MECHANISMS OF HYPOPHOSPHATAEMIA IN ALCOHOLIC PATIENTS

The aim of our study was to determine the possible pathophysiological mechanisms of hypophosphataemia in a group of 127 patients admitted to hospital for alcohol-related causes. Blood and fresh urine specimens were taken to determine acid-base and electrolyte parameters. Thirty-seven patients (29.1%) had hypophosphataemia (serum phosphorus <0.77 mmol/l) with a range of serum phosphorus of 0.32-0.74 mmol/l. In 17 hypophosphataemic patients inappropriate phosphaturia (FEP04 >20%, TmPO₄/GFR<0.80 mmol/l) was evident, possibly due to hypomagnesaemia, metabolic acidosis, metabolic alkalosis, or a proximal tubular defect in phosphate transport. The causes of hypophosphataemia in the remaining 20 patients were alcohol withdrawal syndrome, respiratory alkalosis and diarrhoea. Patients with hypophosphataemia were more often found to have hypomagnesaemia and respiratory alkalosis than normophosphataemic patients. In conclusion, hypophosphataemia is frequently observed in alcoholic patients due to various pathophysiological mechanisms, such as inappropriate phosphaturia, increased phosphorus entry into cells and increased gastrointestinal loss of phosphate.     

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

Decompensated cirrhosis-related admissions in a large urban hospital in Uganda: prevalence,clinical and laboratory features and implications for planning patient management

Background

Cirrhosis-related complications are a major cause of morbidity and mortality in areas where its risk factors are endemic.

Objective

We determined the prevalence of decompensated cirrhosis among patients on the gastroenterology service of Mulago Hospital and described the clinical and laboratory features of these patients.

Methods

All patients admitted to the unit were assessed and their diagnosis documented. Patients with cirrhosis had clinical features of decompensation recorded. History of alcohol consumption was taken and testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) performed.

Results

Between September 2010 and January 2011, we enrolled 482 patients. The majority (53.7%) were male, overall median age 38 years. Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients, 47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%) patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%).

Conclusion

Cirrhosis is common in Mulago hospital presenting mainly with ascites and variceal bleeding. Aside from controlling causes of liver diseases, especially alcohol and hepatitis B virus infection, in the interim it is necessary to manage complications in patients who already have cirrhosis.     

Moderate caloric restriction increases diaphragmatic antioxidant enzyme mRNA, but not when combined with lifelong exercise

Diaphragmatic antioxidant enzymes are upregulated following acute and long-term treadmill exercise, but the effect of lifelong voluntary exercise (E) on diaphragmatic antioxidants is unknown. Therefore, 10-week old Fisher 344 rats were assigned to either: (a) sedentary ad libitum (AL) fed (24AL; n = 6); (b) E + 8% caloric restriction (24ECR; n = 9); or (c) sedentary + 8% caloric restriction (24CR; n = 9) groups. Diaphragms were harvested from animals at 24 months of age. Heme oxygenase-1 (HO-1) mRNA in addition to catalase (CAT), glutathione peroxidase (GPX), copper-zinc superoxide dismutase (Cu-ZnSOD) and manganese superoxide dismutase (MnSOD) mRNA and protein levels were measured. Reduced glutathione (GSH) and citrate synthase (CS) activity were measured to assess antioxidant status and oxidative capacity, respectively. The 24CR group demonstrated increased GPX, HO-1, MnSOD, and CAT mRNA compared to 24AL and 24ECR. Interestingly, the increased mRNA in 24CR animals did not result in elevated protein levels. No group differences in Cu-ZnSOD mRNA, CS activity, or GSH were observed, although GSH was 30% greater in 24CR animals (p = 0.085). In summary, although CR elevated the mRNA of key antioxidant enzymes in the diaphragm, lifelong CR alone or in combination with voluntary exercise did not alter diaphragm CS activity, antioxidant protein quantity, or GSH levels.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.