The long-term learning curve of holmium laser enucleation of the prostate (HoLEP) in the en-bloc technique: a single surgeon series of 500 consecutive cases.

PURPOSE: To evaluate perioperative parameters, clinical outcomes, and the learning curve of holmium laser enucleation of the prostate (HoLEP) of a single surgeon in 500 consecutive cases. METHODS: Demographic parameters, outcomes, and adverse events were evaluated. The learning curve for HoLEP in en-bloc technique of the first 500 consecutive patients was analyzed in clusters of 100 (clusters 1-5) using the Wilcoxen rank test, Chi² test and Kruskal Wallis test. RESULTS: Enucleation weight was similar in the clusters 1,2,3, and 5 (62 g, 63 g, 61 g, 61 g), in cluster 4 it was slightly higher at 73 g. There was a significant reduction in operating time from 67 min (cluster 1) to 57 min (cluster 2), 46 min (cluster 3), 53 min (cluster 4), and 43 min (cluster 5), p < 0.001. Enucleation efficiency (g/min) showed a steady increase (1.72, 2.24, 2.79, 2.92 vs. 2.99, p < 0.001). Laser energy efficiency also improved (2.17 vs. 2.12 vs. 1.71 vs. 1.65 vs. 1.55; p < 0.001). There was no measurable learning curve regarding the length of hospital stay (mean 2.5 days), catheterization time (1.9 days), hemoglobin drop (approx. 1 g/dl) or complications (p > 0.1). CONCLUSIONS: HoLEP using the en-bloc technique is a safe and highly effective method. Over time, a slight but steady learning curve and improvement in operation time, enucleation efficiency and laser energy efficiency were shown even for an experienced surgeon - after 500 cases, still no plateau was reached. There was no measurable learning curve regarding blood loss, complications, length of hospital stay, and catheterization time.

[S3 guidelines on "full-term vaginal birth" from an anesthesiological perspective : Worthwhile knowledge for anesthesiologists]. / S3-Leitlinie "Vaginale Geburt am Termin" aus anästhesiologischer Sicht : Wissenswertes für den Anästhesisten.

The publication of the new S3 guidelines on "full-term vaginal birth" and the guidelines on cesarean section, also published in 2020, provide further steps towards the promotion of evidence-based medicine in obstetrics, even if the exact configuration of neonatal monitoring during birth, in particular, is still the subject of current discussions. The multiprofessionality in the medical supervision of a birth is also fundamentally well-represented in the compilation of the S3 guidelines by the participating actors and specialist societies. Important from an anesthesiological perspective is the fact that neuraxial procedures still represent the gold standard in obstetric analgesia. With remifentanil PCA an alternative option is available that enables a reliable analgesia to be accomplished, e.g. when there are contraindications to performing neuraxial methods, if this is appropriate under the prevailing circumstances (1:1 support and appropriate monitoring). During an uncomplicated birth the strict fasting rules are relaxed. Overall, the guidelines underline the importance of self-determination and self-control for the expectant mother and give the highest priority to the safety and well-being of mother and child; however, this presupposes that the expectant mother is sufficiently informed about the value of neuraxial analgesia. For this it appears to be of importance to initiate information proposals, which go beyond the usual information sessions for parents that are often organized exclusively by midwives.

[Non-cardiac surgery in adults with congenital heart defects : Most important parameters in anesthesia management]. / Nichtkardiale Eingriffe bei Erwachsenen mit angeborenen Herzfehlern : Wichtigste Parameter des anästhesiologischen Managements.

BACKGROUND: Adults with congenital heart disease (CHD) represent an increasing proportion of patients undergoing non-cardiac surgery. OBJECTIVE: To identify the most important parameters for management of anesthesia. MATERIAL AND METHODS: Evaluation and discussion of the current original research and guideline recommendations. RESULTS: There are approximately 300,000 patients with CHD living in Germany. The preoperative evaluation is an important influencing factor affecting perioperative morbidity and mortality. Echocardiography is the key instrument for identifying cardiac conditions predisposing to adverse events. The subdivision of CHD into lesions with left-to-right shunt, obstructive lesions and complex congenital heart diseases facilitates the classification of the pathophysiology. CONCLUSION: Decisive for the perioperative outcome of patients with CHD are the identification of high-risk patients, understanding of the individual situation with respect to the underlying pathophysiology and the intraoperative maintenance of cardiac output.

Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance.

Human infections with tick-borne encephalitis (TBE)virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here,we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones,but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.

[Pelvic floor reconstruction-update 2024: prolapse-associated symptoms and their treatment]. / Rekonstruktive Beckenbodenchirurgie ­ Update 2024: prolapsassoziierte Symptome und deren Heilung.

Pelvic organ prolapse (POP) and associated symptoms of urinary incontinence, fecal incontinence, obstructive micturition, defecation, and pain are frequent and a widespread disease with relevant reduction of quality of life and high costs. New insights into functional anatomy and pathophysiology of these pelvic floor dysfunctions let us recognize how ligamentous laxities/defects lead to these dysfunctions. Results of the PROpel study (ClinicalTrials.gov-Identifier: NCT00638235) are shown in which a detailed observation of symptoms (patient-related outcome measures) pre- and postoperatively was performed. Ligamentous vaginal repair of POP enables symptom cure in high percentages for urinary urge incontinence (up to 82%), nocturia (up to 92%), obstructive micturition (up to 87%), fecal incontinence (58-72%), obstructive defecation (71-84%), and pain (53-90%), if caused by POP. Women with POP­Q stage 2 have similar symptom frequencies as women with POP­Q stage 3-4, and also similar cure rates of their symptoms. If good anatomical prolapse repair (in responders) was achieved, the cure rates for obstructive micturition, urinary urgency incontinence, and nocturia were significantly higher than in those women with less effective surgical repair. In the future, pelvic floor surgery should have symptom cure as the primary objective and should lead to improved quality of life. The different, currently performed techniques for POP repair have to be investigated concerning this matter.

Long-term quality of sleep after remifentanil-based anaesthesia: a randomized controlled trial.

BACKGROUND: Clinical and pre-clinical data agree that opioids disrupt sleep architecture. Recently, remifentanil has been suggested to cause possible long-term disturbances of sleep quality. This randomized controlled clinical trial was designed to substantiate or refute a possible long-term effect of remifentanil on the quality of sleep. METHODS: One hundred patients undergoing elective surgery were randomized to receive either fentanyl or remifentanil-based anaesthesia. Before operation (T0) and 3 (T3) and 6 (T6) months after operation, the quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Overall, the quality of sleep for patients in the remifentanil or fentanyl group was not significantly different at any time point. Patients in the fentanyl group screened as good sleepers before operation showed no differences across time course of the study in PSQI scores. In contrast, good sleepers in the remifentanil group had significantly impaired sleep quality for at least 3 months after operation. Patients who were before operation screened as poor sleepers showed no significant changes in PSQI scores at T3 and T6 in both groups. CONCLUSIONS: The intraoperative use of remifentanil in a general patient population does not significantly alter the quality of sleep in the postoperative period. However, it may result in a significant reduction in the quality of sleep in patients before operation considered good sleepers. These changes were not observed in the group of patients receiving fentanyl. The relevance of these findings in terms of patient recovery and quality-of-life warrants further investigation. Trial Registration. ACTRN12610000362099.

Hormonal male contraception in men with normal and subnormal semen parameters.

