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Biomedical subjects

K Knutson

Publications and source records attributed to K Knutson.

At least 19 recordsLinked to original sources

In situ study of insulin aggregation induced by water-organic solvent interface.

PURPOSE: The aim of this study was to assess insulin stability by monitoring in situ time-course of insulin aggregation induced by a water-organic solvent (o/w) interface that occurs during the microencapsulation process. METHODS: Insulin aggregation at a simple o/w interface was monitored spectrophotometrically by detecting the percentage of turbidity changes (%T) at 350 nm. The effects of protein concentration and agitation and the presence of poly (lactic-co-glycolic acid) (PLGA) in methylene chloride (MC) on insulin aggregation were observed. For the 0.72 mg/ml insulin in phosphate-buffered saline (PBS), the effect of nonionic (dodecyl maltoside [DDM]) and anionic (sodium dodecyl sulfate [SDS]) surfactant in PBS were also evaluated at various protein/surfactant mol ratios. The conformation of insulin protected by a 10-fold molar excess of SDS recovered after 1 h of contact with MC was evaluated via circular dichroism (CD) spectroscopy. RESULTS: A typical turbidity-time profile was represented by a sigmoidal curve. Greater change in %T was observed with increasing insulin concentration, in the presence of PLGA in MC and in the presence of agitation. DDM failed to delay insulin aggregation at all ratios used, whereas a less than 10% change in %T was observed in 1 h when a 10- - approximately 20-fold excess of SDS was used. CD spectra indicated that the presence of insulin in SDS after 1 h of contact with MC qualitatively retained its secondary structure integrity. CONCLUSIONS: An experimental method was designed for an in situ assessment of protein stability at the o/w interface.

Chemical Phenomena↗

The Swedish Knee Arthroplasty Register 1975-1997: an update with special emphasis on 41,223 knees operated on in 1988-1997.

From 1975, when the Swedish Knee Arthroplasty Register (SKAR) started, until the end of 1997, 57,533 primary arthroplasties and revisions have been registered. Recently, the register underwent a comprehensive validation and update regarding revisions. We now report on general demographic and epidemiological data for the whole period and on the survivorship of arthroplasties performed in Sweden during 1988-1997. During this 10-year period, 41,223 primary knee arthroplasties were performed on 34,877 patients. We found, as in our earlier reports, that survivorship was affected by patient-, time-, implant- and method-related factors but, apart from an overall higher cumulative revision rate, general conclusions reported from the register in recent years appeared to be unaffected.

Aged↗

The routine of surgical management reduces failure after unicompartmental knee arthroplasty.

A total of 10,474 unicompartmental knee arthroplasties was performed for medial osteoarthritis in Sweden between 1986 and 1995. We sought to establish whether the number of operations performed in an orthopaedic unit affected the incidence of revision. Three different implants were analysed: one with a high revision rate, known to have unfavourable mechanical and design properties; a prosthesis which is technically demanding with a known increased rate of revision; and the most commonly used unicompartmental device. Most of the units performed relatively few unicompartmental knee arthroplasties per year and there was an association between the mean number carried out and the risk of later revision. The effect of the mean number of operations per year on the risk of revision varied. The technically demanding implant was most affected, that most commonly used less so, and the outcome of the unfavourable design was not influenced by the number of operations performed. For unicompartmental arthroplasty, the long-term results are related to the number performed by the unit, probably expressing the standards of management in selecting the patients and performing the operation.

Aged↗

92nd AACR. Immunologic approaches to the treatment and prevention of cancer.

Tumor immunology is advancing at a rapid rate and an increased number of investigators are providing important contributions to the field. Greater than 250 abstracts dealing directly with tumor immunology were presented at the 92nd Annual Meeting of the American Association of Cancer Research in New Orleans, LA, USA. All facets of tumor immunology were represented by excellent abstracts addressing dendritic cells, mechanisms of effective tumor immunity, immune defects in cancer patients, tumor antigens, cancer vaccines, and cancer immunotherapies.

Journal Article↗

Past incidence and future demand for knee arthroplasty in Sweden: a report from the Swedish Knee Arthroplasty Register regarding the effect of past and future population changes on the number of arthroplasties performed.

By combining data from the Swedish Knee Arthroplasty Register and Swedish census registers we have calculated the past age-specific incidence of primary knee arthroplasties and predicted the demand. During the last 20 years, osteoarthrosis has accounted for the largest increase in number of knee arthroplasties while operations for rheumatoid arthritis remained constant. The mean yearly number of operations between the periods 1976-1980 and 1996-1997 increased more than five-fold, while only 6% of that increase could be explained by changes in the age-profile of the population. Most operations were performed on persons of 65 years and older who also had the largest increase in incidence. By using the incidences for 1996 and 1997 and taking into account the expected future changes in the age profile of the Swedish population, we estimate that, in the absence of an effective preventive treatment, the number of knee arthroplasties will increase by at least one third until 2030.

Age Distribution↗

Patient satisfaction after knee arthroplasty: a report on 27,372 knees operated on between 1981 and 1995 in Sweden.

During a validation process of the Swedish Knee Arthroplasty Register (SKAR), living registered patients were sent a questionnaire to ask if they had been reoperated on. This gave an opportunity to pose a simple four-point question with respect to patient satisfaction which 95% of patients answered. We analyzed the answers of patients operated on between 1981 and 1995 and found that only 8% of the patients were dissatisfied regarding their knee arthroplasty 2-17 years postoperatively. The satisfaction rate was constant, regardless of when the operation had been performed during the 15-year period. The proportion of satisfied patients was affected by the preoperative diagnosis, patients operated on for a long-standing disease more often being satisfied than those with a short disease-duration. There was no difference in proportions of satisfied patients, whether they had primarily been operated on with a total knee arthroplasty (TKA) or a medial unicompartmental arthroplasty (UKA). For TKAs performed with primary patellar resurfacing, there was a higher ratio of satisfied patients than for TKAs not resurfaced, but this increased ratio diminished with time passed since the primary operation. Unrevised knees had a higher proportion of satisfied patients than knees that had been subject to revision, and among patients revised for medial UKA, the proportion of satisfied patients was higher than among patients revised for TKA. We conclude that satisfaction after knee arthroplasty is stable and long-lasting in unrevised cases and that even after revision most patients are satisfied.

Arthroplasty, Replacement, Knee↗

Validation of the Swedish Knee Arthroplasty Register: a postal survey regarding 30,376 knees operated on between 1975 and 1995.

The Swedish Knee Arthroplasty Register is dependent on the participating clinics regarding accuracy of information. As the register is prospective, and since revision is used as the endpoint in survival analyses, it is important that all revisions of registered primary arthroplasties are reported. To validate the register, we sent a questionnaire to all living patients with 30,796 knees registered as having been operated on from 1975-1995. Of living patients, 99% could be located and 93% answered. We found that one fifth of the revisions had not been reported and that relatively fewer revisions were lost to follow-up during the first decade of the register than in the following years. To investigate whether the Patient Administrative System (PAS), a database based on ICD coding and run by the Swedish health authorities, could be used to locate missing revisions found by the postal survey, we compared this database with the Swedish Knee Arthroplasty Register. 84% of the missing revisions revealed by the postal survey were found by using this method. Hence after the survey and the use of the PAS to find unreported revisions in deceased and non-responding patients, we estimate that 94% of all revisions are accounted for. Apart from a generally higher cumulative revision rate, conclusions reported from the Register in recent years regarding survivorship seem to be unaffected by the underreporting.

Arthroplasty, Replacement, Knee↗

Use of unicompartmental instead of tricompartmental prostheses for unicompartmental arthrosis in the knee is a cost-effective alternative. 15,437 primary tricompartmental prostheses were compared with 10,624 primary medial or lateral unicompartmental prostheses.

