Monitoring and adverse events in relation to ACE inhibitor/angiotensin receptor blocker initiation in people with diabetes in general practice: a population database study.

BACKGROUND AND AIM: To determine whether angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) initiation in people with diabetes is monitored as recommended by recent guidelines and the incidence of associated adverse renal events. DESIGN: Retrospective population database analysis of 4056 people in Tayside, Scotland with type 2 diabetes prescribed an ACEI/ARB between 1 January 2005 and 31 December 2009. METHOD: Measurement of urea and electrolytes (U&Es) before and after ACEI/ARB initiation and renal adverse events; defined as a ≥30% rise in serum creatinine and post-initiation potassium of ≥5.6 mmol/L. Associations of adverse events with patient demographics or co-prescription of drugs with known renal effects were examined. RESULTS: Overall, 89% of initiations were with an ACE inhibitor. A total of 18.84% (CI 95% 18.82-18.86) of patients initiating ACE inhibitor or ARB had U&Es measured in the 90 days before initiation and within 5-14 days after initiation. Only 1.7% of patients had an adverse renal event. Patients prescribed with an ARB were less likely to be monitored than those prescribed with an ACE inhibitor, but no less likely to suffer harm. CONCLUSIONS: Current clinical practice of biochemical monitoring of ACE inhibitor/ARB is poor, but adverse events are rare. Further studies with serial U&Es are needed to establish the critical time window for adverse renal events and evaluate whether intensive biochemical monitoring recommended is required in low-risk groups.

The role of TH1 and TH2 cells in a rodent malaria infection.

CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.

Stent graft exclusion of pseudo-aneurysm arising from PTFE hemodialysis graft after recurrence following ultrasound guided thrombin injection.

There are various non-invasive or minimally invasive techniques for management of pseudoaneurysms including ultrasound guided compression, ultrasound guided thrombin injection and covered stent placement. We report a case where a covered stent graft was successfully used for the treatment of a pseudoaneurysm directly arising from a PTFE graft which recurred 3 months following treatment with ultrasound guided thrombin injection.

A convenient human whole blood culture system for studying the regulation of tumour necrosis factor release by bacterial lipopolysaccharide.

Bacterial lipopolysaccharide (LPS, endotoxin) induces a dose-dependent release of TNF in whole human blood which has been diluted five-fold. It is modulated by interferon-gamma, prostaglandin E2 and indomethacin in the same manner as observed with tumour necrosis factor (TNF) release from human monocyte/macrophage cells cultured in vitro. The whole blood culture system (WBCS) can provide up to 250 samples from 10 ml of venous blood and enables an individual blood to be assessed in terms of TNF inducibility and its modulation by other biological agents. The whole blood culture system was used to demonstrate the individual variation between blood donors. The results demonstrated that the information provided by induced cytokine release and its regulation in the ex vivo system would be a valuable addition to that obtained from in vitro methods.

The case of the floating gel.

In patients with chronic renal failure, blood samples for laboratory analysis are often taken via dialysis catheters. This report describes a case of gross spurious hypernatraemia in a blood sample collected from a patient undergoing haemodialysis. After centrifugation of the blood sample in question, the separator gel formed the topmost layer, with the serum in the middle and the clot at the bottom. Subsequent analysis of the serum showed severe hypernatraemia (serum sodium, 744 mmol/litre). It was established that the blood sample had been taken from the patient's dialysis catheter into which 3 ml of Citra-Lock (46.7% trisodium citrate) had been instilled previously as a "catheter locking" solution. The hypernatraemia seen in this case was recognised immediately as an artefact, but it was found that even minimal contamination of blood samples with Citra-Lock may significantly affect sodium concentrations. This contamination may be missed, with potentially adverse consequences for patient management.

Severe pulmonary hemorrhage and systemic vasculitis in association with circulating anti-neutrophil cytoplasm antibodies of IgM class only.

We report an association of severe pulmonary hemorrhage with circulating autoantibodies to neutrophil cytoplasmic antigens (ANCA) restricted to IgM class in three patients with systemic vasculitis. ANCA were detected by indirect immunofluorescence and isotype specific solid phase radioimmunoassay (SPRIA). Institution of immunosuppressive therapy was accompanied by an isotype switch to IgG ANCA and recovery in all three patients. In an associated study, ANCA activity was found in eluates from the washed glomeruli of two postmortem cases, with the same isotype distribution as was present in the sera.

