Two-year migration results of the ReCap hip resurfacing system��a radiostereometric follow-up study of 23 hips

There has been renewed interest for metal-on-metal hip resurfacing due to improved design and manufacturing of implants, better materials, and enhanced implant fixation. In contrast to conventional total hip replacements, only a few clinical hip resurfacing trials using radiostereometry (RSA) have been reported, and solely for the Birmingham hip resurfacing arthroplasty. The purpose of this RSA trial was to describe the migration pattern of a new hip resurfacing system (ReCap) within the first two years after primary surgery. Twenty-six patients underwent total hip replacement. The patients were followed-up for up to 24 months and were evaluated with the use of radiostereometric measurements. The prosthesis showed mean translations and rotation close to zero. Maximum translation was seen along the transverse axis in the medial direction (0.13 mm). No statistically significant translation or rotation was seen at two-years follow-up, (t-test, p <0.05, translation or rotation).     

The Western Denmark Heart Registry: Its Influence on Cardiovascular Patient Care

The WDHR (Western Denmark Heart Registry) is a seminational, multicenter-based registry with longitudinal registration of detailed patient and procedure data since 1999. The registry includes as of January 1, 2017 approximately 240,000 coronary angiographies, 90,000 percutaneous coronary interventions, 60,000 cardiac computed tomographies, 40,000 cardiac operations, and 2,000 transcatheter aortic valve replacements. Positron emission tomography/computed tomography, single-photon emission computed tomography, and magnetic resonance imaging are soon to be added. Each procedure is registered with 50 to 200 administrative, patient, and procedure variables. Lesion data are also registered for percutaneous coronary intervention, and cardiac surgeries also include variables for EuroSCORE, anesthesia, perfusion, and intensive care. The registry has high completeness and accuracy. The Danish registry infrastructure allows for complete follow-up for medical events and mortality, which greatly enhances the research potential of the data. This review describes why the WDHR is a unique data resource and how it continues to influence cardiovascular patient care.     

Irrigation with isoproterenol during ureterorenoscopy causes no systemic side-effects

OBJECTIVE: Ureterorenoscopy causes complications that may be related to high intrarenal pressures generated during irrigation. Endoluminal isoproterenol administration has been shown to reduce pelvic pressure in pigs. The objective of this study was to investigate possible systemic side-effects of isoproterenol irrigation during ureterorenoscopy in humans. MATERIAL AND METHODS: Seven patients undergoing ureterorenoscopy due to renal stone disease were included. A 5-Fr catheter was retrogradely placed in the renal pelvis for pressure measurements. Prior to irrigation with isoproterenol (0.1 microg/ml), ureterorenoscopy was performed with saline irrigation. Renal pelvic pressure, blood pressure and heart rate were measured before and after isoproterenol irrigation. Venous blood was drawn for isoproterenol measurements. RESULTS: Endoluminal isoproterenol irrigation produced no changes in mean heart rate (HR) or mean arterial pressure (MAP). MAP (+/- SEM) was 56 (2.7) mmHg during saline irrigation and 58 (+/- 2.4) mmHg during isoproterenol irrigation. HR was 60 (+/- 4) beats/min before and 61 (+/- 4) beats/min during isoproterenol irrigation. Neither the difference in MAP = 0.10) nor the difference in HR (p = 0.23) were significant. Pelvic pressure was significantly lower during isoproterenol irrigation [19 (+/- 3) mmHg] compared to saline irrigation [35 (+/- 2.6) mmHg] (p = 0.0006). Pelvic pressure reached very high levels (> 300 mmHg), especially during injection of contrast medium. CONCLUSION: Endoluminal isoproterenol irrigation during ureterorenoscopy causes no cardiovascular side-effects and the drug may reduce renal pelvic pressure.     

Irrigation with isoproterenol diminishes increases in pelvic pressure without side-effects during ureterorenoscopy: a randomized controlled study in a porcine model

OBJECTIVE: Recently, we showed that endoluminally administered isoproterenol (ISO) inhibits muscle function of the pyeloureter in swine. This may be of value in managing increases in pelvic pressure during upper urinary tract endoscopy. The purpose of this study was to examine the effect of endoluminally administered ISO on increases in pelvic pressure and cardiovascular function during flexible ureterorenoscopy. MATERIAL AND METHODS: The study was performed in anaesthetized female pigs. In terms of endoscopic procedures, the pigs were randomized as follows: Group 1, irrigation with 0.1 microg/ml ISO added to saline (n=12); and Group 2, irrigation with saline (n=10). A 5-Fr catheter was retrogradely placed in the renal pelvis and an 8-Fr catheter in the bladder for pressure measurements. Flexible ureterorenoscopy was performed with constant irrigation at a perfusion rate of 8 ml/min. Pelvic, bladder and blood pressure and heart rate were registered continuously. RESULTS: Mean baseline pelvic pressure was identical in both groups: 12+/-2.3 mmHg in Group 1 and 14+/-3.6 mmHg in Group 2 (p=0.26). During ureterorenoscopy, mean pelvic pressure increased to 26+/-2.3 mmHg in Group 1 and to 38+/-3.1 mmHg in Group 2. Hence ISO reduced the pressure increase due to ureterorenoscopy by 42% (p<0.001). Pelvic pressure seemed to be independent of bladder pressure, which showed no difference between the two groups (p=0.067). Blood pressure and heart rate showed no significant differences between the two groups: p=0.425 and p=0.166, respectively. CONCLUSIONS: ISO (0.1 microg/ml) added to irrigation fluid significantly reduces the increase in pelvic pressure during ureterorenoscopy in pigs, without concomitant side-effects.     

