[Treatment of persistent postmastectomy pain with 5% Lidocaine medicated plaster]. / Trattamento del "persistent postmastectomy pain" con Lidocaina cerotto 5%.

Persistent postmastectomy pain (PPMP) syndrome is characterized by neuropathic pain that develops following surgery in breast cancer patients. The reported incidence of PPMP ranges between 30% and 50% and is estimated to increase as the number of women surviving cancer continues to rise. Though effective, today's drug treatments are poorly tolerated, limiting their use and reducing adherence to therapy. Since neuropathic pain is localized, international guidelines suggest that topical treatment with 5% Lidocaine medicated plaster either alone or combined with systemic drugs can be considered for pain management. In this retrospective study we reviewed the medical records of 11 patients treated with 5% lidocaine medicated plaster for moderate-to-severe PPMP at our institute between November 2013 and October 2014. Analysis showed that treatment with 5% Lidocaine medicated plaster, either alone or in combination with systemic drugs, achieved significant pain control already after the first week of therapy. The effectiveness and tolerability of 5% Lidocaine medicated plaster we observed suggests that it is a viable option in the management of PPMP.

Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique.

The study aimed to produce solid lipid insulin-loaded micro-particles by the solvent-in-water emulsion-diffusion technique, using isobutyric acid as solvent phase, glyceryl monostearate or cetyl palmitate as lipid, soya lecithin and taurodeoxycholate as emulsifiers. Isobutyric acid, a partially water-miscible solvent with low toxicity, was used due to its high insulin-solubilization capacity. Solid lipid micro-particles of spherical shape were prepared by simple dilution of the emulsion with water. To increase the lipid load the process was conducted at 50 degrees C, and in order to reach sub-micron size, a high-shear homogeniser was used. Insulin encapsulation efficiency was about 80%. Analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within the micro-particles. The in vitro release of insulin from the micro-particles was very low, and an initial burst effect of 20% of the dose was observed. After treatment of the solid lipid micro-particles with pepsin solution, an insulin loss of about 24% of the total englobed insulin was observed. The solid lipid micro-particles appear to have interesting possibilities as delivery systems for oral administration of insulin.

Elastic liposomes for skin delivery of dipotassium glycyrrhizinate.

The aim of this study was to evaluate the possibility of using liposomes for skin delivery of dipotassium glycyrrhizinate (KG), an anti-inflammatory agent employed in treating acute and chronic dermatitis, and of formulating such liposomes in an oil-in-water emulsion (O/W). KG had emulsifying properties and the possibility of producing elastic liposomes was verified. Liposomes containing soya lecithin (PC) or hydrogenated soya lecithin (HPC) mixed with KG in w/w ratios of 2:1, 4:1 or 8:1 were prepared by the solvent evaporation method and then passed through a high pressure homogeniser. Liposome size and entrapment efficiency were determined and the interaction between KG and HPC was investigated using differential scanning calorimetry (DSC). Transepidermal permeation through intact pig skin and skin deposition of KG from liposomes and O/W emulsion containing liposomes were assessed and compared with values for aqueous control solutions. No marked differences were observed between PC and HPC liposomes. Liposome sizes ranged from 90 to 120 nm. Entrapment efficiency depended on the lipid:KG ratio; the maximum efficiency was obtained at 4:1 w/w. KG interacted with liposomes disrupting and fluidising the lipid bilayer, forming elastic liposomes able to penetrate through membrane pores of diameter much smaller than their own diameter. The liposome structure was maintained when dispersed in an O/W emulsion. The skin fluxes were less than the HPLC detection limit for all systems, while skin deposition increased 4.5-fold compared with aqueous solutions when KG was formulated in liposomes.

[Analgesic effects of natural growth hormone release inhibitors and their synthetic analogs. Intraspinal administration]. / Effetti analgesici degli inibitori della liberazione degli ormoni della crescita (GHRIH) nativi ed analoghi sintetici. Luci ed ombre sulla somministrazione intraspinale.

The authors examine the pharmacological characteristics, distribution and clinical effects of natural (somatostatin) and synthetic (octreotide) growth hormone release inhibitors (GHRIH). They mainly discuss the analgesic effect of these substances using intraspinal, epidural and subarachnoid administration. The intraspinal use of somatostatin and its synthetic analog, octreotide, are not without risks: among these, it is worth recalling the neurotoxic and vasomotor effects. Further studies may more clearly define these and other secondary effects and also the real indications for these drugs in the context of analgesics for intraspinal use. It is hypothesised that somatostatin and octreotide, owing to their analgesic capacities, may replace the intraspinal administration of opioids in a number of clearly defined clinical conditions, such as severe pain in which opioids are contraindicated.

Vitamin A palmitate photostability and stability over time.