Immunoscintigraphy with a 99Tcm-labelled anti-granulocyte monoclonal antibody in patients with human immunodeficiency virus infection and AIDS.

The value of immunoscintigraphy with technetium-99m (99Tcm) labelled anti-granulocyte monoclonal antibody (BW250/183) was studied prospectively in human immunodeficiency virus (HIV-1) antibody-positive patients presenting with fever without localizing symptoms or signs. Twenty-three studies were performed in 23 patients and the results of 99Tcm-anti-granulocyte imaging were compared with the definitive microbiological or cytological diagnosis. Twenty-one patients had an infective cause of pyrexia, one patient had disseminated lymphoma and one Kaposi sarcoma. 99Tcm-anti-granulocyte antibody imaging correctly identified the sites of infection in only five (24%) patients, four of whom had infective colitis (one also had bacterial pneumonia) and one of whom had cellulitis. Sixteen foci of infection were not localized by 99Tcm-anti-granulocyte immunoscintigraphy (false-negative scans). Six of these patients had Pneumocystis carinii pneumonia; other diagnoses in this group included bacterial or fungal pneumonia and bacteraemia secondary to line infections. 99Tcm-anti-granulocyte antibody did not accumulate in the patients with disseminated lymphoma and Kaposi sarcoma (true-negative scans). 99Tcm-anti-granulocyte imaging, therefore, appears useful in identifying extrathoracic infection in HIV-1 positive patients. Its lack of sensitivity for the identification of pulmonary infection means that its role in the investigation of HIV-1 antibody-positive patients with fever without localizing symptoms or signs is limited.

The delivery of renal replacement therapy in Scotland--why the geographic variation?

BACKGROUND: The incidence of patients starting renal replacement therapy (RRT) for established renal failure (ERF) in Scotland has fallen from 2005 to 2011 due to a reduction in older patients starting RRT; there are significant differences between NHS Health board areas. AIM: To understand the apparent inequality in provision of RRT between NHS board areas in Scotland. DESIGN: Retrospective population analysis of Scottish renal registry (SRR) data, population statistics and quality outcomes framework summary statistics. RESULTS: The incidence of patients starting RRT for ERF in Scotland fell from 123 per million population (pmp) in 2005 to 96 pmp in 2011. The incidence of ≥75 year olds fell from 406 to 274 pmp. There are significant differences between NHS board areas when standardized for age and social deprivation. There is no relationship between the population prevalence of CKD as reported by QOF and the incidence of RRT for ERF. Those areas with high incidence rates of ≥75 year olds have higher 90-day [Spearman's rank correlation: coefficient = 0.662; P = 0.03] and 1-year [Spearman's rank correlation: coefficient = 0.776; P = 0.003] mortality rates. CONCLUSION: The significant variation in provision of RRT for ERF between Scottish NHS Board areas is not explained by age or social deprivation. There is evidence of change in practice towards RRT for patients aged ≥75 years but variation between NHS Board areas. This disparity must be further investigated to ensure equity of access to RRT for those who will benefit from it, and to non-dialytic care for those who would not.

Vascular access type and risk of mortality in a national prospective cohort of haemodialysis patients.

BACKGROUND: Central venous catheters (CVC) are a potential source of bacteraemia and have been associated with increased mortality in haemodialysis patients. We aimed to investigate the relationships between haemodialysis vascular access, taking into account changes in vascular access type during patients' lives, and cause specific mortality risk in a national cohort of dialysis patients. METHODS: Prospective cohort study including all patients receiving haemodialysis in Scotland at annual cross sectional surveys in 2009, 2010 and 2011. Data were collected through the Scottish Renal Registry and by a structured review of case records following death. Cox proportional hazards regression and multivariable logistic regression were used to model survival and risk of death from septicaemia respectively. RESULTS: Of a cohort of 2666 patients, 873 (32%) died during follow-up. After case-mix adjustment, patients using only tunnelled CVC during follow-up had a higher risk of all cause mortality across all strata of prior renal replacement therapy exposure [adjusted hazard ratio (HR): 1.83-2.08]. Case-mix adjusted risks of cardiovascular death (adjusted HR: 2.20-2.95) and infection-related death (adjusted HR: 3.10-3.63) were also higher in this group. Patients using tunnelled CVCs during follow-up and prior to death had 6.9-fold higher odds of death from septicaemia compared with those using only arteriovenous fistulae or grafts. CONCLUSION: Compared with an arteriovenous fistula or graft, sustained use of tunnelled CVCs for vascular access is associated with higher risks of all-cause, cardiovascular and infection-related mortality.

