Friction properties of a new silk fibroin scaffold for meniscal replacement.

The menisci protect the articular cartilage by reducing contact pressure in the knee. To restore their function after injury, a new silk fibroin replacement scaffold was developed. To elucidate its tribological properties, friction of the implant was tested against cartilage and glass, where the latter is typically used in tribological cartilage studies. The silk scaffold exhibited a friction coefficient against cartilage of 0.056, which is higher than meniscus against cartilage but in range of the requirements for meniscal replacements. Further, meniscus friction against glass was lower than cartilage against glass, which correlated with the surface lubricin content. Concluding, the tribological properties of the new material suggest a possible long-term chondroprotective function. In contrast, glass always produced high, non-physiological friction coefficients.

Traumatic lumbar disc herniation: A systemic case review and meta-analysis.

Introduction: Traumatic lumbar disc herniation (TLDH) without fracture in the in-situ motion segment is a rare occurrence compared with degenerative herniation. Research question: This study provides a systematic discussion of various aspects related to the diagnosis of TLDH. Material and methods: This review includes 12 cases of TLDH with MR-images since 2009 published in the PubMed and one adjunct illustration. The cases were categorized into two groups for a comprehensive analysis, TLDH with or without in-situ segment fracture. Additionally, we reported a case of a 43-year-old female patient with a recent stenosing TLDH at L5/S1, accompanied by a large sequestration (disc herniation stage-4, and Michigan State University Classification: MSU 3-AB) and an endplate compression fracture at L2 (AO A1). Results: Isolated traumatic lumbar disc herniation is possible, but it is required exclude cases with fractures in the in-situ motion segment. Discussion and conclusion: Trauma with related injury mechanisms is the highest priority for the diagnosis of TLDH. Low-grade disc degeneration without significant instability could be accepted for diagnosing TLDH. A TLDH on MR images might show a slightly lower T2-signal compared to the CSF and a homogeneous T1-signal like the spinal cord, as well as a similar STIR-signal of the sequestration and CSF. If necessary, a histological examination could be performed to evaluate the degenerative changes in the injured disc, especially to assist the evaluation due to legal reasons.

Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial.

OBJECTIVE: To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint. DESIGN: Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) (P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2. CONCLUSIONS: Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue. TRIAL REGISTRATION: NCT03319797; EudraCT No.: 2016-002817-22.

Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis.

BACKGROUND: POL6014 is a novel, orally inhaled neutrophil elastase (NE) inhibitor in development for cystic fibrosis (CF). METHODS: Two studies, one in healthy volunteers (HVs, doses 20 to 960 mg) and one in subjects with CF (doses 80 to 320 mg) were conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending doses of inhaled POL6014 with a Pari eFlow® nebuliser. PK was evaluated over a period of 24 h. In addition, NE activity in CF sputum was measured. RESULTS: After single doses, POL6014 was safe and well tolerated up to 480 mg in HVs and at all doses in subjects with CF. POL6014 showed a dose-linear PK profile in both populations with Cmax between 0.2 and 2.5 µM in HVs and between 0.2 and 0.5 µM in subjects with CF. Tmax was reached at approximately 2-3 h. Mean POL6014 levels in CF sputum rapidly reached 1000 µM and were still above 10 µM at 24 h. >1-log reduction of active NE was observed at 3 h after dosing. CONCLUSION: Inhalation of POL6014 can safely lead to high concentrations within the lung and simultaneously low plasma concentrations, allowing for a clear inhibition of NE in the sputum of subjects with CF after single dosing. TRIAL REGISTRATION: European Medicines Agency EudraCT-Nr. 2015-001618-83 and 2016-000493-38.

Order of intron removal during splicing of endogenous adenine phosphoribosyltransferase and dihydrofolate reductase pre-mRNA.

