Lithium toxicity

We report a case of severe lithium toxicity precipitated by a thiazide diuretic and compounded by an angiotensin converting enzyme inhibitor. There was severe vasodilatation refractory to noradrenaline.     

Interleukin-1 stimulates rapid release of cytokine-induced neutrophil chemoattractant (CINC) in rat lungs

We found that intratracheal insufflation of interleukin-1 (IL-1) in rats rapidly increased lung lavage cytokine-induced neutrophil chemoattractant (CINC) concentrations, lung tissue myeloperoxidase (MPO) activity, and lung lavage neutrophil counts, and that CINC elevation preceded the migration of neutrophils into the lung. Further, we found that bolus CINC insufflation increased CINC concentrations in plasma, and we found that alveolar macrophages (AM) in lung tissue selections or AM recovered by lavage from rats given IL-1 intratracheally stained positively for CINC by immunohistochemistry. In addition, incubating rat AM with increasing doses of IL-1 in vitro progressively increased CINC concentrations in the culture medium. Our results suggest that the potent neutrophil chemoattractant CINC is rapidly produced and released by rat AM following challenge with IL-1 in vivo or in vitro, and support the hypothesis that CINC is an important mediator in the development of pulmonary inflammation in the rat.Parker B. Francis Fellow in Pulmonary Research.     

Can one stop nucleic acid sampling (OSNA) predict nodal positivity following neoadjuvant chemotherapy? A prospective cohort study of 293 patients

Until recently, axillary node clearance had long been the standard of care in patients with axillary node-positive disease. One stop nucleic acid sampling (OSNA) has been used to guide intraoperative decision-making regarding suitability for axillary node clearance (ANC). The aim of this study is to evaluate the use of OSNA following neoadjuvant chemotherapy (NACT) and whether it can predict lymph node burden in ANC. A single center, prospective cohort study was performed on 297 patients having OSNA between 2016 and 2019. Patients were sub-classified according to node positivity at diagnosis and those treated with NACT and outcomes included copy number and lymph node harvest. Axillary complete pathological response was observed in 24/36 patients (67%) following NACT. 14/16 patients (87%) having axillary node clearance had axillary node disease limited to 4 nodes. OSNA copy numbers were significantly higher in patients showing disease progression following NACT. Overall, 73% of patients with lymph node positivity at diagnosis could be successfully treated with a combination of NACT and lymph node excision of four nodes. De-escalating axillary surgical treatment to resection of four nodes following NACT may be effective in balancing oncological resection and limiting treatment morbidity. ONSA can correctly identify patients experiencing disease progression who would benefit from traditional three-level ANC.     

A randomized controlled trial of sedation in the critically ill

A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P <0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/distressed) was significantly greater in the midazolam group (Chi-squared P <0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.     

p.R254Q mutation in the aquaporin‐2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin‐induced phosphorylation

Vasopressin regulates human water homeostasis by re‐distributing homotetrameric aquaporin‐2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells, a process in which phosphorylation of AQP2 at S256 by cAMP‐dependent protein kinase A (PKA) is thought to be essential. Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by AQP2 gene mutations. Here, we investigated a reported patient case of dominant NDI caused by a novel p.R254Q mutation. Expressed in oocytes, AQP2‐p.R254Q appeared to be a functional water channel, but was impaired in its transport to the cell surface to the same degree as AQP2‐p.S256A, which mimics non‐phosphorylated AQP2. In polarized MDCK cells, AQP2‐p.R254Q was retained and was distributed similarly to that of unstimulated wt‐AQP2 or AQP2‐p.S256A. Upon co‐expression, AQP2‐p.R254Q interacted with, and retained wt‐AQP2 in intracellular vesicles. In contrast to wild‐type AQP2, forskolin did not increase AQP2‐p.R254Q phosphorylation at S256 or its translocation to the apical membrane. Mimicking constitutive phosphorylation in AQP2‐p.R254Q with the p.S256D mutation, however, rescued its apical membrane expression. These date indicate that a lack of S256 phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a loss of function instead of a gain of function mutation in dominant NDI. © 2009 Wiley‐Liss, Inc.     

Large particle hyaluronic acid for the treatment of facial lipoatrophy in HIV‐positive patients: 3‐year follow‐up study

Objectives

Facial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV‐infected patients. We sought to evaluate the long‐term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow‐up.

Methods

Twenty patients received injections of Restylane SubQ^™. Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self‐esteem scale.

Results

Seventeen patients remained at 36 months. Mean (± standard deviation) total cutaneous thickness increased from 6 ± 1 mm at baseline to 12 ± 1 mm (P<0.001) at 36 months. Response rate (total cutaneous thickness >10 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 ± 25 to 70 ± 20 (P<0.05) and higher self‐esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months.

Conclusions

Our results indicate that a large particle hyaluronic acid formulation is a durable and well‐tolerated dermal filler for treating HIV‐positive patients with facial lipoatrophy.