Diuretics and bone loss in rats with aldosteronism

OBJECTIVES: We hypothesized that the increased urinary Ca2+ and Mg2+ excretion and bone loss that accompanies aldosteronism is aggravated with furosemide and is attenuated by spironolactone. BACKGROUND: Furosemide, a loop diuretic, is commonly used in patients with congestive heart failure (CHF), in which chronic, inappropriate (dietary Na+) elevations in plasma aldosterone (ALDO) and a catabolic state that includes bone wasting are expected. METHODS: In age- and gender-matched, untreated controls, four weeks of aldosterone/salt treatment (ALDO/salt, 0.75 microg/h + 1% NaCl/0.4% KCl in drinking water), four weeks of ALDO/salt + furosemide (40 mg/kg in prepared food), and four weeks of ALDO/salt + furosemide + spironolactone (200 mg/kg/day in divided doses by twice-daily gavage), we monitored: 24-h urinary Ca2+ and Mg2+ excretion; plasma-ionized [Ca2+]o and [Mg2+]o, K+, and parathyroid hormone (PTH); and bone mineral density (BMD) in the femur. RESULTS: The ALDO/salt increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (4,969 +/- 1,078 and 3,856 +/- 440 microg/24 h, respectively) compared with controls (896 +/- 138 and 970 +/- 137 microg/24 h, respectively); furosemide co-treatment further increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (6,976 +/- 648 and 6,199 +/- 759 microg/24 h, respectively), whereas spironolactone co-treatment attenuated (p < 0.05) these incremental losses (4,003 +/- 515 and 3,915 +/- 972 microg/24 h). Plasma [Ca2+]o was reduced (p < 0.05) at week 4 ALDO/salt + furosemide and was accompanied by hypokalemia (<3.4 mmol/l) that were rescued by spironolactone. Plasma PTH was increased (p < 0.05) compared with controls (30 +/- 4 vs. 11 +/- 3 pg/ml, respectively), whereas BMD was decreased (p < 0.05) with ALDO/salt and ALDO/salt + furosemide, but not with spironolactone co-treatment. CONCLUSIONS: In aldosteronism, hypercalciuria and hypermagnesuria and accompanying decrease in plasma-ionized [Ca2+]o and [Mg2+]o lead to hyperparathyroidism that accounts for bone wasting. Furosemide exaggerates these losses, whereas its combination with spironolactone attenuates these responses to prevent bone loss.     

Non Surgical Management of Pseudoaneurysms

Background

The incidence of pseudoaneurysm has increased due to the large number of vascular procedures performed and the widespread use of anticoagulation therapy during procedures. Non-invasive methods for management of pseudoaneurysms comprise of ultrasound guided compression (USGC), thrombin therapy, arterial embolisation and endovascular stent graft insertion. We discuss our experience in the management of fourteen cases of pseudoaneurysms using non surgical techniques.

Methods

During a two year period, fourteen patients presenting with pseudoaneurysms of different regions were treated.

Result

Of the fourteen patients, eleven were iatrogenic and three were attributable to trauma. There were six cases of pseudoaneurysms of the femoral artery following coronary angiography studies. One patient developed pseudoaneurysm of right popliteal artery after external fixation of fracture right tibia and fibula. Three cases of renal artery pseudoaneurysms occurred following percutaneous nephrolithotomy (PCNL). The cases were evaluated using a varying combination of color doppler, multidetector computerised tomography (CT) and angiography. These cases were treated with ultrasound guided compression (USGC), stent graft and coil embolisation. The selection of method was based on the location and size of pseudoaneurysms besides the efficacy of the technique. USGC was performed in seven, of which six were in the femoral artery and one supraorbital. The technique was unsuccessful in three of the seven, wherein stent graft was deployed in the femoral artery. Coil embolisation was utilised in three cases of renal artery pseudoaneurysms following PCNL.

