Bilateral endoscopic total extraperitoneal (TEP) inguinal hernia repair does not induce obstructive azoospermia: data of a retrospective and prospective trial.

BACKGROUND: The endoscopic totally extraperitoneal (TEP) mesh repair is nowadays a well-established tension-free method for inguinal hernia repair. Mainly based on animal studies and case reports, a concern about the risk of postoperative infertility was expressed. This clinical study aimed to evaluate the risk of infertility due to obstructive azoospermia in men of fertile age who underwent a bilateral hernia repair. METHODS: Over 3 years (2005-2008) 59 male patients, 18-60 years of age, underwent a bilateral TEP repair. Twenty-one of them were prospectively ("light mesh") and 38 retrospectively ("heavy mesh") evaluated for testicular volume and perfusion, serum levels of sexual hormones, ejaculate volume, and number of spermatic cells. Those parameters were determined preoperatively (prospective group) and not earlier than 3 months postoperatively (both groups). RESULTS: No significant difference between pre- and postoperative values was detected in the prospectively studied group. All postoperative parameters were within the normal range in the retrospective group. There was no evidence of impaired fertility in any patient due to the operation. CONCLUSION: The standardized TEP technique for simultaneous bilateral inguinal hernia repair in male patients was not associated with a higher risk for postoperative infertility after mesh implantation. The use of heavy-weight meshes had no negative effect on fertility.

[(section sign) 115 b SGB V threatens outpatient treatment for inguinal hernia. Analysis of outcome and economics]. / Das Aus für die minimal-invasive Leistenhernienversorgung durch (section sign) 115 b SGB V. Eine Analyse zu Patientenoutcome und Okonomie.

BACKGROUND: Current German legislation ( (section sign) 115 b SGB V) allows groin hernia inpatient treatment only under particular circumstances. That allows the operative technique of first choice for outpatient groin hernia repair to be determined by basic market principles. The aim of this paper was to study the feasibility of outpatient minimally invasive hernia surgery with regard to complication rates, patient satisfaction, and economic considerations. METHODS: For 1 year, a total of 571 patients with inguinal hernias (131 male, eight female, mean age 46 years, all ASA I) were treated at two surgical centers. Twenty-four percent (139/571) underwent outpatient total extraperitoneal repair (TEP). Complication rates were recorded. Patient satisfaction with the procedure was evaluated by a standard questionnaire. Cost calculations were compared with revenues according to the EBM2000plus. RESULTS: Of the patients, 96.4% were discharged on the day of operation without subsequent rehospitalization, 84% had no fears of complications at home, 54% went back to work in less than 14 days, and 88.7% were willing to undergo TEP a second time if necessary. Calculated average total cost of euro 709 exceeded the revenue of euro 565 by 20%. CONCLUSION: For a carefully selected group, outpatient TEP is patient-friendly and safe. Despite these advantages, it still remains economically unattractive to hospital management because of the 20% cover shortage. Improvements in the current legislation are urgently desired.

Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study.

HYPOTHESIS: Perioperatively administered enteral immunonutrition will improve early postoperative morbidity and cost-effectiveness after gastrointestinal tract surgery. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Surgical departments in German university and teaching hospitals. PATIENTS: One hundred fifty-four patients with upper gastrointestinal tract malignant neoplasms who were eligible for analysis. INTERVENTION: Preoperatively, patients received 5 days of oral immunonutrition (an arginine-, RNA-, and omega3 fatty acid-supplemented diet) or an isoenergetic control diet (1 L/d). Early postoperative enteral feeding with immunonutrition or an isoenergetic, isonitrogenous control diet using a catheter jejunostomy was performed for 10 days. MAIN OUTCOME MEASURES: Postoperative infectious complications, their treatment costs, and cost-effectiveness of immunonutrition were analyzed. Plasma levels of the fatty acids eicosapentaenoic acid and docosahexaenoic acid were measured. RESULTS: In the immunonutrition group, significantly fewer infectious complication events occurred (14 vs 27; P = .05). The number of patients with complications was significantly lower in the supplemented diet group after postoperative day 3 (7 vs 16; P = .04). The treatment costs of complications in the supplemented diet group were suggestively lower than in the control diet group (DM 75172 vs DM 204273). Cost-effectiveness was DM 1503 in the experimental group vs DM 3587 in the control group, where DM denotes deutsche mark (German currency). CONCLUSION: The perioperative administration of an enteral immunonutrition significantly (P = .05) decreased the early occurrence of postoperative infections and reduced substantially the treatment costs of the complications after major upper gastrointestinal tract surgery.

Pharmacodynamic and pharmacokinetic evaluation of a new transdermal delivery system with a time-dependent release of glyceryl trinitrate.