Unicompartmental knee arthroplasty (UKA) is known to have a higher risk of revision than tricompartmental arthroplasty (TKA), while UKA implants are generally less expensive than TKA implants. We estimated the costs of implants and hospital stay of both procedures and related the cost difference at primary operation to the difference in number of revisions to be expected. We compared 15,437 primary TKAs and 10,624 primary medial or lateral UKAs. The operations were all done on patients with arthrosis during 1985-1995. By matching patients in the Swedish Patient Administration System with the Swedish National Knee Arthroplasty Register, the groups could be compared regarding the length of the hospital stay. The cumulative revision rate (CRR) and the relative risk of revision were calculated with survival statistics, as well as the risk of a second revision and the risk of infection. The weighted mean cost of the commonest implants in each group was used as an estimate of the implant cost. We found that the TKA patients were, on average, 2 years older at operation and had a lower CRR than the UKA patients-i.e., 10-year CRR of 12% and 16%, respectively. After adjusting for age, gender and year of operation, UKA patients were found to have a 2-day shorter hospital stay and fewer serious complications than TKA patients. The mean estimated cost of a unicompartmental implant was 57% of that of a tricompartmental implant. We conclude, that by using UKA instead of TKA in appropriate patients, money can be saved, even after taking into account the increased number of revisions to be expected.

Age Distribution↗

Revision of unicompartmental knee arthroplasty: outcome in 1,135 cases from the Swedish Knee Arthroplasty study.

From 1975 through 1995, 45,025 knee arthroplasties were recorded in the prospective Swedish Knee Arthroplasty study. By the end of 1995, 1,135 of 14,772 primary unicompartmental knee arthroplasties (UKA) for localized, mainly medial arthrosis had been revised. The Marmor/Richards and St. Georg sledge/Endo-Link prostheses were used in 65%. Mean age at revision was 72 (71) years. 232 revisions were performed as an exchange UKA (partial in 97) and 750 as a total knee arthroplasty (TKA). 153 were revised by other modes. In medial UKA, the indication for revision was component loosening in 45% and joint degeneration in 25% and in lateral UKA, the corresponding figures were 31% and 35%, respectively. In 94 cases, unicompartmental components were added to the initially untreated compartment, in 14 with partial exchange of a component. The CRRR was estimated using survival statistics. After only 5 years, the risk of having a second revision was more than three times higher for failed UKAs revised to a new UKA (cumulative rerevision rate (CRRR 26%) than for those revised to a TKA (CRRR 7%). This difference remained, even if those revised before 1985, when modern operating technique was introduced, were excluded (CRRR 31% and 5%, respectively). UKA is a safe primary procedure, when performed with well-designed components and modern surgical technique. It gives documented good patient satisfaction, range of motion, pain relief and relatively few serious complications. However, once failed, the knee should be revised to a TKA. This applies to most modes of failure. Not even joint degeneration of the unoperated compartment can be safely treated by adding contralateral components; CRRR after this procedure was 17%, while it was 7% when converted to a TKA.

Aged↗

Knee arthroplasty in rheumatoid arthritis. A report from the Swedish Knee Arthroplasty Register on 4,381 primary operations 1985-1995.

The Swedish Knee Arthroplasty Register has data on 4,381 primary operations performed 1985-1995 for rheumatoid arthritis. Of these, 192 were performed with unicompartmental prostheses and 4143 with tricompartmental. 77% were women and the mean age was 66 years. There were 126 first, 20 second, and 1 third revision in tricompartmental arthroplasties, mainly for loosening, infection and patellar problems. There were 38 first, 3 second, and 1 third revision in unicompartmental arthroplasties, mainly for progression of RA and loosening. Cumulative revision rates (Kaplan-Meier) were calculated. Tricompartmental knees had a 10-year cumulative revision rate of 5% and uni-knees 25%. Patients treated before 1990, men and patients younger than 55 had higher revision rates than patients treated after 1990, women and older patients, respectively. Cemented tibial components resulted in lower revision rates than uncemented ones. There was no significant difference in revision rates between patellar replaced and unreplaced knees or between the 9 commonest implant types.

