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Biomedical subjects

J Schmidt

Publications and source records attributed to J Schmidt.

At least 19 recordsLinked to original sources

Bulk chemical shifts in hydrogen-bonded systems from first-principles calculations and solid-state-NMR.

We present an analysis of bulk (1)H NMR chemical shifts for a series of biochemically relevant molecular crystals in analogy to the well-known solvent NMR chemical shifts. The term bulk shifts denotes the change in NMR frequency of a gas-phase molecule when it undergoes crystallization. We compute NMR parameters from first-principles electronic structure calculations under full periodic boundary conditions and for isolated molecules and compare them to the corresponding experimental fast magic-angle spinning solid-state NMR spectra. The agreement between computed and experimental lines is generally very good. The main phenomena responsible for bulk shifts are packing effects (hydrogen bonding and pi-stacking) in the condensed phase. By using these NMR bulk shifts in well-ordered crystalline model systems composed of biologically relevant molecules, we can understand the individual spectroscopic signatures of packing effects. These local structural driving forces, hydrogen bonding, pi-stacking, and related phenomena, stand as a model for the forces that govern the assembly of much more complex supramolecular aggregates. We show to which accuracy condensed-phase ab initio calculations can predict structure and structure-property relationships for noncovalent interactions in complex supramolecular systems.

Journal Article↗

Comparison of biomaterials: three meshes and TAPP for inguinal hernia.

BACKGROUND: In laparoscopic hernia repair the use of biocompatible materials is necessary. A prospective, double-blind study was projected to compare three different meshes. METHODS: Ninety male patients with primary inguinal hernia undergoing transabdominal preperitoneal (TAPP) implant procedures were included. Three different types of mesh were tested: a monofile, heavy-weight, rigid mesh (group A), a smooth, heavy-weight variant of polypropylene (group B), and a polyglactin/polypropylene compound mesh (group C). Complications, pain development, inability to work, physical conditions, testicular volume, and blood circulation were documented. RESULTS: Convalescence in group A was slower than in groups B and C: Postoperative values of visual scales for pain development were higher, inability to work was 7.3 days longer, urologic effects were more severe, activities of everyday life were more reduced, and data of the German SF-36 Health Survey Test showed a significant reduction of physical condition (p < 0.05). CONCLUSION: The compound mesh did not create more comfort for the patients than the smooth variant of the heavy-weight polypropylene mesh.

Aged↗

Development and evaluation of a training module for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery.

BACKGROUND: With the increasing use of the surgical robotic system in the clinical arena, appropriate training programs and assessment systems need to be established for mastery of this new technology. The authors aimed to design and evaluate a clinic-like training program for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery. METHODS: Four trainees with different surgical levels of experience participated in this study using the da Vinci telemanipulator. Each participant started with an initial evaluation stage composed of standardized visceral and vascular operations (cholecystectomy, gastrotomy, anastomosis of the small intestine, and anastomosis of the aorta) in a porcine model. Then the participants went on to the training stage with the rat model, performing standardized visceral and vascular operations (gastrotomy, anastomosis of the large and small intestines, and anastomosis of the aorta) four times in four rats. The final evaluation stage was again identical to the initial stage. The operative times, the number of complications, and the performance quality of the participants were compared between the two evaluation stages to assess the impact of the training stage on the results. RESULTS: The operative times in the final evaluation stage were considerably shorter than in the initial evaluation stage and, except for cholecystectomies, all the differences reached statistical significance. Also, significantly fewer complications and improved quality for each operation in the final evaluation stage were documented, as compared with their counterparts in the initial evaluation stage. These improvements were recorded at each level of experience. CONCLUSIONS: The presented experimental small and large animal model is a standardized and reproducible training method for robotic surgery that allows evaluation of the surgical performance while shortening and optimizing the learning-curve.

Animals↗

PEG-hirudin/iloprost coating of small diameter ePTFE grafts effectively prevents pseudointima and intimal hyperplasia development.