Hormonal male contraception based on testosterone alone or on a combination of testosterone with a gestagen has been shown to suppress spermatogenesis effectively and to be fully reversible. However, clinical studies to date have only included volunteers with so-called 'normal' semen values by WHO standards. As a male contraceptive should be available to all interested men regardless of their semen parameters, we investigated how volunteers with subnormal semen parameters would respond to hormonal male contraception. During a 34-week treatment phase, the volunteers received injections of 1000 mg testosterone undecanoate in weeks 0, 6, 14 and 24. This was followed by a 24-week recovery and follow-up period. As it was not known whether men with subnormal semen parameters would recover to starting levels, cryopreservation of semen was offered to all subnormal volunteers. Twenty-three men with normal semen parameters and 18 with sperm counts below 20 million completed the trial. The normal volunteers showed the expected response with 17 suppressing sperm counts below 1 million/ejaculate (13 showing azoospermia) and six not-suppressing below 1 million sperm/ejaculate. By the end of the recovery period, all sperm counts had returned to the range of starting values. The subnormal group showed a similar pattern with 13 of 18 (= 72%) men suppressing below 1 million/ejaculate (8/18 = 44% showing azoospermia) and the remaining 5 of 18 (= 28%) not-suppressing sperm counts below 1 million/ejaculate. All sperm counts returned to the starting range. The study shows that in Caucasian men with normal sperm counts as well as in men with subnormal sperm counts, testosterone alone can produce azoospermia in about half and suppression below one million in about two-thirds of the volunteers. The same proportion of men in both groups appears to require an additional gestagen for full contraceptive protection. Most importantly, regarding suppressibility and reversibility, volunteers with normal and subnormal sperm counts display the same pattern.

Tenascin-C suppresses Rho activation.

Cell binding to extracellular matrix (ECM) components changes cytoskeletal organization by the activation of Rho family GTPases. Tenascin-C, a developmentally regulated matrix protein, modulates cellular responses to other matrix proteins, such as fibronectin (FN). Here, we report that tenascin-C markedly altered cell phenotype on a three-dimensional fibrin matrix containing FN, resulting in suppression of actin stress fibers and induction of actin-rich filopodia. This distinct morphology was associated with complete suppression of the activation of RhoA, a small GTPase that induces actin stress fiber formation. Enforced activation of RhoA circumvented the effects of tenascin. Effects of active Rho were reversed by a Rho inhibitor C3 transferase. Suppression of GTPase activation allows tenascin-C expression to act as a regulatory switch to reverse the effects of adhesive proteins on Rho function. This represents a novel paradigm for the regulation of cytoskeletal organization by ECM.

13-cis-retinoic acid: inhibition of bladder carcinogenesis in the rat.

Transitional cell and squamous cell cancer of the bladder was induced in Wistar/Lewis female rats by direct instillation of N-methyl-N-nitrosourea into the bladder. Feeding of the synthetic retinoid, 13-cis-retinoid acid, inhibited the incidence and extent of bladder cancer in these rats, even when 13-cis-retinoic acid administration was begun after completion of the carcinogen treatment.

Feasibility of infusion pumps for continuous spinal administration of local anesthetics in post-operative pain therapy.

BACKGROUND AND OBJECTIVES: For completion of perioperative care and for general ethical considerations, any intraoperatively used catheter technique should be utilizable for post-operative pain therapy. Continuous spinal anesthesia (CSA) is an established form of local anesthetic application. However, for its use in post-operative therapy, infusion pumps are required that are technically able to deliver low rates and are distinctive in design to avoid possible pump or medication swaps. Because of a lack of devices specifically designed for CSA, we investigated the potential deployability of infusion pumps for post-operative pain therapy via CSA microcatheters, which were originally designed and approved for different applications. METHODS: The accuracy of infusion rates of three different pumps was measured in a liquor model environment. Furthermore, we investigated safety and user-friendliness by interviewing 30 anesthesiologists and 15 pain nurses. RESULTS: Except for the first hour of infusion, all pumps provided comparable and adequate flow profiles. However, interviews revealed significant risk factors for all pumps in terms of swapping devices, lines or medications and misprogramming the units. DISCUSSION: All pumps tested were technically able to deliver accurate flow rates; however, because the non-CSA-specific design involves the risk of medication overdosage and syringe swaps, none of the systems tested can be recommended for routine use in post-operative CSA, irrespective of the fact that it was an off-label application anyway. Therefore, to ensure patient safety, continuous spinal administration of local anesthetics via microcatheters is a questionable method of post-operative pain therapy as long as non-specific pumps are used.

[Scoliosis surgery in children from the viewpoint of anaesthesiology]. / Skoliosechirurgie bei Kindern aus anästhesiologischer Sicht.