The pharmacokinetics of glyceryl trinitrate (GTN) and its main metabolites as well as the hemodynamic effects of a new transdermal delivery system (TDS) were investigated in ten healthy male volunteers using a single blind, placebo-controlled study design with an application period of active drug of 4 successive days. The adhesive-type matrix system contains 20-mg GTN and released about 75% in a time-dependent manner. The plasma concentrations of GTN and its metabolites 1-2- and 1-3 glyceryl dinitrate reflected the time-dependent release with higher plasma concentrations during the first 12 hours than during the second 12 hours. Continuous administration of the TDS, which released 15 mg GTN/day, caused an accumulation of GTN in the plasma (about 70% greater AUC at the fourth day in comparison with the first day). The total effect per dose on the a/b-ratio of the digital pulse (height of the peak of the systolic wave divided by height of the peak of the dicrotic wave) and the reflex tachycardia were diminished by about 50% and 37%, respectively, at the fourth treatment day. The effect on systolic blood pressure measured under orthostatic conditions was blunted already 8 hours after the first application. The effect of sublingually administered GTN on digital pulse was attenuated during administration and also 1 hour after removal of the last TDS. The effect was restored 8 to 12 hours after removal of the TDS. Thus, the discontinuous release of GTN from the new system does not prevent the decline of hemodynamic efficacy during continuous therapy.

Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery.

Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens.

Analysis of polar organic micropollutants in water with ion chromatography-electrospray mass spectrometry.

The coupling of ion chromatography (IC) with electrospray mass spectrometry (ES-MS) opens new ways for the determination of polar organic micropollutants in water samples. The technique of conductivity suppression has been found to reduce the background signal in the range of about two orders of magnitude leading to a significant increase in sensitivity. In addition, the formation of salt adducts has been avoided. The usefulness of this method was proven on several polar and environmentally relevant micropollutants such as the herbicide glyphosate and its metabolite aminomethylphosphonic acid (AMPA), the chelating agent ethylenediamine tetraacetate (EDTA) and diacetonketogulonic acid (DAG). This present study has shown that IC-ES-MS is a simple, sensitive and quick method for the determination of these polar organic traces in water samples after separation on an anion-exchange column without any derivatization. In this work, several possibilities of applications of IC-ES-MS (with varying conditions) are presented. Analysis of glyphosate, AMPA, DAG and EDTA in ground and surface water has been achieved by IC-ES-MS without additional sample preparation at a concentration level of 1 microgram/l.

Preliminary applicability tests of different methacrylic acid copolymers, type C NF, particularly relevant to spreading and film formation.

The intention of this study was to show under which conditions a film forming methacrylic acid copolymer coating excipient, corresponding to the requirements of pharmacopoeia, but obtained from different sources, can be substituted without severe problems. The mechanical properties of the film coats were investigated by dynamic-mechanical thermo-analysis (DMTA) experiments to determine with respect to the glass transition the storage modulus E', the loss modulus E'', and the loss factor tan delta. Further determinations concerned the surface tensions of the different coating dispersions. This attribute plays an important role in spreading, distribution and coalescence of the film forming preparations. Finally by a series of small experimental fluidized bed batches cores containing a model drug were coated with the different methacrylic acid copolymers. The resistance of these coated tablets in 0.1 N HC1 as well as their dissolution rates in artificial intestinal juice were tested. The coatings proved themselves so similar that in this case substitutions of products of different provenance are possible. The determinations of surface tension and the DMTA measurements seem to be useful and reliable preliminary applicability tests.

Lauroyldextran and crosslinked galactomannan as coating materials for site-specific drug delivery to the colon.

Lauroyldextran (LD) and crosslinked galactomannan (XGM) were investigated as microbiologically degradable film coating materials for site-specific drug delivery to the colon. LD was used with degrees of substitution between 0.12 and 0.40, and swelling in aqueous media between 195 and 50%, XGM-batches showed swelling between 309 and 520%. Theophylline tablets were coated in a Hüttlin Kugelcoater with coating quantities of 4-17 mg/cm2. Sprayable coating formulations were obtained with 4% aqueous dispersions of XGM or 4% dispersions of LD in a 1:1 mixture of 1-propanol and water with 10% glycerol (based on the polymer) as a plasticizer. Theophylline dissolution was monitored in a USP XXIII paddle dissolution apparatus with buffer pH 5.5. After 4 h, which is an average small intestine transit time, colon conditions were simulated by adding galactomannanase or dextranase, respectively. Results showed similar dissolution rates for all XGMs and high-swelling LDs during the first 4 h and a relatively quick disintegration after enzyme addition. Both parameters decreased with increasing coating quantities. Dissolution from low-swelling lauroyldextrans was very low but no disintegration was observed after enzyme addition. The disintegration rate was found to be proportional to the square root of the enzyme activity. All swollen materials exhibited low mechanical stability. XGM coatings, especially at higher coating quantities, showed small transient ruptures at the edges not caused by enzyme addition. This behaviour was explained by internal stress due to the high degree of swelling. In principle, materials of both types proved to be suitable as degradable coating materials. The ideal zero-dissolution before and quick disintegration after enzyme addition, however, was not realized with the present materials.

