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Biomedical subjects

S Pahernik

Publications and source records attributed to S Pahernik.

At least 19 recordsLinked to original sources

[Urethroplasty and simultaneous perineal prostatectomy after traumatic urethral disruption and carcinoma of the prostate].

We present a case of post-traumatic posterior urethral stricture and localized prostate cancer, which could be treated successfully with simultaneous radical perineal prostatectomy and membranous urethral stricture excision. After 6 months follow-up, the patient is continent with no evidence of stricture recurrence. Post-traumatic posterior urethral strictures can be managed surgically through a perineal approach with high success rates. Prostate surgery after pelvic fracture with posterior urethral distraction defects does not necessarily lead to stress urinary incontinence.

Abdominal Injuries↗

Pudendal nerve branch injury during radical perineal prostatectomy.

We report the first case of direct surgical injury to a pudendal nerve branch during radical perineal prostatectomy. A 65-year-old patient presented with typical symptoms of a pudendal nerve lesion after radical perineal prostatectomy. As the patient did not respond to conservative treatment, surgical exploration and exeresis of the injured sensory branch of the pudendal nerve was necessary, resulting in pain improvement. Urologic surgeons should be aware of the typical symptoms after iatrogenic injury to the pudendal nerve or its branches. Early diagnosis and neurosurgical intervention are important to obtain a more favorable outcome.

Aged↗

[Drug therapy of female urinary incontinence].

Drug treatment for female urinary incontinence requires a thorough knowledge of the differential diagnosis and pathophysiology of incontinence as well as of the pharmacological agents employed. Pharmacotherapy has to be tailored to suit the incontinence subtype and should be carefully balanced according to efficacy and side effects of the drug. Women with urge incontinence require treatment that relaxes or desensitizes the bladder (antimuscarinics, estrogens, alpha-blockers, beta-mimetics, botulinum toxin A, resiniferatoxin, vinpocetine), whereas patients with stress incontinence need stimulation and strengthening of the pelvic floor and external sphincter (alpha-mimetics, estrogens, duloxetine). Females with overflow incontinence need reduction of outflow resistance (baclofen, alpha-blockers, intrasphincteric botulinum toxin A) and/or improvement of bladder contractility (parasympathomimetics). If nocturia or nocturnal incontinence are the major complaints, control of diuresis is obtained by administration of the ADH analogue desmopressin. Future developments will help to further optimize the pharmacological therapy for female urinary incontinence.

Adrenergic alpha-Antagonists↗

[Changes in the receptor profile of the aging bladder].

Future demographic developments will challenge urology with a steadily increasing incidence of lower urinary tract symptoms (LUTS) derived from the aging bladder. Obstruction, instability and hypocontractility, which may be caused by changes in the receptor profile of the detrusor, are typical pathophysiologic findings in geriatric bladder dysfunction. Benign prostatic hyperplasia and diabetes mellitus are age-associated comorbidities with an additional influence on bladder receptors. Muscarinic (M(2), M(3)), purinergic (P2X, P2Y) and adrenergic receptors (alpha(1), beta(3)) are targets of efferent sympathetic and parasympathetic bladder innervation. Although the results from animal experiments are somewhat inconsistent, aging and bladder outlet obstruction (BOO) probably cause partial cholinergic denervation of the detrusor with a subsequent upregulation of muscarinic receptor sensitivity leading to bladder instability. The non-cholinergic (atropine-resistant) component of the detrusor contraction rises with aging and BOO to 50%, emphasizing the increasing impact of purinergic receptors in geriatric LUTS. alpha(1)-adrenergic receptors are modulated in the aging bladder by a shift from the predominant alpha(1a) subtype to the alpha(1d) subtype, which shows 100-fold higher affinity towards norepinephrine and increases alpha-adrenergic bladder susceptibility. No data are available on the changes in beta(3) receptor density or sensitivity with aging. Moreover, the role of sensory C-fiber receptors in geriatric LUTS remains completely unclear, although specific C-fiber blockers are already under clinical evaluation (capsaicin, resiniferatoxin).

Aged↗

Complete gangrene of penis in patient with arterial vascular disease.

