Abbreviated dosing of N-acetylcysteine prevents contrast-induced nephropathy after elective and urgent coronary angiography and intervention

BACKGROUND AND HYPOTHESIS: Several studies have utilized low-dose regimens of N-acetylcysteine (NAC) for 48 hours to prevent contrast-induced nephropathy (CIN) after cardiac catheterization (cath) and percutaneous coronary intervention (PCI). A lengthy pretreatment period with NAC may not be feasible in urgent situations. The purpose of this study was to assess the efficacy of an abbreviated, higher dose regimen of NAC for the prevention of CIN after elective and urgent coronary angiography (cath) and/or percutaneous coronary intervention (PCI). METHODS: We prospectively evaluated 80 patients referred for elective or urgent cath and/or PCI with stable chronic renal insufficiency (creatinine clearance <50 cc/min). Patients were randomized to: NAC 1000 mg PO 1 hour before cath/PCI and 4 hours later, or placebo. All patients received hydration (0.9% saline) before and after cath/PCI (minimum total volume > or = 1500 mL). CIN was defined as an increase of Cr > or = 0.5 mg/dL or > or = 25% 48 hours after cath/PCI. RESULTS: CIN occurred in 3 of 36 (8%) patients of the NAC group vs. 11 of 44 (25%) in the placebo group (P = 0.051; OR 3.7, 95% CI 0.94-14.4). Serum creatinine (mean +/- SD) remained stable in the NAC group after cath/PCI (2.02 +/- 0.56 vs. 2.10 +/- 0.81 mg/dL; P = 0.34), but increased after cath/PCI in the placebo group (1.93 +/- 0.53 vs. 2.10 +/- 0.74 mg/dL; P < 0.01). CONCLUSIONS: An abbreviated, higher dose regimen of NAC prevents the rise of serum creatinine 48 hours after cath/PCI, and may prevent CIN after cath/PCI.     

Reversing established sepsis with antagonists of endogenous high-mobility group box 1

Despite significant advances in intensive care therapy and antibiotics, severe sepsis accounts for 9% of all deaths in the United States annually. The pathological sequelae of sepsis are characterized by a systemic inflammatory response, but experimental therapeutics that target specific early inflammatory mediators [tumor necrosis factor (TNF) and IL-1beta] have not proven efficacious in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late mediator of endotoxin-induced lethality that exhibits significantly delayed kinetics relative to TNF and IL-1beta. Here, we report that serum HMGB1 levels are increased significantly in a standardized model of murine sepsis, beginning 18 h after surgical induction of peritonitis. Specific inhibition of HMGB1 activity [with either anti-HMGB1 antibody (600 microg per mouse) or the DNA-binding A box (600 microg per mouse)] beginning as late as 24 h after surgical induction of peritonitis significantly increased survival (nonimmune IgG-treated controls = 28% vs. anti-HMGB1 antibody group = 72%, P < 0.03; GST control protein = 28% vs. A box = 68%, P < 0.03). Animals treated with either HMGB1 antagonist were protected against the development of organ injury, as evidenced by improved levels of serum creatinine and blood urea nitrogen. These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame.     

Acute lung injury and acute respiratory distress syndrome in malaria

Malaria is an important treatable cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the tropics and in the returning traveller in the non-endemic areas. ARDS is an important complication in severe, complicated falciparum malaria and has been described in P. vivax and P. ovale malaria also. Malarial ALI/ARDS is more common in adults than in children. Pregnant women and non-immune individuals are more prone to develop this condition. Increased alveolar capillary permeability resulting in intravascular fluid loss into the lungs appears to be the key pathophysiologic mechanism. In malaria, ARDS can develop either at initial presentation or after initiation of treatment when the parasitaemia is falling and the patient is improving. Patients present with acute onset dysnoea that can rapidly progress to respiratory failure. The diagnosis of malaria is confirmed by slide microscopy supported by the use of rapid antigen tests. Patients with malarial ARDS should be managed in an intensive care unit. Careful attention must be paid to haemodynamic stabilisation and optimising fluid balance. Currently, specific treatment choices for malaria include parenteral artemisinins or intravenous quinine along with doxycycline. Respiratory failure requires endotracheal intubation and assisted mechanical ventilation. Co-existent bacterial sepsis is frequently present in patients with malarial ARDS eventhough an obvious focus may not be evident. Appropriate broad spectrum antibiotic therapy must be started when there is a clinical suspicion after procuring the microbiological specimens. ARDS in malaria is a disease with a high mortality. Early diagnosis, institution of specific antimalarial treatment and assisted ventilation can be life-saving.     

Chronic mesenteric ischemia and therapeutic paradigm of mesenteric revascularization

Chronic mesenteric ischemia is a life-threatening clinical problem resulting in death from inanition and/or bowel infarction, if left untreated, albeit low disease prevalence. Typical presentation is postprandial abdominal pain, severe weight loss, and altered bowel habit. Surgical revascularization of the superior mesenteric artery provides effective long-term treatment for chronic intestinal ischemia. Eleven patients underwent superior mesenteric artery revascularization, nine of them with open retrograde superior mesenteric artery bypass and two with angioplasty and stenting. All patients except one made a satisfactory recovery in this cohort. Major complication included one graft thrombosis leading to bowel ischemia and death. The rest all recovered weight in 3–6 months with a follow up period of 6 to 28 months. Two patients had recurrence of symptoms due to failing bypass requiring stenting for assisted primary patency. Superior mesenteric artery revascularization can be performed with minimal morbidity and mortality, providing excellent symptom relief and quality of life.     

Genetic portrait of North-West Indian population based on X chromosome Alu insertion markers

International Journal of Legal Medicine - In the present study, allele frequencies and forensic parameters of four ethnic groups (Brahmin, Khatri, Jat Sikh, and Scheduled Caste) of Punjab, India,...     

Optical properties of hematoporphyrin monomethyl ether (HMME), a PDT photosensitizer

We report on some of the optical properties of Hemoporfin(?) (hematoporphyrin monomethyl ether, HMME), a photodynamic therapy (PDT) photosensitizer that has been in clinical trials in China since the early 1990s. We characterized the photosensitizer on the basis of one- and two-photon absorption and fluorescence emission. The effects of photobleaching were probed to characterize its decay kinetics. Additionally, we determined time resolved fluorescence and thermal effects on fluorescence and absorption properties.