Suturing methods in prolapse surgery: a biomechanical analysis.

INTRODUCTION: Pelvic organ prolapse is a common problem in urogynecological surgery. Abdominal and laparoscopic sacrocolpopexy is currently considered to be the gold standard of treatment. The main problem remains the anatomical point of fixation as well as how sutures are placed. We evaluated the biomechanical difference between an in-line ligament suture versus an orthogonal ligament suture and a single suture versus a continuous suture at the anterior longitudinal ligament in an in-vitro, sacrocolpopexy model. METHODS: Biomechanical in-vitro testing was performed on human, non-embalmed, female cadaver pelvises. An Instron test frame (tensinometer) was used for load/ displacement analysis. The average patient age was 75 years. Ligament preparation yielded 15 ligaments available for testing. Recorded parameters were the ultimate load, failure displacement, and stiffness. RESULTS: This in-vitro analysis of different suturing methods showed the difference between an orthogonal and an in-line approach to be the ultimate load. Orthogonal sutures displayed an ultimate load of 80 N while in-line suturing yielded only 57 N (p < 0.05). For the anterior longitudinal ligament, this study demonstrated that continuous suture is significantly superior to a single suture regarding failure displacement (p < 0.05). CONCLUSION: We established baseline biomechanical parameters for the sacrospinous ligament and anterior longitudinal ligament. An orthogonal suture is superior to an in-line suture in an in-vitro model. A continuous suture is superior to a single suture at the anterior longitudinal ligament. Clinical trials might be able to evaluate whether any clinical significance can be established from these findings.

Laparoscopic pectopexy: a follow-up cyclic biomechanical analysis determining time to functional stability.

INTRODUCTION: Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in previous transient testing by this group. It was shown that a single suture, yielding an ultimate load of 35 N, was equivalent to continuous suturing. This was demonstrated in an in vitro cadaver study. This transient data were used to establish an elastic stress-strain envelope. It was now possible to proceed to dynamic in vitro analysis of this surgical method to establish time to functional stability. METHODS: Cyclic testing of this fixation method was performed on human female embalmed cadaver (cohort 1) and fresh, non-embalmed cadaver (cohort 2) pelvises. The testing envelope was 5-25 N at a speed of 1 mm/s. 100 load regulated cycles were applied. RESULTS: 100 cycles were completed with each model; no overall system failure occurred. Steady state, i.e., functional stability was reached after 14.5 (± 2.9) cycles for the embalmed group and after 19.1 (± 7.2) cycles for the non-embalmed group. This difference was statistically significant p = 0.00025. CONCLUSION: This trial showed in an in vitro cyclic testing of the pectopexy method that functional stability may be achieved after no more than 19.1 cycles of load exposure. When remaining within the established load envelope of below 25 N, patients do not need to fear global fixation failure. Testing did demonstrate differences in non-embalmed and embalmed cadaver testing. Embalmed cadaver testing tends to underestimate time to steady state by 26.3%.

Laparoscopic Pectopexy: A Biomechanical Analysis.

INTRODUCTION: Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in recent literature. Further improving this approach by reducing surgical time may decrease complication rates and patient morbidity. Since laparoscopic suturing is a time consuming task, we propose a single suture /mesh ileo-pectineal ligament fixation as opposed to the commonly used continues approach. METHODS: Evaluation was performed on human non-embalmed, fresh cadaver pelves. A total of 33 trials was performed. Eight female pelves with an average age of 75, were used. This resulted in 16 available ligaments. Recorded parameters were ultimate load, displacement at failure and stiffness. RESULTS: The ultimate load for the mesh + simplified single "interrupted" suture (MIS) group was 35 (± 12) N and 48 (± 7) N for the mesh + continuous suture (MCS) group. There was no significant difference in the ultimate load between both groups (p> 0.05). This was also true for displacement at failure measured at 37 (± 12) mm and 36 (±5) mm respectively. There was also no significant difference in stiffness and failure modes. CONCLUSION: Given the data above we must conclude that a continuous suture is not necessary in laparoscopic mesh / ileo-pectineal ligament fixation during pectopexy. Ultimate load and displacement at failure results clearly indicate that a single suture is not inferior to a continuous approach. The use of two single sutures may improve ligamental fixation. However, overall stability should not benefit since the surgical mesh remains the limiting factor.

Platelet-rich plasma in the treatment of subcutaneous venous access device scars: a head-to-head patient survey.