We present a clinical case of distal penile gangrene in a patient with peripheral vaso-occlusive disease that did not correlate with the extension of the intraoperative finding and required total penectomy. Surgical intervention at the onset of wet gangrene avoids the complication of sepsis.

Blood Coagulation Disorders↗

Mainz Pouch II technique: 10 years' experience.

OBJECTIVE: To report the long-term results with the Mainz Pouch II procedure. PATIENTS AND METHODS: Between 1990 and 2000 a Mainz Pouch II ureterosigmoidostomy was used in 123 patients (49 females and 74 males, mean age 43.6 years, range: 1-73). The indications for urinary diversion were cystectomy for bladder cancer in 92 patients, bladder exstrophy and/or incontinent epispadias in 26, irreparable traumatic loss of the sphincteric urethra in four and cloacal malformation (sinus urogenitalis) in one. In all, 102 patients with a follow-up of >/= 12 months were evaluated (mean 46.2 months). RESULTS: Day- and night-time continence rates were 97% and 95%, respectively. The remaining patients occasionally lose some drops of urine during coughing or straining, or reported minimal soiling of undergarments during the night. The mean voiding frequency was six during the day and once at night. There were 14 ureteric implantation stenoses (7.2% of 194 evaluated reno-ureteric units) and they were treated successfully by open repair (13) or antegrade balloon dilation (one). For metabolic disturbances, 69% of the patients had a capillary base excess of <-2.5 mmol/L and use oral alkalinizing drugs to prevent hyperchloraemic acidosis. There was no clinically evident metabolic acidosis. CONCLUSION: Applying the principles of detubularization and spherical reconfiguration to create a low-pressure reservoir and stratifying ureteric implantation between submucosal and serous-lined extramural tunnel techniques succeeded in giving better continence rates and long-term preservation of the upper urinary tract than a classical ureterosigmoidostomy. The Mainz Pouch II ureterosigmoidostomy is simple and reliable as a viable alternative for continent urinary diversion in selected patients.

Adolescent↗

Soluble complement receptor 1 preserves endothelial barrier function and microcirculation in postischemic pancreatitis in the rat.

Components of the activated complement cascade are considered to play a pivotal role in ischemia-reperfusion-induced organ injury. With the use of intravital epifluorescence microscopy, we investigated the effect of complement inhibition by the recombinant soluble complement receptor 1 (sCR1; TP10) on the effect of macromolecular microvascular permeability, functional capillary perfusion, and leukocyte endothelium interaction in postischemic pancreatitis. Anaesthetized Sprague-Dawley rats were subjected to 60 min of normothermic pancreatic ischemia induced by microclipping of the blood-supplying arteries of the organ. Rats who received sCR1 (15 mg/kg body wt iv; n = 7) during reperfusion showed a significant reduction of permeability (1.77 +/- 1.34 x 10(-8) cm/s; n = 7) of tetramethylrhodamine isothiocyanate-labeled albumin injected 90 min after the onset of reperfusion compared with vehicle-treated animals (6.95 +/- 1.56 x 10(-8) cm/s; n = 7). At 120 min after the onset of reperfusion, the length of red blood cell-perfused capillaries (functional capillary density) was significantly improved (from 279 +/- 15.7 to 330 +/- 3.7 cm(-1); n = 7) and the number of leukocytes adherent to postcapillary venules was significantly reduced (from 314 +/- 87 to 163 +/- 71 mm(-2); n = 7) by sCR1 compared with vehicle treatment. Complement inhibition by sCR1 effectively ameliorates pancreatic ischemia-reperfusion-induced microcirculatory disturbances and might be considered for treatment of postischemic pancreatitis.

Animals↗

[Epidemiology and etiology of overactive bladder].

