Dielectric Analysis of Phosphorylcholine Head Group Mobility in Egg Lecithin Liposomes

Purpose. A knowledge of the interfacial properties of lecithin underpins our understanding of many of the physicochemical characteristics of drug delivery systems such as liposomes and lecithin stabilized microemulsions. In order to further this understanding, a high frequency dielectric study of the interfacial properties of egg lecithin liposomes was undertaken. Methods. The effect of temperature, lecithin concentration and probe sonication on the interfacial dielectric properties of liposomal suspensions was investigated by high frequency dielectric relaxation spectroscopy between 0.2–6 GHz. Results. The frequency dependent permittivity of each suspension exhibited a dielectric dispersion centred around 100 MHz, corresponding to the relaxation of zwitterionic head groups. The activation energy for head group reorientation was estimated as H = 6.3 kJ mol^–1. There was an increase in extent of inter-head group interactions on increasing the liposome volume fraction, whereas the effect of probe sonication showed that: (i) head groups in both the outer and inner lamellae contribute to the dielectric response; (ii) the head groups may be less restricted in liposomes of high surface curvature with few lamellae; (iii) the high frequency permittivity of the suspension increased on sonication, as a result of a reduction in the amount of (depolarized) interlamellar water following a reduction in the number of lamellae per liposome. Conclusions. Dielectric analysis of the zwitterionic head groups of lecithin therefore provides a means for investigating the surface of lecithin liposomes, and may be used to investigate the effect of drugs and other solutes on membranes.     

A case-control study of persons with elevated blood levels of dieldrin

Twenty-seven pesticide workers with elevated blood levels of dieldrin (15 ppb) were involved in a case-control study which included history and physical examination, comprehensive neurological evaluation, laboratory tests, and psychological and psychomotor testing. No clinically important differences were found on history, physical, specialized neurological tests, or laboratory examination. The exposed group showed a statistically significant difference in five out of 58 psychological (P) and psychomotor (PM) tests—at least three would be expected by chance (p .05). In only one of these tests was there any significant correlation with dieldrin levels. Even though the exposed group had worse scores than the control group in 47 of 58 P-PM tests, such scores were, with a few exceptions, in the normal range of values. Elevated blood levels of dieldrin encountered in this study do not appear to have any chronic deleterious effects on health, as measured by conventional medical work-up and extensive central nervous system testing.     

American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer.

PURPOSE: To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer. METHODS: An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors. RESULTS: The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes. CONCLUSION: SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown.     

The effect of wet granulation on the erosion behaviour of an HPMC-lactose tablet, used as a rate-controlling component in a pulsatile drug delivery capsule formulation.

The purpose of this study was to investigate the variability in the performance of a pulsatile capsule delivery system induced by wet granulation of an erodible HPMC tablet, used to seal the contents within an insoluble capsule body. Erodible tablets containing HPMC and lactose were prepared by direct compression (DC) and wet granulation (WG) techniques and used to seal the model drug propranolol inside an insoluble capsule body. Dissolution testing of capsules was performed. Physical characterisation of the tablets and powder blends used to form the tablets was undertaken using a range of experimental techniques. The wet granulations were also examined using the novel technique of microwave dielectric analysis (MDA). WG tablets eroded slower and produced longer lag-times than those prepared by DC, the greatest difference was observed with low concentrations of HPMC. No anomalous physical characteristics were detected with either the tablets or powder blends. MDA indicated water-dipole relaxation times of 2.9, 5.4 and 7.7x10(-8)ms for 15, 24 and 30% HPMC concentrations, respectively, confirming that less free water was available for chain disentanglement at high concentrations. In conclusion, at low HPMC concentrations water mobility is at its greatest during the granulation process, such formulations are therefore more sensitive to processing techniques. Microwave dielectric analysis can be used to predict the degree of polymer spreading in an aqueous system, by determination of the water-dipole relaxation time.     

Adherence to nebulised therapies in adolescents with cystic fibrosis is best on week-days during school term-time

ObjectivesTreatment regimen for families of children with cystic fibrosis (CF) is considerable, particularly when nebulised therapies for chronic Pseudomonas aeruginosa airway infection are prescribed. Adherence to these regimens is variable, particularly in adolescence. Previously, we reported children to be more adherent in evenings compared to mornings, suggesting an association with time-pressure. The aim of this study was to determine whether adherence would be better in adolescent patients at weekends and during school holidays when time-pressures may be less.Study design24 patients (14 male, median [range] age 13.9 [11.1–16.8] years) were enrolled from two regional paediatric CF centres in the United Kingdom. Data for a full scholastic year, were downloaded openly from a breath-activated data logging nebuliser (I-neb?). Adherence (% of doses taken ÷ expected number) was calculated during term-times, holidays, weekends and weekdays, for each patient.ResultsLarge variations in adherence were seen between patients. However, adherence during term-time was significantly better than holidays (p < 0.001). Weekday adherence was better than weekend adherence in term-time but not holidays. Interestingly, patients prescribed three daily treatments took on average 1.4 treatments/day, a similar number to those prescribed two daily treatments.ConclusionOverall adherence to inhaled therapies was reasonable, but significantly reduced during holiday periods. This suggests a need for families to have not only time, but also structure in their daily routine to maintain optimal adherence to long-term therapies. It is important for CF teams to appreciate these factors when supporting families.     

Acute kidney injury and the critically ill

Acute renal failure is commonly encountered in the intensive care unit. It is associated with considerable morbidity and mortality. There are many possible aetiologies in the critically ill, including nephrotoxic agents, hypovolaemia and sepsis. While many classification systems for acute renal failure exist, the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria and the Acute Kidney Injury Network (AKIN) criteria are the most commonly utilized. Many supportive therapies are employed to minimize the degree of renal injury once recognized, such as fluid resuscitation, maintenance of an adequate mean arterial pressure (with the use of vasopressors in persistent hypotension despite fluid and treatment of the underlying aetiology). However, if renal failure becomes established, then renal replacement therapy (RRT) may be needed to maintain homeostasis. While there are no clear guidelines with respect to the ideal mode or timing of RRT, we will discuss pros and cons of the various options.