Using a strategy based on reverse transcription and the polymerase chain reaction, we have determined the order of splicing of the four introns of the endogenous adenine phosphoribosyltransferase (aprt) gene in Chinese hamster ovary cells. The method involves a pairwise comparison of molecules that retain one intron and have either retained or spliced another intron(s). A highly preferred order of removal was found: intron 3 > 2 > 4 = 1. This order did not represent a linear progression from one end of the transcript to the other, nor did it correlate with the conformity of the splice site sequences to the consensus sequences or to the calculated energy of duplex formation with U1 small nuclear RNA. By using actinomycin D to inhibit RNA synthesis, the in vivo rate of the first step in splicing was estimated for all four introns; a half-life of 6 min was found for introns 2, 3, and 4. Intron 1 was spliced more slowly, with a 12-min half-life. A substantial amount of RNA that retained intron 1 as the sole intron was exported to the cytoplasm. In the course of these experiments, we also determined that intron 3, but not intron 4, is spliced before 3'-end formation is complete, probably on nascent transcripts. This result is consistent with the idea that polyadenylation is required for splicing of the 3'-most intron. We applied a similar strategy to determine the last intron to be spliced in a very large transcript, that of the endogenous dihydrofolate reductase (dhfr) gene in Chinese hamster ovary cells (25 kb). Here again, intron 1 was the last intron to be spliced.

Effects of nonsense mutations on nuclear and cytoplasmic adenine phosphoribosyltransferase RNA.

We have analyzed Chinese hamster ovary (CHO) cell mutants bearing nonsense codons in four of the five exons of the adenine phosphoribosyltransferase (aprt) gene and have found a pattern of mRNA reduction similar to that seen in systems studied previously: a decrease in steady-state mRNA levels of 5- to 10-fold for mutations in exons 1, 2, and 4 but little effect for mutations in the 3'-most exon (exon 5). Nuclear aprt mRNA levels showed a similar decrease. Nonsense-containing aprt mRNA decayed at the same rate as wild-type mRNA in these cell lines after inhibition of transcription with actinomycin D. Nonsense-containing aprt mRNA is associated with polysomes, ruling out a model in which stable residual mRNA escapes degradation by avoiding translation initiation. A tetracycline-responsive form of the aprt gene was used to compare the stability of nonsense-containing and wild-type aprt mRNAs without globally inhibiting transcription. In contrast to measurements made in the presence of actinomycin D, after inhibition of aprt transcription with tetracycline, a nonsense-mediated destabilization of aprt mRNA was indeed demonstrable. The increased rate of decay of cytoplasmic aprt mRNA seen here could account for the nonsense-mediated reduction in steady-state levels of aprt mRNA. However, the low levels of nonsense-bearing aprt mRNA in the nucleus suggest a sensibility of mRNA to translation or translatability before it exits that compartment. Quantitation of the steady-state levels of transcripts containing introns revealed no accumulation of partially spliced aprt RNA and hence no indication of nonsense-mediated aberrancies in splicing. Our results are consistent with a model in which translation facilitates the export of mRNA through a nuclear pore. However, the mechanism of this intriguing nucleocytoplasmic communication remains to be determined.

Uncompromised quality of the cement mantle in Exeter femoral components implanted through a minimally-invasive direct anterior approach. A prospective, randomised cadaver study.

A complete cement mantle is important for the longevity of a total hip replacement. In the minimally-invasive direct anterior approach used at the Innsbruck University hospital, the femoral component has to be inserted into the femoral canal by an angulated movement. In a cadaver study, the quality and the extent of the cement mantle surrounding 13 Exeter femoral components implanted straight through a standard anterolateral transgluteal approach were compared with those of 13 similar femoral components implanted in an angulated fashion through a direct anterior approach. A third-generation cementing technique was used. The inner and outer contours of the cement mantles was traced from CT scans and the thickness and cross-sectional area determined. In no case was the cement mantle incomplete. The total mean thickness of the cement mantle was 3.62 mm (95% confidence interval 3.59 to 3.65). The mean thickness in the group using the minimally-invasive approach was 0.16 mm less than that in the anterolateral group. The distribution of the thickness was similar in the two groups. The mean thickness was less on the anteromedial and anterolateral aspect than on the posterior aspect of the femur. There is no evidence that the angulated introduction of Exeter femoral components in the direct anterior approach in cadavers compromises the quality, extent or thickness of the cement mantle.

Higher strains in the inner region of the meniscus indicate a potential source for degeneration.

