Natural history of hyperlactataemia in human immunodeficiency virus-1-infected patients during highly active antiretroviral therapy

A study on the course of hyperlactataemia during highly active antiretroviral therapy (HAART) and the association between hyperlactataemia and antiretroviral drugs was conducted at the outpatient department, Rigshopitalet, Copenhagen. Lactate levels were monitored in 848 patients during a study period of 1 y. Longitudinal analysis was performed on all human immunodeficiency virus-1-infected patients who had plasma lactate > 2.1 mM. Hyperlactataemia was found in 178 patients (21%), of whom 7 patients needed treatment modification, owing to symptomatic hyperlactataemia in 3 and neuropathy in 4 patients, while 171 remained on unchanged therapy. Lactate levels increased in 20 patients during the study period, but the increases were modest with a mean of 0.6 mM (range 0.1-1.7 mM). The association between antiretroviral drugs and hyperlactataemia was studied using logistic regression in 263 patients with data on their treatment regimen available in electronic form. Only stavudine and ritonavir were significantly associated with hyperlactataemia, with odds ratios of 5.1 and 2.6, respectively. In conclusion, symptomatic hyperlactataemia is uncommon, while asymptomatic hyperlactataemia is a frequent and apparently benign condition unlikely to progress to lactic acidosis. A significant association between stavudine and hyperlactataemia was confirmed. The unexpected association between ritonavir and hyperlactataemia will need confirmation in future studies.     

Adrenal function during coronary artery bypass grafting

OBJECTIVE: To assess adrenal function in patients undergoing coronary artery bypass grafting (CABG) by means of the low-dose (1 microg) ACTH test, and to correlate the adrenal function with clinical outcome. METHODS: During a 5-Month period we prospectively included 45 patients undergoing elective CABG with cardiopulmonary bypass and without symptoms of endocrine disease. Low-dose (1 microg) ACTH tests were performed on the day before surgery (day -1), immediately after the operation (day 0), on the two subsequent days in the intensive care unit (day 1 and day 2), and on the day of discharge from the hospital. A number of clinical, hemodynamic and laboratory parameters were monitored throughout. RESULTS: On day -1, 75% of the study patients had normal stimulated plasma cortisol concentrations. Eleven patients (25%) had an impaired adrenal response to 1 microg ACTH. The stimulated plasma cortisol concentrations in patients who had an inadequate adrenal response on day -1 remained significantly reduced on day 1 (756+/-205 vs 949+/-259 nmol/l, P=0.03) (mean+/-s.d.), day 2 (644 (580-793) vs 885 (713-1087), P=0.03) (median (interquartile range)), and on the day of discharge (698+/-201 vs 854+/-186, P=0.05). In patients with a normal adrenal response in the preoperative setting peak cortisol concentrations were reached on day 1, in patients with a blunted adrenal response they were reached on day 2. There were significant correlations between the stimulated plasma cortisol concentrations and the blood loss (r=-0.50, P=0.002) and Volume balance (r=0.41, P=0.015). CONCLUSIONS: Occult (partial) adrenal insufficiency is common in patients undergoing CABG who are otherwise asymptomatic as regards endocrine disease. The adrenal function in these patients differs both in the magnitude of cortisol response to ACTH and in the time course, with significantly delayed peak cortisol concentrations. Adequate regulation of Volume balance and the amount of blood loss seem to correlate with adequacy of adrenal function.     

Human VAT-1: a calcium-regulated activation marker of human epithelial cells

Background and aims Human VAT-1 (hVAT-1) is a homologue of the synaptic vesicle membrane protein of Torpedo californica. Its coding gene is located near the BRCA1 locus and thus hVAT-1 may be linked to an inherited predisposition to breast and ovary cancer. However, the hVAT-1 protein expression pattern in normal epithelial tissues such as skin, mammary gland and ovary, as well as in tumours of the mammary gland and ovary, has not been studied.Methods To address this issue, an immunohistological analysis of biopsies of normal epidermis and lesional epidermis of bullous pemphigoid and pemphigus vulgaris patients was undertaken.Results hVAT-1-expression was observed in basal keratinocytes of lesional epidermis of bullous pemphigoid patients but not in normal epidermis or in lesional epidermis of pemphigus vulgaris patients. Moreover, hVAT-1 expression in HaCaT cells was found to be calcium-dependent. Normal and malignant mammary and ovary epithelium were found to be hVAT-1-negative.Conclusions Our results indicate that hVAT-1 exerts a specific function in keratinocyte physiology, in particular in calcium-regulated processes, with no evident deregulation in malignancies of the breast and ovary.Abbreviations BRCA1 Breast-related cancer antigen 1 - DMEM Dulbecco's modified Eagle's medium - EDTA Ethylenediamine tetraacetate - ELISA Enzyme-linked immunosorbent assay - FCS Fetal calf serum - GAPDH Glyceraldehyde-3-phosphate dehydrogenase - GST Glutathione-S-transferase - HRP Horseradish peroxidase - hVAT-1 Human VAT-1 - NHEK Normal human epidermal keratinocytes - PBS Phosphate-buffered saline - TBS Tris-buffered saline - VAT-1 Vesicle-amine-transport protein-1