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.

Inappropriate antidiuretic hormone secretion, abdominal pain and disseminated varicella-zoster virus infection: an unusual and fatal triad in a patient 13 months post Rituximab and autologous stem cell transplantation.

We report a case of varicella-zoster virus (VZV) infection associated with severe abdominal pain, inappropriate antidiuretic hormone (ADH) secretion (SIADH) and death, 13 months post-autologous peripheral blood stem cell transplantation (PBSCT). This unusual clinical triad has been reported twice in the setting of allogeneic bone marrow transplantation, however it has not been reported after autologous transplantation and never so long after transplantation. We speculate as to why this occurred, as early recognition might have altered the clinical outcome.

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.

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.

Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak.

BACKGROUND: The largest number of adult cases of haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) during an Escherichia coli O157 outbreak occurred in 1996 in central Scotland. Adults who develop HUS/TTP induced by E. coli O157 tend to be elderly and have a historical mortality rate of almost 90% when treated conservatively. Therefore the decision was made to treat adults who developed HUS/TTP during this outbreak with therapeutic plasma exchange (TPE). We report our outcome with this controversial treatment. METHODS: A case definition for HUS/TTP was developed at the beginning of the outbreak. All cases meeting this definition were considered for TPE. Information on demographics, clinical features, treatment and outcome of patients was obtained by retrospective case note review. FINDINGS: 22 adults developed HUS/TTP. They had a mean age of 71 years. 16 cases received TPE. Six cases had contraindications to TPE or died before the procedure could be done. Ten of the 22 (45%) adults with HUS/TTP died. Five of the 16 (31%) TPE-treated cases died, four of eight aged over 70 years compared with one of eight aged less than 70 years. Premorbid illness, neurological features, treatment with ciprofloxacin or prostacyclin, and the laboratory severity of HUS/TTP were not associated with death; the number of cases, however, was too small to allow statistical conclusion. INTERPRETATION: The mortality rate is high in adults who develop HUS/TTP induced by E. coli O157. TPE appears to be a promising treatment that was well tolerated in our elderly patients. A national register of adult cases of HUS/TTP induced by E. coli O157 should be established.

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.

Multiple myeloma in north east Scotland: a review of incidence and survival over three decades.

STUDY OBJECTIVE: (1) To review the pattern of published world age-standardised registration rates for myeloma (ICD8 and ICD9 203) for the five Scottish regional cancer registries between 1973-77 and 1983-87. (2) To review the patterns of world age-standardised incidence and survival for myeloma in Grampian region over the time period 1960-89. DESIGN: Retrospective analysis of cancer registration data and linked mortality data. SETTING: The five Scottish regional cancer registries (East, North, North East, South East and West Scotland). PATIENTS: Incidence: a total of 405 patients with myeloma resident in Grampian region (153 diagnosed between 1960-69, 252 diagnosed between 1980-89 inclusive). Survival: a total of 420 patients with myeloma treated in Grampian hospitals between 1968 and 1987 inclusive. MEASUREMENTS AND MAIN RESULTS: On average, the world age-standardised registration rates for the five regional registries increased from 2.8 to 3.1 cases per 100,000 in males and from 1.8 to 2.4 per 100,000 in females between 1973-77 and 1983-87. No clearcut pattern in the trends for individual registries was evident for males but, in general, an increasing trend in female rates was observed for the registries with the lowest rates initially, whilst those with the highest initial rates increased only slightly or even fell. After age and sex standardisation, the annual incidence of myeloma in NE Scotland has increased by 20 per cent between 1960-69 and 1980-89, from 2.4 to 2.9 cases per 100,000 population per year with a disproportionate increase in older patients. Between the two time periods female rates remained stable or increased over all age groups while male rates fell for ages under 69 years and rose for ages above this, a pattern which was reflected in changes in the male:female ratio. The five year survival rate for all ages (14%) has not improved since 1968-72 similar to overall Scottish figures. In NE Scotland, younger patients appear to fare better, and older patients worse, compared with the overall Scottish experience. CONCLUSIONS: The increase in myeloma incidence may be due to a combination of improved ascertainment, especially in the elderly and a possible true increase in incidence in females, suggestive of increased exposure to an aetiological agent in the past. A formal year birth cohort analysis is required to confirm this finding. The overall prognosis for myeloma remains poor, especially for elderly patients and efforts to elucidate the aetiology must continue.

A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion.

There is debate in the literature about the frequency and importance of delayed transfusion reactions. This uncertainty could reflect the endpoints used (clinical or serological) and the type of study (typically retrospective or case series). In this report we describe a prospective investigation to determine the frequency of alloimmunization post transfusion and whether the alloantibody production is a laboratory event or has clinical relevance. A total of 2490 patients were transfused 11,218 red cell concentrates. One or more blood samples were collected within 7 d post transfusion and screened for serological evidence of alloimmunization. If any antibody was detected the patient's post-transfusion sample was screened for biochemical evidence of haemolysis and the patient's chart reviewed for documentation of clinical signs of a transfusion reaction. Post transfusion alloimmunization occurred in 2.6% of the patients (95% CI 2.1-3.6%), who had no detectable alloantibody in pre-transfusion testing. For those 86 patients (3.5%) with alloantibodies detectable pretransfusion, 8.9% (95% CI 3.6-17.4%) developed additional aloantibodies. The most common alloantibodies detected were anti-Jka, anti-E and anti-K. Despite the high frequency of serological evidence of delayed transfusion reactions, only one patient (0.05%) had clinical evidence of a delayed haemolytic transfusion reaction (95% CI 0.0-0.27%). Serological evidence of a delayed transfusion reaction is common; however, these reactions rarely cause clinical symptoms.

Recent advances in the development and use of plasma concentrates.

The consequences of blood donations infected with human immunodeficiency virus, the rapid advances in protein fractionation and the introduction of recombinant DNA technology have revolutionized the range of plasma products available to the clinician. This article reviews these developments and describes recent recommendations on their use.

Air crescent sign and fatal haemoptysis in pulmonary mucormycosis.

A case of invasive pulmonary mucormycosis complicated by fatal, massive haemoptysis in a patient with acute myeloid leukaemia is reported. This patient represents the twelfth reported case of fatal haemoptysis due to mucormycosis. The other 11 cases are reviewed and the aetiology of cavity formation and massive haemoptysis is discussed. The development of the air crescent sign on chest radiograph is an important clinical indicator of potentially fatal haemoptysis and should lead to appropriate antifungal and surgical therapy.