Germline Polymorphisms may Act as Predictors of Response to Preoperative Chemoradiation in Locally Advanced T3 Rectal Tumors

Purpose Patients with locally advanced T3 rectal tumors who present with complete pathologic response to preoperative chemoradiation have a low rate of local recurrence and an excellent prognosis. Predictive markers for complete pathologic response are needed with the perspective of improving individualized treatment of these patients. This study was designed to investigate the predictive value of a new combination of three gene polymorphisms: thymidylate synthase, epidermal growth factor receptor Sp1-216, and epidermal growth factor A61G. Methods Pretreatment blood samples from 60 patients with locally advanced T3 rectal tumors were analyzed for thymidylate synthase, epidermal growth factor receptor Sp1-216, and epidermal growth factor A61G gene polymorphisms by polymerase chain reaction. Treatment consisted of preoperative radiotherapy (total dose 65 Gy) and concomitant chemotherapy (Uftoral) followed by total mesorectal excision eight weeks after treatment. Pathologic response was evaluated according to the tumor regression grade system. Results Thirty percent (18/60) of patients presented with complete pathologic response. Patients with thymidylate synthase genotype 2/2 had a significantly higher rate of complete pathologic response with 53 percent (8/15) compared with 22 percent in the 2/3 or 3/3 group. When combining thymidylate synthase and epidermal growth factor A61G genotype analysis, a small subgroup with a complete pathologic response rate of 100 percent was identified. Only a minor proportion of the complete responders were identified by this combination. Adding the epidermal growth factor receptor Sp1-216 genotype analysis, a complete pathologic response rate of 64 percent in the combination group was found compared with 21 percent and an 87 percent risk of being a noncomplete responder in the noncombination group. Conclusions A promising new combination of predictive markers for complete pathologic response was presented and warrants further investigation in prospective clinical trials.     

Muscle performance relates to physical function and quality of life in long-term chronic inflammatory demyelinating polyradiculoneuropathy

The aim of the present study was to determine the severity and distribution of assessed muscle weakness and to relate muscle performance to measures of function and quality of life in long-term chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Fourteen patients with 8.7 years (3.3-11.5) of confirmed CIDP consecutively referred to the referral center for CIDP patients at Aarhus University Hospital, Denmark, during the period 1992-2002 were compared with matched healthy controls. The main outcome parameter was muscle performance assessed with isokinetic dynamometry. Overall disability sum score (ODSS), neurological symptom score (NSS), neuropathy impairment score (NIS), health-related quality-of-life survey (SF-36), nerve conduction studies, physical fitness, hand and walking performance, and quantitative sensory testing were secondary variables. The mean (95% CI) isokinetic strength of all measured muscles was reduced by 19.4% (5.9-32.8%) (p < 0.01). In the legs, distal weakness was predominant, strength at ankle being 37.0% (14.7-59.2%) reduced. Isokinetic strength was closely related to manual muscle strength, ODSS, NIS, walking performance, and physical components of SF-36. In conclusion, isokinetic strength relates to measures of function, impairments, gait performance, and physical components of health-related quality of life in long-term CIDP. Furthermore, a detailed characterization of severity and distribution of weakness has been provided using this technique.     

Ca2+/calcineurin regulation of cloned vascular KATP channels: crosstalk with the protein kinase A pathway

Background and purpose:

Vascular ATP-sensitive potassium (K_ATP) channels are activated by cyclic AMP elevating vasodilators through protein kinase A (PKA). Direct channel phosphorylation is a critical mechanism, though the phosphatase opposing these effects is unknown. Previously, we reported that calcineurin, a Ca²⁺-dependent phosphatase, inhibits K_ATP channels, though neither the site nor the calcineurin isoform involved is established. Given that the type-2 regulatory (RII) subunit of PKA is a substrate for calcineurin we considered whether calcineurin regulates channel activity through interacting with PKA.

Experimental approach:

Whole-cell recordings were made in HEK-293 cells stably expressing the vascular K_ATP channel (K_IR6.1/SUR2B). The effect of intracellular Ca²⁺ and modulators of the calcineurin and PKA pathway on glibenclamide-sensitive currents were examined.

Key results:

Constitutively active calcineurin Aα but not Aβ significantly attenuated K_ATP currents activated by low intracellular Ca²⁺, whereas calcineurin inhibitors had the opposite effect. PKA inhibitors reduced basal K_ATP currents and responses to calcineurin inhibitors, consistent with the notion that some calcineurin action involves inhibition of PKA. However, raising intracellular Ca²⁺ (equivalent to increasing calcineurin activity), almost completely inhibited K_ATP channel activation induced by the catalytic subunit of PKA, whose enzymatic activity is independent of the RII subunit. In vitro phosphorylation experiments showed calcineurin could directly dephosphorylate a site in Kir6.1 that was previously phosphorylated by PKA.

Conclusions and implications:

Calcineurin Aα regulates K_IR6.1/SUR2B by inhibiting PKA-dependent phosphorylation of the channel as well as PKA itself. Such a mechanism is likely to directly oppose the action of vasodilators on the K_ATP channel.British Journal of Pharmacology (2009) 157, 554–564; doi:10.1111/j.1476-5381.2009.00221.x; published online 7 May 2009This article is commented on by Tammaro, pp. 551–553 of this issue and is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009