Cationic nanoemulsions as potential carriers for intracellular delivery.

Successful cytosolic delivery enables opportunities for improved treatment of various genetic disorders, infectious diseases and cancer. Cationic nanoemulsions were designed using alternative excipients and evaluated for particle size, charge, effect of sterilization on its stability, DNA condensation potential and cellular uptake efficiency. Various concentrations of non-ionic and ionic stabilizers were evaluated to design formula for colloidally stable cationic nanoemulsion. The nanoemulsion comprised of 5% Capmul MCM, 0.5% didodecyldimethylammonium bromide (DDAB), 1% phospholipid, 1% Poloxamer 188 and 2.25% glycerol and possessed particle size of 81.6 ± 3.56 nm and 137.1 ± 1.57 nm before and after steam sterilization, respectively. DNA condensation studies were carried out at various nanoemulsion: DNA ratios ranging from 1:1 to 10:1. Cell uptake studies were conducted on human embryonic kidney (HEK) cell lines which are widely reported for transfection studies. The nanoemulsions showed excellent cellular uptake as evaluated by fluorescence microscopy and flow cytometry. Overall, a colloidally stable cationic nanoemulsion with good DNA condensation ability was successfully fabricated for efficient cytosolic delivery and potential for in vivo effectiveness.

Decreasing amputation rates in patients with diabetes-a population-based study.

AIMS: To assess the changing rate of amputation in patients with diabetes over a 7-year period. METHODS: All patients undergoing lower extremity amputation in Tayside, Scotland between 1 January 2000 and 31 December 2006 were identified. Temporal linkage of cases to the diabetes database was used to ascertain which amputations were in patients with diabetes. RESULTS: The incidence of major amputations fell from 5.1 [95% confidence interval (CI) 3.8-6.4] to 2.9 (95% CI 1.9-3.8) per 1000 patients with diabetes (P < 0.05). There is a clear linear trend in the adjusted incidence of major amputation (P = 0.023 and 0.027 for age- and sex-adjusted, and duration- and sex-adjusted incidences, respectively). The adjusted incidence of total amputations followed decreased linear regression trend over the whole study period when adjusted for age and sex or diabetes duration and sex (P = 0.002). CONCLUSIONS: There has been a significant reduction in the incidence of major lower extremity amputation in patients with diabetes over the 7-year period.

Fixation of first metatarsal basal osteotomy using Acutrak screw.

BACKGROUND: The purpose of this study is to determine clinical and radiological outcome following the internal fixation of first metatarsal basal osteotomy using Acutrak screw. METHODS: Between May 1999 and December 2003, 37 feet undergoing basal closing wedge osteotomy were stabilised using Acutrak screw. The minimum follow-up period was 18 months. The position and fate of the screw, complications, hallux valgus, intermetatarsal and metatarsal declination angles, and time for bony union were assessed postoperatively and at the final follow-up. RESULTS: Seventy-nine percent of the corrected feet had achieved excellent or good AOFAS score, 13% fair, and 8% poor score. The average preoperative intermetatarsal, hallux valgus and first metatarsal declination angles were 17.3 degrees (12-20 degrees), 38 degrees (17-53 degrees) and 22.5 degrees (16-30 degrees), respectively. These were reduced to 10.3 degrees (0-16 degrees), 14.6 degrees (9-26 degrees) and 20.4 degrees (16-26 degrees) following surgery and 11.2 degrees (0-18 degrees), 16.0 degrees (12-22 degrees) and 20.1 degrees (16-23 degrees), respectively, at the final follow-up. Clinical and radiological union has been achieved in all cases. CONCLUSION: Our technique provides stable fixation with minimal loss of position at the osteotomy site.

Traumatic floating clavicle. A case report.

Dislocation of both ends of the clavicle simultaneously is an injury usually sustained in a major accident; in this unusual case it resulted from a minor fall at home. The mechanism of injury and the treatment are discussed.

A simple inexpensive post-operative management regime following surgery for Dupuytren's contracture.

A simple regime has been devised for the post-operative management of patients following surgery for Dupuytren's contracture; this includes splintage of the hand for two weeks and active and passive mobilisation by the patient according to precise instructions. Selective help was provided by minimal occupational therapy in 5 of 50 patients. The results of the method were assessed prospectively by subjective criteria and objective assessment by measuring the deformity of the finger joints, lateral and tip pinch and grasp and shear forces.

Clinical assessment of hand strength using a microcomputer.