Steam sterilisation of vesicular phospholipid gels.

Vesicular phospholipid gels (VPGs), highly concentrated phospholipid dispersions of semisolid consistency and vesicular morphology are under investigation as potential implantable depots for sustained release of drugs and as intermediates for subsequent dilution into 'conventional' liposome dispersions. It was investigated here if VPGs can be steam sterilised. VPGs prepared from 400 mg/g egg-phosphatidylcholine by high-pressure homogenisation retained their vesicular structure but showed a slight increase in vesicle size (freeze-fracture electron microscopy). However, autoclaving slowed down both, the in vitro release of the hydrophilic marker carboxyfluorescein and vesicles from VPGs. This was assumed to be due to bigger vesicle sizes and corresponding increase in packing density of the vesicular matrix. Upon dilution into a liposome dispersion both negative staining electron microscopy and dynamic laser light scattering analysis confirmed a distinct increase in liposome size, mainly due to fusion of small (20 nm) vesicles with unfavourable curvature. This was consistent with the observed increase in encapsulation efficiency of carboxyfluorescein. Phospholipid hydrolysis during autoclaving was negligible with lysophosphatidylcholine formation of less than 2% (thin layer chromatography). Despite significant change of their morphological and functional properties during autoclaving VPGs retained their main characteristics, such as vesicular structure, sustained release and dilutability to liposome dispersions, and are, therefore, considered as autoclavable.

[The hemolysis and solubilization behavior of nonionic polymer surface-active agents classes]. / Untersuchungen zum Hämolyse- und Solubilisationsverhalten einiger nichtionischer polymerer Tensidklassen.

The solubilization of poorly water soluble drugs in surfactant solutions is still a problem in pharmaceutical technology. There doesn't exist any surfactant which can be applied unrestricted in parenteral dosage forms. For this reason, alkylpolyglycosides and fatty esters of dextran were investigated. Their solubilization behaviour and hemolytic activity was tested and compared to established surfactants. For solubilization, only water soluble surfactants can be used. That means, that only alkylpolyglycosides with two or more glucose units and dextran esters with a degree of substitution of 0.1 or less may be applied. The determination of the CMC of alkylpolyglycosides by solubilization of fluorescent substances shows a plot, typical for monomeric surfactants. The dextran esters show no CMC. They actually are polymeric surfactants and form monomolecular micelles. The differences in hemolytic activity of the alkylpolyglycosides run up to the factor 100. The hemolytic activity increase in this class of surfactants with the elongation of the alkyl chain and decreases with increasing degree of glycosylation. It doesn't exist any correlation between the CMC and the hemolytic activity. For diazepam the differences in solubilization behaviour are rather low. The solubilization behaviour is more effective than that of Solutol HS 15. The hemolytic activity of the dextran fatty esters is low, compared with the alkylpolyglycosides.

[Preparation and characterization of amphiphilic membranes with lyotropic mesophases for simulation of skin permeation resistance]. / Herstellung und Charakterisierung amphiphiler Membranen mit lyotropen Mesophasen für die Simulation des Hautpermeationswiderstandes.

New amphiphilic polymer networks based on methacrylates with amphiphilic side-chains were prepared by cross-linking. Undecanol was the lipophilic part and tetraoxyethylen the hydrophilic part of the side-chain. The cross-linking was performed by a similarly derived amphiphilic dimethacrylate connecting structure. To characterize the relevant membrane features, like solvatation, degree of cross-linking, phase behavior and glass transition temperature, predominantly the swelling properties in water as well as in certain organic solvents, but also polarisation microscopic examinations were used. It was intented to assess the dependence of these parameters from the degree of cross-linking. For this reason the different systems were ranked accordingly to their cross-linking. Their swelling degree was determined in the indifferent dioxane as swelling medium. In the binary phase diagram with water the systems show a prominent laminary phase in the area with water contents of about 20-80% up to a maximum temperature of 35 degrees C. The phase behavior was also confirmed by thermal analysis, and the results of swelling measurements in water. Despite the relatively small hydrophilic part of the molecule, the swelling of the tested new cross-linked systems is more intensive in water than in nonpolar organic solvents. The swelling characteristics and phase behavior show a certain comparability to the human skin.

