Nuclear DNA in intestinal carcinoid tumors. A study before and after cytotoxin (streptozotocin and 5-fluorouracil) treatment

Imprint cytology specimens of metastases of intestinal carcinoids obtained by percutaneous biopsy were analysed cytofluorometrically with regard to nuclear DNA records. All untreated tumors (nine cases) exhibited diploid DNA values with a relatively low proliferative activity (less than 2% nuclei in S-phase region). The mean number of tetraploid cells was 5%. Cytofluorometry also was performed on five tumor metastases treated with the cytotoxin streptozotocin and 5-fluorouracil. After treatment, an increase in the number of tetraploid cells (mean value, 30%) was noted, indicating that the cytotoxin treatment (possibly streptozotocin) on the tumor cells in vivo blocked progression from G2 to M phase. The current cytofluorometric analyses show that diploid nuclear DNA records and a low proliferative activity is a characteristic of malignant carcinoid tumors of the intestine. Due to regular DNA histograms in the carcinoid tumors, it is suggested that reliable studies are permitted of the effect of cytotoxins on the different phases of the cell cycle in vivo.     

Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation

Allogeneic haematopoietic cell transplantation (HCT) can cure a variety of non-malignant haematological disorders. Although transplant outcomes for selected patients with severe aplastic anaemia (SAA) and paroxysmal nocturnal haemoglobinuria (PNH) have improved, older age, allo-immunisation from transfusions, prior immunosuppressive therapy and a prolonged time from diagnosis to transplantation are associated with worse outcome. Because of its potent immunosuppressive effects, we investigated a fludarabine-based non-myeloablative conditioning regimen in patients with transfusion-dependent non-malignant haematological disorders at increased risk for graft rejection with conventional transplant conditioning. Twenty-six patients with transfusion dependent/anti-thymocyte globulin (ATG)-refractory SAA, PNH or pure red cell aplasia underwent HCT from a human leucocyte antigen (HLA)-compatible relative. Transplant conditioning consisted of cyclophosphamide (120 mg/kg) and fludarabine (125 mg/m2) with or without ATG. Ciclosporine, alone or combined with mycophenolate mofetil or methotrexate, was used as graft-versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment and transfusion-independence. Twenty-four of 26 patients are alive at a median of 21 months following transplantation. Although a high cumulative incidence of acute (65% grades II-IV, 54% grades III-IV) and chronic GVHD (56%) was observed, only one patient died from transplant-related causes (cumulative incidence 7%). These data show that HCT following fludarabine-based non-myeloablative conditioning results in durable engraftment and excellent survival in SAA and PNH patients at high risk for graft rejection.     

Narratives about resuscitation--family members differ about presence.

BACKGROUND: Healthcare professionals disagree about admitting family members into the resuscitation room. AIM: The aim of this study was to illuminate family members' experiences and views about being present in the resuscitation room with a relative requiring resuscitation. RESULTS: Seventeen family members were interviewed. Their narratives were analysed using content analysis. The main theme was interpreted as family members being "afraid of disturbing the resuscitation efforts, meaning that the most important person for them was the patient". Three groups of persons were in focus: patients, family members, and healthcare professionals. The theme related to the patient was "to be caring for the good of oneself and others" describing what family members believed the patient would want and what they themselves would have wanted if in the same situation. The themes related to family members were "to be dependent on the interplay between trusting oneself and advocating the patient and to be sensitive to one's own emotions and to be reasonable". The theme related to healthcare professionals was "to submit to or ignore the guidance of the healthcare professionals". CONCLUSION: Family members differ about their presence in the resuscitation room. Omnipresent in the narratives was being afraid of disturbing the resuscitation efforts.     

Immunoglobulins of the non-galliform birds: antibody expression and repertoire in the duck

Galliform and non-galliform birds express three immunoglobulin isotypes, IgM, IgA and IgY. Beyond this we should not generalize because differences in gene organization may have functional consequences reflected in the immune response. At present, studies on non-galliform birds are largely restricted to ducks. Ducks express an alternatively spliced form of their IgY heavy chain (upsilon) gene, the IgY(DeltaFc), that lacks the Fc region and Fc-associated secondary effector functions. It is not known how common the expression of the IgY(DeltaFc) is among birds, nor the functional consequences. It is also not known whether the unusual organization of the duck IgH locus, also shared with the chicken, having the gene order of mu, alpha and upsilon, with alpha inverted in the locus, is unique to the galloanseriform lineage. Ducks, like chickens, have a single immunoglobulin light chain of the lambda (lambda) type. Evidence suggests that ducks, like chickens, generate their immunoglobulin repertoire through a single functional rearrangement of the variable (V) region, and generate diversity through gene conversion from a pool of pseudogenes. In Southern blots of germline and rearranged bursal DNA, both the heavy and light chain loci of ducks appear to each undergo one major rearrangement event. For both heavy and light chains, the functional V region element and the pseudogenes appear to consist of a single gene family. Further analysis of 26 heavy chain joining (JH) and 27 light chain JL segments shows there is use of a single J segment in ducks, which is diversified presumably through somatic mutations and gene conversion events. Despite this limitation on the rearrangement of immunoglobulin genes, analysis of 26 DH and 122 VL sequences suggests that extensive sequence diversity is generated.     

Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy

Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.     

Aberrant cellular immune responses in humans infected persistently with parvovirus B19

A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study, ex-vivo cellular immune responses were assessed by enzyme linked immunospot assay mounted against the majority of the translated viral genome. Compared to seropositive healthy individuals, individuals with B19 persistence (2-8 years) showed larger number of responses to the structural proteins (P = 0.0022), whereas responses to the non-structural protein were of lower magnitude (P = 0.012). These observations provide the first findings of immunological discrepancies between individuals with B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion.