Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC).

Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.

[The value of X-ray examinations for elective arthroscopy]. / Vaerdien af røntgenundersøgelse før elektiv artroskopi.

In 1990 elective arthroscopy was performed on 327 knees at this department. In all cases X-ray pictures were taken preoperatively. The arthroscopic findings were registered consecutively in a predesigned form. The radiographs were evaluated by an experienced specialist at the radiography department. In 35 cases the X-ray diagnosis was arthrosis, 25 of these cases were confirmed by arthroscopy. Osteochondritis dissecans was found in 10 cases by arthroscopy, four of these were found by X-ray examination. Free bodies were found in six cases at arthroscopy, only three were detected by X-ray examination. As a consequence we find that routine X-ray examination before elective knee arthroscopy is unnecessary provided that clinical signs of conditions expected to be seen by X-ray are absent.

Mortality after hip fracture: results of operation within 12 h of admission.

This retrospective study was undertaken to evaluate the mortality and morbidity of patients undergoing hip fracture surgery within 12 h of admission, compared with surgery more than 12 h after admission, the patients had no acute medical conditions that required preoperative treatment. Mortality rates were based on survival of the patients up to 1 year after surgery. For patients with fractures of the femoral neck, and in whom surgery was performed within 12 hours of admission, the mortality rate was significantly lower from 5 months after the operation. Time of surgery did not influence the mortality of patients with trochanteric fractures. It is suggested that a fractured neck of the femur in an otherwise fit elderly patient should be regarded as a surgical emergency.

[Unicompartmental knee alloplasty by the St. Georg method. A follow-up of 42 knees after 5-10 years]. / Unikompartmental knaealloplastik a.m. St. Georg. En 5-10 års efterundersøgelse af 42 knae.

The results are presented of 42 arthroplasties by the St. Georg method in 37 patients who could be followed-up clinically and radiologically after median periods of observation of 66 months. The HSS-scoring method (Hospital for Special Surgery Score) was employed to assess the results. Good or excellent results (HSS score greater than 69 points) were obtained in 79% of the arthroplasties and 86% were relieved of pain on weightbearing. In selected patients, the St. Georg hemiarthroplasty is found to be a usable alternative to total condylar arthroplasty in the treatment of unicompartmental osteoarthritis of the knee.

[Late hemorrhage after pelvic fracture]. / Senblødning efter baekkenfraktur.

Vascular lesions in connection with fractures of the pelvis frequently cause massive internal haemorrhage and are the most common cause of death among these patients. As a rule, the first 48 hours after the injury are considered to be the most critical as regards the risk of haemorrhage. A case of a man aged 20 years with a pelvic fracture is presented here. More than five months after the fracture, severe haemorrhage endangering life occurred following incision of an apparently subcutaneous haematoma in the left flank. The importance of continued control of patients with known retroperitoneal haematomata after pelvic fractures is emphasized.

[Explosion accidents during work with tires and wheel rims]. / Eksplosionsulykker ved arbejde med daek og faelge.

The object of this work is to draw attention to injuries resulting from explosions caused by work with wheel rims and tyres, the extent of the problem and the safety rules which already exist. Seven illustrative cases are presented. A not inconsiderable but frequently disregarded risk for accidental explosions is present in connection with pumping tyres and repairs of tyres and wheel rims. During the explosions, pressure waves of enormous violence may frequently be released. In connection with four accidental explosions of this type, a total of seven persons were injured. Four of these sustained life-threatening injuries. On the basis of the serious accidents, the authors consider it important to draw attention to the fact that the rules, which exist already and which are aimed primarily at avoiding and possibly limiting the extent of the violent explosive energy, should be brought to the notice of all who work with tyres and wheel rims.

[Data registration of postoperative complications in connection with orthopedic surgery. A review of 4,346 surgical wounds]. / Dataregistrering af postoperative komplikationer ved ortopaedkirurgiske operationer. En opgørelse af 4,346 operationssår.

A personal computer program to monitor surgical wound infections and other complications in orthopedics was developed. Internationally accepted definitions were used. The program was tested in four Danish orthopedic wards. The test period was from 1 January 1988 to 30 June 1989. Results from four wards consisting of 4,346 wounds in 3,570 patients are presented. The overall superficial wound infection rate was 2.4%, deep wound infection rate was 0.9%, other infection rate was 3.1%, and other complications were developed in 4.3% of the cases. In contrast to previous computer systems presented, this system also registers other nosocomial infections, and other complications. We found the system easy to use, and during the period, the overall registration rate was over ninety percent. If a registration system is introduced in the ward, a combined system which registers all infections and complications is preferable, instead of a simple wound infection system.

The use of a personal computer program for monitoring wound infections and other complications in orthopedics.

A personal computer program to monitor wound infections and other complications after orthopedic operations was developed, adopting international criteria and definitions. The program offers fixed data entry screens, and a free text editor, and produces user-specified variations of seven screen pages comprising most of the epidemiological data needed for surveillance and complication control. Furthermore a number of special lists can be generated for use in the daily work. For all reports and lists it is possible to generate subpopulations with up to twelve criteria. The program was tested in four danish orthopedic departments and serves well as a simple local tool for the operating staff, offering fast information on complication rates. Results consisting 2,583 operations are presented. The overall rates of complications were 1.8% superficial wound infections, 0.6% deep wound infections, 2.6% other infections and 3.8 other complications. The system is lowcost and an effective method of providing a widespread uniform surveillance of surgical wound infections and other complications in the orthopedic wards.

[Immediate postoperative complications after total hip replacement]. / Umiddelbart postoperative komplikationer efter total hoftealloplastik.

With the object of illustrating the immediate postoperative complications connected with total hip replacement, a material of 512 hip replacements carried out in the Orthopaedic Department in Viborg Hospital during the period 1982-1987 was reviewed. Complications of significance for the postoperative course occurred in 16% and the mortality was 0.4%. The complications of greatest significance were cardiac (3.3%), renal involvement (2.5%) and thromboembolic complications (3.5%) (pulmonary embolism 1.8% and deep venous thrombosis 2.9%). Advanced age, preoperative cardiovascular conditions and obesity predisposed to these complications and, similarly, increased frequency of cardiac complications was found with increased duration of anaesthesia. Finally, a connection was found between peroperative and postoperative episodes of hypotension and renal involvement.