Scintigraphic visualization of intrathecal liposome biodistribution

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered ⁹⁹Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.     

Free vascularized jejunum interposition for pharyngoesophageal reconstruction after total laryngopharyngectomy

The records of 28 patients who underwent free jejunal graft reconstruction after resection for cancer involving the pharynx were analysed. Seven patients had a T₃ carcinoma, 15 patients T₄ and six patients recurrence after laryngectomy. Ten patients had received radiotherapy in the past. Post-operatively, 15 patients (54%) had complications and two patients (7%) died. No significant difference was observed in the complication rate between the group that received radiotherapy in the past and those who did not. Nineteen patients received post-operative radiotherapy. Nine patients had no radiotherapy on the basis of complete resection or because of serious complications. For the whole group the 2-year recurrence free period and survival were 42% and 51% respectively. The postoperative radiotherapy group had a significantly better survival (73%) and recurrence free period (63%) than the group without post-operative radiotherapy (0%). Thus, post-operative radiotherapy seems indicated irrespective of resection margins.     

Mechanisms and patient compliance of dust-mite avoidance regimens in dwellings of mite-allergic rhinitic patients

We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite-extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group. Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned. About 90% were willing to spend two weekends (70%), or at the most one weekend (20%) per year sanitizing the dwelling by cleaning it with the whole family. The authors of this report consider acaricidal cleaning to be a significant improvement in the management of mite-allergic diseases, such as rhinitis. Compared with the replacement of home textiles, this treatment is less expensive and more effective. Patient compliance is acceptable, but depends on acceptance by physicians and the initial motivation and consequent burden on the patient.     

Effects of cocaine and ethylcocaine on schedule-controlled responding in rats.

The effects of cocaine and benzoylecognine ethyl ester (ethylcocaine), its metabolite found only in simultaneous users of cocaine and ethanol, were studied in rats responding for food under a multiple fixed-ratio fixed-interval schedule of food presentation. Both cocaine and ethylcocaine increased rates of responding under the fixed-interval component and decreased the quarter life. Both drugs only decreased rates of responding under the fixed-ratio component. Cocaine was approximately equipotent to ethylcocaine. Ethylcocaine may contribute to interactions between cocaine and ethanol by exerting cocaine-like effects not seen with other cocaine metabolites.     

Non-invasive stimulation of the P6 (Neiguan) antiemetic acupuncture point in cancer chemotherapy.

The beneficial effects of transcutaneous electrical stimulation of the P6 antiemetic point (Neiguan) as an adjuvant to standard antiemetics was studied in over 100 patients in whom chemotherapy-induced sickness was not adequately controlled by antiemetics alone. Although the results were not quite as good as with invasive acupuncture, more than 75% patients achieved considerable benefit from what was a non-toxic procedure. The use of large diffuse low impedence electrodes simplifies the technique. The 2 hourly application of Sea Bands prolongs the antiemetic action. Best results were obtained from the 2 hourly self-administration of 5 min of transcutaneous electrical stimulation of P6 using a simple battery-operated TENS machine (15 Hz) to activate a large, easy-to-place surface electrode and increasing current until Qi is elicited.     

Cardiac tamponade after intrapericardial diaphragmatic hernia

An unusual case of intrapericardial diaphragmatic hernia ispresented. Cardiac tamponade occurred in the operating roomsoon after induction of anaesthesia. Surgical removal of theherniated omentum and stomach allowed haemodynamic improvement.The pathophysiology is discussed and patients with cardiac tamponadereviewed.