A microcomputer based system has been designed for precise, objective quantification of hand strength. Pinch, grasp and shear strengths are measured using force transducers. The system, which is quick and easy to operate, not only measures these strengths accurately, but also collects, stores and displays this data numerically or in graphical form, at the touch of a button. The data can be manipulated to answer any type of statistical question related to any group of patients. The assessment of hand strength in ninety-six people, representing normal hand function, by means of this system, is reported.

Dundee revisited--25 years of a total amputee service.

The Dundee Limb Fitting Centre has provided an integrated rehabilitation programme for the amputee since 1965. A review of 1846 primary amputees is discussed. During this period a dramatic change in the above-knee/below-knee (AK/BK) ratio has been achieved with 71% BK and 26% AK occurring in 1989. Over 80% of all amputees, the majority being elderly with peripheral vascular disease, were successfully fitted with a prosthesis. Final discharge home or to a residential home for the elderly was achieved in 76.2% of cases with 3.6% dying in the Unit. Bilateral amputation occurred in 18% of cases of whom 48% were BK-BK. Overall 66% were successfully fitted with a prosthesis. The results demonstrate the advantages of an integrated approach to the amputation and consequent rehabilitation.

Congenital limb anomalies and amputees Tayside, Scotland 1965-1994.

The purpose of this study was to review the 68 patients who had been referred to Dundee Limb Fitting Centre during the period 1965-1994, with a congenital anomaly of a major limb requiring prosthetic replacement. A profile of the incidence of congenital anomalies, amputation levels and prosthetic fitting was obtained. During the period only 68 cases with 80 congenital anomalies were referred. During these 29 years, 20 cases required surgical amputation and overall 35 surgical procedures were performed in these cases, only 3 were in the upper limb. The incidence of upper and lower limb deficiency was similar. The patients represented a small proportion (1.6%) of the patients who were reported to have congenital anomalies. Figures indicated that about 8% of all live/still births have some form of anomaly. Prosthetic fitting and use was successful in all 68 cases but long term life follow-up is necessary to ensure continued prosthetic use.

An epidemiological study of war amputees and the cost to society.

The purpose of this study was to assess the overall financial cost of the prosthetic care which war amputees have incurred since the injury occurred. Records of 98 war veteran amputees who had attended the Dundee Limb Fitting Centre were scrutinised, they revealed 52 survivors and 46 who had died by 1997 and represented all the records available at the time of the review. The number and nature of visits, the number of prosthetic limbs ordered were counted and using today's costs, the cost of these services calculated. The costs of stump socks, transport and social security payments were not included. The cost of the artificial limbs was calculated at Pound Sterling(GBP)69 million with the recognition that it is an underestimate and approximation. Despite this it shows that the cost, allowing for the underestimation, has been relatively insignificant in the total cost of a major war and the war machinery. The cost however to the individuals has been considerable with a substantial disability occurring at the prime of life resulting in a significant handicap. It is a continuing legacy that society is responsible for, as a direct result of armed conflict.

Cause of death of lower limb amputees.

A study was carried out on the cause of death of 100 lower limb amputees who had been admitted to the Dundee Limb Fitting Centre, Tayside, Scotland for prosthetic management or wheelchair training. A comprehensive database has been established in the Centre for 25 years and the database is updated regularly. The date of death was collected and recorded. One hundred sequential deaths were investigated to review the cause of their death and compare this with the recorded causes of death for the Tayside population for the year of study. Ninety three per cent had an amputation for vascular related causes, with 73% having a below-knee amputation and 17% above-knee. Heart disease was the most frequent recorded cause of death (51%) of the amputee whereas only 28.1% of the Tayside group died from this pathology (p less than 0.01). Carcinomatosis was reported as a cause of death in 14% of the amputees and 23.5% of the Tayside group. Cerebrovascular disease caused death in 6% of the amputees and in 12.3% of the Tayside group (both p less than 0.01). These findings confirm earlier suggestions that vascular amputees die from heart disease more often than the general population.

A versatile hand splint.

Splintage plays a major part in the management and rehabilitation of the hand following injury, infection and operation. It is essential to have a simple, comfortable, and firm but flexible splint. This should be available "off the shelf", but be acceptable to the patient and to the treating clinician. This paper will describe a splint which not only has these qualities, but is cheap and is re-usable after washing. The splint is made of high density Plastazote and is available in two sizes for each hand. It is moulded into the shape of the functional position of the hand and can easily be trimmed with bandage scissors to give a precise fitting. The splint has been evaluated following surgery on fifty hands. Its fabrication, use and simplicity are discussed.

Tumour related lower limb amputation: a 23 year experience.

