Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma

Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense mutation in c-MET. The original pathology report of four primary kidney cancers (1988–1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of revised pathology examinations in possible hereditary renal-cell carcinomas especially when described before 1997.     

Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.     

The final follow-up plain radiograph is sufficient for clinical evaluation of polyethylene wear in total hip arthroplasty: A study of validity and reliability

Background and purpose

Radiostereometric analysis (RSA) is a highly accurate tool for assessment of polyethylene (PE) wear in total hip arthroplasty (THA); however, PE wear measurements in clinical studies are often limited to plain radiographs. We evaluated the agreement between PE wear measured with PolyWare software, which uses plain radiographs, and by model-based RSA, which uses stereo radiographs.

Methods

Measurements of PE wear postoperatively and at final follow-up (after mean 6 years) on plain radiographs of 12 patients after cementless THA were evaluated with PolyWare software and the results were compared with those from RSA as the gold standard (Model-based RSA using elementary geometrical shape models; EGS-RSA). With PolyWare, we either used the final radiographic follow-up (PW1) only or both the postoperative follow-up and the final follow-up (PW2).

Results

The 2D mean wear measured (in mm) was 0.80, 1.07, and 0.60 for the PW2, PW1, and RSA method. 2D intra-method repeatability was similar for PW1 and RSA with limits of agreement (LOAs, in mm) of ± 0.22, and ± 0.23, respectively. 2D inter-method concurrent validity was best between PW1 and EGS-RSA with LOAs of ± 0.55. For 2D linear wear measurements, the PW1 method had a clinical repeatability similar to that of RSA.

Interpretation

PW1 is sufficient for retrospective determination of 2D wear from medium-term wear measurements above 0.5 mm, It alleviates the need for baseline plain radiographs, has a clinical precision similar to that of RSA, and is easy and inexpensive to use.Wear of polyethylene (PE) components is widely regarded as the main factor limiting longevity of total hip arthroplasty (THA) (Cooper et al. 1992). Clinical studies have shown that periprosthetic osteolysis and aseptic loosening is strongly related to wear rates of above 0.2 mm/year (Sochart 1999, Dowd et al. 2000).Radiostereometric analysis (RSA) is the most accurate tool for in vivo assessment of PE wear (Kärrholm et al. 1997, von Schewelov et al. 2004, Bragdon et al. 2006), and it is regarded as the gold standard (Ilchmann et al. 1995). However, many radiographic in vivo studies of PE wear in THA are restricted to measurements on plain radiographs because the RSA set-up is expensive and not widely available. Measurement of PE wear on plain radiographs is often limited to 2D analysis because poor quality of cross-table lateral radiographs is a common problem (Sychterz et al. 1999b, 2001). Although PE wear is known to occur multidirectionally (Yamaguchi et al. 1997, Akisue et al. 1999), the bulk of the wear is detectable on the anterior-posterior radiographs alone (Sychterz et al. 1997, Hui et al. 2003, Martell et al. 2003). Based on the availability of radiographs and investigator preferences, some authors favor analysis of serial radiographs (Sychterz et al. 1997, Kim et al. 2001, Hernigou and Bahrami 2003) to describe the pattern of wear and the steady-state wear (Sychterz et al. 1999a, Bragdon et al. 2006), whereas others use 2 radiographic follow-ups (postoperative and latest) (Kraay et al. 2006), or only the latest radiographic follow-up with the assumption of zero wear at baseline (Norton et al. 2002)Little is known about the conformity between PE wear results measured with RSA and computerized methods using plain radiographs (Ilchmann et al. 1995, von Schewelov et al. 2004, Bragdon et al. 2006). Our group has questioned the conformity of 2D PE wear measurements based on serial, 2, or 1 radiographic follow-up (Stilling et al. 2009b). We determined that there was a statistically significant difference between all approaches, but we were unable to determine which strategy best reflected the true extent of wear (Stilling et al. 2009b). In addition, we recently showed that model-based RSA is an accurate tool for measurement of PE wear in good agreement with the true wear (Stilling 2009).We have now studied the intra-method repeatability and concurrent validity between 2 methods (PolyWare and EGS-RSA) for measurement of PE wear in THA, in a group of patients with an average follow-up of 6 years. We wanted to determine (1) whether there would be a difference in repeatability between the methods, (2) whether there would be a difference in wear measured using 1 or 2 radiographic follow-ups with the PolyWare method, and (3) whether either of the 2 PolyWare measurement strategies (1 or 2 radiographic follow-ups) would give results similar to the wear measured by RSA (concurrent validity).     

