Negative sural nerve biopsy in neurolymphomatosis

Patients with non-Hodgkin’s lymphoma occasionally develop widespread invasion of peripheral nerves by tumor cells or neurolymphomatosis (NL). Clinically this usually results in asymmetrical, progressive, and painful polyneuropathy. Diagnosis rests on the identification of tumor cells in peripheral nerves. To avoid false-negative biopsy findings in patients with malignant lymphomatous infiltration of peripheral nerves it has been recommended to biopsy clinically involved nerves. We present two patients with histologically confirmed NL in whom sural the nerve biopsy finding was negative despite clinical and neurophysiological evidence of involvement of the sural nerve a. The clinical features of NL are reviewed. Some patients with neurolyphomatosis have only focal or proximal involvement of nerves, requiring the biopsy of an affected part of these nerves. Magnetic resonance imaging may be useful in identifying affected nerves. Received: 28 January 1999 Received in revised form: 7 July 1999 Accepted: 17 July 1999     

Drugs hazardous to healthcare workers. Evaluation of methods for monitoring occupational exposure to cytostatic drugs.

We review the literature concerning possible health risks for individuals (e.g. healthcare workers and pharmaceutical plant employees) occupationally exposed to cytostatic drugs. Cytostatic drugs possess toxic properties and may therefore cause mutagenic, carcinogenic and teratogenic effects. Hence, individuals handling these drugs in the course of their employment may face health risks. For this reason, it is important to monitor occupational exposure to these drugs. An overview of exposure monitoring methods is presented and their value is discussed. Most studies involve nonselective methods for biological monitoring and biological effect monitoring, such as the urinary mutagenicity assay and analysis of chromosomal aberrations and sister-chromatid exchanges in peripheral blood lymphocytes. The disadvantages of these biological methods are that their sensitivity is low and it cannot be proved beyond any doubt that the results found were caused by occupational exposure to cytostatic drugs. For occupational health services it is important to have sensitive and specific methods for monitoring exposure to cytostatic drugs. One of the most promising methods seems to be the determination of cyclophosphamide in urine using gas chromatography-tandem mass spectrometry. Several studies have demonstrated exposure to cyclophosphamide and other cytostatic drugs, even when protective measures were taken and safety guidelines were followed. To estimate the magnitude of any health effects arising from this exposure, we calculated the risk of cancer due to occupational exposure to cyclophosphamide on the basis of available human and animal dose-response data and the amounts of cyclophosphamide found in urine. The initial results show an extra cancer risk for pharmacy technicians and nurses.     

Detection of the tick-borne encephalitis virus (TBEV) in ticks in several federal “Länder” of Germany by means of the polymerase chain reaction (PCR) — Characterization of the virus

Summary The aim of the present study was to analyse the current epidemiological situation with respect to TBE in the new federal Länder of Germany and in Saarland through detection of the TBEV genome in unengorged ticks using an RT-PCR technique. 22,273 ticks (Ixodes ricinus) were collected in the five new Länder (and some in Bavaria and Baden-Württemberg) and divided into 294 pools. It was possible to detect TBEV RNA in six pools of ticks from Mecklenburg Western-Pomerania [4], Brandenburg [1], Thuringia [1] (and in three pools from Bavaria and Baden-Württemberg). The nucleotide sequence data of the PCR products were analysed and compared. In Saarland 8,780 ticks were collected in 70 habitats from all the geographic regions and analysed using the PCR in 21 pools; two pools produced positive PCR signals (Saarlouis, Perl). We cannot as a result make a general recommendation that TBE-immunization be introduced in Saarland and in the new federal Länder of Germany. In Germany, however, TBE immunoprophylaxis in Bavaria and Baden-Württemberg is very important.

