), were evaluated using three diagnostic tests: Microscopic morphology (Giemsa stain); Microscopic controlled inhibition of lymphocyte acid phosphatase by tartrate; Flow-cytometric immunophenotyping with monoclonal antibodies (Epics Profile, Coulter Co.). A characteristic immunophenotype was found on all typical hairy cell leukemias (except two) by positivity of CD11c, CD19, CD22, and CD25. The above-mentioned immunophenotype on peripheral lymphocytes, which can moreover be supported by demonstrating positivity for FMC7, is diagnostic for hairy cell leukemia. It therefore represents a rather straightforward tool to the bone-marrow diagnosis.

[Diagnosis of hydroxyapatite disease]. / Beitrag zur Diagnostik der Hydroxyapatitkrankheit.

The possibility of detecting hydroxyapatite crystals in synovia in a routine setting has been studied prospectively. Coloration of the crystals with alizarin red-S was the method of choice. The diagnostic results were markedly improved by simultaneous observation of a freshly prepared positive control synovia.

[Which are the most frequent enteropathogenic parasites found in clinical practice?]. / Welches sind die häufigsten enteropathogenen Parasiten in der Praxis?

Infectious diarrhea is seen with increasing frequency in general practice. The main reason is growing tourism in countries with conditions of public health different from ours, where the incidence of enteropathogenic parasites is higher. To obtain an overview of these parasites, the results of 23,276 stool samples from patients in general practice throughout Switzerland were analyzed. Protozoa were found in 32% of samples (4.6% pathogenic protozoa, 24% facultative pathogenic protozoa and 3.4% apathogenic protozoa). Helminths were demonstrated in 2.9% of stool samples. The helminth spectrum covered 15 types, with Trichuris trichiuria predominating (one third). 8% of the Swiss population travel every year to areas with a higher diarrhea incidence. A proportion of these subjects constitute a health risk on their return to Switzerland. They chiefly consist of people working in, or living with someone working in, the food industry. Specific parasitologic diagnosis of diarrhea contributes significantly to reducing this risk.

[Which are the most frequently occurring enteropathogenic bacteria in clinical practice?]. / Welches sind die häufigsten enteropathogenen Bakterien in der Praxis?

Diarrhea is an increasingly frequent clinical finding in Swiss medical practice. One reason is the volume of tourism in countries with different climatic and social circumstances. To obtain an overview of the enteropathogenic bacteria spectrum as a cause of diarrhea, we analyzed 11,163 stool specimens from a representative group of patients throughout Switzerland. Enteropathogenic bacteria were found in 15.2% of all specimens; 50% were Campylobacter jejuni/coli, 35% Salmonella spp., 8% Aeromonas hydrophila group, 4% Shigella spp. and 3% Yersinia enterocolitica. This distribution is taken for all age groups and for both sexes. In the infant age there was a maximum evidence of enteropathogenic bacteria of the female sex. In childhood this maximum concerned to the male sex. Patients older than fifty had no positive stool specimens. As expected the most frequent positive stool specimens were in summer.

[Myeloperoxidase deficiency--blemish or disease? Evaluation of 60,337 differential blood pictures]. / Der Myeloperoxydase-Defekt--Schönheitsfehler oder Krankheit? Eine Auswertung von 60 337 Differentialblutbildern.

Leukocyte differential counting by flow cytochemistry (H 6000, Technicon) has shown 32 subjects with partial or complete leukocyte myeloperoxidase deficiency in a population of 60,337 patients screened at a reference laboratory over a one year period. Some of the patients were hospitalized, but most were outpatients. Partial (27 patients) or complete (5 patients) myeloperoxidase deficiency was confirmed by examination of cytochemical stains (Graham-Knoll method). None had hematologic malignancy. Eleven of these 32 patients had recurrent infections; 3 of these patients were found to have a hereditary disturbance which also involved other members of the family. The findings suggest that the incidence of myeloperoxidase deficiency is much higher than was previously suspected.

Aspergillus sinusitis in cancer patients.

Paranasal sinusitis occurred in 52 immunosuppressed cancer patients treated over 5 years at the University of Maryland Cancer Center. Twenty-one patients had aspergillus sinusitis; Aspergillus sp, including flavus and niger were directly recovered from sinus in 19 of the 21 infections. Two other patients with sinus involvement and positive nose cultures for Aspergillus flavus or fumigatus and microbiologically documented pulmonary aspergillosis were considered clinically, although not microbiologically, documented. Predisposing factors for aspergillus sinusitis during the 60 days prior to infection diagnosis were granulocyte count less than 500 microliter (mean duration, 42 days versus 14 days for sinusitis of other etiology; P less than 0.001), prolonged hospitalization (mean duration, 22 days versus 14 days for patients with nonfungal sinusitis; P less than 0.001), and prolonged antibiotic therapy (mean duration, 22 days versus 9 days; P less than 0.001). Treatment with amphotericin B was initially successful for 18 of 21 patients; however, 11 of 18 patients had infection recurrence that always developed at time of tumor exacerbation and reinstitution or intensification of chemotherapy. These findings suggest that aspergillus sinusitis in cancer patients is seen in association with prolonged neutropenia and antibiotic therapy, is amenable to therapy, but tends to recur with relapse of malignancy.

Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin.

We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins--ticarcillin, mezlocillin and piperacillin alone and in combination with 80 mg gentamicin in normal volunteers. Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin. Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350 mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l. Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin-gentamicin combination. However, except for the mezlocillin-gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin-gentamicin regimes were greater than 1:8 at zero and 2 h after the infusion against the organisms tested. It is unlikely that these differences in the three penicillin-gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.

[To what extent do indications for or questioning of the 24-hour ECG in ambulatory practice correlate with established ECG findings?]. / Wie weit stimmen die Indikationen bzw. Fragestellungen in der ambulanten Praxis für das 24-Stunden-Ekg. mit den festgestellten Ekg.-Befunden überein?

In 1312 patients the Holter 24-h ECG method served to detect 3190 abnormalities of the cardiac rhythm (mean 2.43 different types of arrhythmia per patient), and were classified into 14 arrhythmia groups. The main groups of indications for Holter ECG were classified as follows: palpitation; syncopes, dizziness; life-threatening arrhythmias. The positivity of the test correlated extremely well with the severity of the clinical symptoms: if syncope or dizziness were the indications for Holter ECG, abnormalities were found in 57%; if life-threatening arrhythmias were suspected, abnormalities were found in 54.7% of the patients.

[Disseminated myelogenous sarcoma with tumor-associated lactic acidosis]. / Disseminierte myelogene Sarkome mit tumor-assoziierter Lactatazidose?

A 24-year-old Hispanic patient underwent surgery for multicentric granulocytic sarcomas. 17 days after reduction of the tumors he developed severe acute lactic acidosis, which responded only to aggressive chemotherapy but in a surprisingly short lapse of time.

[High-dose ifosfamide therapy: systemic use of a mucolytic agent for the reduction of urotoxicity]. / Hochdosierte Ifosfamidtherapie: systemischer Einsatz eines Mukolytikums zur Verminderung der Urotoxizität.

Ifosfamid is an alkylating cytostatic agent which appears to differ in its clinical spectrum from the chemically similar cyclophosphamid. So far, however, its pronounced urotoxicity has limited dosage. In spite of prophylactic measures such as forced diuresis and alkalinization of the urine, the treatment has frequently has to be broken off because of macrohematuria and hemorrhagic cystitis. By repeated intravenous administration of sodium-mercapto-ethan-sulfonate (NNI: Mesnum) the urotoxic side effects of ifosfamid can largely be prevented. During 26 cycles of treatment in 18 patients, asymptomatic microhematuria was observed 6 times and macrohematuria only once in a patient with vesico-vaginal fistula. In another case where therapy had had to be discontinued because of hemorrhagic cystitis in spite of conventional prophylaxis, the treatment could be continued without change in the urine sediment under prophylaxis with Mesnum. Mesnum does not affect the antitumoral activity of ifosfamid.

[Granulocyte defence against bacterial infection in diabetes mellitus with special reference to bactericidal activity]. / Granulozytäre Infektabwehr bei Diabetes mellitus unter besonderer Berücksichtigung der Bakterizidie.

Granulocytic defence against bacterial infection has been studied in a group of diabetic patients. With the skin chamber method markedly reduced leukocyte mobilization in vivo which was independent of metabolic compensation was found in all diabetic patients. Investigation of phagocytic function of Latex particles and bacterial killing of E. coli revealed firm dependence on metabolic regulation: in decompensated diabetes mellitus the two function tests were clearly pathological, whereas in the compensated metabolism there was no difference between normal individuals and diabetics. Thus, on granulocytic defence pathway analysis, this appears to confirm that reduction of infection depends on how diabetes is controlled.

[Curability of advanced malignant lymphoma under conditions of modern combination chemotherapy]. / "Heilbarkeit" fortgeschrittener maligner Lymphome unter moderner Kombinations-Chemotherapie.

102 patients from the same oncologic center with malignant lymphomas (52 with Hodgkin's disease, 50 with non-Hodgkin lymphomas) have been analyzed. One population received monochemotherapy only and the other polychemotherapy: the first remission and survival results were published in 1975 on the basis of calculated life expectancy. Now, 3 years later, the same populations are again analyzed and "real" survival data are compared with those calculated. All patients now have a minimal observation time of 6 years. Even if our first published data were too optimistic, polychemotherapy still appears to offer the better life expectancy.