A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty

Background

There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty (TKA). In this study, we assessed the efficacy of wound infiltration combined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA.

Methods

40 consecutive patients undergoing elective, primary TKA were randomized into 2 groups to receive either (1) intraoperative wound infiltration with 150 mL ropivacaine (2 mg/mL), 1 mL ketorolac (30 mg/mL), and 0.5 mL epinephrine (1 mg/mL) (total volume 152 mL) combined with intraarticular infusion (4 mL/h) of 190 mL ropivacaine (2 mg/mL) plus 2 mL ketorolac (30 mg/mL) (group A), or (2) epidural infusion (4 mL/h) of 192 mL ropivacaine (2 mg/mL) combined with 6 intravenous administrations of 0.5 mL ketorolac (30 mg/mL) for 48 h postoperatively (group E). For rescue analgesia, intravenous patient-controlled-analgesia (PCA) morphine was used.Morphine consumption, intensity of knee pain (0–100 mm visual analog scale), and side effects were recorded. Length of stay and corrected length of stay were also recorded (the day-patients fulfilled discharge criteria).

Results

The median cumulated morphine consumption, pain scores at rest, and pain scores during mobilization were reduced in group A compared to group E. Corrected length of stay was reduced by 25% in group A compared to group E.

Interpretation

Peri- and intraarticular analgesia with multimodal drugs provided superior pain relief and reduced morphine consumption compared with continuous epidural infusion with ropivacaine combined with intravenous ketorolac after TKA.Total knee arthroplasty (TKA) usually results in severe postoperative pain. Continuous epidural infusion with a local anesthetic is a standard regime for postoperative analgesia after TKA. Epidural analgesia and also peripheral nerve block analgesia have been shown to reduce opioid consumption compared with intravenous patient-controlled analgesia (PCA). Even though both modalities reduce the occurrence of the well-known side effects of opioid drugs, they involve extra equipment and are associated with substantial side effects (Choi et al. 2003, Davies et al. 2004, Boezaart 2006). Wound infiltration with multimodal analgesia has been a controversial issue for many years (Dahl et al. 1994). Different modes of perioperative analgesia either without or combined with intraarticular infusion or bolus injection(s) for both TKA and total hip arthroplasty have been described (Bianconi et al. 2003, Rasmussen et al. 2004, Reilly et al. 2005, Andersen et al. 2007a, b). Only a few studies have described high-volume peri- and intraarticular analgesia for TKA (Busch et al. 2006, Vendittoli et al. 2006, Toftdahl et al. 2007). The hypothesis in our trial was that wound infiltration and intraarticular infusion of ropivacaine and ketorolac would reduce opioid consumption during the active treatment period (0–48 h postoperatively) after TKA compared to epidural infusion of ropivacaine and intravenous ketorolac. Primary outcome was 48-h opioid use. Secondary outcomes included pain at rest and during mobilization, side effects, length of hospital stay (LOS), and corrected length of stay (the day-patients fulfilled discharge criteria).     

Improved contrast agent bolus tracking using T1 FARM.

Current MRI bolus tracking techniques, such as saturation recovery Turbo-FLASH (srTFL), suffer from signal saturation at high contrast concentrations. In this study T1 Fast Acquisition Relaxation Mapping (T1 FARM) was compared to srTFL. In phantoms, T1 FARM maps were linear with [Gd-DTPA] up to 7.0 mmol/L while srTFL images saturated above 2.0 mmol/L. In the canine left ventricle, blood concentration curves determined from T1 FARM saturated with bolus injections exceeding 0.075 mmol/kg, while srTFL curves saturated above 0.025 mmol/kg of Gd-DTPA. Also, T1 FARM improved contrast-to-noise ratio in tissue concentration curves since higher contrast concentrations could be measured without saturating.