Anaesthesia for scoliosis surgery in children is a challenge for the paediatric anaesthesiologist. The large range of underlying pathologies causing deranged physiology in an inhomogeneous patient group ranging from neonates to adolescents necessitates diligent and individual preparation for each case. Due to the invasiveness of the operation demanding anaesthetic care is necessary. This review highlights current approaches to monitoring, anaesthetic regimen, positioning of the patient, blood conservation and transfusion, age-related pathophysiology, ventilation and postoperative pain therapy. The introduction of neurophysiologic spinal cord monitoring requires certain adaptations of the anaesthetic regimen to suit technological advances.

Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin.

Coordination between sequential steps in synaptic vesicle endocytosis, including clathrin coat formation, fission, and uncoating, appears to involve proteinprotein interactions. Here, we show that compounds that disrupt interactions of the SH3 domain of endophilin with dynamin and synaptojanin impair synaptic vesicle endocytosis in a living synapse. Two distinct endocytic intermediates accumulated. Free clathrin-coated vesicles were induced by a peptide-blocking endophilin's SH3 domain and by antibodies to the proline-rich domain (PRD) of synaptojanin. Invaginated clathrin-coated pits were induced by the same peptide and by the SH3 domain of endophilin. We suggest that the SH3 domain of endophilin participates in both fission and uncoating and that it may be a key component of a molecular switch that couples the fission reaction to uncoating.

PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse.

Disruption of the presynaptically enriched polyphosphoinositide phosphatase synaptojanin 1 leads to an increase of clathrin-coated intermediates and of polymerized actin at endocytic zones of nerve terminals. These changes correlate with elevated levels of PI(4,5)P(2) in neurons. We report that phosphatidylinositol phosphate kinase type Igamma (PIPKIgamma), a major brain PI(4)P 5-kinase, is concentrated at synapses. Synaptojanin 1 and PIPKIgamma antagonize each other in the recruitment of clathrin coats to lipid membranes. Like synaptojanin 1 and other proteins involved in endocytosis, PIPKIgamma undergoes stimulation-dependent dephosphorylation. These results implicate PIPKIgamma in the synthesis of a PI(4,5)P(2) pool that acts as a positive regulator of clathrin coat recruitment and actin function at the synapse.

Gender differences in serotype 2 adeno-associated virus biodistribution after administration to rodent salivary glands.

Salivary glands (SGs) have proven useful targets for clinical applications of gene therapeutics. In this toxicology and biodistribution study, which conforms to U.S. Food and Drug Administration Good Laboratory Practice regulations, four doses (10(7)-10(10) particles) of a serotype 2 adeno-associated viral (AAV2) vector encoding human erythropoietin were directly administered to the right submandibular gland of male and female BALB/c mice (n = 21 per gender dose group). Control-treated (saline administered; n = 66) and vector-treated (n = 168) animals did not differ in clinical appearance, morbidity and mortality rates, food and water consumption, weight gain ratios, and final weight. Clinical hematology values also were unaffected by AAV2 administration except for parameters influenced by the expression of the recombinant protein (e.g., hematocrit). Mice were killed on days 3, 30, 55, and 92. No major vector-related toxicity was uncovered after complete pathology and histopathology review. However, a significant gender-related difference in vector biodistribution was revealed by quantitative polymerase chain reaction. In male mice vector (group receiving 10(10) particles/animal) effectively transduced, and was primarily confined within, the SGs (i.e., approximately 800 times more copies in SGs than in liver; day 3) and long lived. In contrast, in female mice, SG transduction was less efficient (260-fold less than in males; day 3) and short lived, and vector was disseminated widely via both the bloodstream (SG:liver copy ratio, approximately 1) and saliva (30-fold greater than in males). The observed vector biodistribution is likely due to differences in AAV2 receptor targets and structural differences affecting SG integrity. Sexual dimorphism is a factor of major significance that could potentially affect gene therapy clinical applications in SGs.

Activated K-ras and N-ras oncogenes in primary renal mesenchymal tumors induced in F344 rats by methyl(methoxymethyl)nitrosamine.