Bladder overactivity (OAB) is a common disease with a socioeconomic impact comparable to diabetes mellitus. As life expectancy rises in industrialized countries the importance of OAB will further increase. The International Continence Society (ICS) recently reported a modified terminology for lower urinary tract function and established the symptom-based term OAB. The etiology of OAB comprises neurogenic and non-neurogenic detrusor hyperactivity as well as detrusor hypersensitivity. Neurogenic detrusor hyperactivity may be caused by insufficient cortical inhibition, degenerative neuropathies, and spinal cord lesions, whereas bladder aging, bladder outlet obstruction, and chronic bladder irritation (UTI, stones, tumors) are possible causes for non-neurogenic detrusor hyperactivity. Since most epidemiologic surveys focus on urge incontinence without considering urgency frequency without incontinence, epidemiologic data concerning OAB are rare. Two recently published multinational prevalence studies from Europe and Asia show different prevalence values [Europe: 15.6% (men), 17.4% (women); Asia: 53.1%(women)], which may be due to methodological differences. Both studies report an increase of OAB prevalence corresponding with age. The cumulative incidence of OAB is rising faster in aging males than in aging females. Two-thirds of the European and one-fourth of the Asian individuals affected by OAB complained about impaired quality of life, but only 60% of the European and 21% of the Asian sufferers have talked to a doctor or sought treatment. One out of four patients visiting their health care professional for OAB symptoms is currently under medication. To avoid high treatment costs and side effects, pharmacotherapy (e.g., antimuscarinics) should only be given after detailed diagnostic evaluation.

Adolescent↗

[Diabetes mellitus and bladder function. What should be considered?].

Increasing prevalence of diabetes mellitus and rising patient life expectancy are causing an accumulation of urologic late complications-despite or due to steadily improving medical health care. The prevalence of diabetic cystopathy (impaired bladder sensation, increased bladder capacity, sometimes accompanied by voiding difficulties and residual urine) is 25% in non-insulin-dependent diabetics and 48% in insulin-dependent diabetics. Autonomic and peripheral neuropathy lead to detrusor hyposensitivity, and chronic overstretching of the bladder causes myogenic detrusor hypocontractility. Since diabetic cystopathy often develops insidiously and asymptomatically, prevention of secondary complications such as recurrent urinary tract infections, vesicorenal reflux, nephrolithiasis, and pyelonephritis requires the urologist's full attention as well as early and repeated urodynamic diagnostics. Comorbidities can lead to a variety of urodynamic findings. Therapeutic options are generally conservative (timed voiding, micturition training, CIC, pharmacotherapy) and should be part of an integrated interdisciplinary health care approach since undiscovered complications involving non-urologic organ systems create a higher long-term socioeconomic burden than preventive support provided by other specialists.

Diabetes Mellitus↗

[The disturbing development of resistance in urinary tract infections].

Despite recent caveats about the rapid development of resistance to fluoroquinolones in the treatment of urinary tract infections (UTI), the good tolerability, bioavailability and the broad antibiotic spectrum of fluoroquinolons explain their increased use. We investigated the changes of bacterial spectra and cross resistance profiles in ambulatory and hospitalized UTI patients. A total of 430 positive urine cultures and resistograms were classified according to patient status as either ambulatory or hospitalized and retrospectively analyzed. Cross-resistance profiles of the most effective antibiotics (cotrimoxazol, levofloxacin, amoxicillin/clavulanic acid) were made before an analysis of cost-effectiveness was performed. Whereas Escherichia coli remains the predominant cause of UTI in ambulatory patients, Enterococcus faecalis is the most frequently detected bacterium in the urine cultures of hospitalized patients. This is one reason for the unacceptably high rate of primary resistance of UTI bacteria against cephalosporins. Primary resistance to cotrimoxazol, amoxicillin/cavulanic acid and levofloxacin are impressive and tend to favor the use of levofloxacin. However, high cross-resistance rates reduce the usability of one antibiotic in case of the lack of effectiveness of the other. The broad use of potent antibiotics in hospitals has led to a higher primary resistance and cross-resistance of UTI bacteria in hospitalized patients than in ambulatory patients. The primary resistance of UTI causing bacteria is generally high and worrying. The new fluoroquinolone levofloxacin exhibits surprisingly high primary resistance rates and shares high cross-resistance with other antibiotics that are as effective but much cheaper. Thus, we consider that it should not be a first line treatment option for ambulatory UTI patients in the absence of any resistogram, in order to ensure cost-effectiveness and a slow down in the rapid development of resistance.

