Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial.

Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods).

Bone marrow cytokeratin 19 mRNA level is an independent predictor of relapse-free survival in operable breast cancer patients.

Purpose: To study the prognostic significance of elevated cytokeratin 19 (CK19) mRNA levels in the bone marrow (BM) of operable breast cancer patients.

Patients And Methods: From 1998 to 2000, BM was collected from 195 consecutive breast cancer patients immediately prior to surgery and from 34 healthy volunteers. The patients received surgical and adjuvant treatment according to national guidelines at the time.

An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy.

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.

Modulation of the systemic inflammatory response by recombinant human interleukin-11: a prospective randomized placebo controlled clinical study in patients with hematological malignancy.

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.

Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients.

Conventional therapies for primary chronic cold agglutinin disease (CAD) are ineffective, but remissions after treatment with the anti-CD20 antibody rituximab have been described in a small, prospective trial and in some case reports. In this study we report on 37 courses of rituximab administered prospectively to 27 patients. Fourteen of 27 patients responded to their first course of rituximab, and 6 of 10 responded to re-treatment.

Serial quantitative PCR analysis of bone marrow samples from breast cancer patients to monitor systemic micrometastases.

Background: We have previously developed a quantitative calibrated PCR assay to measure cytokeratin 19 (CK19) expression in haematopoietic tissue in order to detect systemic micrometastases.

Patients And Methods: Serial measurements of CK19 expression in bone marrow of patients with primary breast cancer were performed at operation, at 3 weeks and 6 months postoperatively.

Results: Reference values for CK19 expression were established by analysing bone marrow samples from 48 healthy female volunteers or patients without epithelial cancer.

Fluorescence-based method for measuring and determining the mechanisms of recombination in quantitative PCR.

We quantitatively measured the amount of recombinant molecules formed during PCR when the break point cluster region (BCR) cDNA was coamplified with a homologous internal standard using Taq polymerase. The products were analysed under denaturing conditions using capillary electrophoresis followed by detection of the fluorescently labelled products and the recombinant molecules were differentiated by their size. Early termination of chain synthesis and reannealing of incomplete fragments, to each other as well as to BCR and internal standard, is one mechanism for generating recombinants during PCR since prolonging extension time reduced, but did not totally suppress recombinant molecule formation.

Quantitative analysis of cytokeratin 20 gene expression using RT-PCR and capillary electrophoresis with fluorescent DNA detection.

Objective: We developed a quantitative reverse-transcription polymerase chain reaction (RT-PCR) to determine CK20 expression in colorectal tumor and hematopoietic tissue.

Design And Methods: Our method incorporates a calibrated PCR with an internal competitor and an external standard.

Results: The RT-PCR assay is sensitive detecting 10 target molecules of CK20 in solution with one round of 38 amplification cycles.

Sensitive and quantitative one-step polymerase chain reaction using capillary electrophoresis and fluorescence detection for measuring cytokeratin 19 expression.

An improved quantitative assay to measure cytokeratin 19 (CK19) expression has been developed. The assay utilizes reverse transcription and a one-step polymerase chain reaction (PCR), with capillary electrophoresis and fluorescent labelling, to separate and detect the PCR products. Calibration curves were constructed from a serial dilution of CK19 cDNA coamplified with a fixed amount of CK19 internal standard, which was found to be linear between 10 and 500 molecules.

Clinical immunology of chronic cold agglutinin disease.

We studied clinical and immunological characteristics of 15 patients with chronic cold agglutinin disease (CAD). Mean age at disease debut was 68 years for female and 67 years for male patients. The patients had no signs of other autoimmune diseases.

[Chronic myeloid leukemia in health regions 1, 3, 4 and 5 during the period 1990-96].

The aim of the present investigation was to obtain information about treatment, clinical course and outcome for all patients with chronic myeloid leukaemia through a six-year period in a defined part of Norway. A total number of 141 patients fulfilled the diagnostic criteria. This is equivalent to 0.

[Secondary myelodysplastic syndrome].

Secondary or therapy related myelodysplastic syndrome may develop following treatment with alkylating agents and radiotherapy. The condition may also follow high dose therapy for malignant lymphomas. We describe two patients who developed secondary myelodysplasia.

Chronic cold agglutinin disease of the "idiopathic" type is a premalignant or low-grade malignant lymphoproliferative disease.

We investigated the clinical, pathological, and immunological features of "idiopathic" cold agglutinin disease (CAD) in a population-based study. Fourteen patients were studied, giving a prevalence of about 14 per million with a mean age of 75 years. Haemolysis was present in all cases, but only eight patients had clinical symptoms of peripheral haemagglutination.

Thrombotic microangiopathy in a patient with chronic myelogenous leukemia on hydroxyurea.

We describe the case of a 57-year-old woman with chronic myelogenous leukemia who was on hydroxyurea and developed a fatal thrombotic microangiopathy with renal, retinal and central nervous system involvement. There was no evidence of medullary or extramedullary leukemia transformation. Repeated examinations of the peripheral blood film revealed only minimal morphological changes of microangiopathic hemolysis.

[Diagnosis and follow-up in chronic myeloid leukemia. Detection and quantification of specific transcripts with the help of reverse transcriptase-polymerase chain reaction].

The Philadelphia chromosome in cells of patients with chronic myeloid leukemia and acute lymphoblastic leukemia can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR). We have tested two new methods for this purpose. For diagnostic purposes, three different BCR-ABL translocations (b3a2, b2a2 and ela2) can be detected in a multiprimed, one step PCR reaction.

Serum concentrations of tumour necrosis factor-alpha during chemotherapy-induced leukopenia in patients with acute leukaemia and bacterial infections.

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) increase during septicaemia in previously healthy individuals. To investigate whether a similar increase in TNF-alpha can be seen in severely immunocompromised patients with acute leukaemia and chemotherapy-induced leukopenia, serum TNF-alpha was analysed in leukopenic patients with bacterial infections. Pretherapy serum levels of TNF-alpha were decreased in leukaemia patients compared with healthy controls, and serum TNF-alpha levels showed a further decrease when patients developed chemotherapy-induced leukopenia.

Vulvar fibroepithelial polyp with myxoid stroma: an unusual presentation.

A case of fibroepithelial polyp arising from the labium majus is described. The tumor measured 12 cm in its largest diameter and was connected to the left labium majus by a 12-cm pedicle. The microscopic examination showed hypocellular connective tissue and focal myxoid areas.

Cisplatin and 5-fluorouracil in advanced cancer of the penis.

A total of 8 patients with advanced squamous cell carcinoma of the penis (Jackson stages III and IV) received chemotherapy with 100 mg./m2. cisplatin intravenously on day 1 and a 24-hour infusion of 1,000 mg.

Clinical pharmacokinetics in heart failure. An updated review.

Pharmacokinetics is the study of the effect that the body has on drug absorption, distribution, metabolism and excretion. The pharmacokinetics of a specific drug are assessed by the volume of distribution, bioavailability, clearance and elimination half-life. Elimination half-life is directly related to the volume of distribution and inversely related to clearance.

Glycogen content and PAS staining pattern of human megakaryocytes.

The glycogen content of human megakaryocytes was studied using a quantitative method. Smears of bone marrow from 13 individuals were stained with the modified PAS reaction with and without prior treatment with alpha-amylase. The intensity of the reaction was determined by microspectrophotometry in 50 megakaryocytes from each individual.