Administration of methyl(methoxymethyl)nitrosamine to newborn Fischer 344 rats results in the preferential induction of renal tumors arising from the mesenchymal component of the kidney. DNA from a significant proportion of these tumors was capable of transforming NIH/3T3 cells. This report describes the renal tumor model, the detection of two different ras transforming genes in the kidney tumors (the N-ras oncogene in 1 and K-ras oncogene in 10 kidney tumors) and the characterization of DNA sequences specifying the transformed phenotype.

A novel missense mutation responsible for factor VII deficiency in research Beagle colonies.

BACKGROUND: Canine factor VII (cFVII) deficiency, an autosomal recessive trait originally identified in research Beagles, is associated with a mild to moderate bleeding tendency. OBJECTIVE: Our aim was to identify and characterize the mutation causing cFVII deficiency. METHODS: In order to sequence the coding regions of the cFVII gene, we cloned the cFVII cDNA. Genomic DNA and plasma from FVII-deficient Beagles and obligate carriers were utilized. RESULTS: In all FVII-deficient dogs, we identified a single causative G to A missense mutation in exon 5, encoding the second epidermal growth factor-like domain, resulting in substitution of glycine 96 by glutamic acid, with plasma FVII coagulant activity of

Preventive and enhancing effects of retinoids on the development of naturally occurring tumors of skin, prostate gland, and endocrine pancreas in aged male ACI/segHapBR rats.

The effects of dietary retinoids on the development of naturally occurring tumors in retired breeder male ACI/segHapBR rats were investigated. Groups of rats (21-25 mo of age, an age when early neoplasms first appear and tumor incidences are generally low) were fed diets containing 1 of 3 retinoids--all-trans-N-4-(4-hydroxyphenyl)retinamide (4-HPR), 783 mg/kg diet; all-trans-N-(4-pivaloyloxyphenyl)retinamide (4-PPR), 951 mg/kg; or all-trans-4-N-(2-hydroxyethyl)retinamide (2-HER), 687 mg/kg--or control diet for up to 54 weeks (average, 33 wk). Rats were maintained until less than 20% remained and the experiment was terminated. Contributing causes of death were determined, and a complete necropsy was performed for each rat. There was no difference between the retinoid-treated rats and control rats in the average age at death (30-31 mo) or in the average experimental survival time (29-35 wk), in the proportions of tumor-bearing rats (95.6-100%), or in the average number of organs with tumor per rat (2.1-2.5). The incidences of pancreatic islet cell adenoma and skin tumors were significantly different between control and some retinoid-treated groups. 4-PPR and 2-HER significantly enhanced pancreatic islet cell adenoma yields (P less than .025 and 0.05, respectively) whereas 4-HPR significantly inhibited epithelial and connective tissue skin tumor yields (P less than .025). Incidences of skin and prostate tumors were lower than in controls, but not significantly, in rats receiving 4-PPR and 2-HER. Most of the islet cell adenomas were shown, by avidin-biotin-peroxidase complex immunocytochemistry, to be insulinomas. 4-HPR would seem to be the most effective retinoid in the group, inasmuch as it prevented skin tumor development, may have slightly decreased the incidence of prostate tumors, and did not enhance islet cell tumor incidence.

Expression of RNA of an endogenous replication-defective retrovirus in rat mammary adenocarcinomas induced by 7,12-dimethylbenz[a]anthracene.

An investigation into the possible relationship between chemical carcinogen induction of rat mammary tumors and the expression of an endogenous retroviral genome was initiated. Mammary tumors were induced in female SD rats with 7,12-dimethylbenz[a]anthracene (DMBA). Tumors, identified histologically as mammary adenocarcinomas, were analyzed for RNA of a replication-defective endogenous retrovirus or RNA of a helper-independent endogenous type C virus. Expression of RNA of the replication-defective virus was detected in mammary tumors weighing 0.2--2.0 g. Larger tumors, for which histologic examination revealed proportionally more fibroblastic tissue than epithelial cells, did not contain comparable concentrations of this viral RNA. RNA homologous to a helper-independent rat type C retrovirus was not detected in tumors of any size. A cell line was established from a primary DMBA-induced mammary adenocarcinoma and appeared similar to the small mammary tumors with respect to endogenous type C viral RNA expression. We discuss possible implications of the expression of endogenous replication-defective viruses for use as markers for the effects of chemical carcinogens.