Adolescent↗

Orthogonal polarisation spectral imaging as a new tool for the assessment of antivascular tumour treatment in vivo: a validation study.

Tumour angiogenesis plays a key role in tumour growth, formation of metastasis, detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour angiogenesis is an indispensable prerequisite for developing novel treatment strategies such as anti-angiogenic and antivascular treatment options. Therefore, it was our aim to establish and validate a new and versatile imaging technique, that is orthogonal polarisation spectral imaging, allowing for non-invasive quantitative imaging of tumour angiogenesis in vivo. Experiments were performed in amelanotic melanoma A-MEL 3 implanted in a transparent dorsal skinfold chamber of the hamster. Starting at day 0 after tumour cell implantation, animals were treated daily with the anti-angiogenic compound SU5416 (25 mg kg x bw(-1)) or vehicle (control) only. Functional vessel density, diameter of microvessels and red blood cell velocity were visualised by both orthogonal polarisation spectral imaging and fluorescence microscopy and analysed using a digital image system. The morphological and functional properties of the tumour microvasculature could be clearly identified by orthogonal polarisation spectral imaging. Data for functional vessel density correlated excellently with data obtained by fluorescence microscopy (y=0.99x+0.48, r2=0.97, R(S)=0.98, precision: 8.22 cm(-1) and bias: -0.32 cm(-1)). Correlation parameters for diameter of microvessels and red blood cell velocity were similar (r2=0.97, R(S)=0.99 and r2=0.93, R(S)=0.94 for diameter of microvessels and red blood cell velocity, respectively). Treatment with SU5416 reduced tumour angiogenesis. At day 3 and 6 after tumour cell implantation, respectively, functional vessel density was 4.8+/-2.1 and 87.2+/-10.2 cm(-1) compared to values of control animals of 66.6+/-10.1 and 147.4+/-13.2 cm(-1), respectively. In addition to the inhibition of tumour angiogenesis, tumour growth and the development of metastasis was strongly reduced in SU5416 treated animals. This new approach enables non-invasive, repeated and quantitative assessment of tumour vascular network and the effects of antiangiogenic treatment on tumour vasculature in vivo. Thus, quantification of tumour angiogenesis can be used to more accurately classify and monitor tumour biologic characteristics, and to explore aggressiveness of tumours.

Angiogenesis Inhibitors↗

Quantitative imaging of tumour blood flow by contrast-enhanced magnetic resonance imaging.

Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T(1)-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 x 250 microm(2). Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future.

Animals↗

Neoadjuvant photodynamic therapy before curative resection of proximal bile duct carcinoma.

BACKGROUND: Hilar bile duct carcinoma has an 80% probability of local recurrence after curative resection, which might be reduced if neoadjuvant photodynamic therapy is feasible. CASE AND TREATMENT: After intravenous injection of sodium porfimer we treated an adenocarcinoma of the proximal common bile duct (T2 N0 M0, Bismuth type II) in a 72-year-old man with red laser light (applied from the lumen at a dose 250 Joules/cm2), and the adjacent right and left hepatic and common bile duct at a dose of 125 Joules/cm2. After 23 days the tumor was completely resected (adenocarcinoma pT2 pNO; G2). RESULTS: In the lumenal, 4-mm-thick layer the bile duct specimen exhibited complete tumor necrosis with pigmentation of photodegraded porfimer and no viable tumor cells, while in the outer layer of the wall (at 5-8-mm depth) viable cancer cell nests without degraded porfimer were seen. The bile duct tissue showed little damage. Eighteen months after surgery, neither tumor recurrence nor stricture formation was found at the pretreated bilioenteric anastomoses. CONCLUSIONS: a) Photodynamic therapy with sodium porfimer seems to be confined to the superficial 4-mm layer of bile duct cancer. b) Neoadjuvant photodynamic therapy is feasible for hilar bile duct carcinoma.

Adenocarcinoma↗

New non-woven polyurethane-based biomaterials for the cultivation of hepatocytes: expression of differentiated functions.