Complex structural properties of menisci can be characterized in part by their inhomogeneous strain response under compression. This pilot study explored the feasibility to quantify characteristic strain distributions on meniscus cross-sections subjected to static compression using electronic speckle pattern interferometry (ESPI). Cross-sectional specimens of 5-mm thickness were harvested from eight human menisci. After application of 20% pre-strain, strain maps in response to 10µm compression were captured with ESPI. The 10µm compression induced an aggregate strain of nominally 0.14% and resulted in highly non-uniform strain distributions. Local compressive strain captured by ESPI ranged from 0.03% to 0.7%. The highest strain was in the central region of meniscus cross-sections, and the lowest magnitude of strain was at the femoral surface of the meniscus. After stratifying for age, peak compressive strain in older menisci (71±6 years, n=4) was 0.33%±0.09, compared to 0.25%±0.06 in younger menisci (34±9 years, n=4). In conclusion, this study captured for the first time continuous strain distribution maps over entire meniscus cross-sections. The non-uniform strain distributions demonstrated inhomogeneous structural properties. Age-related differences in characteristic strain distributions likely represent degenerative changes. As such, ESPI provides a novel strategy of further characterize meniscal function and degeneration.

Intrarenal neuroblastoma masquerading as Wilms' tumor.

OBJECTIVES: To better characterize intrarenal neuroblastoma. METHODS: We retrospectively reviewed the records of 5 children with neuroblastoma initially diagnosed as Wilms' tumor. RESULTS: Five patients, aged 11 months to 3.5 years, were preoperatively diagnosed as having intrarenal Wilms' tumor, prior to operative or histopathologic diagnosis of neuroblastoma. In 3 children the diagnosis of neuroblastoma involving the kidney was confirmed; in the fourth child subcutaneous metastatic disease precluded biopsy confirmation of the intrarenal tumor; and in the fifth child the kidney was severely displaced but not actually involved by neuroblastoma. All patients were hypertensive and 4 patients had elevated urinary catechol levels. Molecular genetic studies showed N-myc amplification in both patients who were evaluated. All patients had poorly differentiated histopathology. One patient is presently alive at 8 months with recurrent disease and another patient is free of disease 13 years after diagnosis. The remaining 3 patients died of the malignancy. CONCLUSIONS: Intrarenal neuroblastoma is a rare entity that clinically and radiographically may resemble Wilms' tumor. Our limited experience indicates that intrarenal neuroblastoma is an aggressive malignancy, and long-term survival is rare.

Metachronous renal cell carcinoma metastasis to the contralateral adrenal gland.

OBJECTIVES: Metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland is very rare. We review our experience with 5 such patients and compare it with reports in the literature. METHODS: The records of all 350 patients who underwent nephrectomy for renal cell carcinoma in our center between 1975 and 1992 were reviewed. Five patients were found to have had solitary metachronous metastases to the contralateral adrenal gland on follow-up. RESULTS: The adrenal metastasis was discovered 18 to 210 months (mean 66.8) after nephrectomy. In 2 patients the lesion was found incidentally on routine computed tomography scan; in the other 3 patients, diagnosis was by ultrasonography, performed because of flank pain and weight loss or routine follow-up. All patients underwent adrenalectomy. Survival ranged from 8 to 64 months (mean 36.4); 3 patients had no evidence of disease at 42, 44, and 64 months postoperatively, and 2 patients died of pulmonary metastasis at 8 and 24 months. Analysis of the clinical data of our 5 patients together with the 9 we found in the published reports revealed that the mean interval between nephrectomy and the appearance of adrenal metastasis was shorter in the patients who died. CONCLUSIONS: The results of adrenalectomy for metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland are unpredictable. The prognosis is somewhat better when the mean interval between the nephrectomy and the appearance of the adrenal metastasis is longer than 18 months. We recommend adrenalectomy because long-term survival is expected in some of these patients.

Does the narrow operating field in perineal radical prostatectomy lead to more positive surgical margins?

AIMS: To assess the risk of leaving cancer-positive surgical margins in the perineal approach for radical prostatectomy as compared to the retropubic approach. METHODS: Seventy-six patients with clinically organ-confined prostate cancer (stage T1-2 NoMo) underwent radical prostatectomy. The 57 patients who underwent retropubic prostatectomy were compared to 19 patients in whom the perineal approach was undertaken. The two groups were compared for pre-operative PSA levels, clinical stage, biopsy Gleasson score, and any correlation between pre- and post-operative stage and grade of the disease and rate of cancer-positive surgical margins. RESULTS: Although there were no significant differences in the rate of organ-confined diseases and specimen Gleasson score in the two groups, the rate of positive surgical margins in the perineal approach was significantly lower (15.7 vs 29.8%) and the rate of extracapsular disease with negative margins was significantly higher (15.7 vs 7%). CONCLUSIONS: The narrow surgical field in the perineal approach for radical prostatectomy does not pose a higher risk for positive surgical margins and it might be the procedure of choice in stage T1C prostate cancer with a Gleasson score of below 7.

