Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X-linked adrenoleucodystrophy

OBJECTIVE: In X-linked adrenoleucodystrophy (X-ALD) the peroxisomal beta-oxidation of saturated very long-chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. Most patients have a primary adrenocortical insufficiency with low levels of cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S), collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma cortisol and ACTH levels are normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the beta-oxidation of fatty acids. PATIENTS AND DESIGN: To study the effect of DHEA on fatty acids in X-ALD patients, we conducted a randomized double-blind study in which 14 men (age range 21-63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1-month wash-out period, then 3 months of placebo or vice versa. RESULTS: A significant rise was seen in the plasma levels of DHEA-S, Delta4-androstenedione and IGF-I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4omega-6, C22:5omega-6, C18:1omega-9, C20:1omega-9 and C20:3omega-9. In plasma, decreases were found for C18:1omega-9 and increases for C20:1omega-9. CONCLUSIONS: Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long-chain fatty acids in patients with X-linked adrenoleucodystrophy. Instead, a decrease in saturated and mono- and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1omega-9 was found in plasma only.     

Necrotizing enterocolitis in a married couple due to a staphylococcal toxin

A married couple affected by necrotizing enterocolitis is described. Both had the same toxin-producing Staphylococcus aureus which was considered to be responsible for the necrotizing enterocolitis.     

Efficacy of opioid rotation to continuous parenteral hydromorphone in advanced cancer patients failing on other opioids

Purpose

The effectiveness of an opioid rotation to parenteral hydromorphone in advanced cancer patients has never been investigated. Therefore, the purpose of this study was to investigate the analgesic efficacy and side effects of parenteral hydromorphone on serious cancer-related pain.

Methods

We included 104 consecutive advanced cancer patients who were extensively pretreated with opioids. They were rotated to parenteral hydromorphone because they failed to achieve adequate pain relief on other opioids. Pain intensity and side effects were daily assessed. The moment of adequate pain control was defined as the first of at least 2 consecutive days when the mean pain intensity at rest was ≤4 (on a 0–10 numeric rating scale) and side effects were tolerable.

Results

The reasons for rotation to parenteral hydromorphone were inadequate pain control with/without expected delivery problems due to high opioid dosages (n?=?61) and intolerable side effects with persistent pain (n?=?43). Adequate pain control was achieved in 86 patients (83%) within a mean of 5?days. Eight of 86 patients still had side effects, but these were scored as acceptable. The mean pain intensity at rest decreased from 5.4 [standard deviation (sd)?=?2.1] to 2.4 (sd?=?1.5; p?<?0.001). The median failure-free treatment period was 57?days and covered a substantial part of the median survival of 78?days in the responding patients.

Conclusions

In advanced cancer patients with serious unstable cancer-related pain refractory to other opioids, continuous parenteral administration of hydromorphone often results in long-lasting adequate pain control and should be considered even after extensive pretreatment with opioids.     

Influence of acute exercise on hyperglycemia in insulin-treated type 2 diabetes

INTRODUCTION: The impact of exercise on blood glucose homeostasis has not been assessed in long-standing type 2 diabetes patients receiving exogenous insulin treatment. PURPOSE: To study the effects of an acute bout of exercise on the subsequent 24-h blood glucose excursions under free-living conditions in insulin-treated type 2 diabetes patients. METHODS: Eleven male type 2 diabetes patients (59 +/- 2 yr) performed an acute bout of exercise. One day before the exercise bout, a continuous glucose monitoring system (GlucoDay, A. Menarini Diagnostics) was inserted subcutaneously in the periumbilical region. The glucose sensor continuously measured glucose concentrations in the dialysate during a 48-h period. RESULTS: The prevalence of hyperglycemic glucose excursions was reduced by 39% during a 24-h period (equivalent to 3 h) after an acute bout of exercise (P < 0.05). Average glucose concentrations 24 h before and after the exercise bout did not differ (NS). Mean dialysate glucose concentrations and the prevalence of hyperglycemic periods correlated strongly with baseline blood HbA1c concentrations (Pearson's R = 0.69, P < 0.05). CONCLUSION: An acute bout of exercise effectively reduces the prevalence of hyperglycemia during a 24-h period under free-living conditions in long-standing type 2 diabetes patients on exogenous insulin therapy.     

When patients’ invisible work becomes visible: non‐adherence and the routine task of pill‐taking

While the biographical dimensions of chronic illness have been well researched, the concrete dimensions of patients’ work have not been as thoroughly investigated as yet. With the growing concern for self‐management, such research would be timely. This study aims to better understand patients’ invisible work by highlighting the causes of unintentional non‐adherence as well as strategies for adherence. For this purpose, it defines medical treatment adherence as the repetition of the pattern of tasks through which a patient succeeds, in a technical sense, in taking the right medication at the right time, in the right amount, for the right duration. Applying a failure modes and effects analysis approach to 48 semi‐structured interviews with Dutch patients, it shows the negative impact of schedule changes, pressure, positioning changes, lack of backup pills and lack of verification tools. Symmetrically, it highlights the role of anchoring, sequencing, positioning, cueing, correcting and verifying. This result points to the need for an analytical approach of patients’ work and treatment adherence that would build on the role of routines in organisations and in the workplace.