A new non-woven polyetherurethane support suitable to host cultured hepatocytes has been developed. Prior to its use in bioreactors and artificial liver devices, the biocompatibility of this new material was investigated. The experiments have shown that the survival and functionality of hepatocytes entrapped in the non-woven polymer were longer than that of monolayer cultured hepatocytes, under serum-free culture conditions. Hepatic specific metabolic functions, namely, synthesis of urea and synthesis and secretion of plasma proteins, were well maintained by hepatocytes entrapped in non-woven polyetherurethane sheets. Cells also retained the expression of biotransformation activities of 7-ethoxycoumarin-O-deethylase as well as CYP2A1, CYP2B1 and CYP3A1. The results presented in this paper point to non-woven polyetherurethane sheets as a suitable biocompatible support for functional, three-dimensional hepatocyte cultures.

Journal Article↗

Active and higher intracellular uptake of 5-aminolevulinic acid in tumors may be inhibited by glycine.

Topical 5-aminolevulinic acid is used for the fluorescence-based diagnosis and photodynamic treatment of superficial precancerous and cancerous lesions of the skin. Thus, we investigated the kinetics of 5-aminolevulinic acid-induced fluorescence and the mechanisms responsible for the selective formation of porphyrins in tumors in vivo. Using amelanotic melanomas (A-Mel-3) grown in dorsal skinfold chambers of Syrian golden hamsters fluorescence kinetics were measured up to 24 h after topical application of 5-aminolevulinic acid (1%, 3%, or 10%) for 1 h, 4 h, or 8 h by intravital microscopy (n = 54). Maximal fluorescence intensity in tumors after 1 h application (3% 5-aminolevulinic acid) occurred 150 min and after 4 h application (3% 5-aminolevulinic acid) directly thereafter. Increasing either concentration of 5-aminolevulinic acid or application time did not yield a higher fluorescence intensity. The selectivity of the fluorescence in tumors decreased with increasing application time. Fluorescence spectra indicated the formation of protoporphyrin IX (3% 5-aminolevulinic acid, 4 h; n = 3). The simultaneous application of 5-aminolevulinic acid (3%, 4 h) and glycine (20 microM or 200 microM; n = 10) reduced fluorescence in tumor and surrounding host tissue significantly. In contrast, neither decreasing iron concentration by desferrioxamine (1% and 3%; n = 10) nor inducing tetrapyrrole accumulation using 1, 10-phenanthroline (7.5 mM; n = 5) increased fluorescence in tumors. The saturation and faster increase of fluorescence in the tumor together with a reduction of fluorescence by the application of glycine suggests an active and higher intracellular uptake of 5-aminolevulinic acid in tumor as compared with the surrounding tissue. Shorter application (1 h) yields a better contrast between tumor and surrounding tissue for fluorescence diagnosis. The additional topical application of modifiers of the heme biosynthesis, desferrioxamine or 1,10-phenanthroline, however, is unlikely to enhance the efficacy of topical 5-aminolevulinic acid-photodynamic therapy at least in our model.

Aminolevulinic Acid↗

Formation of cholic acid and chenodeoxycholic acid from 7 alpha-hydroxycholesterol and 27-hydroxycholesterol by primary cultures of human hepatocytes.

It has been suggested that chenodeoxycholic acid is preferentially formed by the alternative or 'acidic' pathway of bile acid biosynthesis starting with 27-hydroxylation of cholesterol, while cholic acid is derived from 7 alpha-hydroxycholesterol which initiates the 'neutral' pathway. We have studied bile acid formation from each of these precursors using human hepatocytes cultured in a novel sandwich collagen configuration. Culture supernatants were analyzed using capillary gas chromatography and gas chromatography-mass spectrometry. 27-Hydroxycholesterol and 7 alpha-hydroxycholesterol were both found to be efficiently converted to cholic acid as well as chenodeoxycholic acid. Analysis of acidic intermediates after addition of 7 alpha-hydroxycholesterol to the cultures revealed a significant increase of side-chain oxygenated C24- and C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure. These data indicate that (i) the 'neutral' pathway is connected to the 'acidic' pathway by side-chain oxidation of C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure and that (ii) the relative formation of cholic acid and chenodeoxycholic acid is regulated by metabolic events distal to the initial hydroxylation at either position 7 or position 27 of the cholesterol molecule.

Adult↗