OBJECTIVES: Small diameter PTFE grafts are prone to thrombosis and intimal hyperplasia development. Heparin graft coating has beneficial effects but also potential drawbacks. The purpose of this study was to evaluate the experimental efficacy of PEG-hirudin/iloprost coated small caliber PTFE grafts. METHODS: Thirty-six femoro-popliteal ePTFE grafts (expanded polytetrafluoroethylene, diameter 4 mm) were inserted into 18 pigs. Grafts were randomised individually for each leg and grouped for 3 groups. Group I consisted of native ePTFE grafts, group II were grafts coated with a polylactide polymer (PLA) without drugs and group III grafts were coated with PLA containing a polyethylene glycol (PEG)-hirudin/iloprost combination. The follow-up period was 6 weeks. Patency rates were calculated and development of pseudointima inside the grafts was noted. Thickness of intimal hyperplasia at the distal anastomoses was measured using light microscopy. RESULTS: Patency rates for group I were 6/9 (67%), for group II 9/10 (90%) and 12/12 (100%) for group III. In groups I and II there was a significant reduction of blood flow proximal to the graft at graft harvest, to 29+/-12 and 28+/-20 ml/min respectively (both p<0.01 versus preoperative value), whilst in group III blood flow, 99+/-21 ml/min, remained at the preoperative level. Subtotal stenosis due to development of pseudointima was noted in each of the native and PLA coated grafts but not in group III grafts. Intimal hyperplasia at the distal anastomosis was lowest in group III. CONCLUSIONS: The PEG-hirudin/iloprost coating of ePTFE prostheses effectively reduced pseudointima and intimal hyperplasia development and led to superior graft patency.

Anastomosis, Surgical↗

A new Puumala hantavirus subtype in rodents associated with an outbreak of Nephropathia epidemica in South-East Germany in 2004.

A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East Germany, starting in April 2004. While only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by June 2005. To determine the reservoir responsible for the infections, a total of 43 rodents were trapped in Lower Bavaria. Serological and genetic investigations revealed that Puumala virus (PUUV) is dominant in the local population of bank voles. Partial PUUV S segment nucleotide sequences originating from bank voles at four different trapping sites in Lower Bavaria showed a low divergence (up to 3.1%). This is contrasted by a nucleotide sequence divergence of 14-16% to PUUV strains detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be responsible for the observed increase of human hantavirus infections in 2004-2005.

Animals↗

Structural and dynamical properties of ribbonlike self-assemblies of a fluorinated cationic surfactant.

The structural and dynamic properties of low ionic strength micellar solutions of the cationic surfactant perfluorooctylbutane trimethylammonium bromide have been investigated by cryo-TEM, small-angle neutron scattering, small-angle X-ray scattering, T-jump and rheological experiments. The surfactant molecules self-assemble into narrow ribbons with average dimensions on the order of 4 nm x 3 nm, either under salt-free conditions or in the presence of up to 30 mM KBr or NaF. Cryo-TEM also reveals in the salt-free systems the presence of networks of multiconnected micelles. Rheological experiments showed that these surfactant systems exhibit a strong shear-thickening effect even in the presence of up to 30 mM KBr. The T-jump response of the micellar solutions was found to be multiexponential. This observation rules out the presence of only linear micelles with an exponential length distribution and suggests more complex topologies of the micellar aggregates. The relaxation time associated with the predominant process in the T-jump relaxation is strongly correlated to the critical shear rate beyond which shear thickening occurs, thus indicating that this critical shear rate is controlled by the micellar kinetics.

Journal Article↗

Effect of Flt3 ligand gene transfer in experimental pancreatic cancer.

BACKGROUND: Fms-like tyrosine kinase 3 receptor (Flt3) is an important receptor expressed on the cell membrane of immature antigen-presenting cells. The binding of Flt3 to its ligand (FL) activates the proliferation of dendritic cells (DCs). This mechanism is currently being evaluated in the therapy of malignant tumors. The aim of the present study was to study the effect of FL gene transfer on the immune response and tumor growth in experimental pancreatic cancer. MATERIALS AND METHODS: The rat FL was sequenced and cloned from total mRNA extract of the spleen. Transfection efficiency of subcutaneously growing rat duct-like pancreatic cancer (DSL6A) with DOTAP-/cholesterol-based liposomes was tested using a pcDNA3.1-lacZ construct. Flt3 ligand production of in vitro transfected tumor cells and in vivo transfected tumors was measured by enzyme-linked immunosorbent assay. Tumor induction was achieved in Lewis rats by a subcutaneous inoculation of syngeneic pancreatic tumor cells (DSL6A). The animals were allocated into three groups: control, mock treatment, and treatment with FL plasmid. The plasmid was injected intratumorally three times per week for 2 weeks. The total observation time was 6 weeks. RESULTS: The tumor volume was significantly lower in the FL-transfected group during the first 3 weeks. The number of responders was significantly higher in the FL group compared with control and mock treatment. The number of CD80+ DCs in the spleen was significantly higher after FL gene transfer. The responders showed a significantly higher number of splenic natural killer (NK) cells. There were no differences of infiltrating lymphocytes, proliferation, and tumor blood vessels between the groups. CONCLUSION: Intratumoral gene transfer of FL in rats activated proliferation of DCs and NK cells, which causes a moderate reduction of tumor growth. This improvement of local tumor control during the first weeks could be explained by an improved antigen presentation.

