Strain rate imaging for the assessment of preload-dependent changes in regional left ventricular diastolic longitudinal function.

BACKGROUND: Strain rate imaging is a new and intriguing way of displaying myocardial deformation properties by means of echocardiography. With high frame rate strain rate imaging we observed a spatial inhomogeneity in diastolic longitudinal strain rates in healthy persons. A base-to-apex time delay in diastolic lengthening could be seen both in early diastole and at atrial contraction. METHODS AND RESULTS: We investigated this consistent finding and its dependence on loading conditions in 20 healthy volunteers. Propagation velocities of lengthening of 91 +/- 31 cm/s (E-wave) and 203 +/- 11 cm/s (A-wave) at rest (equal to time delays of 104 +/- 29 ms and 56 +/- 24 ms, respectively) increased significantly to 101 +/- 27 cm/s (E) and 283 +/- 17 cm/s (A) with lifting the volunteers' legs. Applying nitroglycerin sublingually and sitting upright significantly decreased propagation velocities (E-wave 76 +/- 20 cm/s, A-wave 172 +/- 93 cm/s and E-wave 66 +/- 17 cm/s, A-wave 150 +/- 64 cm/s, respectively). Free lateral walls showed a lower propagation velocity than septal walls. CONCLUSION: We conclude that the propagation velocities of left ventricular lengthening waves are dependent on preload changes and increase with increasing preload.     

Rosiglitazone Dampens Pulmonary Inflammation in a Porcine Model of Acute Lung Injury

The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.     

The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement

In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.     

Volume independent stimulation of renin secretion by a single dose of amiloride in man

The regulation of renin secretion is not understood in detail. There is evidence that amiloride (CAS 17440-83-4) has a stimulatory effect on the renin secretion but it is still in question whether this is volume and/or sodium independent. The purpose of this study was to investigate whether a single dose of amiloride has a direct stimulatory effect on the renin secretion in humans independent of its diuretic effect. Blood pressure, plasma renin activities and plasma aldosterone concentrations as well as serum electrolytes and serum creatinine were assessed in 11 healthy male humans over a period of 6 hours after a single dose of 20 mg of amiloride (Midamor), or placebo. Furthermore every hour urine was collected for analysis of urinary creatinine and electrolytes. To avoid a possible effect on the renin secretion via augmented diuresis induced by amiloride the urinary volume loss was replaced by 0.9% NaCl solution. There was a decrease in plasma renin activities and plasma aldosterone concentrations after amiloride and placebo administration, but the plasma renin activity after amiloride was significantly higher compared with placebo. Also the plasma aldosterone concentration was higher after amiloride compared with placebo, but the difference did not reach statistical significance. Serum and urinary concentrations of sodium and potassium clearly confirmed the known potassium-saving and natriuretic effect of amiloride. Serum creatinine concentrations decreased and urinary sodium chloride concentrations increased due to the administered volume load using physiologic sodium chloride solution. The present study provides evidence that amiloride induces renin secretion by direct mechanisms in man, which might go along with augmented aldosterone secretion.     

Serotonin fibre densities in subcortical areas: differential effects of isolated rearing and methamphetamine

Serotoninergic neurons interact with dopaminergic cells on all levels and are physiologically affected by both isolated rearing (IR) and a single early methamphetamine (MA) injection. We therefore checked for anatomical effects of both interventions by immunohistochemically staining serotonin fibres and assessing fibre densities in the caudate-putamen (CPu), nucleus accumbens (NAc) and amygdala of Mongolian gerbils. IR led to significantly increased 5-HT fibre densities in the dorsal part of the CPu and in the central and basolateral amygdala. No effects were seen in the ventral CPu, in the NAc and in the lateral amygdala. The early MA injection resulted in a denser 5-HT innervation in the dorsomedial and ventromedial CPu, in the NAc shell of animals reared in an enriched environment and in the NAc core of both rearing conditions, leaving the lateral CPu and the amygdala unaffected. Thus, the single pharmacological versus the environmental challenge exerts an almost complementary effect on the 5-HT innervation in different areas of the brain, which demonstrates that systemic interactions, e.g. with dopaminergic and glutamatergic afferents, must be taken into account when the seemingly uniform 5-HT projections are investigated.     

Patient satisfaction with the outcome of surgery for urethral stricture

PURPOSE: We assessed patient satisfaction with the outcome of surgery for urethral strictures and compared it with objective clinical data. MATERIALS AND METHODS: A total of 267 consecutive patients who underwent surgery for urethral stricture between March 1993 and December 1999 were questioned regarding satisfaction. Mailed questionnaires or a telephone interview, if questionnaires were not returned, provided information on the urinary tract, voiding, sexual function, overall satisfaction and miscellaneous impairments after surgery for urethral strictures. The response rate was 87% (233 of 267 patients). Subjective data were compared with objective clinical findings. RESULTS: Of the 203 patients who underwent successful urethroplasty 159 (78%) and 24 of the 30 (80%) in whom urethroplasty was considered a failure from the physician viewpoint were satisfied or very satisfied with the outcome of urethral surgery. Patients who underwent re-intervention for complications other than re-stricture and those who complained of a weak or very weak urinary stream were considerably less satisfied. Factors influencing sexual function also had an important impact on patient satisfaction. Patients with marked or severe penile curvature, penile shortening, erection deterioration and a markedly or severely impaired sexual life were especially dissatisfied. CONCLUSIONS: Patients consider the outcome of surgery for urethral strictures differently than physicians. The outcome of urethroplasty should be assessed not only by objective, but also by subjective criteria. Patients need appropriate preoperative counseling. With realistic expectations most men are satisfied with surgery for urethral stricture.     

Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine

Budipine is a non-dopaminergic antiparkinsonian drug causing acquired forms of Long QT syndrome (aLQTS). As a consequence, the manufacturer has restricted the use of budipine in patients who exhibit additional risk factors for the development of Torsades-de-Pointes tachycardias (TdP). The molecular basis of this serious side effect has not been elucidated yet.Human ether-a-go-go related gene (HERG) channel block being the main cause of drug induced QT prolongation, we investigated the effect of budipine on the rapid component of the delayed-rectifier potassium current (I_K(r)) in guinea pig cardiomyocytes and on HERG potassium channels heterologously expressed in Xenopus oocytes.In guinea pig cardiomyocytes, budipine (10 M) inhibited I_K(r) by 86% but was without any effect on calcium currents. In Xenopus oocytes, HERG potassium channels were blocked by budipine with an IC₅₀ of 10.2 M. Onset of block was fast and block was only slowly and incompletely reversible upon washout.Budipine blocked HERG channels in the open and inactivated state, but not in the closed states. The half-maximal activation voltage was slightly shifted towards more negative potentials. Steady-state inactivation of HERG was also influenced by budipine. Budipine block was neither voltage- nor frequency-dependent.In HERG channel mutants Y652A and F656A, drug affinity was reduced dramatically. Therefore, these two aromatic residues in the channel pore are likely to form a main part of the binding site for budipine.In summary, this is the first study that provides a molecular basis for the budipine-associated aLQTS observed in clinical practice. Furthermore, these findings underline the importance of the aromatic residues Y652 and F656 in the binding of lipophilic drugs to HERG channels.Abbreviations I_K(r) The rapid component of the delayed-rectifier potassium current - HERG Human ether-a-go-go related gene - aLQTS Acquired Long QT syndrome - TdP Torsade-de-Pointes tachycardia E.P. Scholz and E. Zitron contributed equally to this work