Early clearance of hairy cell leukaemia in the bone marrow after first-line treatment with cladribine predicts a favourable outcome.

First-line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long-lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression-free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine.

Pan-American marine coastal distribution of the acanthocephalan Profilicollis altmani based on morphometric and phylogenetic analyses of cystacanths from the mole crab Emerita brasiliensis.

Thorny-headed acanthocephalan worms of the genus Profilicollis are widely distributed in the oceans of the world and present complex life cycles with intermediate and definitive hosts. The genus is still poorly known, with an unstable taxonomy and, for most species, incompletely characterized geographical distributions. In this study, based on molecular and morphological evidence, we report that the species Profilicollis altmani is also distributed along the South American Atlantic coast, using the mole crab Emerita brasiliensis as an intermediate host. As such, our record shows that P. altmani has a Pan-American distribution where five species of Emerita are utilized as intermediate hosts.

The phylogeny and life cycle of two species of Profilicollis (Acanthocephala: Polymorphidae) in marine hosts off the Pacific coast of Chile.

Resolving complex life cycles of parasites is a major goal of parasitological research. The aim of this study was to analyse the life cycle of two species of the genus Profilicollis, the taxonomy of which is still unstable and life cycles unclear. We extracted individuals of Profilicollis from two species of crustaceans (intermediate hosts) and four species of seagulls (definitive hosts) from sandy-shore and estuarine habitats along the south-east Pacific coast of Chile. Mitochondrial DNA analyses showed that two species of Profilicollis infected intermediate hosts from segregated habitats: while P. altmani larvae infected exclusively molecrabs of the genus Emerita from fully marine habitats, P. antarcticus larvae infected the crab Hemigrapsus crenulatus from estuarine habitats. Moreover, P. altmani completed its life cycle in four seagulls, Chroicocephalus maculipennis, Leucopheus pipixcan, Larus modestus and L. dominicanus, while P. antarcticus, on the other hand, completed its life cycle in the kelp gull L. dominicanus. Accordingly, our results show that two congeneric parasites use different and spatially segregated species as intermediate hosts, and both are capable of infecting one species of definitive hosts. As such, our analyses allow us to shed light on a complex interaction network.

A new allopatric lineage of the rodent Deltamys (Rodentia: Sigmodontinae) and the chromosomal evolution in Deltamys kempi and Deltamys sp.

Deltamys Thomas 1917 is a poorly studied and rarely collected taxon of Akodontini (Sigmodontinae). The single described species, Deltamys kempi (DKE), has a basic karyotype with a diploid number of 2n = 37 in males and 2n = 38 in females, a fundamental number FN = 38 for both sexes, and an X(1)X(1)X(2)X(2)/X(1)X(2)Y sex determination system. Herein, a new allopatric form, Deltamys sp. (DSP), is reported, based on specimens from southern Brazil, with 2n = 40, FN = 40 and XX/XY sex chromosomes. We describe the karyotype and mechanism of chromosomal differentiation between both Deltamys complements. Phylogenetic analyses, based on the complete sequence (1,140 bp) of the mitochondrial cytochrome b gene, grouped Deltamys sp. as sister species to D. kempi, with up to 12% genetic divergence between them. The GTG-banding patterns show complete autosomal correspondence between D. kempi and Deltamys sp. and identify a tandem rearrangement involving DSP7, DSP19 and DKE4 that is responsible for the differences in 2n and FN. Chromosome painting with Akodon paranaensis chromosome 21 (a small metacentric akodont marker) paint revealed total homology with the smallest acrocentric Deltamys sp. chromosome, DSP19. This suggests the occurrence of a pericentric inversion or centromeric shift when compared to other akodontines, with a posterior tandem rearrangement giving rise to DKE4. In DKE, large blocks of pericentromeric constitutive heterochromatin are present on the autosomes and the X, and the Y/autosome has an entirely heterochromatic short arm. In DSP, small heterochromatic blocks are observed on autosomes and X, and the Y is a very small, mostly heterochromatic acrocentric. The cytogenetic analyses suggest that the Deltamys sp. karyotype is ancestral, with the derived condition resulting from a tandem fusion (DSP7 + DSP19) and the Y/autosome translocation giving rise to the multiple sex chromosome system. The autosomal rearrangements, the differences in CBG-banding patterns and Ag-NOR localization, as well as the presence of X(1)X(1)X(2)X(2)/X(1)X(2)Y and XX/XY sex determination mechanisms, possibly acting as a reproductive barrier, and the phylogenetic position within the Deltamys genus, with high genetic divergence, call for a taxonomic review of the genus.

