Primary extragonadal germ cell tumor of the prostate in a young man

We report on a case of malignant prostatic teratoma treated with radical cystoprostatectomy and cisplatin-based chemotherapy because of intraoperative tumor rupture. During chemotherapy the patient suffered acute myocardial infarction and was treated with percutanous coronarangiography and stenting.     

In-vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Influence of the Partition Coefficient Octanol/Water and the Water Solubility of Drugs on their Permeability and Maximum Flux

Penetration of homologous nicotinic acid esters through the human nail and a keratin membrane from bovine hooves was investigated by modified Franz diffusion cells in-vitro to study the transport mechanism. The partition coefficient octanol/water PC_Oct/w of the esters was over the range 7 to > 51000. The permeability coefficient P of the nail plate as well as the hoof membrane did not increase with increasing partition coefficient or lipophilicity of the penetrating substance. This indicates that both barriers behave like hydrophilic gel membranes rather than lipophilic partition membranes as in the case of the stratum corneum. Penetration studies with the model compounds paracetamol and phenacetin showed that the maximum flux was first a function of the drug solubility in water or in the swollen keratin matrix. Dissociation hindered the diffusion of benzoic acid and pyridine through the hoof membrane. Since keratin, a protein with an isoelectric point of about 5, is also charged, this reduction can be attributed to an exclusion of the dissociating substance due to the Donnan equilibrium. Nevertheless, the simultaneous enhancement of the water solubility makes a distinct increase of the maximum flux possible. In order to screen drugs for potential topical application to the nail plate, attention has to be paid mainly to the water solubility of the compound. The bovine hoof membrane may serve as an appropriate model for the nail.     

Relationship between gross motor capacity and daily‐life mobility in children with cerebral palsy

Aim The aim of this study was to examine the relationship between gross motor capacity and daily‐life mobility in children with cerebral palsy (CP) and to explore the moderation of this relationship by the severity of CP. Method Cross‐sectional analysis in a cohort study with a clinic‐based sample of children with CP (n=116; 76 males, 40 females; mean age 6y 3mo, SD 12mo, range 4y 8mo–7y 7mo) was performed. Gross motor capacity was assessed by the Gross Motor Function Measure (GMFM‐66). Daily‐life mobility was assessed using the Pediatric Evaluation of Disability Inventory (PEDI): Functional Skills Scale (FSS mobility) and Caregiver Assistance Scale (CAS mobility). Severity of CP was classified by the Gross Motor Function Classification System (48% level I, 17% level II, 15% level III, 8% level IV, 12% level V), type of motor impairment (85% spastic, 12% dyskinetic, 3% ataxic), and limb distribution (36% unilateral, 49% bilateral spastic). Results Scores on the GMFM‐66 explained 90% and 84% respectively, of the variance of scores on PEDI‐FSS mobility and PEDI‐CAS mobility. Limb distribution moderated the relationship between scores on the GMFM‐66 and the PEDI‐FSS mobility, revealing a weaker relationship in children with unilateral spastic CP (24% explained variance) than in children with bilateral spastic CP (91% explained variance). Interpretation In children aged 4 to 7 years with unilateral spastic CP, dissociation between gross motor capacity and daily‐life mobility can be observed, just as in typically developing peers.     

A Sensitive Assay for Studying Dopaminergic Activity in Cultures of Rat Pituitary Cells

The dopaminergic and antidopaminergic activity of drags is frequently assayed in pituitary cell cultures. Here we describe a modified version of the assay based on the use of pituitary cells from prepubertal female rats. Under our experimental conditions (50000 cells well^?1, 2-day culture and 2-h drug-exposure) the assay yielded high selectivity and sensitivity for drug dopaminergic activity. D₂ agonistic activity of bromocriptine could be observed at a concentration as low as 10^?15 m, the antagonistic activity of haloperidol at 10^?16 m. The assay also proved reproducible and simple enough for routine screening of dopaminergic activity. The assay enabled dopaminergic agonist and antagonist activity to be revealed at very low drug concentrations. The high sensitivity of the assay could be of advantage in studying dopaminergic activity in samples containing active substances present at low concentrations or for disclosing the activity of substances with low dopaminergic potency.     

Synthesis and conformational study of a cyclic hexapeptide analogue of somatostatin: cyclo(Phe-D-Trp-Lys-Thr-o-AMPA)

The active sequence Phe⁷-D-Trp⁸-Lys⁹-Thr¹⁰ of somatostatin has been cyclized through o-(aminomethyl)phenylacetic acid, a spacer molecule, designed to mimic a Gly-Gly dipeptide containing a cis-constrained peptide bond. The resulting analogue shows no GH-inhibition. A 2D n.m.r. study reveals conformations different from the proposed bio-active one and still sensitive to the medium (solvent).     

Importance of Heart Rate During Exercise for Response to Cardiac Resynchronization Therapy

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60–70% of patients.
Objectives: To study exercise-related factors predicting response to CRT.
Methods: We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months.
Results: We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO₂ significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3–76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0–5.7], P = 0.04) as predictive for response.
Conclusions: Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.     

Comparison of Different Regimens of Prednisone Therapy in Frequently Relapsing Nephrotic Syndrome

Abstract. The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was adminstered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received a cumulative dosage of prednisone of 10 mg/m²/day and those with steroid dependency received 19 mg/m²/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75 d); however, they were significantly shorter with short-term prednisone therapy (median 33 d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

Evaluation of a Dual Chamber Implantable Cardioverter Defibrillator for the Treatment of Atrial and Ventricular Arrhythmias

BORIANI, G., et al .: Evaluation of a Dual Chamber Implantable Cardioverter Defibrillator for the Treatment of Atrial and Ventricular Arrhythmias. Eighty-nine patients with a documented history of atrial tachyarrhythmias or fibrillation (AF) received a cardioverter defibrillator designed to selectively differentiate and treat atrial and ventricular arrhythmias. Twenty-two patients received a coronary sinus lead and, therefore, could use a separate shock vector for selective treatment of atrial tachyarrhythmias/AF. The device is designed to treat tachyarrhythmias with antitachycardia pacing (ATP) and/or shock therapy using an atrial and/or a ventricular shock vector. Patients underwent induction and shock termination of atrial or dual tachyarrhythmias (AF/VF) to verify proper device function and to measure the arrhythmia detection time with enhancements and preventive algorithms programmed On and Off, respectively. Detection time for 329 VF inductions was   2.41 ± 0.64  seconds   with enhancements On and   2.29 ± 0.47   with enhancements Off (NS). At implant or predischarge, 283 AF and/or AF/VF (121 atrial and 162 atrial/ventricular fibrillation) were induced. Shock conversion efficacy was 89.8% with AF conversion energies ranging from 0.9 to 27 J. Thirteen of the 23 patients had atrial shock conversions using the separate shock vector with an average conversion energy of   1.9 ± 1.4  J   . (range 0.5–5 J). During follow-up the efficacy of ATP on atrial tachyarrhythmias was 59% and the efficacy of delivered shocks on AF was 85%. This new dual chamber cardioverter defibrillator appropriately detected and classified atrial arrhythmias, and shock therapy for AF was highly effective. The detection algorithm differentiated atrial tachyarrhythmia/AF and did not delay VF detection. The separate shock vector converted induced AF with energies ranging from 0.6 to 5 J. (PACE 2003; 26[Pt. II]:461–465)