Vitamin A palmitate photostability in relation to UVA and UVB was tested in hydroxy ethyl cellulose hydrogels at pH 4.0, 5.6, 7.0, and 8.0, alone and with the addition of sunscreens (3,4-methylbenzilidencamphor or butyl methoxy dibenzoylmethane) or an antioxidant (butylated hydroxy toluene). The photostability of vitamin A palmitate was also tested in encapsulated systems (Tagravit A1 microcapsules, Lipotec liposomes, phosphatidylcholine liposomes, and Lipotec nanocapsules) dispersed in gels at pH 5.6 and 7.0. The stability of retinyl palmitate over time in hydroxy ethyl cellulose hydrogels at pH 5.6 and 7.0 (stored one month at 25 degrees C or 40 degrees C), alone or with butylated hydroxy toluene, was also tested. The stability of retinyl palmitate over time in encapsulated systems, dispersed in gels at pH 5.6 and 7.0, was also studied. O/W emulsions were also prepared to compare the stability of vitamin A palmitate introduced in a lipophilic/hydrophilic medium (O/W emulsions) and a hydrophilic medium (hydrogels). HPLC analysis showed that encapsulated systems such as Lipotec nanocapsules, Tagravit A1 microcapsules, phosphatidylcholine liposomes, and Lipotec liposomes protect the vitamin A ester over time from hydrolysis and from oxidation to retinaldeide and retinoic acid, and that Lipotec nanocapsules and phosphatidylcholine liposomes also improve the vitamin's photostability. A change in pH (from 5.6 to 7.0) of the gels did not influence the vitamin ester's stability. pH levels of 4.0 and 8.0 determined a decrease in the stability of retinyl palmitate in the gels. A high concentration of sunscreens improved the photostability of retinyl palmitate in the gels at pH 5.6 and 7.0. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light at all the pH levels studied and by heat at pH 5.6 and 7.0, as can be seen from the study of the photostability of vitamin A palmitate under UVB and UVA and of stability over time. Rheological studies showed a slight decrease in the viscosity of the gels after UVB-UVA irradiation and a higher decrease in the viscosity of the gels and the emulsions after storage at 25 degrees C and 40 degrees C. This decrease can be attributed to a partial degradation of hydroxy ethyl cellulose and of emulsifier, as can be seen from the decrease in shear stress versus shear rate values under these conditions of storage, denoting a depolymerization of the rheological modifier.

Forgoing life sustaining treatments: differences and similarities between North America and Europe.

BACKGROUND: As evidence exist that severe neurological damage or prolonged death after inappropriate CPR could occur, restraints and indications for CPR were perceived as necessary. The objective of this review is to examine policies and attitudes towards end-of-life decisions in Europe and North America and to outline differences and similarities. METHODS: A bibliographic database search from 1990 to 2006 was performed using the following terms: do-not-resuscitate orders, end-of-life decisions, withholding/withdrawal of life-sustaining treatments, medical futility and advanced directives. Eighty-eight articles, out of 305 examined, were analyzed and their data systematically reported and compared where possible. They consisted of studies, questionnaires and surveys answering the following questions: percentage of deaths of critical patients preceded by do-not-resuscitate orders, factors affecting the decision for do-not-resuscitate orders, people involved in this decision (patient, surrogates and medical staff) and how it was performed. RESULTS: There is an evident gap between the North American use of standard and formal procedures compared with Europe. Second, they diverge in the role acknowledged to surrogates in the decisional process, as in Europe, restraints and reserves to accept surrogates as decision makers seem still strong and a paternalistic approach at the end-of-life is still present. CONCLUSION: Incidentally, despite the predictable differences between Europe and North America, concerns do exist about the actual extent of autonomy wished by patients and surrogates. It is important to highlight these findings, as the paternalistic attitude, too often negatively depicted, could be, according to the best medical practice, justified and more welcomed in some instances.

[Neurolytic block of the celiac plexus and splanchnic nerves with computed tomography. The experience in 150 cases and an optimization of the technic]. / Il blocco neurolitico del plesso celiaco e dei nervi splancnici con Tomografia Computerizzata. Esperienza su 150 casi e ottimizzazione della tecnica.

INTRODUCTION: CT-guided celiac plexus and splanchnic nerve neurolytic blocks are procedures for pain relief in patients with upper abdominal malignancies. In the last 20 years, the technique has been modified by the introduction of CT guidance providing improved precision and safety. We report our personal experience and provide suggestions for technique optimization. MATERIALS AND METHODS: In 1991-1998 we performed 150 celiac plexus and/or splanchnic nerve neurolytic blocks with ethyl alcohol in 144 cancer patients; the procedure was repeated in 6 patients. In 69% of cases the patient had a pancreatic lesion. We prefer an anterior approach with very thin needles (22 Gauge). The sites of alcohol injection (celiac plexus, splanchnic nerves or both) are chosen after evaluation of anatomy by preliminary CT scans, or during the procedure, depending on alcohol (mixed with a contrast agent) spread. RESULTS: The mean duration of the procedure ranged 50 min (1991) to 22 min (1998). 48 hours after the block we obtained major pain relief in 79% of cases. After 15 days, 21% of patients had no pain (drugs: none), 29% had mild pain (therapy: non-steroid anti-inflammatory drugs), 32% had marked pain (therapy: non-steroid anti-inflammatory drugs and, occasionally, opioids), 18% had severe pain (only opioid therapy). Pain relief was more frequent in splanchnic nerve blocks. DISCUSSION: Our experience confirms that neurolytic celiac plexus and/or splanchnic nerve block is a good choice in the treatment of upper abdominal cancer pain. We would also like to add that: 1) celiac plexus block with CT guidance (with the needle tip positioned anterior to aorta) and splanchnic nerve block (with the needle tip positioned posterior to diaphragmatic crura) are no longer two separated techniques, but they can be chosen and combined according to patients needs. 2) All procedures can be performed with anterior approach, in supine position, with a single thin needle, allowing to reach the target without any complication, even after puncturing stomach, liver, bowel, pancreas or aorta. 3) With CT guidance, even splanchnic nerve neurolysis is a low-risk technique, which should be adopted in all cases of insufficient alcohol spread in the celiac plexus. 4) When the operators are skilled and experienced enough, the time required for the block can be significantly decreased to nearly the time required for US-guided or fluoroscopic-guided procedures.