Simulation model of renal replacement therapy: predicting future demand in England.

BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Uterine stromal sarcoma cell line. A cytogenetic and electron microscopic study.

Uterine sarcomas constitute approximately 3% of all malignant uterine corpus tumors. Of these, the tumors that originate solely in the stromal elements of the uterine wall are relatively infrequent and have not been well characterized cytogenetically. We report data from a low-grade endometrial stromal sarcoma both at the time of resection and after months in long-term tissue culture. Cytogenetic analysis showed a clonal population of cells with an abnormal karyotype of 46,XX,del(5)(q31.1),der(7)t(6;7)(p21;p22) which remained unchanged in long-term culture. Electron microscopy suggests that these cells are similar to other neoplastic cells in having immature-appearing nuclei surrounded by a relatively mature cytoplasm (with well-developed organelles). Determination of the specificity of these observations must await study of additional stromal sarcomas.     

Are there any successful men from criminogenic backgrounds?

In the Cambridge Study in Delinquent Development, a prospective longitudinal survey of 411 London males, a vulnerable group of 63 boys from criminogenic backgrounds was defined on the basis of the best nonbehavioral predictors of delinquency at age 8-10 (low family income, large family size, convicted parents, low intelligence, and poor parental child-rearing behavior). These males were followed up to age 32, and the more successful men were defined according to criteria such as the absence of convictions and of other deviant behavior, good relationships with wives and children, and good accommodation and employment histories. Hence, "success" here refers to satisfactory social adjustment. The more successful men were those who had been neurotic at age 10, those who had few or no friends at age 8, those without convicted parents or behavior problem siblings, those with mothers who had a high opinion of their sons, and those who did not spend their leisure time with their fathers. At age 8-10 they were already better behaved and less daring than those later judged as the unsuccessful men. There was some tendency for shyness to act as a protective factor against delinquency for non-aggressive boys but as an aggravating factor for aggressive boys.     

Serological Cross-Reaction between Legionella pneumophila and Citrobacter freundii in Indirect Immunofluorescence and Rapid Microagglutination Tests

We describe the first case in which a diagnostic rise in titers of antibody to formalinized Legionella pneumophila serogroup 1 yolk sac antigen was shown to be caused by a cross-reaction between L. pneumophila and another organism, Citrobacter freundii.     

Mast cell phagocytosis of red blood cells.

The prevalence of mast cells infiltrating bone marrow of different rats varied widely, as did the staining properties and size of their cytoplasmic granules. Bone marrow mast cells from several rats revealed large membrane-limited inclusions which stained metachromatically or orthochromatically and resembled inclusions in some macrophages. Ultrastructurally, mast cells varied widely in content of uniform dense granules or enlarged granules with less dense, fine grained content. Some of the large inclusions observed ultrastructurally in mast cells were heterophagic vacuoles which contained erythrocytes or reticulocytes, or remnants from other phagocytized cells, possibly neutrophils or unidentified homogeneous material. Smaller bodies, interpreted as fragments of erythrocytes, lay extracellularly near mast cells and occupied small, membrane-limited, heterophagic vacuoles in some mast cells. In other mast cells, communal vacuoles enclosed several specific cytoplasmic granules in various stages of disruption. The communal vacuoles occasionally opened to the extracellular space. A few large indeterminate vacuoles in mast cells contained amorphous flocculent matter which apparently derived either from coalescence of cytoplasmic granules through fusion of granule membranes or from endocytosis.     

A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease

Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity.