Impact of implementing respiratory point-of-care testing in a regional haemato-oncology unit.

Respiratory point-of-care testing (POCT) for the detection of influenza A, influenza B and respiratory syncytial virus (RSV) was implemented in response to recent RSV outbreaks at a regional haemato-oncology unit in Glasgow. This descriptive study, undertaken pre- and post-POCT implementation, suggests that POCT reduces the time taken to receive results and increases diagnostic rates in outpatients. It is likely that the reduction in turnaround time afforded by POCT also leads to a faster time to antiviral treatment, prompt isolation and a reduction in the number of hospital-acquired infections.

Multiple myeloma in chronic kidney disease. Utility of discretionary screening using serum electrophoresis.

INTRODUCTION: The incidence of multiple myeloma (MM) has increased in Scotland over the last 20 years. Approximately 25% of cases present directly to renal services. Serum electrophoresis is commonly included in the diagnostic screening tests performed in patients with chronic kidney disease (CKD). We examined the utility of serum electrophoresis in the population presenting to renal outpatient services in Glasgow. METHODS: All new patient attendances at general nephrology clinics in the Glasgow renal units between 1/08/2004 and 31/07/2006, along with clinical data, were retrieved from the electronic patient records. Patients with acute kidney injury were excluded. All serum and urine electrophoresis requests and results for the same period were identified from Biochemistry and Immunology Laboratory Services. RESULTS: A total of 2,544 new patients attended a renal clinic for the first time in the inception period, of whom 1,608 (63.2%) had serum electrophoresis tested. One patient with MM was identified, but the diagnosis was clinically apparent before the serum electrophoresis result was requested. A further 40 subjects had abnormal serum electrophoresis with mean paraprotein of 8.3 g/l (SD 6.1); none of these patients have subsequently developed MM, and the renal abnormalities are felt to be unrelated. This prevalence of monoclonal gammopathy of uncertain significance in 2.5% of the cohort is consistent with the expected prevalence in the general population. CONCLUSION: Our data demonstrate that serum electrophoresis in patients with CKD is not a useful screening test to identify MM.

Outbreak of cryptosporidiosis among veterinary students.

In January 2007, six veterinary students became infected with Cryptosporidium species, and records indicated that another student had been diagnosed in November 2006. It was established that the seven students had worked with cattle from the same farm. Microbiological tests indicated that they were infected with Cryptosporidium parvum. Subtyping by sequence analysis indicated a common source of infection for five of the students, but there was insufficient material to type the other two samples. Investigations indicated that the outbreak was caused by a lapse in hygiene, particularly handwashing, on a farm with enzootic C parvum in calves.

Consecutive yearly outbreaks of respiratory syncytial virus in a haemato-oncology ward and efficacy of infection control measures.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant respiratory tract infection in immunosuppressed patients. AIM: To describe two consecutive yearly outbreaks of RSV in our haemato-oncology ward. METHODS: Haematology patients presenting with respiratory symptoms were screened by polymerase chain reaction for viral respiratory pathogens using a saline gargle. FINDINGS: None of our patients had undergone bone marrow transplant but all had underlying haematological malignancies. Eight patients were affected in the first outbreak (mortality rate: 37.5%) and 12 patients were affected in the second (mortality rate: 8.3%). Extensive infection control measures were implemented in both outbreaks and were successful in preventing further cross-transmission. CONCLUSION: There was significant learning from both outbreaks and actions implemented with the aim of reducing the likelihood and impact of future outbreaks.

Impact of 144 weeks of laronidase therapy on body functions, endurance and general well-being in a Hurler-Scheie patient.

The quality of life of a Hurler-Scheie patient who experienced improvement in several organ functions and regained mobility after 144 weeks of laronidase enzyme replacement therapy is described.

A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation.

The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) (Nanbru et al., 1997; Stoneley et al., 1998) and thus c-myc protein synthesis can be initiated by a cap-independent as well as a cap-dependent mechanism (Stoneley et al., 2000). In cell lines derived from patients with multiple myeloma (MM) there is aberrant translational regulation of c-myc and this correlates with a C-T mutation in the c-myc-IRES (Paulin et al., 1996). RNA derived from the mutant IRES displays enhanced binding of protein factors (Paulin et al., 1998). Here we show that the same mutation is present in 42% of bone marrow samples obtained from patients with MM, but was not present in any of 21 controls demonstrating a strong correlation between this mutation and the disease. In a tissue culture based assay, the mutant version of the c-myc-IRES was more active in all cell types tested, but showed the greatest activity in a cell line derived from a patient with MM. Our data demonstrate that a single mutation in the c-myc-IRES is sufficient to cause enhanced initiation of translation via internal ribosome entry and represents a novel mechanism of oncogenesis.

Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma.