INTRODUCTION: Platelet-rich plasma (PRP) is a product widely used in sports medicine, tissue repair, and general surgery. A recent meta-analysis showed this product to be beneficial when introduced into a wound area, be it intra-articular (i.e., joint-injections) or direct introduction onto the wound surface. METHODS: Between the years of 2012 and 2014 a questionnaire evaluating surgical outcome after port (venous access device) removal was answered by 100 patients in the control group and 20 patients in a PRP group, leading to a total of 120 patients in this single center, retrospective, subjective outcome evaluation. RESULTS: No statistical difference was shown in postsurgical complication rates, postsurgical pain, decreased mobility, and overall quality of life. A significant difference was shown in overall patient satisfaction and the desire to further improve port area scarring. Results differed significantly in favor of the PRP group. Interestingly, approximately 40.2% of patients are dissatisfied with the surgical outcome after port removal in the control group. This result, though surprising, may be improved to 10% dissatisfaction when a PRP product is used. CONCLUSION: PRP products such as Arthrex ACP are safe to use and present an additional option in improving surgical outcome.

[Transvaginal/transumbilical hybrid NOTES appendicectomy : Comparison of techniques in uncomplicated and complicated appendicitis]. / Transvaginale/transumbilikale Hybrid-NOTES-Appendektomie : Vergleich der Technik bei unkomplizierter und komplizierter Appendizitis.

BACKGROUND: Appendicectomy (AE), the most frequent emergency surgical procedure, can be performed as a transvaginal hybrid natural orifice translumenal endoscopic surgery (NOTES) technique (TVAE). The question of feasibility also arises in cases of advanced inflammation with perforation. MATERIAL AND METHODS: Since May 2012 all female patients with suspected acute appendicitis were offered a TVAE as an alternative to the standard procedure. Preoperative, intraoperative and postoperative parameters were registered prospectively. RESULTS: Until October 2013 a total of 13 TVAEs had been performed. The median age of the patients was 41 years (range 20-76 years), median BMI was 23.1 (range 18.1-28.3 kg/m(2)) and the American Society of Anesthesiologists score (ASA) distribution (I/II/≥ III) was 8/5/0. Histology revealed three cases of perforated, one hemorrhagic necrotizing and seven phlegmonous appendicitis. Furthermore, there were two findings without inflammation, namely one neurogenic appendicopathy and one neuroendocrine tumor. For the three patients with perforated appendicitis, there was a trend for higher age (67.0 years versus 33.5 years, p=0.063) and a higher C-reactive protein (CRP) level on admission (134.4 mg/l versus 26.4 mg/l, p=0.043). Also, procedural time and hospital stay were longer (64 min versus 47 min, p=0.033 and 14 days versus 3 days, p=0.004, respectively). The former was mostly due to more extensive intraoperative flushing (volume 3000 ml versus 500 ml, p=0.013 and duration 13 min versus 2 min, p=0.011). None of the cases required conversion but two of the three postoperative complications occurred in patients with perforation, which also resulted in the longer hospital stay. CONCLUSION: Technically, TVAE seems feasible also in cases of perforated appendicitis. However, in these cases procedural time is prolonged due to more extensive flushing. Whether or not the longer hospital stay can be attributed to the perforation or if TVAE results in a higher rate of complications in cases of perforated appendicitis needs further evaluation.

Cys-tRNACys formation and cysteine biosynthesis in methanogenic archaea: two faces of the same problem?

Aminoacyl-tRNA (transfer RNA) synthetases are essential components of the cellular translation machinery as they provide the ribosome with aminoacyl-tRNAs. Aminoacyl-tRNA synthesis is generally well understood. However, the mechanism of Cys-tRNACys formation in three methanogenic archaea ( Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus and Methanopyrus kandleri) is still unknown, since no recognizable gene for a canonical cysteinyl-tRNA synthetase could be identified in the genome sequences of these organisms. Here we review the different routes recently proposed for Cys-tRNACys formation and discuss its possible link with cysteine biosynthesis in these methanogenic archaea.

Lack of germline mutations in the preproglucagon gene region coding for glucagon-like peptide 1 in Type 2 diabetic (NIDDM) patients.

Glucagon-like peptide 1 (GLP-1) has antidiabetic effects and many facets of Type 2 diabetes could theoretically be the consequence of a reduction in or lack of GLP-1 function. Exogenous GLP-1 is exquisitely effective in Type 2 diabetic patients, making receptor defects unlikely. GLP-1 responses after meals as detected by radioimmunoassay are not overtly reduced in Type 2 diabetic patients. Therefore, a sequence analysis of exon 2 of the preproglucagon gene coding for the GLP-1 protein was initiated in order to exclude potential germline mutations. 24 Type 2 diabetic patients and in 14 control subjects with normal oral glucose tolerance (WHO criteria) were studied. In all specimens of peripheral blood leukocyte DNA examined, no germline mutations of the GLP-1 sequence were identified, thus excluding mutations in the GLP-1 sequence as a major contributor to the pathophysiological appearance of the Type 2 diabetic phenotype. Rare mutations, however, cannot be excluded due to the small number of Type 2 diabetic patients examined.

