Clinical review: Use of renal replacement therapies in special groups of ICU patients

Acute kidney injury (AKI) in ICU patients is typically associated with other severe conditions that require special attention when renal replacement therapy (RRT) is performed. RRT includes a wide range of techniques, each with specific characteristics and implications for use in ICU patients. In the present review we discuss a wide range of conditions that can occur in ICU patients who have AKI, and the implications this has for RRT. Patients at increased risk for bleeding should be treated without anticoagulation or with regional citrate anticoagulation. In patients who are haemodynamically unstable, continuous therapies are most often employed. These therapies allow slow removal of volume and guarantee a stable blood pH. In patients with cerebral oedema, continuous therapy is recommended in order to prevent decreased cerebral blood flow, which will lead to cerebral ischemia. Continuous therapy will also prevent sudden change in serum osmolality with aggravation of cerebral oedema. Patients with hyponatraemia, as in liver failure or decompensated heart failure, require extra attention because a rapid increase of serum sodium concentration can lead to irreversible brain damage through osmotic myelinolysis. Finally, in patients with severe lactic acidosis, RRT can be used as a bridging therapy, awaiting correction of the underlying cause. Especially in ICU patients who have severe AKI, treatment with RRT requires balancing the pros and cons of different options and modalities. Exact and specific guidelines for RRT in these patients are not available for most clinical situations. In the present article we provide an update on the existing evidence.     

Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.     

Design of the Verbiest trial: cost-effectiveness of surgery versus prolonged conservative treatment in patients with lumbar stenosis

Background  

Degenerative changes of lumbar spine anatomy resulting in the encroachment of neural structures are often regarded progressive, ultimately necessitating decompressive surgery. However the natural course is not necessarily progressive and the efficacy of a variety of nonsurgical interventions has also been described. At present there is insufficient data to compare surgical and nonsurgical interventions in terms of their relative benefit and safety. Previous attempts failed to provide clear clinical recommendations or to distinguish subgroups that substantially benefit from a certain treatment strategy. We present the design of a randomized controlled trial on (cost-) effectiveness of surgical decompression versus prolonged conservative treatment in patients with neurogenic intermittent claudication caused by lumbar stenosis.     

Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes

Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A_2BR was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A_2BR induced the expression of osteoblast‐related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A_2AR was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A₁R and A_2AR expression, and their activation was associated with increased adipogenesis. Enhanced A_2AR expression was sufficient to promote expression of adipocyte‐related genes (PPARγ and C/EBPα), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A₁R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage‐specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation. © 2011 American Society for Bone and Mineral Research     

Analysis of omega-3 fatty acid content of South African fish oil supplements

Introduction

Substantial evidence describes the protective effects of marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFA) on cardiovascular diseases as well as many other conditions. Numerous fatty acid preparations are marketed for supplementing the Western diet, which is low in n-3 fats. Since these preparations may vary in their n-3 PUFA content, we tested 45 commercially available products on the South African market for their fatty acid composition.

Method

Forty-five commercially available n-3 fatty acid supplements were analysed using gas–liquid chromatography to determine their fatty acid content.

Results

More than half of the n-3 supplements available on the South African market contained ≤ 89% of the claimed content of EPA and/or DHA as stated on the product labels. To meet ISSFAL’s recommendation of 500 mg EPA + DHA/day can cost consumers between R2 and R5 per person per day (R60 to R150 p/p/month). Regarding rancidity, the majority of capsules contained conjugated diene (CD) levels higher than that of vegetable oil obtained from opened containers (three months) used for domestic cooking purposes, despite the addition of vitamin E as antioxidant.

Conclusion

Since no formal regulatory structure for dietary supplements currently exists in South Africa, consumers depend on self-regulation within the nutraceutical industry for assurance of product quality, consistency, potency and purity. Our results indicate that more than half of the n-3 fatty acid supplements on the South African market do not contain the claimed EPA and/or DHA contents as stated on product labels, and they contained CD levels higher than that in unused vegetable oils obtained from opened containers used for domestic cooking purposes.     

Cue-conditioned alcohol seeking in rats following abstinence: involvement of metabotropic glutamate 5 receptors

Background and purpose:

The current study was designed to: (i) examine whether functional interactions occur between receptors known to regulate alcohol self-administration; and (ii) characterize relapse to alcohol seeking following abstinence.

Experimental approach:

The selective cannabinoid CB₁ receptor antagonist SR141716A (0.03–1.0 mg·kg⁻¹ i.p.) resulted in a dose-dependent reduction in ethanol self-administration in ethanol-preferring Indiana-preferring rats. SR141716A was then co-administered with either the selective glutamate metabotropic glutamate 5 (mGlu₅) receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) or the selective adenosine A_2A receptor antagonist {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261.

Key results:

When administered at individually sub-threshold doses, a combination of SR141716A (0.1 mg·kg⁻¹) and {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (0.5 mg·kg⁻¹ i.p.) produced a reduction (28%) in ethanol self-administration. Combinations of threshold doses of SR141716A (0.3 mg·kg⁻¹) and {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (2.0 mg·kg⁻¹, i.p.) caused an essentially additive reduction (68%) in alcohol self-administration. A combination of individually sub-threshold doses of CB₁ and mGlu₅ receptor antagonists did not affect alcohol self-administration; however, combined threshold doses of SR141716A (0.3 mg·kg⁻¹) and MTEP (1.0 mg·kg⁻¹ i.p.) did reduce ethanol self-administration markedly (80%). Cue-conditioned alcohol seeking was attenuated by pretreatment with MTEP (1.0 mg·kg⁻¹) co-administered with SR141716A (0.3 mg·kg⁻¹ i.p.). In contrast, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (2.0 mg·kg⁻¹) co-administered with SR141716A (0.3 mg·kg⁻¹ i.p.) did not reduce cue-conditioned alcohol seeking.

Conclusions and implications:

Adenosine A_2A and cannabinoid CB₁ receptors regulated alcohol self-administration additively, but combined low-dose antagonism of these receptors did not prevent cue-conditioned alcohol seeking after abstinence. In contrast, combined low-dose antagonism of mGlu₅ and CB₁ receptors did prevent relapse-like alcohol seeking after abstinence, suggesting a prominent role for mGlu₅ receptors in this paradigm.     

THE OCULAR AND PERIOCULAR FEATURES OF MULTICENTRIC RETICU-LOHISTIOCYTOSIS WITH PARAPROTEINEMIA A report of two cases

Two patients with atypical multicentric reticulohistiocytosis are reported. Skin rigidity with mobile rubbery nodules, and telangiectases, are typical of this disease and occurred around the eyes and elsewhere. One patient also had subconjunctival nodules and corneal crystal formation probably due to her paraproteinaemia.
Some literature on this disease and on the occurrence of corneal crystal deposition in dysproteinaemia is reviewed.