Aged↗

Fourier transform infrared spectroscopy investigations of protein structure.

Infrared spectroscopy can provide insight into protein structure. This technique is sensitive to the backbone amide arrangement of peptide and protein molecules. In many cases, complementary as well as more expansive information is obtained as opposed to information obtained by other methods that examine the molecule's environmental surroundings, require molecular probes, or perhaps cannot investigate the molecule in its native environment. The foundation for spectroscopic differences between the various secondary structures arises not only from geometrical differences and hydrogen bond variations but also transition dipole coupling between neighboring oscillators. Theoretical predictions of protein spectra have been made using normal mode analysis and combined with experimental data. At present the amide I band has provided the most insight into secondary structure. Even more convincing results are obtained when both H2O and D2O are used as solvents. Recent advances in computerized technology and mathematical techniques have expanded the potential contributions of infrared spectroscopy in the area of protein structural determination. However, the limitations of resolution enhancement and curve-fitting techniques must be taken into consideration. The parameters must be carefully and optimally chosen and evaluated on a case-by-case basis. The subjectivity of these techniques makes a thorough understanding of the algorithms necessary, especially those commercially available. Infrared spectroscopy continues to provide insight into protein and peptide structures under biologically relevant conditions that enable the structure-function relationships for such molecules to be better understood.

Amides↗

Oxford meniscal bearing knee versus the Marmor knee in unicompartmental arthroplasty for arthrosis. A Swedish multicenter survival study.

In the Swedish Knee Arthroplasty Study, all 699 Oxford meniscal bearing cemented unicompartmental prostheses (Biomet, Bridgend, UK) were identified and analyzed regarding failure pattern and compared with all Marmor prostheses (Smith & Nephew Richards, Orthez, France) and with a time-, age-, and sex-matched subset of Marmor prostheses using survival statistics expressed as cumulative revision rates. After 1 year there was already a higher rate, and after 6 years the rate of the Oxford group was more than twice that of the Marmor group. There were 50 revisions in the Oxford group: dislocating meniscus in 16, loosening of the femoral component in 6, tibial component in 4, both components in 4, contralateral arthrosis in 10, infection in 4, and technical failure with instability, pain, and/or impingement of the meniscal bearing anterior in the femoral condyle in 6. It is still unclear if the design with the sliding menisci will, in the long turn, reduce wear and loosening, thereby compensating for the initially inferior results. It is recommended that until this question is clarified, the Oxford knee should be used on a limited scale for long-term comparative studies only.

Adult↗

Accurate determination of skin flux from flow-through diffusion cell data.

PURPOSE: The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS: Mathematical modeling, applied to transdermal diffusion, was used to calculate receiver concentration data for single layer and bilayer membranes. The data were interpreted using two apparent flux values, Japp1 and Japp2. Japp1 has been used extensively in the literature, but did not account for accumulation in the receiver. Japp2 did take the accumulation into consideration. RESULTS: The results confirm that, generally, Japp1 values were not accurate estimates of the intrinsic flux. Japp2 values were significantly more accurate, especially prior to the maximum in receiver concentration. CONCLUSIONS: Japp2 was an accurate measurement of intrinsic flux over the entire experimental time period, except at time zero. It was more accurate because it accounted for solute accumulation in the receiver compartment. The accuracy of the Japp2 approximation was practically independent of receiver volume, flow rate and donor volume. For very slowly permeating drugs, or a very small receiver volume combined with a high flow rate, the Japp1 estimate accurately reflected the intrinsic flux. Early time data were required to properly account for accumulation in the receiver cell. If such data were not available, the inverse Laplace method of determining intrinsic flux was preferable to the Japp2 calculation.