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Nachweis des Virus der Frühsommer-Meningoenzephalitis in Zecken einiger Bundesländer mittels Polymerase-Kettenreaktion und nähere Charakterisierung des Virus

Zusammenfassung Das Ziel der vorgelegten Studie ist die Einschätzung der aktuellen epidemiologischen Situation der Frühsommer-Meningoenzephalitis in den fünf neuen Bundesländern und im Saarland mit Hilfe des Nachweises von FSMEV-RNA in ungesogenen Zecken (Ixodes ricinus) durch eine RT-PCR-Technik. 22 273 Zecken wurden in den fünf neuen Ländern (einige auch in Bayern und Baden-Württemberg) gesammelt und in 294 Pools untersucht. Der spezifische RNA-Nachweis gelang viermal in Zecken aus Mecklenburg-Vorpommern, einmal in solchen aus Brandenburg und einmal aus Thüringen. In Bayern und Baden-Württemberg gelang der Virus-RNA-Nachweis dreimal. Die Sequenzdaten der PCR-Amplifikate zeigten, auch im Vergleich mit denen des Prototypstammes Neudoerfl, den hohen Grad der Konservierung im Bereich der 5 NCR. 8780 saarländische Zecken aus allen Gebieten des Bundeslandes wurden in 21 Pools untersucht, positive PCR-Signale konnten in zwei Pools aus Saarlouis und Perl und Umgebung gefunden werden. Der relativ seltene FSMEV-RNA-Nachweis in den neuen Ländern und im Saarland berechtigt nicht, eine generelle Impfempfehlung für diese Gebiete zu geben. Ein Impfschutz sollte jedoch vor Einreise in die Endemiegebiete Bayerns und Baden-Württembergs bestehen.

     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: FUNCTIONS OF ANGIOTENSIN PEPTIDES IN THE ROSTRAL VENTROLATERAL MEDULLA

• 1 It was first shown several years ago that the rostral part of the ventrolateral medulla (VLM) contains a high density of receptor binding sites for angiotensin II (AngII). In the present paper we briefly review recent studies aimed at determining the actions of both exogenous and endogenous angiotensin peptides in the rostral VLM, as well as their specific sites of action.
• 2 The results of these studies have shown that angiotensin peptides can excite pressor and sympathoexcitatory neurons in the rostral VLM, but do not appear to affect non-cardiovascular neurons in this region.
• 3 It is known that pressor neurons in the rostral VLM include both catecholamine and non-catecholamine neurons. There is evidence that, at least in conscious rabbits, both of these types of neurons are activated by AngII. The specific endogenous angiotensin peptide or peptides that affect pressor neurons in the rostral VLM have not yet been definitively identified.
• 4 It is also possible that different angiotensin peptides may have different effects on pressor neurons in the rostral VLM, mediated by different receptors. Further studies will be needed to define these different functions as well as the specific receptors and cellular mechanisms that subserve them.

     

The stereoisomers of 17α-[123I]iodovinyloestradiol and its 11α-methoxy derivative evaluated for their oestrogen receptor binding in human MCF-7 cells and rat uterus,and their distribution in immature rats

We studied the potential of both stereoisomers of 17-[¹²³I]iodovinyloestradiol (E- andZ-[¹²³I]IVE) and of 11-methoxy-17-[¹²³I]iodovinyloestradiol (E-andZ-[¹²³I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[¹²³I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their¹²³I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[¹²³I]MIVE being higher than that ofE- andZ-[¹²³I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [¹²³I]MIVE. The uterus-to-blood uptake ratio was higher for^E-[¹²³I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [¹²³I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[¹²³I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted.     

Occupational exposure to antineoplastic agents at several departments in a hospital