The contribution of proangiogenic factors to the progression of malignant disease: role of vascular endothelial growth factor and its receptors.

Vascular endothelial growth factor is a major inducer of angiogenesis and a vascular permeability inducing factor. Its expression is upregulated in many types of tumors and it is thought to be a major inducer of tumor angiogenesis. This article focuses on the role of vascular endothelial growth factor in tumor progression and on current efforts aimed at the inhibition of tumor progression through the inhibition of vascular endothelial growth factor activity.

Ambulatory blood pressure monitoring in children with a solitary kidney - a comparison between unilateral renal agenesis and uninephrectomy.

BACKGROUND: In experimental animals, a reduction in renal mass leads to glomerulosclerosis of the residual parenchyma and eventual renal failure. In humans, however, data on the influence of nephrectomy or agenesis on future functional parameters and hypertension are as yet controversial. OBJECTIVE: To evaluate blood-pressure patterns in children with a solitary kidney as a result of either unilateral renal agenesis (URA) or uninephrectomy (UNX) and correlate them to the increase in size of the remaining kidney. METHODS: Twenty-eight children with a solitary kidney were divided into two groups: the URA group, with 18 subjects (13 male and five female, with a mean age of 9.6 +/- 3.9 years), and the UNX group, which contained 10 subjects (four male and six female, with a mean age of 14.0 +/- 2.7 years). The mean time since nephrectomy was 8.7 years. Each study group was assigned an age-, weight- and height-matched control group. In all subjects, ambulatory blood pressure monitoring was performed using the SpaceLabs model no. 90207. Daytime and night-time were defined as 0800-2200 h and 2200-0800 h, respectively. Urinalysis, serum creatinine and urea results were recorded for all the study group participants. The size of the remaining kidney was determined by ultrasound examination. The percentage increase in kidney size, as calculated from standard kidney-length-against-age nomograms was correlated to the percentage deviation from normal blood pressure values. RESULTS: The mean 24 h, daytime and night-time systolic blood pressure (SBP) readings were significantly higher in children in the URA group than in those in the corresponding control group (111.4 +/- 7.5 mmHg versus 106.9 +/- 6.7 mmHg, P < 0.004; 115.2 +/- 3.1 mmHg versus 110.7 +/- 3.4 mmHg, P < 0.004; and 105.2 +/- 2.6 mmHg versus 101.2 +/- 1.8 mmHg, P < 0.002, respectively). Daytime heart rate was found to be significantly reduced (84.4 +/- 5.2 versus 87.8 +/- 8.2 beats/min, P < 0.04). In the UNX group, 24 h mean, systolic and diastolic blood pressure (DBP), as well as heart rate, did not differ from control values. Daytime systolic and diastolic blood pressures were higher than those of the controls (119.8 +/- 4.0 mmHg versus 115.5 +/- 3.8 mmHg, P < 0.02; and 72.7 +/- 4.0 mmHg versus 70.0 +/- 11.0 mmHg, P < 0.02, respectively). Nocturnal dipping was present in all groups and was of equal magnitude in the corresponding control groups. The mean 24 h diastolic blood pressure load was significantly greater in URA patients than in controls (19.6 versus 10.8%, respectively, P < 0.01). In the UNX group, the blood pressure loads were similar to those of controls. The percentage increase in length of the remaining kidney was found to correlate positively with the percentage delta increase in both systolic and diastolic blood pressure. CONCLUSIONS: Compared with the age-, height- and weight-matched controls, the children with a solitary kidney caused by URA had an elevated mean 24 h SBP. In contrast, those with UNX had mean 24 h blood pressure values similar to those of their controls. A rise in SBP was, however, seen in both groups during the daytime hours. Thus, the presence of a solitary kidney, for whatever reason, may be pathogenetically linked to a raised blood pressure, and this linkage may be more pronounced in URA. The delta increase in size of the remaining kidney may serve as a prognostic indicator of blood pressure elevation.

Posterior cloaca: a unique defect.