This paper records the Dundee experience over 23 years and reports on 42 cases of tumour related lower limb amputations. There were 27 males and 15 females with 37 malignant and 5 benign tumours. Four of the 'benign' tumours proved to be osteoclastoma which were locally malignant. Prosthetic rehabilitation was achieved in all but one case. All patients fitted were able to use their prostheses.

Major lower limb amputation following failed infrainguinal vascular bypass surgery: a prospective study on amputation levels and stump complications.

The effect of failed vascular bypass surgery on final amputation level and stump complications is the subject of debate. The aim of this prospective cohort study was to assess the influence of previous infrainguinal bypass surgery on amputees in the authors' centre. Over a three-year period, 234 amputations (219 patients) were performed for critical ischemia. The cause of ischemia was either peripheral obstructive arterial disease (POAD) or diabetes mellitus (DM). Forty-eight percent (48%) (113 amputations) had ipsilateral vascular bypass surgery prior to amputation and 52% (121 amputations) had not. Final amputation level and the post-operative complications of infection, significant stump pain and delayed wound healing were used as the outcome measures for this study. At the end of the study period these outcome measures were used to compare the influence of previous bypass surgery on the two groups of amputees. There was a significantly higher rate of transfemoral amputations (TFA) (32.7%) vs. 16.5%; p < 0.05) and stump infection rate (42% vs. 23%; p < 0.05) in the bypass group. Significant stump pain (p = 0.23) and delayed wound healing (p = 0.24) was more prevalent in the bypass group although statistical significance could not be demonstrated.

Lower limb amputee survival.

A total of 1710 primary amputees have been studied over a 25 year period and their survival time has been calculated. These were all consecutive primary lower limb amputees admitted to the Dundee Limb Fitting Centre during the period 1965-1989. Overall, the median survival was 4 yr 9 mth for the below-knee amputee (1019 patients) and 4 yr 3 mth for the above-knee amputee (586 patients). The vascular related amputees had an overall median survival of 4 yr. In the two decades 1970-1979 and 1980-1989 there were significant differences between the survival time of the below-knee and above-knee amputee. The survival of the amputee has increased during the two decades from 3 yr 6 mth to 6 yr 6 mth (p greater than 0.001). For the first decade male above-knee and male below-knee amputee median survival was 3 yr 1 mth and 3 yr 11 mth respectively and for the second the survival was 5 yr 9 mth and 6 yr 11 mth for these levels of amputation. For 1970-1979 no significant differences were found between male and female peripheral vascular disease (PVD) and diabetes mellitus related amputee survival. For 1980-1989 significant differences were found between PVD related male above-knee amputees (3 yr 10 mth) and male below-knee amputees (6 yr 7 mth) (p greater than 0.01). Similar results were found for the female patients. Operative mortality was found to be 5% over the period 1975-1989 which compared favorably with previous studies.

Limb amputation on renal replacement therapy.

Ten (10) diabetic and 7 non-diabetic patients on renal replacement therapy have undergone limb amputation in the authors' unit in the 1988 to 1996 period. The article examines the course of illness and survival patterns in this distinct and increasing sub-set in the amputee population. Rehabilitation and survival were significantly better in the diabetic group and it is recommended that it would be helpful for both prognosis and analysis if the sub-set of amputees on treatment for chronic renal failure is further divided into diabetic and non-diabetic sub-sets.

Amputation level assessment using lightguide spectrophotometry.

The aim of this experimental study was to investigate whether lightguide spectrophotometry in the visible wavelength range in skin could be used to predict stump healing viability in patients with critical lower limb ischaemia. Remission spectra recorded at two sites (medial and lateral) on the line of a proposed trans-tibial amputation (TTA) and at 10mm intervals along the leg were analysed to give haemoglobin oxygenation (SO2). Degree of tissue hypoxia (DTH) along the leg was defined as the percentage of values along the leg less than 10% SO2. DTH and mean SO2 values were compared with skin blood flow values ((I125) 4-Iodoantipyrine clearance technique) and clinical outcome of trans-tibial amputation, (TTA) or trans-femoral amputation (TFA), in 41 patients. SO2 histograms were also measured in 12 normal subjects for comparison. The results of the study allowed the establishment of criteria for the accurate prediction of flap healing potential. Successful TTAs all displayed a minimum mean SO2 at the medial and lateral measurement sites of 30%, together with a maximum degree of tissue hypoxia of 15% along the limb. The combination of these criteria gave a sensitivity and selectivity of 1.0 for prediction of a successful outcome of TTA.