Summary The occupational exposure to cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5FU), and methotrexate (MTX) of 25 pharmacy technicians and nurses from four departments of a hospital was investigated. Previously developed methods for the detection of exposure to some antineoplastic agents were validated. Exposure to CP, IF, 5FU, and MTX was measured by the analysis of these compounds in the environment (air samples and wipe samples from possible contaminated surfaces and objects). Contamination of the work environment was found not only on the working trays of the hoods and on the floors of the different rooms but also on other objects like tables, the sink unit, cleaned urinals and chamber pots, and drug vials and ampules used for preparation and packing of drugs. The gloves used during preparation of the drugs and during cleaning of the hoods were always contaminated. The uptake of CP or IF was determined by the analysis of both compounds in urine. CP or IF was detected in the urine of eight pharmacy technicians and nurses. The amounts ranged from < 0.01 to 0.5 g (median: 0.1 g). CP and IF were found not only in the urine of pharmacy technicians and nurses actively handling these compounds (n = 2) but also in the urine of pharmacy technicians and nurses not directly involved in the preparation and administration of these two drugs (n = 6). CP and IF were excreted during different periods ranging from 1.40 to 24.15 h after the beginning of the working day, suggesting different times of exposure, different exposure routes, and/or interindividual differences in biotransformation and excretion rate for these compounds. The urinary CP and IF determination method seems to be sensitive and suitable for monitoring the exposure to and measuring the uptake of these toxic compounds by pharmacy technicians and nurses during occupational activities.     

Detection of contamination with antineoplastic agents in a hospital pharmacy department

The contamination with fluorouracil, cyclophosphamide and methotrexate was studied in a hospital pharmacy department where these drugs were prepared. In the preparation room, air samples were taken before and during preparation of the drugs. Methotrexate was detected in one sample which was collected during preparation (0.3g/m³). Spot samples were taken in the vertical laminar airflow safety hood before and after preparation of the drugs and after cleaning of the hood. Contamination of the laminar airflow hood was: cyclophosphamide: 1–160 ng/cm²; fluorouracil: 10–62 ng/cm² and methotrexate: 2–633 ng/cm². Spot samples from the floor in front of and beneath the laminar airflow hood showed contamination with especially fluorouracil (48–236g/m²). The gloves used during preparation of the drugs were contaminated mainly with fluorouracil (5–980 ng/cm²). Urine samples from two workers involved in the preparation of the drugs were analysed for unmetabolized cyclophosphamide; it was not detected. Although no uptake of cyclophosphamide was established, it is shown that the methods for measurement of cyclophosphamide, fluorouracil and methotrexate in the preparation room are applicable for the control of occupational exposure to these drugs.     

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with β-lactams and aminoglycosides

Summary We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

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Teicoplanin in Kombination mit -Laktamen und Aminoglykosiden bei Knochenmarktransplantatempfängern mit schwerer Sepsis

Zusammenfassung Wir untersuchten Teicoplanin bei vermuteten grampositiven Infektionen nach ungenügendem Ansprechen auf die anfängliche Kombinationstherapie von -Laktam-Antibiotika und Aminoglykosiden. Alle 20 in dieser Studie erfaßten Patienten wurden entweder allogen (8 Patienten) oder autolog (12 Patienten) transplantiert mit folgenden Grundkrankheiten: akute myeloische Leukämie (AML), Non-Hodgkin-Lymphom (NHL) oder andere maligne Erkrankungen. Alle Patienten, die eine primäre Septikämie unbekannten Ursprungs entwickelten (18 Patienten) oder unter einer Katheter-bedingten Septikämie (2 Patienten) litten, wurden mit 400 mg Teicoplanin behandelt. Die Verabreichung von Teicoplanin erfolgte einmal täglich intravenös in Kombination mit einem Cephalosporin und einem Aminoglykosid (Ceftazidim 2 g i.v., 3 ×/die, Netilmicin 400 mg, 1 ×/die). Alle behandelten Patienten sprachen auf diese Therapie an. 19 Patienten wurden klinische geheilt, ein Patient besserte sich unter dieser Therapie. Die Kombinationstherapie wurde gut vertragen, unerwünschte Arzneimittelwirkungen traten während der Studie nicht auf. Wir beobachteten kein verzögertes Angehen des Knochenmarks oder eine Verlängerung der Thrombozytopenie unter dieser Behandlung im Vergleich zu anderen knochenmarktransplantierten Patienten, die diese antimikrobielle Behandlung nicht erhielten. Unsere Ergebnisse zeigen, daß Teicoplanin ein wirksames und gut verträgliches Antibiotikum für knochenmarktransplantierte Patienten ist, die primär nicht auf die Kombinationstherapie mit -Laktam-Antibiotika und Aminoglykosiden ansprechen.