The authors present nine cases of a unique defect in which urethra and vagina are fused together forming a urogenital sinus that deviates posteriorly and opens in the anterior rectal wall at the anus or immediately anterior to it. The rectum is essentially normal or may be minimally anteriorly mislocated. The authors call this defect posterior cloaca. The diagnosis requires a suspicious observer and a meticulous examination of the female genitalia. A complete urologic evaluation is mandatory because 88% of these patients have important associated urologic defects. Our patients were operated on via a posterior sagittal transanorectal approach, which allowed a full dissection and mobilization of urethra and vagina together to be placed in a normal location. Rectal dissection and mobilization was avoided to preserve bowel control. Seven patients enjoy bowel and urinary control. One patient was lost to follow-up, and one patient with a severely dysplastic sacrum suffers from fecal and urinary incontinence.

[Surgery for women with urethral diverticulum].

Urethral diverticulum in the female is an acquired lesion following infection of the para-urethral glands. Its symptoms are often nonspecific and only by increased awareness of this condition can delay in diagnosis be avoided. Radiologic imaging of the urethra allows diagnosis of this lesion and determination of its location, extent and the number of lesions. Complete surgical excision is the optimal therapy. In recent years 8 women with this condition were admitted aged 21-52 years. It had been an average of 11 months before their lesions were diagnosed. All had complete surgical excision without perioperative complications. In 5 a Martius labial fat pad was used to facilitate prompt healing of the urethral defect. 6 have been followed for over a year and are completely symptom-free. Judicious choice of surgical technique is required to reduce the rate of complications in the management of these lesions.

[Immunotherapy for metastatic renal cell carcinoma: treatment with PLAK cells and low-dose interleukin-2].

During the past 5 years publications from the NIH (Rosenberg et al.) and other centers have reported encouraging results in the treatment of metastatic renal cell carcinoma. Adoptive immunotherapy was applied, using lymphocytes activated by interleukin-2 (LAK cells) plus high doses of interleukin (IL-2) systemically. The mean clinical response rate was 20-35%. Severe lifethreatening adverse reactions to high doses of IL-2 were noted, although they were all of short duration. Laboratory findings of Novogrodsky et al. from Beilinson Medical Center, Israel showed that oxidizing mitogens can induce lymphocyte activation (PLAK cells). Further studies suggested that a combination of such activated cells with low doses of IL-2 could produce effective toxicity to tumor cells without the need for high doses of IL-2 which could be very toxic for the patient. In the past year we treated 7 patients with PLAK cells and IL-2. 4 completed the treatment, of whom 1 responded partially (regression of more than 50% of lung metastases), 1 is stable and in 1 liver metastases regressed but metastases in lumbar vertebrae and in the pelvis progressed. 1 patient died a month after discharge from hospital, probably due to rapid progression of the disease. Our protocol follows that of the Phase II clinical study of 40 patients treated at the Rogosin Institute, New York Hospital--Cornell Medical Center. The mean clinical response rate was 23.6%. Toxicity of IL-2 is dose-dependent. In this protocol, the low doses of IL-2 gave significantly fewer adverse reactions.

T-RFLP-based differences in oral microbial communities as risk factor for development of oral diseases under stress.

The human oral microbiome is comprised of approximately 800 different bacterial species many of which are as yet uncultivated. Their dynamics and variability in relation to health and disease are still poorly understood. Here we tested the hypothesis that the emergence of stress-induced periodontal diseases is predictable based on the composition of the initial microbiota. As a model, we analysed 58 individuals performing a challenging expedition (exposure to various stress-factors due to changes in diet, hygiene, temperature, physical and mental stress) in remote regions of the Himalayans (Annapurna Himal). Plaque samples were taken at start (Bhulbule) and destination (3000 meter difference in altitude) seven days later (Manang). Twenty-eight individuals remained symptom-free (Group I) while 30 participants developed periodontal problems, mostly gingivitis (Group II). The microbiota was monitored via T-RFLP-analysis of amplified 16S rRNA genes directly from the plaque samples. Based on the Additive-Main-Effects-Multiplicative-Interactions-model (AMMI) using the T-Rex software variation from T-RF main effects was at least 95%, indicating that most variation was due to inherent differences in microbial communities among individuals. However, an interaction signal up to 3% was consistently observed between groups I and II but not between the two time points of sampling regardless of selected analytical parameters. The data, supported by heterogeneity, diversity and similarity indices indicated marked differences between groups I and II already prior the onset of clinical symptoms. These differences may provide the basis for using ecological parameters of oral microbial communities as early diagnostic marker for the onset of oral disorders and infections.

Effect of meniscus replacement fixation technique on restoration of knee contact mechanics and stability.

