Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.

Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance.     

Subretinal cysticercosis

This paper communicates the history of a case of subretinal cysticercosis in the left eye of a 73-year-old female patient. The only subjective complaints were slightly blurred vision in the affected eye. Serological findings in the blood (Agar-Gel precipitation; IFAT; ELISA) and the aqueous humor were negative. However, according to the literature false-negative serological findings are not uncommon. A stool examination for worm eggs or tapeworm segments was also negative. The remaining lab findings, including hemogram and immunoelectrophoresis, were also normal. Neurocysticercosis was ruled out by clinical and roentgenologic (CCT) diagnosis. As the patient declined treatment with praziquantel, a modern treatment for tapeworm, photocoagulation of the cysticercus was performed at two sittings, first peripheral demarcation and subsequently central coagulation.     

A comparison of different cloned genome segments of Epizootic haemorrhagic disease virus as serogroup-specific probes

Summary The eight largest double-stranded (ds) RNA genome segments of Epizootic haemorrhagic disease virus (EHDV) serotype 2 (Alberta strain) have been cloned. Of these, segments 4, 5, 6, 7, and 8 are represented by clones that correspond in size to those predicted for full-length clones. The different clones were used as nucleic acid probes to study the nucleic acid homology of cognate genes of four different EHDV serotypes. The results indicated that the 4 isolates may be subdivided in two geographic groups which include Ibaraki virus as the sole member of one group and EHDV1 (New Jersey), EHDV2 (Alberta) and EHDV6 (XBM67—isolated in South Africa) as a second. Genome segments 1, 3, 4, 6, and 8 were found to be highly conserved with more than 90% homology amongst cognate genes of three of the members of the EHDV serogroup. Of these, segments 1 and 3 showed the largest degree of homology with cognate genes of members of the BTV serogroup. Segment 6 and 8 probes of EHDV2 (Alberta) on the other hand did not hybridize with BTV dsRNA under conditions of moderate to low stringency and are recommended for use as EHDV group-specific probes.     

Ultrasonic Doppler sonography in ophthalmological practice (the Doppler retina)

This paper presents the case histories of two patients with embolism of the central retinal artery. Non-characteristic headache (lasting longer in one patient than in the other) preceded acute vascular obliteration. In the first case the headache symptom occurred simultaneously with organic findings of stenosis of the carotid artery. The author describes the findings obtained with modified Doppler sonography ("central artery Doppler"). "Retinal hemotachygrams" are analyzed.     

Study of blood flow velocity in the central retinal artery using pulsed Doppler sonography]

Using the method of pulsed-wave ultrasound-Doppler-Sonography (2 MHz-probe; sample volume 10 mm; variable invading depth by using a so-called "flow-pipe"; transmission range 10 mW/m2), the author demonstrates an objective, reproducible and exact clinical test to examine blood-circulation in central retinal artery. Because of the fact, that the angle of ultrasound is nearly zero-degrees to central retinal artery, accuracy of measurement flow velocity is nearly hundred percent. Method can be applied without problems by using intracranial Doppler-Sonography (ICD). It is less expensive than Duplex-Sonographie for instance.     

Factors Influencing the Use of Sentinel Lymph Node Biopsy in the Netherlands

Background

In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare.

Methods

Patients diagnosed with a cutaneous invasive melanoma of ≥1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use.

Results

SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p < 0.001). Patients were less likely to undergo SLNB if they had a melanoma located in the head and neck area (p < 0.001), when they were over 55 years (p = 0.001), and if they had a low SES (p = 0.03). SLNB use was more likely when the diagnosis of melanoma was made in the university hospital (p = 0.045) or when the Breslow thickness was 2.01–4.0 mm (p = 0.03).

Conclusions

The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma ≥1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.     

Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome.

Children with Down syndrome (DS) have an increased risk for leukemia. The prognosis for DS acute myeloid leukemia (AML) is better than for non-DS AML, but the clinical outcome of DS acute lymphoblastic leukemia (ALL) is equal to that of non-DS ALL. Differences in prognosis may reflect differences in cellular drug resistance. In vitro drug resistance profiles were successfully investigated on leukemic cells from 13 patients with DS AML and 9 patients with DS ALL and were compared with reference data from 151 non-DS AML and 430 non-DS B-cell precursor (BCP) ALL. DS AML cells were significantly more sensitive to cytarabine (median, 12-fold), the anthracyclines (2-7-fold), mitoxantrone (9-fold), amsacrine (16-fold), etoposide (20-fold), 6-thioguanine (3-fold), busulfan (5-fold), vincristine (23-fold), and prednisolone (more than 1.1-fold), than non-DS AML cells. Compared with DS ALL, DS AML cells were significantly more sensitive to cytarabine only (21-fold). After short-term exposure to methotrexate, DS AML cells were 21-fold more resistant than non-DS AML cells, but no difference was observed after continuous exposure. DS ALL cells and non-DS BCP-ALL cells were equally sensitive to all drugs, including methotrexate. Normal peripheral blood mononuclear cells from DS and non-DS children without leukemia showed highly resistant drug profiles. It was concluded that the better prognosis of DS AML might, at least partially, be explained by a specific, relatively sensitive drug-resistance profile, reflecting the unique biology of this disease. (Blood. 2002;99:245-251)     

Beiträge zur Kenntnis der chronischen leukämischen Reticuloendotheliosen

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