Adenocarcinoma↗

[Septic thrombosis of the axillary vein with unilateral pulmonary abscess. Variation of Lemierre's syndrome].

HISTORY: A man aged 62 was hospitalized for treatment of an axillary abscesses originating from a suppurative hidradenitis. INVESTIGATIONS: Microbiological tests revealed peptostreptococcus and staphylococci. Hepatic enzymes were moderately elevated in association with a mild hyperbilirubinemia. RESULTS: After surgical intervention the patient developed a severe septic illness together with a unilateral pulmonary infection and abscess formation, requiring a thoracotomy. Preoperative serology ruled out active hepatitis as well as atypical pneumonia. The detection of a unilateral septic axillary thrombosis led to the correct diagnosis. Antibiotics and anticoagulation brought about a complete cure. CONCLUSION: In cases of septicemia of uncertain origin septic venous thromboses should be considered in the differential diagnosis.

Anti-Bacterial Agents↗

[Loss of vision after non-ophthalmic surgery: systematic review of the literature on incidence, pathogenesis, treatment and prevention].

BACKGROUND AND GOAL: Postoperative loss of vision is a rare, but devastating complication after non-ocular surgery. It can occur partially or completely and may involve one or both eyes. Since its etiology has not yet been solved, the purpose of this review was to extract potential causes from the case collections reported to propose prophylactic measures. METHODS: A literature search was performed using the "Pubmed" database of the US National Library of Medicine. MeSH terms and combinations used were: blindness, postoperative complications, ischemic optic neuropathy, not ophthalmological surgical procedures, not neurosurgical procedures. Additionally, the results of the interim analysis of the postoperative visual loss (POVL) registry of the ASA were considered. RESULTS: The incidence of permanent loss of vision after non-ophthalmologic surgery is reported to be 0.0008%. However, it is elevated up to 0.11% after cardiac and 0.08% after spine surgery. Risk factors seem to be perioperative anemia, arterial hypotension and prone position, but also pre-existing diseases such as arteriosclerosis. Thus hemodynamic stabilization or correction of anemia may be successful in therapy. CONCLUSION: Patients with pre-existing arteriosclerotic disease scheduled for spine or cardiac surgery, but also for bilateral neck dissection should be informed preoperatively about the rare possibility of POVL. Postoperatively any visual changes should be immediately referred to an ophthalmologist and treated accordingly.

Atherosclerosis↗

[Postoperative pulmonary complications: prophylaxis after noncardiac surgery].

Postoperative pulmonary complications are a major problem after upper abdominal or thoracoabdominal surgery. They lead to a prolonged ICU stay as well as increased costs and are one of the main causes of early postoperative mortality. Even after uncomplicated operations, postoperative hypoxemia occurs in 30-50% of patients. Acute respiratory failure involves a disturbance in gas exchange. The mortality ranges from 10 to 60% according to the severity of respiratory failure. The most important complications are interstitial and alveolar pulmonary edema, atelectasis, postoperative pneumonia, hypoventilation, and aspiration. Preoperative optimization, postoperative prophylaxis according to a stepwise approach, and early mobilization decrease the rate of complications.

Early Ambulation↗

[Evaluation of traditional German undergraduate surgical training. An analysis at Heidelberg University].

BACKGROUND: The medical faculty of Heidelberg University implemented a new problem-based clinical curriculum (Heidelberg Curriculum Medicinale, or Heicumed) in 2001. The present study analyses the evaluation data of two student cohorts prior to the introduction of Heicumed. Its aim was to specify problems of the traditional training and to draw conclusions for implementation of a new curriculum. METHODS: The evaluation instrument was the Heidelberg Inventory for the Evaluation of Teaching (HILVE-I). The data were analysed calculating differences in the means between defined groups, with the 13 primary scales of the HILVE I-instrument as dependent variables. RESULTS: Teaching method and subject had no systematic influence on evaluation results. Thus, didactic lecture in orthopedic surgery achieved better results than small group tutorials, while the data on vascular and general surgery showed opposite results. Major factors for success were continuity and didactic training of lecturers and tutors. This is convincingly reflected by the results of the lecture course "Differential diagnosis in general surgery". The good evaluation data on small group tutorials resulted largely from the "participation" and "discussion" scales, which represent interactivity in learning. CONCLUSION: The results of the present study suggest the importance of two major pedagogic ideas: continuity and didactic training of lecturers and tutors. These principles were widely implemented in Heicumed and have contributed to the success of the new curriculum.