Conclusion

Follow up with color doppler and CT angiography within a week, 6 and 12 months period showed successful regression of pseudoaneurysms in all cases.Key Words: Pseudoaneurysm, Arterial trauma, Ultrasound guided compression, Coil embolisation, Endovascular stent graft     

Comparison of a transfusion preparation of newly formed red cells and standard washed red cell transfusions in patients with homozygous beta- thalassemia

BACKGROUND: Previous studies of transfusions of newly formed red cells (neocytes) demonstrated modest extensions of transfusion interval in patients with homozygous beta-thalassemia. STUDY DESIGN AND METHODS: The clinical benefits of a new system of neocyte preparation (Neocel, Cutter Biological, Berkeley, CA), reported to combine ease of preparation with reduction in the transfusion requirements of thalassemia patients, were evaluated. Sixteen thalassemic patients who had undergone splenectomy received eight consecutive, standard, automated, washed red cell transfusions (standard transfusions), followed by eight transfusions with the neocyte preparation (neocyte transfusions). In each arm of the study, mean pretransfusion hemoglobin and mean red cell mass transfused were carefully controlled and were similar. RESULTS: A significant (p < 0.0001) extension of transfusion interval was observed in patients receiving neocyte transfusions (mean +/− SD; 38.7 +/− 34 days; range, 35.0-44.5), over that in those receiving standard transfusions (32.9 +/− 2.5 days; range, 29.6-38.5). The mean prolongation of transfusion interval by neocyte transfusion corresponded to a mean reduction of 25 mL in packed red cells transfused per kg of body weight per patient per year and a mean reduction in transfused iron of 15 percent per year per patient. During neocyte transfusions, blood preparation costs were considerably increased and donor exposure was significantly (p < 0.0005) higher than during the standard transfusion period. CONCLUSION: These data demonstrate that extension of the transfusion interval, and reduction in transfused iron, may be achieved in thalassemic patients by use of the Neocel system. These benefits are achieved, however, with substantial increases in donor exposure and in component preparation costs.     

Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens

Adenoviruses are potent vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same drawbacks. We have constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1). Here, we report safety and T-cell immunogenicity following vaccination with this novel recombinant simian adenovirus, ChAdOx1 NP+M1, in a first in human dose-escalation study using a 3+3 study design, followed by boosting with modified vaccinia virus Ankara expressing the same antigens in some volunteers. We demonstrate ChAdOx1 NP+M1 to be safe and immunogenic. ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection.     

Coadministration of Seasonal Influenza Vaccine and MVA-NP+M1 Simultaneously Achieves Potent Humoral and Cell-Mediated Responses

Current seasonal influenza vaccines have reduced immunogenicity and are of suboptimal efficacy in older adults. We have previously shown that the novel candidate vaccine MVA-NP+M1 is able to boost memory T cell responses in adults aged 50–85 years. Preclinical studies have demonstrated that viral vectored vaccines can act as adjuvants when coadministered with protein-based vaccines. We have conducted a phase I clinical trial to compare the coadministration of seasonal influenza vaccine and MVA-NP+M1 with seasonal influenza vaccine alone in adults aged 50 years and above. This combination of vaccines was safe and well tolerated. T cell responses to internal influenza proteins were boosted to significantly higher levels in the group receiving MVA-NP+M1 compared with the group receiving seasonal influenza vaccine alone. Rates of seroprotection and seroconversion against the three vaccine strains were similar in both groups; however, there was a significant increase in the geometric mean titer ratio for the H3N2 component of seasonal influenza vaccine in the coadministration group. While some vaccine combinations result in immune interference, the coadministration of MVA-NP+M1 alongside seasonal influenza vaccine is shown here to increase some influenza strain-specific antibody responses and boost memory T cells capable of recognizing a range of influenza A subtypes.     

The origins of a research community in the Majengo observational cohort study,Nairobi, Kenya

Background  

Since the 1980s the Majengo Observational Cohort Study (MOCS) has examined sexually transmitted infections, in particular HIV/AIDS, in a cohort of sex workers in Majengo, an impoverished urban village in Nairobi, Kenya. The MOCS investigators have faced criticism since the women have remained in the sex trade for the duration of their participation in the study, prompting concerns about exploitation. Yet despite these concerns, the cohort has survived for almost 30 years.