Fluids in septic shock: too much of a good thing?

In a recent issue of Critical Care, Brandt and colleagues report the effects of a 'liberal' fluid loading protocol compared to a more 'restrictive' protocol on hemodynamics and mortality in pigs in which septic shock had been induced. It appears that the former protocol was associated with higher mortality in spite of improved hemodynamics compared to the latter. The results of the paper are discussed here in view of the scope and mechanisms of these findings. With regard to fluid resuscitation, they indicate that too much of an otherwise good thing is harmful, even if overhydration and edema formation seem to have been prevented. They also do not exclude a specific toxic effect of the larger volumes of hydroxyethyl starch in the 'liberal' strategy. The precise nature of a toxic effect remains obscure, however, but may involve the kidneys.     

A pilot methodology study for the photographic assessment of post‐inflammatory hyperpigmentation in patients treated with tretinoin

Background Post‐inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual‐controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community‐based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method.     

The effectiveness of adding cognitive behavioural therapy aimed at changing lifestyle to managed diabetes care for patients with type 2 diabetes: design of a randomised controlled trial

Background  

In patients with type 2 diabetes, the risk for cardiovascular disease is substantial. To achieve a more favourable risk profile, lifestyle changes on diet, physical activity and smoking status are needed. This will involve changes in behaviour, which is difficult to achieve. Cognitive behavioural therapies focussing on self-management have been shown to be effective. We have developed an intervention combining techniques of Motivational Interviewing (MI) and Problem Solving Treatment (PST). The aim of our study is to investigate if adding a combined behavioural intervention to managed care, is effective in achieving changes in lifestyle and cardiovascular risk profile.     

The quality of oral anticoagulation before,during and after a period of patient self-management

The study analyzes the quality of anticoagulation during a 3-year follow-up on patients who were treated by an anticoagulation clinic (ACS) for 1 year (Phase I), performed weekly self-management of anticoagulation (PSM) after a specific training for another year (Phase II) and finally returned to be treated by the anticoagulation clinic (ACS) for a third year (Phase III). The mean fraction of INR values within therapeutic target range was higher in Phase II (0.69 +/- 0, 11) compared to Phases I (0.40 +/- 0.20) and III (0.56 +/- 0.18; p < 0.05). Time spent in therapeutic target range was higher in Phase II (0.70 +/- 0.10) compared to Phases I (0.43 +/- 0.25) and III (0.60 +/- 0.17; p < 0.05). Mean square deviation from target value was lower in Phase II (0.39 +/- 0.17) compared to Phases I (0.81 +/- 0.44) and III (0.64 +/- 0.39, p = 0.05). Thus, the quality of anticoagulation during Phase II (PSM) was significantly better compared to Phases I (ACS) and III (ACS) in all endpoints tested. This shows that the quality of oral anticoagulation deteriorates again if patient self-management is stopped and patients return to conventional treatment. Furthermore, the quality of anticoagulation was better in Phase III (post-PSM) compared with Phase I (pre-PSM) although the type of treatment was identical in both phases (ACS). This suggests that the increased patient empowerment and enhanced compliance acquired during PSM (Phase II) might have a positive impact on the quality of anticoagulation, even when patients return to the conventional treatment (ACS).     

The impact of Glu102Lys on the factor X function in a patient with a doubly homozygous factor X deficiency (Gla14Lys and Glu102Lys)

Two homozygous point mutations were found in a patient with factor X (FX) deficiency; One results in substitution of Lys for Gla+ 14 and the second causes a Lys substitution for Glu102. The proposita has a severely reduced FX coagulant activity in the extrinsic (<1% of normal) and in the intrinsic (30% of normal) system of coagulation and after activation with Russel's viper venom (18% of normal). The FX antigen is reduced in this patient to 20% of normal. The substitution of Lys for Glu102 in FX deficiency has been reported previously in a heterozygous state in conjunction with a Lys for Gla+14 substitution and with a Pro for Ser334 substitution. The contribution of the Lys for Glu102 substitution in the observed combined FX defect in these patients was unclear. The mutation causing the Glu102Lys substitution was introduced by site directed mutagenesis into a wild-type FX cDNA, and recombinant protein was expressed in HEK 293 cells. Compared to the wild-type FX cDNA, the mutant construct had a 67% activity upon activation in the extrinsic system, 93% activity upon activation in the intrinsic system and 72% after activation with RVV. The data presented show that the substitution of Lys for Glu102 results in a minor functional defect of the FX molecule.     

Tamoxifen Therapy for Breast Cancer and Endometrial Pathology

Background

Tamoxifen, used as adjuvant therapy for carcinoma breast in postmenopausal women to prevent relapse has estrogenic effect on the endometrium.

Methods

104 patients on tamoxifen for more than six months were subjected to a clinical examination and transvaginal sonography. Patients with endometrial thickness > 8 mm were further evaluated by hysteroscopy and endometrial biopsy.

Results

35(34%) patients were symptomatic. The average endometrial thickness was 11.2 mm which correlated with duration of tamoxifen use. 27(48%) patients had abnormal hysteroscopic findings. 35 (63%) of endometrial biopsies revealed abnormal endometrium. One case of endometrial carcinoma was diagnosed. The results were statistically analysed. There is a significant association between symptomatic status and endometrial thickness and duration of tamoxifen use.

Conclusion

All patients on long term tamoxifen should be annually screened for endometrial pathology.Key Words: Tamoxifen, Endometrium, Transvaginal sonography