Non‐medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

Background

We examined clinical outcomes, patient characteristics and trends over time of non‐medically supervised treatment interruptions (TIs) from a free‐of‐charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada.

Methods

Data from ART‐naïve individuals ≥18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ≥3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment.

Results

A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co‐infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty‐eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS‐defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART.

Conclusion

Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years.

     

Risk factors associated with coronary artery calcification should be examined before kidney transplantation

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.     

25The effect of lipase supplementation on upper gastrointestinal symptoms and gastric myoelectrical activity induced by a high fat meal in healthy volunteers.

Background/Aims: Dyspepsia symptoms of abdominal discomfort, fullness, early satiety, and nausea occur after ingestion of meals in 20–30% of the population. Gastric dysrhythmias are exhibited by approximately 55% of dyspepsia patients. Currently there are limited therapies to reduce these symptoms. Gastric and pancreatic lipases are key enzymes in fat digestion, and hydrolyze fat into fatty acids and monoglycerides. The aims of this study were to characterize the effects of a high fat meal on upper gastrointestinal symptoms and gastric myoelectrical activity, and to evaluate the effect of acid‐resistant lipase supplementation on the same outcomes. Methods: Sixteen healthy volunteers enrolled in a double‐blind, placebo controlled, cross‐over trial were given a high fat meal (Pulmocare^®) that was 55% fat, 28% carbohydrates, and 17% protein (237 ml; 355 Kcal). A capsule containing 280 mg of acid‐resistant lipase (Amano Enzyme USA) or placebo was administered immediately before ingestion of the meal. The order of conditions was counterbalanced, and visits were separated by at least one week. At each visit, individuals completed a Visual Analog Scale (VAS) concerning symptoms of nausea, stomach fullness, hunger, bloating, and abdominal discomfort at baseline, immediately after the meal, and at 10, 20, 30, 45, and 60 minutes after the meal. Electrogastrograms (EGGs) were recorded throughout each visit to assess gastric myoelectrical activity. Results: Nausea, bloating, and stomach fullness were significantly increased 10 min after ingestion of the meal (ps < 0.05), and hunger was significantly decreased (p < 0.001); there was also a significant decrease in normal gastric myoelectrical activity (3 cycles min^?1), and a significant increase in tachygastria (3.7–10 cycles min^?1) at 10 min after the meal (ps < 0.05). By 45 min after the meal, dyspepsia symptoms and tachygastria had decreased significantly from immediately after the meal, and normal gastric myoelectrical activity had increased significantly (ps < 0.05). Stomach fullness was significantly lower with lipase supplementation than with placebo condition at 20 and 30 min after the meal (p < 0.05); no effect of lipase supplementation on gastric myoelectrical activity was detected. Conclusions: (1) The high fat meal induced dyspepsia symptoms and gastric dysrhythmias, suggesting the meal may be a useful test for assessing gastric neuromuscular disorders; and (2) Acid‐resistant lipase supplementation decreased stomach fullness after ingestion of the meal, and warrants further study in individuals with functional dyspepsia.     

Optimal scan time for evaluation of parathyroid adenoma with [18F]-fluorocholine PET/CT

Background

Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [¹⁸F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism.

Patients and methods.

43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUV_mean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated.

Results

Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUV_mean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05).

Conclusions

According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.     

Comparison of topical iodine and silver sulfadiazine as therapies against sulfur mustard burns in a pig model

Sulfur mustard (SM) is a powerful vesicant used as an agent of chemical warfare. The severity of lesions incurred after exposure to SM reiterated the need for an efficient and rapid neutralizing agent against SM. Previous studies have shown that postexposure treatment with iodine is effective against SM lesions in rodents. In the current study we used the pig model to emulate SM-induced burn lesions, and observed the immediate effect of a single dose of iodine formulation treatment on these burns. SSD, a common agent recommended for use in both chemical and thermal burns was used as control. Results indicated that 1.27 mg of SM caused deep lesions and histopathological changes in the pig skin as scored in the biopsies obtained. A single application of an iodine formulation 20 minutes from exposure to SM exhibited no protective action on the skin as evident in the biopsies obtained 1, 3, 5, 10, and 21 days after treatment. SSD treatment induced the least protective action. The SSD-treated wounds also took the longest to heal. Attempts to neutralize the SM action with iodine compounds were not successful in the pig model. Currently, other compounds are being investigated. Attention must be drawn to the adverse effect of SSD on SM-induced wounds. Further studies must be initiated to elucidate this phenomenon.     

De novo minimal change disease

Beyond the acute posttransplantation period, glomerular causes of proteinuria in the renal allograft include recurrent glomerulopathy, transplant-associated entities, and de novo disease. We present a case of de novo minimal change disease with reversible acute renal failure occurring 2.5 years posttransplantation in a 56-year-old man. The cause of end-stage renal disease in the native kidney was membranous glomerulopathy. De novo minimal change disease in the renal allograft is an extremely rare entity requiring stringent clinical-pathological criteria for diagnosis. Many of the cases previously reported as de novo minimal change disease fail to meet these criteria. We review the eight reported cases that appear to fulfill a strict definition of minimal change disease in the context of the current report.     

Imaging Cardiac Stem Cell Transplantation Using Radionuclide Labeling Techniques: Clinical Applications and Future Directions

Stem cell therapy is emerging as a potential new therapy for patients with advanced heart failure. In recent years, advances in molecular imaging have allowed monitoring of stem cell homing and survival. In this review article, we will discuss the clinical application and future directions of stem cell imaging in advanced heart failure.