Attitude of Health Personnel↗

Evaluation of microperfusion disturbances in the transplanted liver after Kupffer cell destruction using GdCl3: an experimental porcine study.

BACKGROUND: Organ function after liver transplantation is determined by ischemia-reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3) has been shown to have a possible preventive effect on the extent of this injury, which can be extrapolated by analyzing the distribution of hepatic microperfusion. The aim of this study was to evaluate the protective effect of GdCl3 on disturbances of microperfusion in the transplanted liver. METHODS: Landrace pigs were randomly divided into three groups. In the control group (CG; n=6) a mapping of the native liver was conducted. For mapping, the four hepatic liver lobes were named from right to left with A to D and every lobe was divided into three vertical segments (cranial, medial, and caudal). In each of these 12 areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100 g/min]). The other two groups were considered as transplanted treated group (TTG; n=10) and transplanted nontreated group (TnTG; n=10). The TTG received an infusion of 20 mg/kg GdCl3 intravenously 24 hours before organ harvesting. Then standardized orthotopic liver transplantation was performed. In TnTG, standardized orthotopic liver transplantation was carried out without prior GdCl3 injection. In the recipients, the microperfusion of transplanted livers were mapped in both TnTG and TTG, in two different time points (1 hour [n=5] and 24 hours (n=5]) after reperfusion. RESULTS: A significant reduction of macrophages in the TTG livers in comparison to the CG and TnTG livers was observed (P<.05). However, the number of macrophages in CG and TnTG livers showed no significant difference (P>.05). Regarding liver microperfusion, in TnTG, a marked heterogeneity was detected in the livers after reperfusion. Significant differences between liver lobes (horizontal planes; P=.032) and vertical layers of intralobar liver parenchyma (P=.029) were observed. The same pattern was seen in TTG livers after reperfusion and a significant difference between horizontal (P=.024) and vertical layers (P=.018) of liver tissue were observed. Comparing intralobar regional flow data between vertical planes 24 hours after reperfusion still showed a prominent variation of hepatic tissue perfusion in TnTG livers (P=.028). Within the same horizontal layers, no significant differences between lobes were measured anymore (P=.16). Contrary to TnTG, in TTG, a homogenous pattern of regional liver tissue perfusion was recorded 24 hours after reperfusion. Comparison of TD data on the liver regions showed no significant microperfusion differences in either horizontal (P=.888) or vertical (P=.841) layers. CONCLUSIONS: Application of GdCl3 resulted in a significant reduction of Kupffer cells. Twenty four hours after transplantation microperfusion showed a homogeneous pattern, which constituted an earlier and better recovery of the transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia-reperfusion injury and seemed to be responsible for the early recovery of microperfusion disturbances and thus for an improvement of graft function.

Animals↗

Results of a randomised controlled cross-over trial on the effect of continuous subcutaneous glucose monitoring (CGMS) on glycaemic control in children and adolescents with type 1 diabetes.

OBJECTIVE: To study the feasibility and the influence on glycaemic control of continuous glucose monitoring (CGMS) in young patients with type 1 diabetes. DESIGN AND METHODS: A double-blinded, cross-over study was performed in 30 children (median age 11.1 years [range: 2.3 - 16.3], diabetes duration 2.1 years [0.2 - 7.1]). Patients were randomised into an open (A) or blind study arm (B). Both groups performed standardised self-monitoring blood glucose (SMBG) and received CGMS at the beginning of the study, at 3 and 6 months, each. In the blinded arm, patients and investigator were concealed from CGMS data. After 3 months, open and blinded study arms crossed over. Average glucose values and area under the glucose curve (AUC) per 24 h, above 180 and below 60 mg/dl were calculated from CGMS. Haemoglobin A1c (HbA1c) was measured at each study point. RESULTS: Despite comparable clinical characteristics between the 15 patients of each arm, mean HbA1c was slightly lower in arm A than in B at baseline (7.8 +/- 1.2 % vs. 8.4 +/- 1.1 %, p = 0.148), at 3 months (7.8 +/- 1.1 % vs. 8.3 +/- 1.1 %, p = 0.233), and significantly lower at 6 months (7.6 +/- 1.1 % vs. 8.5 +/- 0.9 %, p = 0.026). However, no significant change of HbA1c occurred within each arm (A, p = 0.183 and B, p = 0.823), irrespectively whether CGMS data were blinded or not. Likewise, mean glucose and hyper- or hypoglycaemia values did not change significantly. CONCLUSIONS: In this setting, CGMS did not decisively influence glycaemic control of a total study cohort. More frequent use of CGMS at shorter intervals in single patients with hyper- or hypoglycaemic problems may be of greater value than SMBG.

Adolescent↗

The role and value of sirolimus administration in kidney and liver transplantation.

Enormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants.

Graft Rejection↗

Immunosuppressive standards in simultaneous kidney-pancreas transplantation.

Simultaneous pancreas-kidney transplantation is an established procedure for patients with type I diabetes and end-stage renal disease. Continuous advances in the operation techniques with consequent reduction of perioperative morbidity and mortality and the introduction of modern immunosuppressive agents improved not only patients but also graft survival and significantly decreased rejection episodes of both kidney and pancreas grafts. Availability of a variety of new immunosuppressants in the clinical routine and increasing experience of the transplant specialists allowed further developments of therapeutic schemes with application of induction and maintenance immunosuppressive protocols. In this article, we summarize the current status of immunosuppressive regimens in simultaneous pancreas and kidney transplantation.

Graft Rejection↗

How to increase inflow in liver transplantation.

Liver transplantation (LTx) has become the treatment of choice for selected cases of benign and malignant liver disease. Despite becoming increasingly safer in recent years this procedure still incurs several serious postoperative complications. The most significant surgical complications are related to surgical technique, particularly the reconstruction and/or anastomosis of the hepatic artery. Arterial hypoperfusion may lead to graft failure, sepsis, or ischemic biliary lesions. In this review we focus on the Achilles' heel of LTx: the hepatic artery. We provide transplant surgeons with an overview of the technical options that are available to increase arterial inflow and subsequently improve patient outcome. We exemplify some of the discussed techniques using a liver transplant case with an eventful postoperative course because of arterial complications.

Adult↗

Biliary complications after liver transplantation.

Biliary complications remain a substantial cause of morbidity following liver transplantation. They have been reported to occur in a rate of 10-15% of full-size transplantations and may be higher in living donor, split or reduced size liver transplantations. The most common biliary complications following liver transplantations are leaks and strictures. In both, the incidence varies with respect to type of graft and donor as well as the type of biliary anastomosis. The management of the biliary complications requires a multidisciplinary approach and has changed over the past decade, favoring endoscopic and radiological techniques. Surgical revision including retransplantation is reserved for patients in whom endoscopic and interventional modalities are unsuccessful.

Biliary Tract Diseases↗

Wound complications following kidney and liver transplantation.

Advances in surgical techniques and immunosuppression (IS) have led to an appreciable reduction in postoperative complications following transplantation. However, wound complications as probably the most common type of post-transplantation surgical complication can still limit these improved outcomes and result in prolonged hospitalization, hospital readmission, and reoperation, consequently increasing overall transplant cost. Our aim was to review the literature to delineate the evidence-based risk factors for wound complications following kidney and liver transplantation (KTx, LTx), and to present the preventive and therapeutic modalities for this bothersome morbidity. Generally, wound complications are categorized as superficial and deep wound dehiscences, perigraft fluid collections and seroma, superficial and deep wound infections, cellulitis, lymphocele and wound drainage. The results of several studies showed that the most important risk factors for wound complications are IS and obesity. Additionally, there are surgical and/or technical factors, including type of incision, reoperation, and surgeon's expertise, as well as comorbidities such as advanced age, diabetes mellitus, malnutrition, and uremia. Preventive management of wound complications necessitates defining their etiological factors so that their detrimental effects on healing processes can be addressed and reduced. IS modalities and agents, especially sirolimus (SRL), and steroids (ST) should be adjusted according to the patient's co-existing risk factors. SRL should be administered three months after transplantation and ST should be tapered as soon as possible. A body mass index (BMI) lower than 30 kg/m2 is advisable for inclusion in a transplantation program, but higher BMIs do not exclude recipients. Surgical risk factors can be prevented by applying precise surgical techniques. Therapeutic modalities must focus on the most efficient and cost-effective medications and/or interventions to facilitate and improve wound healing.

Humans↗