The menisci are important biomechanical components of the knee. We developed and validated a finite element model of meniscal replacement to assess the effect of surgical fixation technique on contact behavior and knee stability. The geometry of femoral and tibial articular cartilage and menisci was segmented from magnetic resonance images of a normal cadaver knee using MIMICS (Materialise, Leuven, Belgium). A finite element mesh was generated using HyperWorks (Altair Inc, Santa Ana, CA). A finite element solver (Abaqus v6.9, Simulia, Providence, RI) was used to compute contact area and stresses under axial loading and to assess stability (reaction force generated during anteroposterior translation of the femur). The natural and surgical attachments of the meniscal horns and peripheral rim were simulated using springs. After total meniscectomy, femoral contact area decreased by 26% with a concomitant increase in average contact stresses (36%) and peak contact stresses (33%). Replacing the meniscus without suturing the horns did little to restore femoral contact area. Suturing the horns increased contact area and reduced peak contact stresses. Increasing suture stiffness correlated with increased meniscal contact stresses as a greater proportion of tibiofemoral load was transferred to the meniscus. A small incremental benefit was seen of simulated bone plug fixation over the suture construct with the highest stiffness (50 N/mm). Suturing the rim did little to change contact conditions. The nominal anteroposterior stiffness reduced by 3.1 N/mm after meniscectomy. In contrast to contact area and stress, stiffness of the horn fixation sutures had a smaller effect on anteroposterior stability. On the other hand suturing the rim of the meniscus affected anteroposterior stability to a much larger degree. This model emphasizes the importance of the meniscus in knee biomechanics. Appropriate meniscal replacement fixation techniques are likely to be critical to the clinical success of meniscal replacement. While contact conditions are mainly sensitive to meniscus horn fixation, the stability of the knee under anteroposterior shear loads appeared to be more sensitive to meniscal rim fixation. This model may also be useful in predicting the effect of biomaterial mechanical properties and meniscal replacement shape on knee contact conditions.

A method to quantify alteration of knee kinematics caused by changes of TKR positioning.

Few in-vitro studies have investigated changes in kinematics caused by total knee replacement (TKR) implantation. The advent of surgical navigation systems allows implant position to be measured accurately and the effects of alteration of TKR position and alignment investigated. A test rig and protocol were developed to compare the kinematics of TKR-implanted knees for different femoral component positions. The TKR was implanted and the component positions documented using a navigation system. The quadriceps was tensed and the knees were flexed and extended manually. Torques and drawer forces were applied to the tibia during knee flexion-extension, while recording the kinematics with the navigation system. The implant was removed and replaced on an intramedullary fixation that allowed proximal-distal, and internal-external rotation of the femoral component without conducting a repeated arthrotomy on the knee. The implant was repositioned using the navigation system to reproduce the previously achieved normally navigated position and the kinematics were recorded again. The recorded kinematics of the knee were not significantly different between both normal implantation and intramedullary remounting for tibial internal-external rotation, varus-valgus angulation, or posterior drawer, at any angle of knee flexion examined. Anterior drawer was increased approximately 2.5mm across the range 20-35 degrees knee flexion (p<0.05), but was otherwise not significantly different. This method of navigating implant components and of moving them within the closed knee (thus avoiding artefactual effects of repeated soft tissue manipulations) can now be used to quantify the effect on kinematics of alteration of the position of the femoral component.

Bilateral asynchronous renal cell carcinoma: treatment approach.

Two hundred patients underwent nephrectomy for renal cell carcinoma (RCC) at our service in 1978-89. During follow-up four patients developed RCC in the remaining kidney and underwent a parenchymal preserving procedure as curative treatment (one enucleation, and three partial nephrectomies). The interval between the nephrectomy and the diagnosis of asynchronous RCC was 50-84 months (mean 65 months). None of the patients needed dialysis after the operation, and creatinine level in all remained between 1.6 and 1.9 mg. One patient died from a heart attack 8 years after the partial nephrectomy, two patients have no evidence of disease 24 months and 76 months after enucleation and partial nephrectomy, respectively. The fourth patient, who had resection of metastatic lesion in the scalp 36 months before the partial nephrectomy, is alive 34 months after the procedure but has lately developed recurrence in the scalp. Although relatively rare, it is important to be aware of the possible asynchronous development of RCC in the contralateral kidney after nephrectomy for RCC. In such cases, parenchymal preserving procedure (enucleation, partial nephrectomy) is an alternative that should be considered to improve the quality of life and to avoid the need for dialysis.