[Overexpression of laminine-5( LN-5) in peritoneal lavage of colorectal cancer patients preliminary results]. / Overexpression della laminina-5 (LN-5) nel lavaggio peritoneale di pazienti con carcinomi del grosso intestino. Risultati preliminari.

Recent studies show that interaction between LN (heterotrimeric protein formed by a3/b3/g2 chains) and cancer cells plays an important role in tumor invasion, also in colorectal cancer. The overall survival was significantly worse in patients with free peritoneal cancer cells(FPTCs): detection of FPTCs after curative surgery is a challenge, because could improve staging and prognosis. Peritoneal citology is the current standard procedure with very low sensivity. We aimed to study the expression of LN5 in the peritoneal lavage of colorectal cancer pts and in controls with semiquantitative reverse trancriptase-polymerase chain reaction (RT-PCR). LN-5 overexpression was evaluated observing PCR- products intensity at electrophoresis: high intensity is correlated to overexpression. Pre and post-operative peritoneal lavages of 30 pts with colorectal cancer (13M;17F), with median age of 69 (58-84), and of 10 controls, were analyzed by conventional cytology and a semiquantitative RT-PCR. No cancer pts showed pre/postoperative negative cytology and did not express LN-5. In cancer pts. cytology was positive in 2 pts in pre/postoperative lavage. LN-5 overexpression was observed in 56,6% preoperatively and in 76,6% postoperatively. LN-5 g 2 chain was most frequent chain. Our study suggests a relationship between LN-5 and FPTCs, as shown by the low expression of lamimine in controls. LN-5 could be a useful marker to identify a subgroup of early-stage patients at increased risk of recurrence; moreover, mortality seems to correlated to LAMB3 chain. The diagnostic accuracy could be improved by using a quantitative RT-PCR or western-blot and detecting serum laminine. Finally, to validate these findings a larger number of pts with follow-up study is required.

[Budd-Chiari syndrome and splanchnic vein thrombosis: masked myeloproliferative neoplasms and JAK2V617F]. / Sindrome di Budd-Chiari e trombosi delle vene splancniche: neoplasie mieloproliferative mascherate e mutazione di JAK2V617F.

The Budd-Chiari Syndrome (BCS) and the splanchnic vein thrombosis are characterized by hepatic venous outflow obstruction, generally due to venous thrombosis. These rare diseases are usually caused by multiple concurrent factors, including acquired and inherited thrombophilias. Since the diagnosis of myeloproliferative neoplasms (MPNs) is often difficult in patients with BCS and splanchnic vein thrombosis because of spleen enlargement, secondary pancytopenia and bleeding disorders, recent observations have included in the diagnostic work-up the analysis of the JAK2 mutation. The revision of several recent reports clarify the importance of the JAK2V617F detection in the diagnostic work-up of the BCS and splanchnic vein thrombosis, allowing the demonstration of masked MPNs among these cases that may benefit, in the near future, of target molecular therapies directed toward the JAK2 mutation.

Mild ring 17 syndrome shares common phenotypic features irrespective of the chromosomal breakpoints location.

Ring 17 syndrome is a rare disorder with clinical features influenced by the presence or deletion of the Miller-Dieker critical region (MDCR). Presence of the MDCR is associated with a mild phenotype, including growth delay (GD), mental retardation (MR), seizures, cafè au lait skin (CALS) spots and minor facial dysmorphisms. Previous studies have been mainly focused on this locus providing poor information about the role of other genes located on the p- and q-arms. Here, we used bacterial artificial chromosome (BAC)/P1 artificial chromosome (PAC) and fosmid clones as fluorescence in situ hybridization (FISH) probes to perform a cyto-molecular analysis of a ring 17 case and found that the breakpoints were close to the telomeric ends. METRNL is the sole gene located on the q-arm terminal end, whereas two open reading frames and the RPH3AL gene are located on the terminal p-arm. To detect possibly unrevealed small deletions involving the transcription units, we used subcloned FISH probes obtained by long-range polymerase chain reaction (PCR), which showed that the investigated regions were preserved. Comparing our findings with other reports, it emerges that different breakpoints, involving (or not) large genomic deletions, present overlapping clinical aspects. In conclusion, our data suggest that a mechanism based on gene expression control besides haploinsufficiency should be considered to explain the common phenotypic features found in the mild ring 17 syndrome.

Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: further evidence for the arbitrary nature of current classification systems.

From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2-8) developed a peripheral monocytosis >1 x 10(9)/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.

Traumatic anterior glenohumeral instability: quantification of glenoid bone loss by spiral CT.

PURPOSE: We evaluated the role of computed tomography (CT) for quantifying glenoid bone defects in patients with anterior glenohumeral instability and assisting in planning the most appropriate type of surgery. MATERIALS AND METHODS: From January to November 2006, 93 patients were studied by spiral CT with multiplanar reconstructions (MPR) for recurrent posttraumatic anteroinferior instability, chronic multidirectional instability and recurrent glenohumeral dislocation after surgical stabilisation. RESULTS: Quantitative CT enabled us to measure bone defects of the anteroinferior glenoid in terms of area (mm(2)) or surface percentage. Glenoid osseous defects were classified as small (<15%), medium (15%-20%), and large (>20%). CONCLUSIONS: CT quantification of glenoid bone loss is very accurate as well as rapid, simple and easily reproducible. CT therefore provides an important contribution to preoperative selection of patients, assisting in directing those with <20% bone loss towards arthroscopic capsular repair.

Acute myelogenous leukemia in elderly patients not eligible for intensive chemotherapy: the dark side of the moon.

BACKGROUND: Acute Myelogenous Leukemia (AML) is a common disease in people aged>60 years. About 50% of the patients are not eligible for aggressive chemotherapy (CT) and are only managed with conservative approaches. Results in this subset of patients have not been reported so far. PATIENTS AND METHODS: We retrospectively evaluated 244 consecutive elderly AML patients (M/F 143/101, median age 72 years, range 60-90) diagnosed at our institution from January 1989 to December 1998 and not eligible for intensive CT. Eighty-nine patients (36.5%) had evolved from previous myelodysplasia (sAML). Fifty-three out of 192 (26.4%) patients with available bone marrow (BM) analysis had oligoblastic leukaemia (blasts<40% and WBC<15x10(9)/l). RESULTS: Sixty-seven patients (27.5%) were managed with supportive treatment only. One hundred seventy-seven patients (72.5%), in order to control disease, received conservative CT, consisting of Hydroxyurea (HU) (127 patients, 71.7%), Cytarabine and 6-Thioguanine (39 patients, 22%) or low-dose cytarabine (11 patients, 6.3%). Median overall survival was 179 days (1-3278) with 50 patients (20.5%) surviving>12 months. Older age (>75 years), poor WHO PS (>2), lower PLT levels (<50x10(9)/l) and higher absolute peripheral blast count (>5x10(9)/l) showed a negative prognostic impact on survival in multivariate analysis. CONCLUSIONS: Our data outline the great heterogeneity of elderly AML patients not eligible for intensive CT. A simple scoring system including easily evaluable parameters, which could distinguish subjects with different prognosis, is proposed. Moreover, randomized studies in order to establish best conservative approaches are warranted.

Solutions for organ perfusion and storage: haemorheologic aspects.

BACKGROUND: The hydroxyethyl starch (HES) contained in University of Wisconsin (UW) solution causes erythrocyte aggregation. The effect of UW on red blood cell (RBC) deformability is still unclear. HES-free preservation solutions, Celsior (CS) and Custodiol (CU) are available. In this study we evaluated whether they really showed a reduced aggregating and stiffening effect on RBCs when compared with UW. We was also evaluated the effect of these solutions on cellular membranes by measuring acetylcholinesterase (AChE), which is a marker of RBC membrane integrity. METHODS: The determination of RBC aggregation and deformability was performed by a laser-assisted optical rotation cell analyzer (LORCA). AChE measurement was performed with a spectrophotometric technique. RESULTS: The mean RBC aggregation index (AI) measured in pure blood control samples was 28.00 +/- 0.73%. The AI measured samples containing UW was 38.82 +/- 1.58%. In samples with CS, it was 13.307 +/- 0.64% and in samples with CU the mean AI was 12.47 +/- 0.42%. Also the RBC aggregating time was quicker in presence of UW compared with controls. AChE concentration in blood was 3.043 +/- 0.4 nmol. CS and UW did not produce any significant change; a significant reduction was found when CU was added to blood, namely 1.975 +/- 0.1 nmol (P < .05). The use of UW or CS or CU did not result in any significant change in RBC deformability. DISCUSSION: CS and CU solutions do not aggregate erythrocytes, whereas Wisconsin does massively. CU causes an alteration of RBC cellular membrane as demonstrated by depletion of AChE.