Diffusion↗

Intraoperative monitoring of ulnar nerve function during replacement of the rheumatoid elbow via the lateral approach.

Neurography of the ulnar nerve was performed pre-, intra- and postoperatively in 8 arms of 7 patients with rheumatoid arthritis operated on with total elbow replacement via the lateral approach. Ulnar nerve decompression was performed in 4 elbows before implantation. A reduction in the amplitude of compound muscle action potential (CMAP) recorded from the abductor digiti minimi on stimulation of the ulnar nerve in the axilla, was observed during elbow dislocation at surgery in all patients, in 5 cases transiently and in 3 cases until the end of surgery. The ulnar nerve had been decompressed in all patients with lasting amplitude reduction. One of them had a mild sensory ulnar nerve palsy, while the other 2 had normal nerve function at the postoperative clinical examination. All 3 had a reduction in the amplitude of compound sensory nerve action potential (SNAP) and 2 of them also in CMAP amplitude at the postoperative neurographic examination. In patients with transient reduction during surgery, the CMAP amplitude quickly normalized on relocation of the elbow and both the SNAP and the CMAP were preserved at the postoperative neurographic examination. The authors conclude that dislocation of the laterally approached elbow carries a risk of ulnar nerve injury, which is not prevented by decompression of the ulnar nerve, but frequent relocation of the elbow during surgery seems important. It is suggested that the ulnar nerve should not be decompressed routinely, and that the dislocated elbow should be frequently relocated.

Action Potentials↗

Enhanced permeation of polar compounds through human epidermis. I. Permeability and membrane structural changes in the presence of short chain alcohols.

The influence of alcohol chain length on polar compound permeation in human skin was investigated to further understand alcohol-enhanced permeation mechanisms. Both thermodynamic and kinetic variables associated with the enhanced permeation of mannitol were ascertained in the presence of high concentrations of short chain alcohols. Permeation of mannitol through human epidermis in the presence of 75% (v/v) alcohol-saline mixtures was determined in symmetric, side-by-side diffusion cells at 32 degrees C. Permeability coefficients increased with increasing alcohol chain length (iso-propanol > ethanol > methanol). Uptake of mannitol into the epidermal tissue increased in the presence of the short chain alcohols, but was independent of alcohol chain length. In addition, mannitol solubility decreased in the presence of the short chain alcohols, but again was independent of alcohol chain length. Therefore, increased mannitol permeability with increasing alcohol chain length could not be attributed to thermodynamic variables. Changes in the amount and conformation of stratum corneum lipids and proteins were determined by Fourier transform infrared (FTIR) spectroscopy. Stratum corneum lipid conformation and mobility was not significantly altered in the presence of the short chain alcohols. However, decreased absorbance of the alkyl chain suggested lipid extraction, which increased with increasing alcohol chain length. Stratum corneum protein conformation was altered in the presence of the short chain alcohols. Decreased infrared absorbance of the Amide I band maximum suggested extraction of stratum corneum proteins, which increased with increased alcohol chain length. These results suggest a correlation between enhanced permeation and extraction of lipids as well as proteins from human skin in the presence of 75% (v/v) aqueous alcohol solutions.

Cell Membrane Permeability↗

Fracture subluxation of proximal interphalangeal joint treated by palmar plate advancement.

A modified technique of palmar plate advancement (PPA) was used to treat certain patients, most with failed previous treatment, with fracture subluxation of the proximal interphalangeal joint. The modification of the original technique consisted of using two sutures to attach the palmar plate and tying them deep to the skin on the dorsum. This allowed consistent maintenance of reduction, and there were no infections. The results of 11 of 23 patients who were treated with this technique and followed from 2 to 9 years postoperatively are reported. The indications for PPA in this injury are discussed.

Female↗