[Hydrophobic modification of polyelectrolytes as solubility enhancers in preparations for parenteral administration]. / Hydrophob modifizierte Polyelektrolyte als Solubilisationshilfsstoffe in Zubereitungen zur intravasalen Anwendung.

Up to now there is no excipient for the solubilization of poorly watersoluble drugs that can be used without limitations in pharmaceutical preparations for intravasal application. The available surfactants show considerable hemolytic activity, cause anaphylactic reactions are chemically instable or have no sufficient solubilizing capacity. By polymerisation of non-ionic surfactants amphiphilic side-chain-polymers are obtained which show in vitro the same solubilization capacity as the monomers but exhibit practically no hemolytic activity. The objective of this work was to investigate, if this findings are also true for ionic oligomers. For this purpose, polyacrylic acids were substituted with long-chain alkyl amines. The solubilization capacity of these oligomers exceeds that of non-ionic amphiphilic side-chain-polymers and that of other surfactants. The hemolytic activity of the oligomers was below that of common ionic surfactants. The solubilization capacity as well as the hemolytic activity depends on the oligomers degree of substitution. Considering their high solubilization capacity and their low hemolytic activity, these oligomers may be excipients in preparations for parenteral application.

A new physiologically approached in vitro test for quick evaluation of the hemolytic activity of surfactants.

New physiologically approached in vitro assays are presented which allow rather quick and uncomplicated determinations of the hemolytic activity of surfactants, intended mainly to solubilize poorly soluble drugs in parenteral dosage forms. The extent and the rates of the hemoglobin release from erythrocytes during the incubation of blood with increasing additions of surfactants is thought to be a very suitable and realistic estimation of the membrane damaging side effects of amphiphilic substances. In this study the extent of free hemoglobin released into the plasma is determined by a spectrophotometric method, as well as by an enzymatic determination measuring the lactate dehydrogenase (LDH) activity. LDH is released in a similar way from damaged erythrocytes. The results of these two methods are compared. They correspond satisfactorily.

[Development and characterization of water soluble dextran fatty acid esters as excipients for colon-targeting]. / Herstellung und Untersuchung von wasserunlöslichen Dextranfett-säureestern als Umhüllungsmaterialien für das Dickdarm-Targeting.

In this paper production methods of certain colon-degradable dextran fatty acid esters and their relevant properties as excipients for colon-targeting dosage forms are reported. Such dextran fatty acid esters must be insoluble in, resp. resistant against, gastric and small intestinal fluids. But to a certain degree they must be swellable in aqueous liquids in order to allow an enzymatic attack of the colonic microflora. Furthermore, they must be adequately soluble in pharmaceutically accepted solvents to permit the technological application of film coatings. Otherwise, they can only be used as embedding excipients or matrices. As the most suitable excipients for film coatings, biodegradable by the colonic microflora, but resistant against gastric and small intestinal fluids, the dextran lauroyl esters were found. Their molecular weight have to be between 60,000 and 250,000, and their average degree of substitution (DS) between 0.06 and 0.2. Are the molecular weights higher the DS must be correspondingly lower.

[Significance of sonography of the breast for surgical treatment of breast cancer]. / Bedeutung der Sonographie der Brustdrüse für die operative Therapie des Mammacarcinoms.

In a prospective study of 119 patients with breast carcinoma the value of ultrasonography for surgical therapy was compared with the value of clinical results and mammography. The tumor localization (in 96.8%) and the exact preoperative staging following the pTNM-system (tumor size in 85.8%, lymph node involvement in 77.2%) were better predicted by ultrasonography than by mammography and clinical examination. Especially the multicentric-multifocal carcinomas (20 of 29 cases) were better detected. Preoperative ultrasonography especially improves planning a conservative management of breast cancer.

[Effect of euddragit and ethylcellulose coatings. A short review of pH and diffusion controlled drug delivery]. / Effekte von Eudragit- und Ethylzelluloseumhüllungen. Ein kurzer Uberblick über pH- und diffusionsgesteuerte Arzneistoffabgabe.

In this short review the fundamental differences between pH- and diffusion-controlled drug releases are outlined. In a following step the characteristics of single unit- and multiple units-dosage forms are discussed, and the predominantly used excipients for pH- and diffusion-controlled drug release are mentioned. Finally the influences of such special galenical designs for controlled drug release are explained in the light of some selected examples. The exact knowledge and consideration of these facts are extremely important in the development of optimal drug systems, in the interpretation of results, and with respect to interdisciplinary cooperation, e.g. between pharmaceutical technologists and pharmacologists.