Effect of complex decongestive physiotherapy on gene expression for the inflammatory response in peripheral lymphedema.

Complex decongestive physiotherapy (CDP), consisting of manual lymph drainage, compression bandaging, remedial exercises and skin care, mobilizes accumulated edema fluid and increases lymph flow. On the other hand, it also has a beneficial therapeutic effect on fibrosclerosis. Because little is known of its possible mode of action on a molecular level, this preliminary study evaluated CDP in patients with peripheral leg lymphedema as to the potential role of gene expression in the inflammatory response. The quantitative expression of genes for CD14, interferon-gamma receptor (IFN gamma R), tumor necrosis factor-alpha (TNF alpha), integrin alpha 4 beta 1 (VLA-4), tumor necrosis factor receptor p55 (TNFR1) and CD44 (standard form) was examined in 9 patients with primary or secondary leg lymphedema before and after phase 1 of CDP. Overall, there was a decrease of expression of these pro-inflammatory genes after CDP, suggesting that biologic mechanisms implicated in the inflammatory cascades in other disorders are also involved in the fibrosclerotic reactivity in lymphedema. However, whereas each patient acted as his or her own control before and after CDP, gene expression in normal patients and normal limbs before and after CDP needs to be examined before the full meaning of these observations can be understood.

[Lung maturation therapy with glucocorticoids in threatened premature labor. Considerations of risk-benefit in evidence-based medicine]. / Lungenreifetherapie mit Glukokortikoiden bei drohender Frühgeburt. Uberlegungen zur Nutzen-Risiko-Abwägung im Sinne der Evidence-based medicine.

Prematurity is a major cause of perinatal morbidity and mortality. Antenatal administration of glucocorticoids improves the neonatal outcome of preterm born infants. 1994 the NIH published recommendations for the use of glucocorticoids for women at risk of preterm delivery. A recent evaluation by the Cochrane Collaboration in 1999 showed that antenatal administration of glucocorticoids significantly reduced the rate of RDS and IVH in the gestational age between 24 and 34 weeks. Consequences of repeated courses of antenatal glucocorticoids are not sufficiently studied. The effectivity and safety regarding birth weights, infectious diseases, and the best timing remains unknown. Administration of glucocorticoids lowers fetal activity and heart rate variability. Effects on fetal growth, maternal and fetal immunosystem, and the development of atopic diseases are controversely discussed. Thus preterm labour not leading to a cervical ripening is not necessarily a reason for antenatal glucocorticoids. Antenatal glucocorticoids with PROM do not lower the rate of RDS but of IVH. No prospective randomized trial evaluated the effectivity of antenatal glucocorticoids in diabetes mellitus and IUGR. In preeclampsia beta-methason could improve the rate of RDS and the neonatal outcome. Still our knowledge of antenatal glucocorticoid administration is not sufficient. But despite possible (longtime-) risks for mother and child the administration of glucocorticoids according to the guidelines of the NIH is a major part in the treatment of prematurity and improves the outcome of premature infants. The indication for multiple courses of glucocorticoids should be considered carefully.

Influence of glucagon-like peptide 1 on fasting glycemia in type 2 diabetic patients treated with insulin after sulfonylurea secondary failure.

OBJECTIVE: Glucagon-like peptide 1 (GLP-1) has glucose-dependent insulinotropic and glucagonostatic actions in type 2 diabetic patients on diet and on oral agents. It is not known, however, whether after secondary sulfonylurea failure, GLP-1 is still effective. RESEARCH DESIGN AND METHODS: Therefore, 10 type 2 diabetic patients (6 women, 4 men; age 65+/-10 years, BMI 30.4+/-5.1 kg/m2, HbA1c 8.2+/-1.5%, 6+/-3 [2-13] years after starting insulin treatment) were examined in the fasting state after discontinuing NPH insulin on the evening before the two study days. GLP-1 (1.2 pmol x kg(-1) x min(-1) or placebo (NaCl with 1% human serum albumin) were infused over 6 h. Plasma glucose (glucose oxidase) insulin (IMx), and C-peptide (enzyme-linked immunosorbent assay) were measured. Statistical analysis was performed using repeated measures analysis of variance. RESULTS: Fasting plasma glucose was 9.4+/-0.5 mmol/l and was reduced by GLP-1 to 5.3+/-0.3 (3.9-7.3) mmol/l (placebo: 8.2+/-0.7 mmol/l; P < 0.0001). GLP-1 transiently increased insulin (from 115+/-31 to 222+/-64 pmol/l at 150 min; P < 0.0001) and C-peptide (from 1.00+/-0.12 to 1.90+/-0.23 nmol/l at 120 min; P < 0.0001) with no effect of placebo. Glucagon and free fatty acids were lowered transiently. After normalization of plasma glucose, insulin and C-peptide concentrations became lower again during the ongoing administration of exogenous GLP-1, and no hypoglycemia occurred. CONCLUSIONS: It is concluded that exogenous GLP-1 effectively lowers plasma glucose concentrations in advanced type 2 diabetes long after sulfonylurea secondary failure. These findings may broaden the applicability of GLP-1-derived drugs as a new treatment to nearly all type 2 diabetic patients.

Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study.

BACKGROUND: The incidence of actinic keratoses (AK) is rising and there is still a need for therapeutic alternatives. OBJECTIVE: To demonstrate the efficacy and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) in the treatment of AK. METHODS: Ten patients with 36 lesions (19 at hands and arms, 17 on the head) received ALA-PDT once (occlusive application of a 10% ALA emulsion for 6 h, irradiation with red light, 580-740 nm, 150 J/cm2) and were then monitored for 3 months. Therapeutic efficacy was judged using a score evaluating infiltration and keratosis of AK. RESULTS: After 28 days, significantly lower score sums were observed (head: mean = 15%; hand: mean = 67%) compared to the initial score (100%). Complete remission was achieved in 71% of AK localized on the head. No notable side effects were observed. CONCLUSION: This study demonstrated the potential of good efficacy and tolerability in the treatment of AK using topical ALA-PDT. How efficacy for lesions on the hand can be improved and whether PDT is able to concur with established treatment modalities remains to be shown in further studies.

The 5'-flanking region of the rat synapsin I gene directs neuron-specific and developmentally regulated reporter gene expression in transgenic mice.

The expression of the synapsin I gene is neuron-specific and developmentally regulated. As a step toward characterizing the molecular mechanisms that are responsible for its transcriptional regulation in vivo, we have generated transgenic mice that carry the chloramphenicol acetyltransferase (CAT) receptor gene under the control of approximately 4,300 nucleotides of 5'-flanking sequence of the rat synapsin I gene. In four independent transgenic mouse lines, high level CAT expression is observed specifically in the brain and other neural tissues. Two of these lines also exhibit notable CAT expression in testis. The transgene is expressed at similar levels in many different regions of the central nervous system. Immunohistochemical staining detects the CAT marker protein in various cell populations of neuronal morphology within the brain and the spinal cord. Transgene expression is developmentally regulated in a way that correlates well with the expression of the endogenous synapsin I gene. Both follow a characteristic, biphasic postnatal time course with a maximum around day 20. We conclude that the DNA region investigated contains cis-regulatory elements sufficient to drive the expression of a reporter gene in a spatial and temporal pattern that resembles the expression of the endogenous synapsin I gene.

The 5'-flanking region of the synapsin I gene. A G+C-rich, TATA- and CAAT-less, phylogenetically conserved sequence with cell type-specific promoter function.

The 5'-terminal region of the rat gene for the neuron-specific phosphoprotein, synapsin I, was isolated and sequenced. It comprises 1472 nucleotides (nt) of 5'-flanking sequence, 507 nt of the first exon, and 242 nt of the first intron. A single transcription start site was mapped by primer extension and S1 nuclease analysis. A sequence of 340 nt upstream from the transcription start site and the first exon are G+C-rich and enriched in CpG dinucleotides, resembling a CpG island. The 5'-flanking sequence lacks TATA and CAAT consensus elements but contains a consensus motif for the cAMP-responsive element. Furthermore, we notice two potential consensus motifs which are also found in corresponding positions in the genes for the nerve growth factor receptor and the 68-kDa neurofilament protein. The 5'-terminal region of the human synapsin I gene was also cloned and sequenced. A high degree of sequence conservation between rat and human is found in the upstream 340 nt that coincides precisely with the G+C-rich domain and includes the consensus elements, and throughout the first exon including the untranslated sequence. Sequence conservation is also observed further upstream and at the beginning of the first intron. In a transient chloramphenicol acetyltransferase expression assay, 5'-flanking sequences of the rat synapsin I gene function as strong promoters in neuroblastoma cells, but not in fibroblastoid cells. 225 nt of 5'-flanking sequence and 105 nt of 5'-untranslated sequence are sufficient for cell-type specific transcription in this assay.