Renal impairment is a common complication of multiple myeloma occuring in 50% of patients at some stage in their disease. Pathogenesis is multifactorial. Nephrotoxic manifestations of monoclonal immunoglobulin overexpression include the 'myeloma kidney', light chain deposition disease, AL amyloid, plasma cell infiltration and glomerulonephritis. Other factors, such as hypercalcaemia, hyperuricaemia, infection, hyperviscocity and nephrotoxic drugs can precipitate or exacerbate acute and chronic renal failure. Aggressive treatment has dramatically improved outcome in patients who present with acute or acute-on-chronic renal failure. Dialysis has become an accepted treatment acutely and in end stage renal disease due to myeloma. Conventional therapy with melphalan and prednisolone is still advocated for elderly patients. However, renal failure is not a contraindication to aggressive cytoreduction, stem cell collection, double hemibody radiotherapy and autologous transplantation in those otherwise fit to tolerate these procedures. Prognosis is primarily determined by the response of the myeloma clone to chemotherapy. Outcome in chemosensitive patients approaches that of patients with equivalent disease stage without renal dysfunction.

Expression of adhesion molecules in malignant plasma cells in multiple myeloma: comparison with normal plasma cells and functional significance.

Malignant plasma cells in multiple myeloma are predominantly confined to the bone marrow, where they stimulate cytokine production by stromal cells and bone cells leading to osteoclast activation and formation of the characteristic lytic lesions in the skeleton. Adhesion molecules are critically involved in the cellular interactions between myeloma cells and stromal elements and may represent novel therapeutic targets to reduce osteolytic bone disease in multiple myeloma. Here, we review the literature on the adhesion molecule repertoire expressed by malignant plasma cells and discuss the evidence that adhesive interactions between myeloma cells and stromal cells stimulate production of bone-resorbing cytokines.

Cytokine expression in multiple myeloma and monoclonal gammopathy: analysis by reverse transcription/polymerase chain reaction and quantitative PCR.

Cytokine messenger RNA expression was studied using the reverse transcription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGUS), 12 with post menopausal osteoporosis, (OP) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 and M-CSF were sought in view of their reported pathogenic role in myeloma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were found frequently in all four groups of patients. The only significant difference in cytokine expression between the groups was for IL-6 which was expressed in 17% of controls compared with 87% of patients with MM (p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients with osteoporosis (p < 0.02). Further analysis of IL-6 expression by quantitative PCR showed significantly higher IL-6 mRNA levels in MM compared with MGUS (p < 0.006). There was no correlation however between expression of individual cytokines and clinical features of myeloma such as osteolytic bone disease or hypercalcaemia. We conclude that expression of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also associated with a high prevalence of IL-6 expression when compared with controls it is probable that factors other than IL-6 are responsible for the local osteolytic lesions which characterise MM, but which are not seen in MGUS or osteoporosis.

Fungal surveillance of an open haematology ward.

Air sampling and surveillance cultures for fungi were performed in a Scottish general haematology ward over a five-month period in 1997. The mean total fungal count from the air sampling appeared to be correlated with the number of patients colonized by Aspergillus. The most commonly isolated species were Aspergillus versicolor, A. fumigatus and A. niger. Rooms with portable air filtration units had significantly lower total fungal counts than the others. Swabs were taken from 70 patients (mean age 62 years); 114 of the 563 cultures (20.2%) were positive. The most commonly isolated species were A. fumigatus, Candida albicans, C. glabrata and C. parapsilosis. Samples taken from the tongue and perineum showed colonization more often than those taken from the nostrils. Almost half the patients (48.6%) were colonized on, or within seven days of, admission; 11.4% became colonized whilst on the unit. One patient developed fatal aspergillosis. We conclude that colonization or high air-borne spore concentrations are not necessarily predictive of fungal infection but may prompt early treatment or more aggressive prophylaxis of potentially fatal invasive infections.

Herniated thoracic disc mimicking spinal abscess.

Herniated thoracic discs are uncommon. Although uncommon, their potential for spinal cord damage makes them an important cause of backache. History and examination may be unhelpful, and even misleading. A diagnostic clue is disc space calcification on plain radiographs. Diagnosis can be confirmed by myelography or CT scanning. Cord compression can be prevented by surgery, which carries a low risk. Herniated thoracic disc should be remembered as a cause of backache in view of its serious, but treatable nature.

The addition of plerixafor is safe and allows adequate PBSC collection in multiple myeloma and lymphoma patients poor mobilizers after chemotherapy and G-CSF.

We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34(+) cells was always lower than 10 cells/µL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10-11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34(+) cells after plerixafor as compared with baseline CD34(+) cell concentration (from a median of 6.2 (range 1-12) to 21.5 (range 9-88) cells/µL). All patients collected >2 × 10(6) CD34(+) cells/kg in 1-3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.