Mainz Pouch II technique: 10 years' experience.

OBJECTIVE: To report the long-term results with the Mainz Pouch II procedure. PATIENTS AND METHODS: Between 1990 and 2000 a Mainz Pouch II ureterosigmoidostomy was used in 123 patients (49 females and 74 males, mean age 43.6 years, range: 1-73). The indications for urinary diversion were cystectomy for bladder cancer in 92 patients, bladder exstrophy and/or incontinent epispadias in 26, irreparable traumatic loss of the sphincteric urethra in four and cloacal malformation (sinus urogenitalis) in one. In all, 102 patients with a follow-up of >/= 12 months were evaluated (mean 46.2 months). RESULTS: Day- and night-time continence rates were 97% and 95%, respectively. The remaining patients occasionally lose some drops of urine during coughing or straining, or reported minimal soiling of undergarments during the night. The mean voiding frequency was six during the day and once at night. There were 14 ureteric implantation stenoses (7.2% of 194 evaluated reno-ureteric units) and they were treated successfully by open repair (13) or antegrade balloon dilation (one). For metabolic disturbances, 69% of the patients had a capillary base excess of <-2.5 mmol/L and use oral alkalinizing drugs to prevent hyperchloraemic acidosis. There was no clinically evident metabolic acidosis. CONCLUSION: Applying the principles of detubularization and spherical reconfiguration to create a low-pressure reservoir and stratifying ureteric implantation between submucosal and serous-lined extramural tunnel techniques succeeded in giving better continence rates and long-term preservation of the upper urinary tract than a classical ureterosigmoidostomy. The Mainz Pouch II ureterosigmoidostomy is simple and reliable as a viable alternative for continent urinary diversion in selected patients.

[Expression of tissue factor and vascular endothelial growth factor in colorectal carcinoma]. / Espressione del tissue factor e del vascular endothelial growth factor nel carcinoma del colon retto.

Tissue factor (TF) and vascular endothelial growth factor (VEGF) play an important role in tumor progression and metastasis. We analyzed their expression in the carcinoma and normal mucosa of 53 colorectal cancer patients. VEGF levels were significantly higher in the tumor and correlated with TF expression. No correlation was found with tumor stage. TF may influence tumor growth and metastasis by modulating VEGF expression and neoangiogenesis.

[Gene expression of the MAGE-1, -3, and -6 antigens in hepatic carcinoma]. / Espressione genica degli antigeni MAGE-1, -3, -6 nell'epatocarcinoma.

MAGE is a family of genes specifically associated to human melanoma, but also found in hepatocellular carcinoma (HCC). In this study we evaluated the expression of such genes in 41 HCC patients, their correlation with pathological and clinical aspects of cancer, and the impact on prognosis. MAGE are expressed in most of HCC samples (28/41), no correlation was found with type and stage but they may be used as potential target for IT.

Attachment: a biological basis for the therapeutic relationship?

When faced with loss, illness, distress, or threat, we tend to seek out an attachment figure from which we can obtain comfort and protection. The attachment theory, an evolutionary biosocial theory of development, postulates that the propensity to make strong emotional bonds to a differentiated and preferred person, conceived as stronger and or wiser, is a basic component of the human nature, distinct from feeding and sexuality. Attachment behaviour is present in germinal form in the neonate and continues to be present "from the cradle to the grave". On the basis of day-to-day experience of the responsiveness and accessibility of caregivers, children build internal working models of attachment figures and of themselves. Expectations about the likely behaviour of others, initially preverbal, characterize the approach of the individual to other persons. Internal working models are successively modified on the basis of recent experience. The therapeutic relationship can be viewed as the seeking of a secure base, from which the patient and the therapist, in a joint effort, explore the patient's attachment history and the painful feelings associated with it. The therapist, responsive to the patient's verbal and non-verbal attachment signals, is viewed as a supplementary attachment figure.

Granulocytic sarcoma with breast and skin presentation: a report of a case successfully treated by local radiation and systemic chemotherapy.

Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders, but can also occur without overt hematologic disease, i.e. in patients with a normal bone marrow and no history of acute myelogenous leukemia. This primary extramedullary lesion may indeed represent a diagnostic and therapeutic dilemma for both the hematopathologist and oncologist. We describe a case of GS diagnosed in a nonleukemic patient and review the literature regarding the pathologic features and treatment of this condition.