Parkinsonism and the anaesthetist.

There are similarities between the motor disorder of Parkinsonism, the rigidity associated with the use of opioid drugs and the phenomenon of shaking during recovery from anaesthesia. Opioid receptors of the basal ganglia modulate activity of dopaminergic neurones. Opioid induced rigidity, therefore, may be a form of drug-induced Parkinsonism. This has implications for the anaesthetic management of the patient with Parkinsonism. Previous descriptions of the anaesthetic management of Parkinsonism have emphasized the cardiovascular complications of L-Dopa therapy, but have not discussed the importance of opioids.

Non surgical treatment of empyema thoracis with intrapleural streptokinase in a patient with AIDS.

After unsuccessful treatment with intercostal tube drainage and antibiotics intrapleural streptokinase was used to treat successfully an empyema in a man with AIDS and advanced cutaneous Kaposi's sarcoma who was unfit for surgical decortication. The role of this technique in the management of HIV positive patients with empyema is discussed.

The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages.

The role of protein kinase C (PKC) in the induction of nitric oxide synthesis by interferon-gamma (IFN-gamma) was investigated using two murine macrophage cell lines, J774 and RAW 264.7. Nitric oxide (NO) production was markedly reduced by a PKC inhibitor, Ro31-8220 in a dose-dependent manner. Incubation of cells with IFN-gamma resulted in translocation of PKC to the cell membrane. Prolonged incubation of cells with a high concentration of phorbol ester, which down-regulated PKC activity, also reduced nitric oxide production. These findings provide evidence that PKC is involved in the induction of nitric oxide synthesis by IFN-gamma.

Kinetics of nitric oxide production during infection and reinfection of mice with Plasmodium chabaudi.

We have shown previously that at the time of peak primary parasitaemia of P. chabaudi infection in NIH mice, significant levels of nitric oxide are produced, detectable as nitrate in the serum, and that these contribute to the protective immune response to infection. Here, we demonstrate that following reinfection, mice show a markedly diminished ability to produce nitrate. However, if mice are treated with L-NG-monomethyl arginine specifically to block nitric oxide metabolism during the primary infection, and are then reinfected, production of nitrate is restored to levels approaching those attained at peak primary parasitaemia. These experiments, together with others we have reported, indicate that whereas nitric oxide appears to play a significant role in control of the primary parasitaemia of P. chabaudi infection, it performs no such function during subsequent patent parasitaemias. Furthermore, they suggest that factors as yet unknown may regulate nitric oxide activity during malaria infection, such that under normal circumstances its production comes under strict control. This is exemplified by the observation that after the burst of nitric oxide activity that coincides with peak primary parasitaemia, there follows a prolonged period of immunological tolerance during which nitrate levels remain low even at secondary challenge infection. This tolerized state is lifted only several months after initial infection, when the nitric oxide activity at reinfection appears to correlate with the size of the parasite challenge and the presence of a patent parasitaemia. The implications of these findings for protective immunity to malaria, malarial immunosuppression, and immunoregulation in general, are discussed.

Nitric oxide production by murine macrophages is inhibited by prolonged elevation of cyclic AMP.

Murine macrophages produce large amounts of nitric oxide (NO) on stimulation by interferon (IFN)-gamma and lipopolysaccharide (LPS) or a high concentration of LPS alone. Agents which increase intracellular cAMP levels inhibit cytokine production by macrophages. The effect of increased intracellular cAMP levels on NO production was investigated, using a murine macrophage cell line, J774. NO production was reduced by prolonged elevation of cAMP, but not by a transient increase.